Medicinal Plant Monograph

Edited
by: Cassandra L. Quave, Ph.D.

2013 by Casssandra L. Qu
©2 uave
Aug gust 2010. Con ntributions from
m UALR coursee BIOL 4499‐99 99, Summer IV 2010.
Aug gust 2011. Con ntributions from
m UALR coursee BIOL 4399‐99 99, Summer IV 2011.
Deccember 2011. Contributions from Emory University coursse HLTH 385‐001, Fall 2011.
Aprril 2012. Contrributions from Emory Universsity course HLT TH 385‐000, Sp pring 2012.
Aprril 2013. Contrributions from Emory Universsity course HLT TH 385‐002/AN NT 385‐002, Sp pring 2012.

Picctures on the ffront cover: Siilybum marianu
um (L.) Gaertn., Asteraceae (m milk thistle), Boorago officinaliis L., Boraginacceae (borage),
Mallva sylvestris L., Malvaceae (co
ommon malloww), Matricaria rrecutita L., Asteeraceae (Germaan chamomile).. Photos by C.L.. Quave.
TABLE OF CONTENTS
Preface Echinacea purpurea (L.) Moench, Asteraceae

Ephedra sinica Stapf., Ephedraceae
MEDICINAL PLANTS Ficus insipida Willd., Moraceae
Achillea millefolium L., Asteraceae Ginkgo biloba L., Ginkgoaceae
Allium sativum L., Amaryllidaceae Glycyrrhiza glabra L., Fabaceae
Aloe vera (L.) Burm. F., Xanthorrhoeaceae Hamamelis virginiana L. Hamamelidaceae
Ananas comosus (L.) Merr., Bromeliaceae Humulus lupulus L., Cannabaceae
Angelica archangelica L., Apiaceae Hypericum perforatum L., Hypericaceae
Arctostaphylos uva-ursi (L.) Spreng., Ericaceae Ilex paraguariensis A. St.-Hil., Aquifoliaceae
Armoracia rusticana G. Gaertn., B. Mey. & Scherb., Brassicaceae Lavandula angustifolia Mill., Lamiaceae
Artemisia absinthium L., Asteraceae Linum usitatissimum L., Linaceae
Asparagus officinalis L. Asparagaceae Matricaria recutita L., Asteraceae
Atropa belladonna L., Solanaceae Melaleuca alternifolia Cheel, Myrtaceae
Avena sativa L., Poaceae Momordica charantia L., Cucurbitaceae
Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton, Malpighiaceae Nepeta cataria L., Lamiaceae
Calendula officinalis Linn. Asteraceae Panax ginseng C.A. Mey., Araliaceae
Camellia sinensis (L.) Kuntze, Theaceae Papaver somniferum L., Papaveraceae
Cannabis sativa L., Cannabaceae Passiflora incarnata L., Passifloraceae
Capsicum annuum L., Solanaceae Persea americana Mill., Lauraceae
Carica papaya L., Caricaceae Petroselinum crispum (Mill.), Apiaceae
Castanea sativa Mill., Fagaceae Rosmarinus officinalis L., Lamiaceae
Catharanthus roseus (L.) G.Don, Apocynaceae Salix alba L., Salicaceae
Chondrodendron tomentosum Ruiz & Pavón, Menispermaceae Sambucus nigra L., Adoxaceae
Cimicifuga racemosa (L.) Nutt., Ranunculaceae Silybum marianum (L.) Gaertn., Asteraceae
Cinnamomum verum J. Presl, Lauraceae Solidago virgaurea L., Asteraceae
Coffea arabica L., Rubiaceae Taraxacum officinale F.H. Wigg., Asteraceae
Cola nitida (Vent.) Schoot & Endl, Malvaceae Taxus brevifolia Nutt., Taxaceae
Commiphora molmol (Engl.) Engl. ex Tschirch, Burseraceae Theobroma cacao L., Malvaceae
Croton lechleri Mϋll.-Arg., Euphorbiaceae Thymus vulgaris L., Lamiaceae
Curcuma longa L., Zingiberaceae Uncaria tomentosa (Willd. ex Roem. & Schult.) DC., Rubiaceae
Digitalis purpurea L., Plantaginaceae Urtica dioica L., Urticaceae
Diospyros virginiana L., Ebenaceae
1|M e d i c i n a l P l a n t M o n o g r a p h s
Vaccinium macrocarpon Aiton, Ericaceae INDICES
Vaccinium myrtillus L., Ericaceae Contributors
Zingiber officinale Roscoe, Zingiberaceae Common Plant Names
CONTRIBUTORS
Anderson, Sam Hampton, Aerhealle Morris, Alisha

Baerwaldt, Tiffany Healy, Shannan Mosby, Sarah
Beck, Kimberly Henderson, MyKeya Nardo, David
Berlin, Avery Henkel, Sarah Nelson, Katie
Burgess, Erika Howard, Sarah Nwankwo, Ezinne
Cappello, Elizabeth M Howell, Jennifer Ohmart, Kira
Carl, Annalies Jarvis, Ben Okafor, Ijeoma
Carroll, Latavia Jiang, Sandy Paine, Michele
Chanyasubkit, Soraya Jones, Marston Patel, Nina
Chiang, Ellen Kahn, Alexa Pham, Anh-Phoung
Choe, David Kyle Kang, Apollonia Wenting Sefat, Cimma
Chu, Tianjiao King, Dhondup Tso Shalem, Ronni
Clanahan, Michael Kramer-Roach, Benjamin Turner, Samuel
Coleman, Charity Lake, Elsa Tyler, Paula
Cross, Kristen Lam, Ruby M. Wiegert, Carolyn
Dai, Mengshi Martens, Kylee Woodard, Kedra
DeGrazie, Taryn McCabe, Carly Wyeth, Wallace
Demakovsky, Leah McCullough, Ian Yang, Yinan
Dhukani, Anum McMullin, Sarah Yarp, Alison
Elinberg, Jessica McMurtry, Kinsey
Giffen, Elizabeth Mittal, Ashvi
Grady, Corrine Mongue, Andrew
COMMON PLANT NAMES
Absinthe Elderberry Ojé

Aloe Elder tree Opium Poppy
American Coneflower Ephedra Pacific Yew
Angelica European Chestnut Papaya
Asparagus European Goldenrod Parsley
Avocado Flat-leaved Parsley Passionflower
Ayahuasca Vine Flax Pepper
Bearberry Foxglove Persimmon
Bell Pepper Garden Angelica Pineapple
Belladonna Garlic Poppy
Bilberry German Chamomile Portuguese Chestnut
Bitter Melon Ginger Pot Marigold
Black Cohosh Ginkgo Purple Coneflower
Cannabis Ginseng Purple Foxglove
Catmint Goldenrod Purple Passionflower
Catnip Holy Ghost Rosemary
Cat’s Claw Hops Sangre de Drago
Chamomile Horseradish Sangre de Grado
Chile Pepper Italian Parsley Spanish Chestnut
Chocolate Kinnikinnick St. John’s Wort
Cinnamon Kola Nut Stinging Nettle
Coffee Lavender Sweet Chestnut
Common Dandelion Licorice Tea
Common Marigold Madagascar Periwinkle Tea Tree
Cranberry Marijuana Thyme
Curare Marron Turmeric
Dandelion Maté Uña de Gato
Deadly Nightshade Milk Thistle Uva Ursi
Digitalis Myrrh White Willow
Dragon’s Blood Norweigian Angelica Wild celery
Echinacea Oats Witch Hazel
Wormwood Yarrow Yerba maté
PREFACE
Cassandra L. Quave, Ph.D.
Throughout history, mankind has utilized plants as a competing with acetylcholine for the muscarinic receptor
primary source of food, medicine, and shelter. This site in the parasympathetic nervous system (Dewick 2001).
tradition continues today. In 2001, the World Health
Some notable plant-derived drugs still in use today include
Organization estimated that approximately 80% of the
vincristine (Catharanthus roseus (L.) G. Don;
world’s population was directly dependent on plant-based
Apocyanaceae), physostigmine (Physostigma venenosum
medicines (Cox and Heinrich 2001). In contrast with most
Balf. f.; Fabaceae), pilocarpine (Pilocarpus jaborandi
other organisms, plants have the ability to undergo a
Holmes; Rutaceae), reserpine (Rauvolfia serpentina (L.)
process of secondary metabolism, in which unique
Benth. ex Kurz; Apocyanaceae), and digitalis (Digitalis
compounds are produced for the purposes of defense,
purpurea L.; Scophulariaceae) (Cox and Balick 1994; Cox
pollinator attraction, and coloration, among others.
and Heinrich 2001; Dewick 2001; Solomon 2004). Today,
Examples of these important secondary metabolites usually
the search for new drugs coming from vascular plants
fall within the following natural product classes: alkaloids,
continues with particular focus on plants exhibiting
non-protein amino acids, cyanogenic glycosides, coumarins,
antimicrobial, anti-cancer, and antiviral effects. The need
glucosinolates, monoterpenes, sesquiterpene lactones,
for new, structurally unique antimicrobials is of utmost
diterpenoids, saponins, liminoids, carotenoids, phenols,
importance in this era of widespread microbial resistance
flavonoids, and quinones (Dewick 2001).
to existing therapies (Levy 2002; Smith and Coast 2002;
These same compounds, which serve important roles in Walsh 2003).
plant survival, are also useful in mammalian systems. For
Many plants that are used for their antimicrobial activity
example, upon entry into the human body and an
contain polyphenolic compounds, which commonly act as
environment of physiological pH, the very structure of
antiviral agents, or essential oils, which often act as
alkaloid compounds takes on a quaternary form, through
antiseptics (Heinrich et al. 2004). One of the best known
which the compound can interact with human receptors –
antimicrobial plants is garlic, Allium sativum L.,
inhibiting or stimulating activity of the targeted site. This
Amaryllidaceae. Garlic contains a wealth of sulphur
may have a medicinal, or even a toxic, effect on the body.
compounds, glycosides, and monoterpenoids. These
For instance, the alkaloid strychnine acts as a glycine
sulphur compounds have shown remarkable in vitro
mimic, binding to glycine receptor sites in the spinal cord,
antibacterial, antiviral, and antifungal activity (Blumenthal,
and exhibiting a toxic effect. On the other hand, the alkaloid
Goldberg, and Brinckmann 2000; Srinivasan et al. 2001;
atropine can exert a medicinal anticholinergic effect by
Zenner et al. 2003).
Another well-known plant with broad-spectrum applications of their selected species. Each monograph has
antimicrobial activity is the tea tree, Melaleuca alternifolia been formatted following these specifications:
Cheel., Myrtaceae. The monoterpenoids present in tea tree
oil have demonstrated activity against a broad spectrum of
microorganisms, including Staphylococcus aureus, Introduction
Escherichia coli, Candida albicans, Leishmania major, and This section gives an introduction to the plant by listing its
Trypanosoma brucei (Heinrich et al. 2004). scientific name and family, common names, and a brief
Secondary metabolites, or natural products, manufactured overview of how it is used, and what its main constituents
by plants as a means of defense against herbivory or are.
microbial infection, have demonstrated potent activity
against human pathogens. Yet, less than 0.5 % of the more
than 265,000 flowering species that exist on earth have Description
been exhaustively studied for their chemical composition This section contains a general description of the
and medicinal potential (Cox and Balick 1994). It is certain morphological characteristics of the plant. This includes its
that a wealth of novel structures wait to be studied, and habit (tree, shrub, herb, etc.), its habitat (marshy areas, arid
likely that some of these will, in fact, exhibit potential for plains, etc.), and its flower and fruit characteristics (color,
medicinal applications. smell, shape).
EXPLANATION OF MONOGRAPH SECTIONS Traditional Uses

In this e-book, I have compiled the medicinal plant This section pertains to the ethnomedical and other
monographs written by my students as their final paper for ethnobotanical applications of the species, including
“Botanical Medicine and Health” course taught at Emory descriptions of its use as a food, decorative, construction,
University and “Medical Botany” web-based course taught clothing, and etc.
at the University of Arkansas at Little Rock. At the
beginning of the semester, students were asked to select a
medicinal plant and research its uses in CAM and Chemistry and Pharmacology
traditional medicine, the mechanisms of action of its A description of the principle chemical constituents of the
constituents, and assess the data reported in laboratory plant are given here.
and clinical trials. Using this information, they each wrote a
plant monograph which focuses on the medicinal
Biological Activity References Cited
In this section, in vitro and in vivo laboratory studies Blumenthal, Mark, Alicia Goldberg, and Josef Brinckmann. 2000.
conducted on extracts or fractions or purified compounds Herbal Medicine. Expanded Commission E Monographs.
from the plant is described. Mechanisms of action are also Newton, MA: American Botanical Council. Integrative
discussed and issues with drug resistance are addressed. Medicine Communications.
Cox, Paul Alan, and Michael J. Balick. 1994. "The ethnobotanical
approach to drug discovery." Scientific American no. 270
Clinical Studies (1):82-87.
When applicable, results from clinical studies are discussed Cox, Paul Alan, and Michael Heinrich. 2001. "Ethnobotanical drug
in this section. discovery: uncertainty or promise?" Pharmaceutical
News no. 8 (3):55-59.
Dewick, Paul M. 2001. Medicinal Natural Products. Second ed.
Contraindications Chichester, England: John Wiley & Sons, Ltd.
Drug contraindications (interactions with other CAM or Heinrich, Michael, Joanne Barnes, Simon Gibbons, and Elizabeth
allopathic medicines), side effects, toxicity and toxicology of M. Williamson. 2004. Fundamentals of Pharmacognosy
the plant products are discussed here. and Phytotherapy. London: Churchill Livingstone.
Levy, Stuart B. 2002. The Antibiotic Paradox: How the Misuse of
Antibiotics Destroys their Curative Powers. 2nd ed.
Current Use in Allopathic and CAM Therapies Cambridge, MA: Perseus Publishing.
In this section, the applications of the plant products in Smith, R.D., and J. Coast. 2002. "Antimicrobial resistance: a global
both CAM and allopathic medicine are discussed. Products response." Bulletin of the World Health Organization no.
on the market, including dietary supplements, OTC, and 80:126-133.
prescription medications are discussed. Solomon, Jim. Missouri Botanical Garden Vascular Tropicos.
Missouri Botanical Garden 2004.
Discussion Srinivasan, D., S. Nathan, T. Suresh, and P.L. Permalsamy. 2001.

"Antimicrobial activity of certain Indian medicinal plants
In this section, a summary of the utility of this medicinal used in folkloric medicine." Journal of
species is given and the importance of its role in human Ethnopharmacology no. 74:217-220.
health is discussed. Walsh, Christopher. 2003. Antibiotics. Actions, Origins, Resistance.
Washington, D.C.: ASM Press.
Zenner, L., M.P. Callait, C. Granier, and C. Chauve. 2003. "In vitro flagellates of poultry, Tetratrichomonas gallinarum and
effect of essential oils from Cinnamomum aromaticum, Histomonas meleagridis." Parasite no. 10:153-157.
Citrus limon and Allium sativum on two intestinal
Achillea millefolium L., Asteraceae
Tianjiao Chu
Introduction
Achillea millefolium L., commonly known as yarrow, belongs to
the family Asteraceae. Due to its global distribution it goes by
many names and is often also referred to as the milfoil,
thousand-leaf, or old man’s pepper because of its aromatic
smell. The genus name Achillea originates from a Greek legend
in which the hero Achilles applied Yarrow leaf to stop the
bleeding wounds of his soldiers. As suggested by the
mythology, A. millefolium heals wounds and treats blood-
related illnesses giving it the names of bloodwort, soldier’s
woundwort, herb militaris, sanguinary, nosebleed, or knight’s
milfoil. Numbering in eight species, A. millefolium was the
most widely used medicinal plant used by indigenous tribes in
North America (Yaniv, et al 2005), although it was possibly
confused with and used interchangeably with the nearly
identical Achillea lanulosa (Chandler, et al 1982). Yarrow was
also one species of pollen found at Shanidar IV, a Neanderthal
burial cave in Iraq dating 60,000 years ago, suggesting its
early ritual or medicinal use (Yaniv, et al 2005). Hence for
centuries, cultures around the globe have recognized the
many therapeutic effects of yarrow that is still sold as panacea
in herbal supplements and ointments today.
Botanical Description
Achillea millefolium propagates from a small rhizome and is
often recognized by weedy scientists in their compendia. It is a
perennial with a circumpolar distribution across Europe, Asia, Figure 1. Achillea millefolium L. illustrated diagram,
(Source: http://botanical.com/botanical/mgmh/y/yarrow02-l.jpg)
South America and North Africa. Since its introduction in
10 | M e d i c i n a l P l a n t M o n o g r a p h s
colonial times, it has naturalized throughout temperate zones
in North America with ranges across all fifty U.S. states,
Canada, as well as Greenland, demonstrating its ability to
survive in a wide variety of soil types (Yaniv, et al 2005).
Typically, Yarrow can be found in un-shaded, open areas
ranging from cliffs and lowland meadows, to roadsides and
waste grounds (Chandler, et al 1982).
Generally growing 12 to 24 inches (30 to 60 cm) in height, A.
millefolium appears gray-green in color from the numerous
small, silky white hairs that covers it. Its species name
millefolium, or thousand-leaves, refers to its highly segmented
foliage that vary in size from 3-20 cm in length and 1-6 cm in
width (Figure 1). Leaves are arranged in a feathering or fern- Figure 2. Terpenoids from A. millefolium (Si, et al 2006)
like way with clusters at the base of flowering stems and
smaller leaves alternating upwards. When crushed or dried,
the leaves give off a characteristically spicy aroma and have a
bitter and astringent taste when consumed (Chandler, et al
1982).
A. millefolium’s stem is angular instead of round, and has a
rough texture. Its flowers bloom in clusters at the ends of
stalks between May to October, peaking in quality during July,
and are known to attract bees and many other insects. Tiny
and daisy-like, the flowers may be white, pink, or red in color
(Libster 2002). Orange or yellow-blooming yarrow are often
confused as A. millefolium but in actuality belong to other
species of Achillea. Evolution in the A. millefolium group has
been recorded due to this mechanism of polyploidy, with
certain species having a particular number of chromosomes.
As such A. millefolium is widespread as a hexaploid, with
greatest diversity has been found in Europe where diploid,
tetraploid, and octoploid species have also been reported Figure 3. Flavonoids from the A. millefolium (Si, et al
(Chandler, et al 1982). 2006).
Traditional Uses treatment. Other oral therapeutic applications include fluid
Ritual uses extracts or tinctures. For topical applications, Yarrow is
soaked in oil, which can be rubbed as a massage. For external
Perhaps due its strong healing abilities, yarrow has been treatments, Yarrow may be burned and inhaled, or soaked
considered across many cultures to possess special spiritual into baths (Libster 2002).
or magical properties. In East Anglia yarrow, or ‘nosebleed,’
was employed as a plant which can divine future love by
placing the leaf inside the nose and reciting the rhyme, Therapeutic applications
‘Yarroway, yarroway, bear a white blow, if my love love me, my
Due to its world-wide distribution, cultures around the world
nose will bleed now’ (Grigson 1996). In ancient China, yarrow
in China, East India, Russia, across Europe in Serbia (local
was often used as a sacred ritual plant that symbolized the
name “Hajduˇcka trava”), Germany, Great Britain and Hungary
balance between yin and yang. Its stems are still used in to
(where it’s known as ‘kitten tail’), and even as far as Argentina
make divination sticks of the I Ching. In North America, Native
where it grows in the Falkland Islands, have recognized the
American tribes, among their prodigious healing uses for the
variety of therapeutic uses for Achillea millefolium. In many
plant, also burned the yarrow flowers to use as ceremonial
countries, yarrow is used as a panacea drug for all sorts of
smoke.
aliments (Jaric et al 2007). The most common and widespread
uses for yarrow in folk medicine, cross-culturally, is to take it
Commercial uses orally as a tea to treat internal blood-related illnesses,
digestion, cramping, and other gastrointestinal conditions.
In Iran yarrow is found to be a good source for natural dyes Yarrow is also commonly applied topically to slow-healing
for wool, due to the presence of flavonoids luteolin V and skin conditions to stop bleeding and inflammation.
apigenin VI. As an aromatic and editable herb, in Sweden
yarrow, called “field hop,” is sometimes used in the production For example in China, fresh yarrow is applied topically to treat
of especially potent beer. Elsewhere in Europe, yarrow is an wounds and sores, while the dried herb is used for internal
approved additive to foods and beverages as a flavor agent, as bleeding, hemorrhoids, and menstrual disorders. Recorded as
long as the thujone content, a ketone and monoterpene, does far back as the fourteenth century, Russian herbalists also
not exceed 0.5 mg/kg. In the US however, yarrow is only used yarrow as the plant of choice to stop all sorts of internal
approved for flavor uses in alcoholic beverages, with products bleeding (Libster 2002).
that remain thujone-free (Libster 2002). Among the common uses found in other cultures, early Anglo-
Saxons also applied yarrow for snake and dog bites, and ate
the roots on an empty stomach for toothache. Know as
Preparation ‘gearwe’ the medicinal uses of A. millefolium has been
Yarrow may be boiled in water as tea, with or without an documented in three of the oldest Anglo-Saxon texts: the Old
infusion of other herbs, to be drunk as part of a sweating
Table 1. Amino Acid from A. milleforium (Si, et al 2006)
English Herbarium (950 AD), Bald’s Leechbook (900-1000 AD),

and the Lacnuga (1000 AD). (Watkins et al 2011).
Some culturally specific and different uses for A. millefolium
have also been recorded. In ancient times, Aztecs were known
to use yarrow to cure coughs. Modern Hispanics in the
southwestern U.S. know yarrow as plumajillo and currently
use it treat colds, anemia, diarrhea, flatulence, and as a
diuretic. In both Italy and East India, yarrow is recognized for
its antipyretic abilities. In India especially it is used as a
medicated vapor bath for fevers, or powered and drank as a
tonic to dispel internal gas and cramping. In Russia, yarrow
was also given to nursing mothers to increase milk supply,
reduce high blood pressure, stimulate bile flow from liver and
gallbladder, and used to prevent the formation of kidney
stones and gallstones. And in Germany, yarrow is sometimes
used instead of iodine for children’s minor skin lacerations, as
well as to treat mood-swings or depression. German herbalists
also recommended Yarrow to be used with fennel as a
hypnotic, to help with post-surgical recovery (Libster 2002).
Native American tribes perhaps made the most extensive use
of A. millefolium. Yarrow was most commonly used among Table 2. Chemical composition of the essential oil of A.
different tribes to treat bruises, sprains and inflammation, millefolium (Candan et al 2003).
wound healing, and to provide itch relief from rashes and Inactive compounds from Yarrow may be seen in (Table 3)
other causes (Chandler et all 1982). Among the approximately (Chandler et al 1982). This list is by no means exhaustive and
450 species used medically by the Haudenosaunee (Iroquois) further studies of the species may yield additional minor
peoples in Upstate New York, A. millefolium was considered as chemical constituents not mentioned.
one of the four most powerful herbs. Often considered a fix-all,
the Haudenosaunee used yarrow as an analgesic,
antidiarrheal, antiemetic, antihelmintic, antipyretic, Biological Activity
antirheumatic, for blood illnesses, gastrointestinal problems, Anti-inflammatory
and for venereal disease (Fray et al 2010).
Recent pharmacological studies of plant extracts from all parts
of Achillea millefolium have shown anti-inflammatory
Chemistry and Pharmacology properties (Watkins et al 2001). A variety of A. millefolium’s
compounds contribute to its anti-inflammatory and
In 1961, the first flavonoids, cynarosides and cosmosiin, which
antipruritic activities: azulene, chamazulene, the
displayed spasmolytic activity, were isolated from A.
sesquiterpene lactones, some of the other constituents of the
millefolium. In 2006, the two terpenoids were isolated from
volatile oil like menthol and camphor, tannins, and possibly
Achillea millefolium: Angeloyloxy) artabsin 1,4-endoperoxide
the sterols and triterpenes. Some of these active agents may
and 8a-(Tigloyloxy)artabsin 1,4-endoperoxide (Figure 2).
account for the plant's effectiveness in treating some of the
The following eight flavonoids have been isolated from A.
other skin afflictions. Salicylic acid derivatives, eugenol,
millefolium: Luteolin, Cynaroside, Luteolin 7-
menthol and a number of other components present in the
malonylglucoside, Apigenin, Cosmosiin, Apigenin 7-
plant's volatile oil can be responsible for the local analgesia
malonylglucoside, Rutin and 5-Hydroxy-3,6,7,4’-
results. The antipyretic activity may also be a consequence of
tetramethoxyflavone (Figure 3) (Si et al 2006). In addition the
the presence of salicylic acid derivatives, chamazulene or
flavonoids casticin and isorhamnetin were also found in a
similar agents. Thujone, a known abortifacient, may be the
separate study (Chandler et al 1982). The amino acids
active ingredient responsible for the use of these plants to
derived from A. millefolium include: choline, betaine, proline,
treat a wide range of problems associated with the female
stachydrine, and betonicine (Table 1) (Si et al 2006).
reproductive system (Chandler et al 1982). Known A.
The essential oil of A. millefolium is characterized by a high millefolium constituents include matricin and other
number of monoterpenes: Eucalyptol (24.6%), camphor proazulenic sesquiterpene lactones known to yield
(16.7%), α-terpineol(10.2%), β-pinene (4.2%), and borneol chamazulene carboxylic acid, a propionic acid analogue, which
(4.0%). These five monoterpenes are the principal can inhibit cyclooxygenase-2 and has been used for the semi-
components, comprising the 59.7% of the essential oil (Table synthesis of analogues as potential anti-inflammatory drugs.
2). Changes in the composition of A. millefolium essential oil (Watkins et al 2001).
are due to the maturation of the plant, with increasing ratios
of monoterpenes to sesquiterpenes (Candan et al 2003).
al 2006). In a separate study, A. millefolium also demonstrated
antibacterial activity against S. typhimurium and S. aureus,
with predicted MICs of 10 s of μg/mL or 10 s of mg/mL. Two
of the studies found that ether-hexane-methanol extracts of A.
millefolium caused inhibition zones against E. coli in disc
diffusion assays, whereas studies with aqueous extracts of
flower, leaves, roots, and shoots and in a separate study of
essential oil and methanolic extracts did not. These differing
results may be due to the different extraction methods used or
the regional variation in the chemical constituents of the
plants (Frey 2010).
Gastrointestinal effects
In gastrointestinal research, strips of stomach antrum were
taken from six patients who underwent total or subtotal
gastrectomy for gastric carcinoma and treated with a
standardized water extract obtained from the flowering tops
of A. millefolium. Results showed that the extract is able to
contract mice and humans gastric atrum and could provide a
pharmacological basis for the traditional use of A. millefolium
in the treatment of dyspeptic ailments (Borrello et al 2012). In
Table 3. Miscellaneous compounds from Yarrow (Chandler a separate study, tests conducted on mice with gastric ulcers
et al 1982). induced by 80% acetic acid showed significant regeneration
and increased cell proliferation after oral treatment with 1
Antimicrobial and 10mg/kg hydroalcoholic (HE) A. millefolium extract. The
In vitro studies have shown that the essential oil of A. study confirmed the antioxidant and gastroprotective
activities of the HE extract, although the precise mechanism in
millefolium has great antioxidant and antimicrobial properties.
the effect remains to be understood (Potrich 2010).
Extracts from the aerial parts of A. millefolium have been
found to exhibit a broad spectrum of antimicrobial activities
against five bacteria: Staphylococcus aureus, Escherichia coli,
Cardiovascular
Klebsiella pneumoniae, Pseudomonas aeruginosa, and
Salmonella enteritidis. The extracts also demonstrated activity Studies on rats under anaethesia with extracts of A.
against two fungi: Aspergillus niger and Candida albicans (Si et millefolium caused a dose-dependent (1–100 mg/kg) fall in
arterial blood pressure. In spontaneously beating guinea-pig Skin rejuvenation
atrial tissues, the extracts exhibited negative inotropic and
In the superoxide radical inhibition cases, A. millefolium was
chronotropic effects. The results demonstrate that A.
found to be more effective than ascorbic acid (Candan et al
millefolium exhibits BP-lowering, cardio-suppressant,
2003). In vivo, a 2-month treatment with A. millefolium extract
vasodilator and bronchodilator activities possibly mediated
at 2% significantly improved the appearance of wrinkles and
through Ca2+ antagonism in addition to an endothelium-
pores compared with placebo. Results were also directionally
dependent relaxant component and justifies its application in
better than those of glycolic acid that was chosen as a
cardiovascular and congestive airway disorders. (Khan et al
reference resurfacing molecule. A.millefolium extract thus
2010).
represents a relevant cosmetic ingredient useful for
Studies on A. millefolium extract in vitro effects on the growth rejuvenating the appearance and feeling of epidermal
of primary rat vascular smooth muscle cells (VSMCs) as well surfaces. Its properties as a natural water plant extract also
as the potential involvement of estrogen receptors (ERs) has represent a gentle alternative to alpha-hydroxy acids that
demonstrated the ability to modulate the NF-kB pathway. require acidic formulation to preserve their functionality and
Results show that the tested A. millefolium extract, containing efficacy (Pain et al 2011).
flavonoid glycosides and CQA derivatives, is able to enhance
VSMC growth partly by acting through ERs and impair NF-kB
signaling in endothelial cells. These studies justify the Tumor growth
traditional use of the plant, by explaining its activity through In cancer studies, antiproliferative assays demonstrated that
the modulation of the inflammation pathway and centaureidin is the most effective constituent of the aerial
demonstrating that A. millefolium may induce novel potential parts of A. millefolium. High cell growth inhibitory activities
actions in the cardiovascular system (Dall’ Acqua 2011). were reported on HeLa and MCF-7 cells. Casticin and paulitin
were also highly effective against all three tumour cell lines
(IC50 1.286–4.76 μM), while apigenin, luteolin and isopaulitin
Phytoestrogens
proved to be moderately active (IC50 6.95–32.88 μM).
Results show that apigenin can stimulate ERs-dependent Artemetin, psilostachyin C, desacetylmatricarin and sintenin
biological pathways, although with a smaller potency as did not display antiproliferative effects against these cell lines
compared with the endogenous hormone and can activate (Csupor-Loffler, et al 2009). In another case, there is a recently
both subtypes of human estrogen receptors, α and β. Luteolin discovered antitumoural effect of casticin by the induction of
appears to have a very slight effect on the β receptor and does G2/M cell cycle arrest and apoptosis (Watkins et al 2011)
not seem to activate α at all. The study concludes that the role
of apigenin in the emmenagogic effects of A. millefolium, as
traditionally reported, cannot be defined (Innocenti 2007). Clinical Studies
A recent clinical study on kidney disease was conducted with
Achillea millefolium and plasma nitric oxide. Increased plasma
nitric oxide concentration has been understood as one of the application site. The study concluded that there was
possible mechanisms of bleeding tendency in patients who ultimately no significant difference in cure rates of lesions
suffer chronic kidney disease. In a randomized controlled trial, between yarrow and placebo topical gels as an adjuvant drugs
thirty-one chronic kidney disease patients were tested. 16 with intralesional glucantime in treatment of acute cutaneous
patients received 1.5 g of powdered A millefolium flower 3 leishmanial lesions (Jaffary et al 2012).
days a week for 2 months, and 15 received placebo for the
In the last decades more intensive pharmacological studies
same period. Plasma samples were collected before and after
have been conducted on A. millefolium; however most of these
the study period to estimate the effect of A. millefolium on
studies have been conducted in vivo. Published results on
plasma nitric oxide metabolites. The results showed that the
human clinical investigations of A. millefolium still remain rare
plasma nitrite and nitrate concentrations decreased after 2
or with results that are mostly inconclusive.
months administration of A. millefolium. However with the
placebo group, plasma nitric oxide metabolites were only
slightly lowered after A. millefolium administration in chronic Contraindications
kidney disease patients. The study suggested that higher
doses or a longer duration of plant administration might make Achillea millefolium is considered a nonpoisonous plant and is
these changes more significant. Ultimately the study failed to not listed in literature on human poisoning. Long term trials
yield statistically significant results on the effect of A. with A. millefolium extracts on rats have only demonstrated
millefolium and potential therapeutic effects on chronic kidney the gastroprotective activity of the extract and was
disease (Vahid et al 2012). accompanied by no signs of toxicity in any relevant areas
linked to liver, kidney or hematological systems for periods up
A different study in Iran was carried out to evaluate the effect to 90 days, in either female or male rats (Cavalcanti et all
of topically applied A. millefolium in conjunction with 2007).
intralesional glucantime on acute cutaneous leishmanial
lesions, a common parasitic skin infection. Sixty patients with However, due to documentation of the death of a calf
confirmed acute cutaneous leishmaniasis were randomly following its consumption of yarrow it is listed among plants
divided into two groups to receive topical gel of Achilles to avoid for livestock feed. Dermatitis has also been reported
millefolium 5% with 5% polyphenol, or a placebo, twice a day in various studies in conjunction with yarrow application,
for four weeks along with weekly injection of intralesional suggesting it’s a sensitizer at nonirritant concentrations,
Glucantime. The results from the study showed no significant despite no known compounds of α-methylene-α-lactone, that
difference between the two groups according to age, gender, are believed to induce dermatitis, have been found in yarrow
and duration of the infection. Neither was there significant (Chandler et al 1982).
difference in the complete or relative cure rates between the Anti-spermatogenic effects have also been observed in lab
group which received the placebo or the A. millefolium gel studies with mice that were treated with an EtOH extract of A.
(p=0.35). However, some patients in the group which received millefolium. Treatment with the extract showed an increased
the gel reported severe reactions and itching at the
number of metaphases in the mice germ epithelium, which
might be due to cytotoxic substances or substances
stimulating cell proliferation (Si et al 2006).
Pregnant women should avoid taking yarrow, because its
ability to relax the smooth muscle of the uterus may cause a
miscarriage. Yarrow should also be avoided as a means to
treat fevers over 102°F, as it may create a dangerous,
temporary increase in the fever. Those with allergies to plants
in the daisy family should also avoid using Yarrow as it may
cause a similar allergic reaction (Libster 2002).
Current Use in Allopathic and CAM Therapies

A great variety of yarrow supplements and oils can be found
sold through health-food marketing websites for both humans
and for pets. It is marketed primarily for its wound-healing
abilities, with tag lines that highlight the herb’s mythological
names (“military herb”). Nature’s Wonderland Yarrow Herb
supplement highlights uses which include: “maintaining liver
and gallbladder function, immune health, digestion, blood
cleansing, and easing menstrual cramps.” Recommended
doses includes up to 2100 mg per day (Figure 4). Although
extracts and tinctures of Achillea millefolium are more
concentrated than the dried powdered plant, their bitterness
and pungent odor may repel the consumer (Vahid et al 2012).
Due to the current lack of human clinical trials, over the
counter or prescription drugs derived from A. millefolium
remains to be widely marketed. The majority of current
yarrow-drugs are sold in their natural forms as teas or herbal
Figure 4. Example of a Yarrow supplement sold online supplement pills.
(Source: http://www.pennherb.com/milfoil-herb-capsules-
60-vcaps-467x)
Discussion stomach. Neurogastroenterol Motil, 24(2), 164-171, e190.
doi: 10.1111/j.1365-2982.2011.01827.x
Achillea millefolium’s therapeutic applications seem to be as
widespread as its geographic range. The occurrence of several Britton, N.L., and A. Brown. 1913. An illustrated flora of the northern
genotypes of A. millefolium, each with its unique chemical United States, Canada and the British Possessions. 3 vols.
Charles Scribner's Sons, New York. Vol. 3: 515.
composition, might explain why ethnic groups from different
http://plants.usda.gov/java/largeImage?imageID=acla5_00
geographical areas used yarrow for considerably different
1_avd.tif
reasons. Phytochemical studies on A. millefolium flowers from
wild populations have revealed a considerable variation in Candan, Ferda, Unlu, Mehmet, Tepe, Bektaş, Daferera, Dimitra,
these phenolic compounds that seems to arise from the Polissiou, Moschos, Sökmen, Atalay, & Akpulat, H. Aşkın.
(2003). Antioxidant and antimicrobial activity of the
influence of different growing habitats (Benetis et al 2008).
essential oil and methanol extracts of Achillea millefolium
Furthermore, many of these components that are highly
subsp. millefolium Afan. (Asteraceae). Journal of
bioactive (Si et al 2006), such as flavonoids and Ethnopharmacology, 87(2–3), 215-220. doi:
sesquiterpenoids, have demonstrated anti-proliferation http://dx.doi.org/10.1016/S0378-8741(03)00149-1
effects against leukemia (Fray 2010). This suggests the
importance of considering genotypes as well as the age of the Cavalcanti, AM, Baggio, CH, Freitas, CS, Rieck, L, de Sousa, RS, Da
Silva-Santos, JE, . . . Marques, MC. (2006). Safety and
yarrow, geographical location, season of harvest, and plant
antiulcer efficacy studies of Achillea millefolium L. after
parts when collecting plants for phytochemical investigation chronic treatment in Wistar rats. J Ethnopharmacol, 107, 277
(Chandler et al 1982). For modern drug discovery, there - 284.
remains a wealth of opportunities to research A. millefolium
for minor constituents against current diseases not mentioned Chandler, R.F., Hooper, S.N., & Harvey, M.J. (1982). Ethnobotany and
phytochemistry of yarrow,Achillea millefolium, compositae.
in ancient texts or already practiced in current ethobotanical
Economic Botany, 36(2), 203-223. doi: 10.1007/bf02858720
approaches. Clearly the common yarrow holds great potential
as a source for many new drugs. Conti, B., Canale, A., Bertoli, A., Gozzini, F., & Pistelli, L. (2010).
Essential oil composition and larvicidal activity of six
Mediterranean aromatic plants against the mosquito Aedes
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1461. doi: 10.1007/s00436-010-2018-4
Benetis, R., Radusiene, J., & Janulis, V. (2008). Variability of phenolic
compounds in flowers of Achillea millefolium wild Csupor-Loffler, B., Hajdu, Z., Zupko, I., Rethy, B., Falkay, G., Forgo, P.,
populations in Lithuania. Medicina (Kaunas), 44(10), 775- & Hohmann, J. (2009). Antiproliferative effect of flavonoids
781. and sesquiterpenoids from Achillea millefolium s.l. on
cultured human tumour cell lines. Phytother Res, 23(5), 672-
Borrelli, F., Romano, B., Fasolino, I., Tagliatatela-Scafati, O., Aprea, G., 676. doi: 10.1002/ptr.2697
Capasso, R., . . . Izzo, A. A. (2012). Prokinetic effect of a
standardized yarrow (Achillea millefolium) extract and its Dall'Acqua, S., Bolego, C., Cignarella, A., Gaion, R. M., & Innocenti, G.
constituent choline: studies in the mouse and human (2011). Vasoprotective activity of standardized Achillea
millefolium extract. Phytomedicine, 18(12), 1031-1036. doi: Gaillard, C., . . . Andre-Frei, V. (2011). Surface rejuvenating
10.1016/j.phymed.2011.05.005 effect of Achillea millefolium extract. Int J Cosmet Sci, 33(6),
535-542. doi: 10.1111/j.1468-2494.2011.00667.x
Frey, F. M., & Meyers, R. (2010). Antibacterial activity of traditional
medicinal plants used by Haudenosaunee peoples of New Potrich, Francine Bittencourt, Allemand, Alexandra, da Silva, Luísa
York State. BMC Complement Altern Med, 10, 64. doi: Mota, dos Santos, Ana Cristina, Baggio, Cristiane Hatsuko,
10.1186/1472-6882-10-64 Freitas, Cristina Setim, . . . Marques, Maria Consuelo
Andrade. (2010). Antiulcerogenic activity of hydroalcoholic
Grigson, G. (1996) The Englishman’s Flora. Helicon Publishing, Ltd,
extract of Achillea millefolium L.: Involvement of the
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antioxidant system. Journal of Ethnopharmacology, 130(1),
Innocenti, G, Vegeto, E, Dall'acqua, S, Ciana, P, Giorgetti, M, Agradi, E, 85-92. doi: http://dx.doi.org/10.1016/j.jep.2010.04.014
. . . Tome, F. In vitro estrogenic activity of Achillea
Si, Xiao-Tang, Zhang, Man-Li, Shi, Qing-Wen, & Kiyota, Hiromasa.
millefolium L. Phytomedicine.
(2006). Chemical Constituents of the Plants in the Genus
Jaffary, F., Nilforoushzadeh, M., Tavakoli, N., Zolfaghari, B., & Achillea. Chemistry & Biodiversity, 3(11), 1163-1180. doi:
Shahbazi, F. (2012). The Efficacy of Achilles Millefolium 10.1002/cbdv.200690119
Topical Gel Along with Intralesional Injection of Glucantime
Vahid, S., Dashti-Khavidaki, S., Ahmadi, F., Amini, M., & Salehi
in The Treatment of Acute Cutaneous Leishmaniasis Major.
Surmaghi, M. H. (2012). Effect of herbal medicine achillea
(English). Journal Of Isfahan Medical School, 29(172), 1-7.
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Jarić, Snežana, Popović, Zorica, Mačukanović-Jocić, Marina, with chronic kidney disease: a preliminary study. Iran J
Djurdjević, Lola, Mijatović, Miroslava, Karadžić, Branko, . . . Kidney Dis, 6(5), 350-354.
Pavlović, Pavle. (2007). An ethnobotanical study on the
Vitalini, S., Beretta, G., Iriti, M., Orsenigo, S., Basilico, N., Dall'Acqua,
usage of wild medicinal herbs from Kopaonik Mountain
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Khan, A. U., & Gilani, A. H. (2011). Blood pressure lowering,
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Zohara Yaniv, Uriel Bachrach. (2005). Handbook of Medicinal Plants
Retrieved from
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Pain, S., Altobelli, C., Boher, A., Cittadini, L., Favre-Mercuret, M.,
Allium sativum L., Amaryllidaceae
Shannan Healy
Introduction
Allium sativum L., commonly known as garlic, is a member of
the Amaryllidaceae family. More commonly known for its
culinary role, A. sativum has many properties that are useful in
medicine. Originally cultivated in central Asia, garlic is now
cultivated throughout the world, but heavily in the
Mediterranean and Asia (Brewster 2008). A. sativum is largely
composed of sulfur compounds; the enzyme alliinase reacts
with alliin upon crushing or chewing of the clove which
results in the compound allinin (Block 2010). Allicin is a
diallyl sulfinate that is recognized as the constituent
responsible for many of garlic’s medicinal properties, such as
its preventative role in cardiovascular disease, antioxidant
activity, and activity as a broad-spectrum antimicrobial. As
people are more commonly seeking natural health care Figure 1. A bulb of Allium sativum with some cloves
products, there has been extensive research done on A. removed to reveal membranous skin. (Image source:
sativum for its roles as a broad-spectrum antimicrobial, http://www.123rf.com/photo_3369595_a-white-clove-of-garlic-
antioxidant, and for its overall effects on the cardiovascular broken-open-and-isolated-on-a-white-back-ground.html)
system (Block 2010). Unfortunately, many trials report
conflicting results and are not reliable because they do not
specify the form of garlic used, which has tremendous effects softneck garlic, and A. sativum var. ophioscorodon, also known
on the release of active compounds. as hardneck garlic. Both varieties are composed of an
underground bulb made up of cloves, which are prophylls
enclosed by dry membranous skins and held together by a
Botanical Description   basal plate. A bulb with some cloves removed to reveal these
skins can be seen in Figure 1. Flat leaves that point at the ends
Other members of the onion genus, Allium, include A. cepa reach about two feet in length and arise from underground;
(onion), A. schoenoprasum (chives), A. ascalonicum (shallots), they do not originate from the stalk (Brewster 2008).
and A. porrum (leeks). Allium sativum is further divided into
two subspecies, A. sativum var. sativum, also known as The variations differ in that hardneck garlic’s bulb is
Figure 2. Diagram of Allium sativum spp. ophioscorodon.
(Image source: http://saknoffel.co.za/garlic_cultivation.html) Figure 3. Diagram of Allium sativum spp. sativum. (Image
source: http://saknoffel.co.za/garlic_cultivation.html)
composed of six to eleven cloves, circled around a centralized white or light purple flowers, although these are sterile.
woody stalk (Block 2010). This variety of garlic has a scape Softneck garlic does not have a flowering top and contains up
that curls at the top, but it is generally removed after it curls to twenty-four cloves per bulb (Block 2010). The stem is
one to three times. This is because if it continues to grow, less central and soft, hence the name, and the cloves are layered
energy can be utilized towards the bulb (Block 2010). with larger ones on the outside (Block 2010). Figures 2 and 3
Eventually, the scape would give rise to bulbils, containing illustrate the differences between the two subspecies and
miniature cloves. The bulbils are occasionally accompanied by Figure 4 shows an example of a flowering bulbil. While A.
Traditional Uses  
Traditional Medicinal Uses
Medicinal uses of garlic are very prevalent in history, not only
for the treatment of disease but also for the maintenance of
health. Records date back to ~1550 BC: 22 of 875 therapeutic
formulas in Ebers Papyrus contain garlic, including heart
disease and abnormal growths, implying cancer (Block 2010).
In Dioscorides’ De Materia Medica, Allium sativum is
mentioned 23 times and is listed as a remedy for driving out
intestinal parasites, diarrhea and other gastrointestinal
disorders and animal bites (Block 2010). Dioscorides also
recommended garlic because it “cleans the arteries,” and
currently it is being investigated to help treat atherosclerosis,
known as hardening of the arteries (Rivlin 2001). Hippocrates
advised its use as a purgative agent and for pulmonary
Figure 4. Diagram of flowering bulbils. (Image source:
complaints (Moyers 1996).
http://www.wegrowgarlic.com/7422.html)
It is suspected that historically, garlic was given mostly to
laboring classes, as upper classes avoided the pungent smell.
sativum sativum is the more common variation, many studies
When King Tutankhamen’s tomb was excavated (dating to
involving garlic do not specify which subspecies is used, but
~1500 BC), garlic cloves were identified, although it was not
chemical and biological action are assumed to be similar.
evident what their use was (Kahn 1996). A. sativum was
A. sativum is sterile and hence is grown asexually from cloves, consumed by Egyptian slaves to increase their strength when
not requiring a pollinator (Block 2010). It grows best in mild building the pyramids (Kahn 1996). For similar reasons, it was
climates, through hardneck varieties are better adapted to given to Roman soldiers. In Ayurvedic medicine, garlic was
colder environments. A. sativum is a perennial species, as are used to warm the body, likely a result of improved blood
most members of the genus. Garlic is composed of very strong circulation (Moyers 1996). In Traditional Chinese Medicine,
organosulfur compounds that serve as secondary metabolites garlic was used as an ailment for respiration and digestion
as described in the section entitled chemistry and discomfort, diarrhea, and worm infestation (Moyers 1996). In
pharmacology. These compounds are responsible for the very World War II, it was deemed Russian penicillin because it was
pungent smell and taste of raw garlic and act as defenses used to fight infection and gangrene (Petrovska and Cekovska
against predators (Block 2010). 2010). The Cherokees traditionally used it as a diuretic,
expectorant, and for scurvy due to its high vitamin C content
(Hamel and Chiltoskey 1975). It was also used to fight
Nutrient Per Clove (3g) in Table 1. It is believed to have been a regular part of the diet
Water 1.76g in China since 2000 BC (Kahn 1996). Due to the overpowering
Energy 4 kcal taste, garlic does not have an extensive history of culinary use
Protein 0.19 g until the 20th century (Block 2010). In fact, monks, widows
Total lipid (fat) 0.02 g
and children were forbidden from eating it in the Far East due
Carbohydrate 0.99 g
to its aphrodisiac affects and the resulting odor was
Fiber, total dietary 0.1 g
Sugars, total 0.03 g
considered unsuitable for upper classes (Hospodar 2004).
Calcium 5 mg Perhaps the rise in consumption is correlated with cooking
Iron 0.05 mg garlic, as heat mellows the flavor when it destroys the enzyme
Magnesium 1 mg allinase so it cannot react with allin to form allinin, the sulfur
Phosphorus 5 mg compound responsible for the strong taste and smell (Block
Potassium 12 mg 2010). The role of these compounds will be further
Sodium 1 mg investigated in the section entitled chemistry and
Zinc 0.03 mg pharmacology.
Vitamin C, total ascorbic 0.9 mg
acid
Thiamin 0.006 mg
Traditional Spiritual Uses
Riboflavin 0.003 mg
Niacin 0.021 mg Allium sativum is involved in many religious and superstitious
Vitamin B-6 0.037 mg beliefs, and today is referenced in pop culture as a means to
Vitamin K (phylloquinone) 0.1 mg ward off vampires. In the Bible, the Jews are said to miss garlic
Table 1. Nutrient data in raw Allium sativum (USDA 2012) when they leave Egypt: “we remember the fish we did eat in
Egypt, the cucumbers, the melons, leeks, onions and garlic.” An
ancient Islamic myth states that when Satan left the Garden of
infection during the Black Plague (Woodward 1996). Other
Eden, garlic sprouted from his left footprint and onion from
traditional uses include infection, colds, diabetes and heart
his right (Block 2010). According to the Bowers Manuscript, in
disease (Tsai et al. 2011). It is evident that ancient uses of A.
ancient India, garlic is believed to have originated in the blood
sativum inspired many uses today in complementary and
of a demon (Block 2010). In Greece, midwives used garlic
alternative medicine.
when delivering babies to protect them against evil eye and
often advised mothers to sew it into their clothing to protect
Traditional Culinary Uses them (Block 2010). Although some of these tales have
negative connotations, these references all indicate garlic as a
Allium sativum is a very nutritious food, but unfortunately this very powerful substance.
is not reflected since it is generally eaten in such small
quantities. Nutrient information per clove of garlic can be seen
(DATS), ajoene, and hydrogen sulfide (Banerjee and Maulik
2002; Harunobu et al. 2001; Mukherjee et al. 2009, Powolyny
and Singh 2008). The pathways of this reaction can be seen in
Figure 5. DAS, DADS, DATS and ajoene are all oil soluble
(Miroddi et al. 2011).
Chemical Manipulation
When garlic is manipulated to produce alternate forms, the
unstable sulfur compounds react and hence alter active
chemical constituents. It is important to note that these
changes in chemistry can alter the bioavailability of the
compounds. Unfortunately, many studies do not specify the
actions taken, which could possibly account for
inconsistencies in reported data. Traditionally used in its raw
Figure 5. Chemical structures of organosulfur compounds form, garlic is now often heated, dehydrated, and aged. Only
involved in reactions with allicin. (Image source: Powolny and freshly crushed garlic has hydrogen sulfide, which is
Singh 2008) suspected to have significant cardioprotective effects as a
vasodilator (Mukherjee et al. 2009).
Chemistry and Pharmacology   Garlic powder can be made through dehydrating the plant
with heat, but when high temperatures are applied to garlic,
Sulfur compounds are the main chemical constituents alliinase is deactivated and hence cannot react with alliin to
responsible for Allium sativum’s taste, smell, and likely for its form allicin (Tsai et al. 2011). This explains why cooked garlic
biological effects. When a garlic clove is intact, glutamyl has a mellower flavor than raw garlic. Powder can retain some
cysteins are the primary sulfur components (Powolyny and allicin content if the cloves are frozen before being pulverized;
Singh 2008). These are hydrolyzed to form alliin. When garlic acetone removes the water and alliin and alliinase remain
is crushed by chewing, chopping, etc., the alliin promptly separate yet intact until water is added, at which point allicin
reacts with the enzyme alliinase to form allicin; after 30 is formed (Block 2010). While dehydration during the
seconds the reaction is 97% complete (Block 2010). Allicin is a powdering process does not destroy alliinase like heat does,
diallyl thiosulfinate that accounts for 70-80% of the more than half of the alliin is lost (Banerjee and Maulik 2002;
thiosulfinates present in Allium sativum (Harunobu et al. Harunobu et al. 2001). While levels are lower than with raw
2001). Allicin is also highly unstable and quickly decomposes garlic, dried garlic does contain alliin and alliinase, as
to yield sulfur compounds when oxidized such as diallyl explained above. Alliinase is deactivated by the acidic
sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide environment of the stomach (Touloupakis and Ghanotakis
2011). Freeman and Kodera (1995) also came to this suppressed low-density lipoprotein oxidation, which reduces
conclusion by exposing dehydrated garlic powder to lipid content in arterial walls, leading to protection against
simulations of the gastrointestinal fluids; allicin production atherosclerosis, also known as hardening of the arteries. This
decreased by 99%, presumably due to the lack of allinase. This anti-aggregatory response is attributed to the presence of
suggests that it could be beneficial to further research the allicin and thiosulfinates (Cavagnaro et al. 2007).
affects of dehydrated garlic powder when taken in a capsule
In a study of rats, Ali et al. (2000) fed all subjects a diet with
with an enteric coating to protect it from stomach acid. These
increased serum cholesterol. Those who also had a garlic
studies also show that manipulating garlic’s form leads to
powder supplement experienced a reduction in serum
changes in the active constituents and could lead to data
cholesterol and in systolic blood pressure. Diallyl sulfide
inconsistencies in studies.
(DAS), Diallyl disulfide (DADS), and diallyl trisulfide (DATS)
Garlic can also be aged by soaking it in aqueous ethanol and are the oil-soluble sulfur compounds responsible for reducing
then extracting and concentrating essential compounds. When cholesterol (Harunobu et al. 2001). DAT’s presence in garlic
allicin is dissolved in oils, the major compound in the final oil has also been attributed to anticoagulation in rats. Chan et
product is S-Allylcystein (SAC) while ajoene, the most stable al. (2006) found that DATS inactivated thrombin when given
component of garlic, is also present (Rahman 2002). Kodera et in a dose of 5mg per kg of body weight. Ajoene, a component
al. (2002) suggest that SAC could pass through the of aged garlic extract, stops blood from clotting, acting as an
gastrointestinal tract without decomposing and successfully antithrombotic (Block 2010).
be absorbed. Kodera et al. (2002) also suggest that SAC might
Mukherjee et al. (2009) conducted a study comparing the
be stable in blood, whereas allicin is unstable in blood and
effects of freshly crushed and processed garlic in rats. While
cannot reach target organs via circulation (Harunobu et al.
both exhibited cardioprotective effects, the freshly crushed
2001).
garlic’s effects were more significant, likely due to the
presence of hydrogen sulfide (H2S), which is absent in
processed garlic. Red blood cells convert diallyl disulfide and
Biological Activity
diallyl trisulfide to hydrogen sulfide, which then acts as a
Cardiovascular Activity vasodilator and reduces blood pressure.
In a review of in vitro and clinical studies, Rahman and Lowe
(2006) found an inverse correlation between garlic
Anti-cancer Activity
consumption and the progression of cardiovascular disease
with the most significant effects being the inhibition of platelet In looking at multiple studies, Powolny and Singh (2008)
aggregation, reduction of blood cholesterol, reduction of blood conclude that organosulfur compounds such as DAS, DADS,
pressure and increase of antioxidant status. and DATS act by arresting the cell cycle of cancerous cells.
Data from Miroddi et al. (2011) and Omar and Al-Wabel
Banerjee and Maulik (2002) found similar results regarding
(2009) support this, showing that these allyl derivatives act as
the cardioprotective effects of garlic. This was attributed to
antioxidants and arrest the cell cycle. DATS was found to have presumably through thiol enzymes, however this mechanism
the most significant role by Powolny and Singh (2008), and is of action is not fully known (Ankri and Mirelman 1999). In an
even a potential skin cancer fighting compound (Wang et al. in-vitro study, the effectiveness of ajoene at its minimal
2010). More specifically, garlic acts as anti-inflammatory inhibitory concentration, 15 μg/ml, was tested against
agent by altering cytokines and inhibiting NF-kB activity in Candida albicans. Ajoene inhibited 98.2% of fungal growth
surrounding tissues (Keiss et al. 2003). In a study using (Carrero et al. 2009). Ajoene is also known to have more
human promyeloleukemic cells, Dirsch et al. (1998) found that antiviral properties than allicin (Ankri and Mirelman 1999). In
ajoene prompted apoptosis in cancerous cells but not healthy another study involving C. albicans, allicin was not found to
ones; this might be due to peroxide production. In an in-vitro have any antifungal effects on its own, but enhanced the
study involving rats, Jastrzebsk et al. (2007) found that raw effects of the common treatment Amphotericin B both in vivo
garlic had the strongest antioxidant activity. Tsai et al. (2011) and in vitro (An et al. 2009). The wide-spectrum antimicrobial
reviewed animal and cell studies and found an inverse effects of garlic are due to the presence of allicin and ajoene,
correlation between consumption of garlic and presence of which are suspected to inhibit multiple thiol-dependent
cancerous cells, suggesting it has anticancer effects. Eleischur enzymatic systems (Ankri and Mirelman 1999). Allicin is
and Arab (2001) conducted a review of in vitro studies, and effective against microbial cells that do not have an
while multiple reports concluded that garlic prevents cancer intracellular thiol content that can offset its thiol oxidation
of the stomach, colon and rectum, the analyses were not (Harris et al. 2001).
thorough and did not adjust for potential cofounders and
hence are not definitive.
Other Activity
Eidi et al. (2006) conducted a study on both normal and
Anti-Microbial Activity
diabetic rats, comparing the treatment effects of
While Allium sativum only has about 1% of the antibacterial Glibenclamide, a known antidiabetic drug, and garlic. They
activity of penicillin, it is able to act upon both gram-positive found that garlic increases serum insulin. Liu et al. (2005) also
and gram-negative organisms (Ankri and Mirelman 1999). found that garlic oil and DATS increase insulin sensitivity and
While it does act as a bactericidal agent, A. sativum is primarily section, hence improving glycemic control. Both studies
a bacteriostatic agent that destroys sulfhydryl groups suggest the need for further investigation into A. sativum’s
necessary for bacterial growth (Block 2010). Feldberg et al. antidiabetic role.
(1988) found that allicin affects RNA synthesis and inhibits
Ankri and Mirelman (1999) suggest that the short reactive
DNA protein synthesis in Salmonella typhimuriam. Allicin can
time of allicin is an evolutionary adaptation. A larger
also act as an antibiotic by reacting with thiol-containing
production of allicin could be toxic for the entire plant, so the
enzymes such as L-cysteine to form S- allylmercaptocysteine,
actions of allicin in a confined area prevent any self-damage.
which inhibits cysteine proteinases (Ankri and Mirelman
Allicin is not bioavailable and cannot reach target organs by
1999). As an anti-fungal, garlic inhibits mycotoxin formation,
circulating through the blood (Harunobu et al. 2001).
However, it is able to penetrate biological membranes. Shortly Steiner et al. (1996) conducted a double-blind study in
after injection into the bloodstream it is no longer in hypercholesterolemic men in which aged garlic was used. It
circulation (Block 2010). This has made it difficult to study was found that aged garlic led to a significant total serum
allicin’s antibiotic effects outside of in vitro applications. Many cholesterol reduction, low-density lipoprotein (LDL)
studies focusing on the role of garlic as an antibacterial, cholesterol reduction, and systolic blood pressure reduction.
antiviral, and antifungal are only clear in vitro, perhaps due to Aged garlic has strong levels of SAC, which could account for
allicin’s short presence in the blood stream. these results (Rahman 2002). Ali and Thomson (1995) found
that after consuming a single clove of fresh garlic daily for 26
weeks serum cholesterol levels dropped 20% and serum
Clinical Studies thromboxane levels dropped 80%. However, Gardner et al.
Some clinical studies report data that differs from data (2007) compared treatments for adults with moderate
collected through in vivo and in vitro studies. These hypercholesterolemia using raw garlic, powdered garlic, and
differences might be accounted for by the synergistic effects of aged garlic (each the equivalent of an average-sized clove six
compounds in Allium sativum, as the concentration of these days per week for six months) but no significant effects on
compounds and their effects in vivo and in vitro may not LDL levels were found. In a meta—analysis comparing the
determine effectiveness without considering their roles in effects of garlic on serum lipid profiles, Zeng et al. (2012) note
relation to one another (Harunobo et al. 2001). The different that garlic powder and aged garlic were more effective in the
forms of garlic must be considered in clinical studies, as this reduction of serum total cholesterol levels whereas garlic oil
affects the bioavailability of various compounds. It is also was more effective in the reduction of triglyceride levels.
important to note that blinded trials are difficult to conduct These are only a few examples of conflicting results presented
when using raw garlic due to its strong and recognizable scent by clinical studies. However, the majority of studies conclude
and flavor. that fresh garlic can slow atherosclerosis development and
moderately reduce blood pressure, which is caused by the
production of hydrogen sulfide (Mukherjee et a. 2009)
Cardiovascular Clinical Studies Bordia et al. (1996) note that while garlic components leave
In a review of clinical studies, Banerjee and Maulik (2002) the body quickly, active ingredients may build up slowly. This
note reports of both positive and negative results in relation was concluded because a single high dose of garlic did not
to the hypolipidemic role of garlic, possibly due to different affectively inhibit platelet aggregation, but long-term
levels of sulfur compounds in the forms of garlic used. Most administration of low doses was found to be affective. This
studies involving the effects of garlic on hyperlipidemic suggests that including garlic in the diet regularly could have
patients use garlic powder rather than raw garlic. Powdered more beneficial effects than consuming it only during times of
garlic has less allicin available than raw garlic. As far as compromised health.
cardiovascular studies are concerned, results on Cancer Activity Clinical Studies
hypolipidemic patients are the least conclusive.
Most studies involving A. sativum and cancer are carried out in
animal models because there is not enough information to
advise a proper dose for a clinical trial (Thomson and Ali
2003). Ahmend et al. (2001) did find that ajoene enhanced the
activation of two chemotherapeutic drugs, Cytarabine and
Fludarabie, both used in leukemia treatments. Lamm and
Riggs (2000) suggest that regular consumption of aged garlic
extract may reduce the risk of stomach cancer. Thomson and
Ali (2003) also note that aged garlic extract exhibits radical
scavenging activity; these antioxidant properties are thought
to inhibit tumor growth. While there are not many studies
testing the clinical effects of A. sativum on cancer, research
suggests that eating garlic as a regular part of the diet serves
as a form of preventative medicine. More research is also
suggested to investigate the effects of garlic on enhancing Figure 6. Burn wounds from the topical application of A.
modern drugs. sativum. (Image source: Friedman, T., Shalom, A., and Westreich,
M. (2006). Self-inflicted garlic burns: our experience and literature
review, Int J Dermatol 45, 1161-1163.)
Other Clinical Studies
Historically, A. sativum was used to treat the common cold. foot. They found that ajoene (1%) was more effective than
Lissiman et al. (2009) analyzed previous studies and clinical Terbinafine (1.0%), which was only slightly more effective
trials and found that garlic might prevent occurrences but the than the 0.6% ajoene.
evidence is not conclusive; this also warrants future studies.
Borhan-Mojabi et al. (2012) tested the effect of garlic on Contraindications
salivary microbial populations and found it significantly
decreased colony counts. This suggests the potential for use of A common side effect of garlic consumption is halitosis, more
garlic in a mouthwash, however most participants complained commonly known as bad breath. Allyl methyl sulfide (AMS) is
about taste and resulting breath, implying that the product a component of garlic that cannot be digested and is hence
would not be successful commercially. absorbed into the blood where it travels to the lungs and skin,
causing consumers to emit “garlic breath” and “garlic sweat”
Ledezma et al. (2000) compared the effects of ajoene (0.6% (Tatteman 2005). An overconsumption of garlic can cause
and 1.0%) against the topical drug Terbinafine (1%) in the gastrointestinal upset, heartburn, diarrhea and flatulence.
treatment of Tinea pedis, more commonly known as athlete’s Because garlic inhibits platelet aggregation and acts as a
vasodilator, garlic consumption should be avoided two weeks
chemical burns. Some cases included applications to treat
headaches, T. pedis, and self-mutilate. An example of garlic
burns can be seen in Figure 6.
Because garlic is more commonly recognized as a food than as
a medicine, it is not often acknowledged that it can interact
with prescription drugs. Allium sativum and its commercial
products might not be regarded as a drug, but merely as a
form of functional food, which could lead consumers to not
share their use with their physicians. Elmer et al. (2007)
conducted a study evaluating medication use among the
elderly and found that of 393 participants combining
medications, 379 of these involved a risk of bleeding due to
ginkgo, garlic, or ginseng use and its effect on prescription
medications. This further indicates the need to educate people
Figure 7. One example of the many garlic supplements that natural products are not necessarily safe.
available for purchase. (Image source:
http://www.aragonproducts.com/theproducts.cfm?master=7434)
before scheduled surgery and before childbirth due to risk of While Allium sativum is generally recognized as safe and
bleeding (Stanger et al. 2012). For the same reasons, excessive continues to be used as a food across the globe, many studies
garlic should not be used in combination with anticoagulants on garlic supplements are inconclusive, yet these are also
and antiplatelets such as Aspirin and Warfarin (Chen et al. commonly used for medicinal purposes. There are no
2011). Garlic decreases the effectiveness of some non- prescription drugs derived from garlic, but herbal
nucleoside reverse transcriptase inhibitors used for the supplements are available over the counter. An example of a
treatment of HIV/AIDS such as Ritonavir and Saquinavir product can be seen in Figure 7. When the supplements are
(Chen et al. 2011; Berginc et al. 2010). It is also thought to formed, the manipulation from heating, dehydrating and aging
increase the break down of estrogen present in many oral alters the active constituents. Studies use so many different
contraceptives and might decrease their effectiveness, variations of garlic, making the effects of each specific form
although much more research is needed (Pinto and Rivil not easily accessible to potential consumers. Garlic-derived
2001). Dietz et al. (2004) and Friedman et al. (2006) products have a lot of variation among them and can be
investigated the effects of garlic burns. They both cited confusing to consumers. Harunobu et al. (2001) advise careful
patients who applied crushed garlic topically. If there is too reading of products because garlic oil does not contain allicin
much pressure from wound wrapping, diallyl disulfide can and amounts of garlic essential oils are often minimal because
cause severe local inflammation that can develop into customers do not like the smell. Something else to consider is
whether or not garlic supplements in pill form have an enteric References Cited
coating. Without an enteric coating, all compounds will Ahmend, N., Laverick, L., Sammons, J., Zhang, H., Maslin, D.J., and
dissolve in the stomach and will not be present in the Hassan, H.T. (2001). Ajoene, a garlic-derived natural
gastrointestinal tract (Kannar et al. 2001). Tattleman (2005) compound, enhances chemotherapy-induced apoptosis in
recommends the consumption of one to two cloves of raw human myeloid leukaemia CD34-positive resistant cells.
garlic per day for adults. While their effects are not entirely Anticancer Res 21, 3519-3523.
confirmed, many use supplements for presumed Ali, M., Al-Qattan, K.K., Al-Enezi, F., Khanafer, R.M., and Mustafa, T.
cardiovascular, antioxidant, and anti-microbial effects. (2000). Effect of allicin from garlic powder on serum lipids
and blood pressure in rats fed with a high cholesterol diet.
Prostaglandins Leukot Essent Fatty Acids 62, 253-259.
Discussion
Ali, M., and Thomson, M. (1995). Consumption of a garlic clove a day
Allium sativum has long been recognized for its traditional could be beneficial in preventing thrombosis.
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have given rise to its modern uses as a functional food. A. An, M., Shen, H., Cao, Y., Zhang, J., Cai, Y., Wang, R., and Jiang, Y.
sativum has been recognized for its role in maintaining normal (2009). Allicin enhances the oxidative damage effect of
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Aloe vera (L.) Burm. F., Xanthorrhoeaceae
Michele Bennett Paine
Introduction
Aloe vera (L.) Burm. F. belongs to the Aloe genus, which contains
about 500 species of flowering succulent plants, the most well-
known and common being Aloe vera. Aloe has many different
common names even within countries, but it is most commonly
Aloe in English speaking areas. It is known as Sabila in Central and
South America and Ghikumar in India. Known under many
families over the years, Aloe vera is currently listed under the
Xanthorrhoeaceae family, and also under the subfamily
Asphodeloideae. In the past, it has been categorized under the
Figure 1. Aloe vera leaves and flowers. (Image source:
Liliaceae family and was also recognized by the scientific name
http://www.tropicos.org/Name/18403421)
Aloe barbadensis until it was discovered that the name Aloe vera
given by Burman pre-dated the name Aloe barbadensis. The first
record of Aloe vera is dated to Pedanuis Dioscorides’ De Materia to the Canary Islands (S. Carter, 2011). Now, however, it is found
Medica. Dioscorides was an authority on herbal plants around 60 to be cultivated throughout the West Indies, tropical America, and
AD (S. Carter, 2011). Aloe has been used for thousands of years to in the tropics in general (Ross, 1999). The A. vera plant is a short-
topically treat burns and other skin abrasions, as well as for its stemmed or entirely stem-less succulent plant with leaves that
laxative properties when taken orally; it is also used to treat bunch together to form large groups of up to 20 leaves (Ross,
diabetes, asthma, epilepsy, and osteoarthritis, among other 1999). The leaves are thick and fleshy, grayish-green with a
conditions (Medicine, 2011). The latex, or inner leaf, of the aloe brownish tinge in color, have spots when they are young and can
plant contains strong laxative compounds such as aloin, aloe- grow to be 20-60 centimeters long and 6-7 centimeters wide at
emodin, and barbaloin, and the gel from inside the leaf may help the base(S. Carter, 2011). The leaves are also 1 to 2.5 centimeters
to heal burns and abrasions, though more research is needed to thick and have spiny edges (S. Carter, 2011). A. vera produces
verify these claims (Medicine, 2011). yellow flowers that grow on central stalks that can be up to 100
centimeters tall (Ross, 1999). The yellow outer part of the flower
is divided into 6 different lobes with 6 stamens and a three-celled
ovary in each flower (Ross, 1999). The fruit is a capsule that
The origin of Aloe vera (Figure 1) is unknown, but it is native to flowers then fruits from July through January (Gowda, 2004).
North Africa, the Mediterranean region of southern Europe, and
Traditional Uses
According to the National Center for Complementary and
Alternative Medicine (NCCAM), Aloe vera has been traditionally
used as a topical treatment for burns, wounds, and various other
skin conditions, and has also been used orally as a laxative.
Typically, the leaf extract is treated in hot water and then used for
the treatment of burns, sores and other wounds (Ross, 1999). In
Argentina, however, the hot water extracts from the leaves is
taken orally to both alleviate painful menstruation and to induce
abortion (Ross, 1999). It is also used as an abortifacient in
Switzerland and in India (Ross, 1999). A. vera is used extensively
in India: it is often taken orally to treat inflammation and pain Figure 2: Chemical structures of the anthraquinones Aloin A,
(Ross, 1999). The leaves are also applied externally to treat Aloe emodin and Anthralin (Wamer et al., 2003).
wounds and guinea worm infection sites (Ross, 1999). In the
Cook Islands in the South Pacific Ocean, fresh latex from the
leaves is also taken orally, on a regular basis, to prevent high sedative effects, respectively (Duke, 1996). Another major group
blood pressure, cancer, and diabetes (Ross, 1999). It is also used of chemical constituents in aloe include the anthraquinones,
as a diabetes prevention method in Haiti, Mexico, Saudi Arabia, which are aromatic organic compounds that have antiithic,
and Tunisia (Ross, 1999). Most peoples that use A. vera agree that carcinogenic, and laxative effects (Duke, 1996). Aloe emodin,
it should be avoided during pregnancy, as it does appear to have anthralin and aloin A are the better-known anthroquinone
possible abortifacient effects. For a more extensive list of constituents, and have significant antimicrobial activity as well as
traditional uses around the world, see Table 1. laxative, cathartic, anti-leukemic, antiseptic, cytotoxic, estrogenic,
fungicide, pesticide, genotoxic, mutagenic, and tuberculstatic
effects (Duke, 1996). To see the structures of the above
Chemistry and Pharmacology anthraquinones, see Figure 2.
Aloe vera contains numerous chemical constituents that are
shown to have significant activity. Alanine, for example, is found Biological Activity
in the leaf in amounts of about 15,769 parts per million (Duke,
1996). Alanine is an amino acid and is known for displaying In vitro
antioxidant and cancer-preventive activity (Duke, 1996). There Antioxidant properties
are also significant levels of Alocutin-A, which is an analgesic and
cancer-agglutinator (Duke, 1996). Aloesin has purgative and Although the leaves are traditionally used, there are also possible
sunscreen effects, and small amounts (about 20 parts per million) beneficial compounds in the flowers of Aloe vera. A high
of aluminum and amylase (an enzyme) have antimicrobial and polyphenolic content is associated with significant antioxidant
Argentina Hot water extract of leaves is taken orally to induce abortion and to facilitate menstruation.
Bomini Leaf juice is used externally for skin irritations, cuts, boils, and sunburn.
Bolivia Fresh leaf juice is used as an analgesic topically for burns and wounds. Orally, the juice is used as a laxative.
Brazil Fresh leaf juice is taken orally as an anthelmintic and febrifuge. Infusion of dried root is taken orally to treat colic.
Canary Fresh fruit juice (unripe) is taken orally as an antiasthmatic and purgative.
Islands Infusion of fresh leaf juice is taken orally as a laxative, for dental caries, and as a teniafuge.
China Hot water extract of leaf juice is taken orally as an emmenagogue.
Cook Island Fresh sap in water is taken orally, regularly, to prevent high blood pressure, cancer and diabetes. Externally it is used to treat burns and cuts.
Cuba Water extract of leaf pulp is taken as an emmenagogue.
Egypt Fresh leaf juice administered intravaginally is used as a contraceptive before or after coitus. Data was obtained as a result of questioning 1200 puerperal
women about their knowledge of birth control methods.
52.3% practiced a method, and 47.6% of these depend on indigenous methods and/or prolonged lactation.
England Hot water extract of dried leaves with a mixture of Zingiber officinale, Mentha pulegium (essential oil), Ipomoea purga, Glycyrrhiza glabra and Canella alba is tak
en orally for amenorrhea.
Guatemala Hot water extract of dried leaves is used externally for wounds, ulcers, bruises and sores, skin eruptions, erysipelas, dermatitis, inflammations, burns, abscesse
s, and furuncles, and scrofula.
Haiti Hot water extract of dried leaves is taken orally both as a purgative and against diabetes and worms
India Decoction of dried leaves is taken orally to induce abortion, for sexual vitality, and the dried leaf juice is taken as an emmenagogue
Decoction of root is taken orally for venereal disease and externally it is used to treat wounds. Fresh fruit juice (unripe) is taken orally as a laxative, cathartic, a
nd for fever. Fresh leaves are crushed and applied locally for guinea worms. Hot water extract of dried entire plant is taken
orally as an emmenagogue, purgative, anthelmintic, stomachic, for liver enlargement, spleen enlargement, and piles. Hot water extract of fresh plant juice is tak
en orally for inflammation and amenorrhea. The pulp of the plant is mixed together with salt and fermented sugar cane juice and taken orally to treat pain and
inflammation of the body. Hot water extract of leaf juice is taken orally as a cathartic; it should not be used by pregnant women. Leaf pulp is taken orally regula
rly for 10 days by women to preventconception. Leaf juice is taken orally to treat viral jaundice. The juice is taken twice daily for three days.
Malaysia Hot water extract of leaf juice is taken orally as a cholagogue and emmenagogue. Hot water extract of leaves is taken orally as an emmenagogue
Mexico Fresh stem juice is taken orally for diabetes. Infusion of dried leaves is taken orally to treat ulcers.
Nepal Fresh leaf pulp is taken orally to relieve amenorrhea. 10–15 gm of leaf pulp is given with sugar or honey once a day.
Hot water extract of dried entire plant is taken orally as a purgative and to terminate pregnancy.
Panama Fresh leaves crushed with egg white is taken orally as a laxative and demulcent. Sap is taken orally for stomach ulcers and externally for erysipelas and to treat
swellings caused by injuries.
Peru Hot water extract of fresh leaves is taken orally for asthma, as a purgative, and antivenin. Externally, the extract is used as an antiseptic for washing wounds.
Puerto Rico Drink made from fresh leaf pulp plus fruit pulp of Genipa americana is a popular remedy for colds.
Saudi Hot water extract of dried aerial parts is taken orally for liver complaints, piles, as an emetic, antipyretic, against tumors, for enlarged spleen, as a cooling agent
Arabia , purgative, for diabetes, skin diseases and asthma. Hot water extract of dried leaves is taken orally for functional sterility, amenorrhea, piles, thermal burns, co
nstipation, flatulence, intestinal worms, diabetes, to treat functional sterility, amenorrhea, to treat constipation, and piles. Externally used for burns.
South Korea Hot water extract of whole dried plant is taken orally as a contraceptive, an abortifacient, and emmenagogue. Use is contraindicated during pregnancy.
Switzerland Hot water extract of leaves is taken orally as an abortifacient.
Taiwan Decoction of dried leaves is taken orally to treat hepatitis.
Thailand Fresh leaf juice is used on burns. Hot water extract of dried resin is taken orally as a cathartic.
Tunisia Hot water extract of dried leaves is taken orally for diabetes and to treat problems of venous circulation. Externally, the extract is used for eczema.
USA Fresh leaf juice is taken orally for stomach ulcers and used externally to heal wounds. Fluid extract of leaf juice is taken orally as an emmenagogue. Hot water e
xtract of dried leaves is taken orally as a cathartic. Hot water extract of gum is taken orally as an emmenagogue to promote and stimulate menstruation. Water
extract of leaves is used externally for insect bites, myopathies, arthritis, topical ulcers, and other skin conditions. Hot water extract is taken orally to increase
menstrual flow; should be avoided during pregnancy.
Table 1. Comprehensive list of the traditional uses of Aloe vera. Adapted from (Ross, 1999)
not effected by aloe emodin alone (Wamer et al., 2003). The
oxidative damage to both RNA and DNA occurred even at low
levels of photocytotoxicity (Wamer et al., 2003).
Anticancer activity
Aloe emodin may also exhibit antineuroectodermal tumor
activity. Researchers at the Universities of Padova and Genova in
Italy devoted their attention to natural compounds in plants that
have been used traditionally to treat numerous diseases for
hundreds of years and focused on aloe emodin (Pecere et al.,
2000). Neuroblastoma cells that were grown in a complete
Figure 3. Results of a study examining the correlation medium and treated with aloe emodin displayed cytotoxicity; the
between polyphenol and flavonoid content in A. vera flowers growth of the cells was inhibited and cells showed signs of having
and the antioxidant activity (Keyhanian & Stahl-Biskup, 2007). undergone apoptotic cell death, as identified by cell shrinkage,
membrane blebbing, and nuclear fragmentation (Pecere et al.,
activity (Keyhanian & Stahl-Biskup, 2007). Aloin A and B, 2000). It was also determined that, unlike other cancer drugs that
anthraquinones associated with the laxative properties of aloe, are toxic at the necessary therapeutic levels, the aloe emodin did
were not found in the dried flowers, but the antioxidant activity not inhibit the proliferation of hematopoietic progenitors; that is,
measured correlated positively with the amount of flavonoid and it displayed selective toxicity where necessary (Pecere et al.,
polyphenol content (Keyhanian & Stahl-Biskup, 2007)(Figure 3). 2000). To further address this topic, the same researchers
conducted follow-up studies in 2003; aloe emodin induced
apoptosis in p53 mutant cells, p53 being a tumor suppressor gene
Photobiological properties (Pecere et al., 2003).
Aloe emodin and aloin A are two important anthraquinones in
aloe. Since aloe is now often included in topically applied
In vivo
cosmetics because of its moisturizing properties, it is important
that any adverse effects are identified. A recent study indicated Abortifacient effects
that the constituent aloe emodin may make the skin more In one study, aloe that was extracted with water was given to
sensitive to UV light, so a follow-up study was conducted to pregnant rats during the first nine days of gestation ("Final report
examine the events that follow photoexcitation of both aloin A on the safety assessment of AloeAndongensis Extract, Aloe
and aloe emodin (Wamer, Vath, & Falvey, 2003). Human skin Andongensis Leaf Juice,aloe Arborescens Leaf Extract, Aloe
fibroblasts that were treated with aloe emodin then irradiated Arborescens Leaf Juice, Aloe Arborescens Leaf Protoplasts, Aloe
with UV light showed dimished survival, while cell survival was Barbadensis Flower Extract, Aloe Barbadensis Leaf, Aloe
Barbadensis Leaf Extract, Aloe Barbadensis Leaf Juice,aloe levels, indicating hepatoprotective qualities (Gbadegesin,
Barbadensis Leaf Polysaccharides, Aloe Barbadensis Leaf Water, Odunola, Akinwumi, & Osifeso, 2009).
Aloe Ferox Leaf Extract, Aloe Ferox Leaf Juice, and Aloe Ferox Leaf
Juice Extract," 2007). It was found to be an abortifacient and
produced significant skeletal abnormalities in the fetal rats Hypoglycemic and hypolipidemic effects
("Final report on the safety assessment of AloeAndongensis In a study by researchers at ShamYook University in Seoul,
Extract, Aloe Andongensis Leaf Juice,aloe Arborescens Leaf South Korea, a mouse model was used to test the effects of
Extract, Aloe Arborescens Leaf Juice, Aloe Arborescens Leaf processed Aloe vera gel (PAG) on diet-induced non-insulin-
Protoplasts, Aloe Barbadensis Flower Extract, Aloe Barbadensis dependent diabetes mellitus (NIDDM). This is especially
Leaf, Aloe Barbadensis Leaf Extract, Aloe Barbadensis Leaf relevant to humans because of the dramatic increase in rates
Juice,aloe Barbadensis Leaf Polysaccharides, Aloe Barbadensis of NIDDM and the associated complications of the disease
Leaf Water, Aloe Ferox Leaf Extract, Aloe Ferox Leaf Juice, and (Kim et al., 2009). Processing the A. vera gel involves
Aloe Ferox Leaf Juice Extract," 2007). incubating the gel with cellulase (the enzyme that catalyzes
the hydrolysis of cellulose) followed by passing the gel
through a charcoal column in order to remove the
Immunostimulatory effects
anthraquinones, responsible for the laxative effects of aloe
A study was conducted on industrial broiler chickens to test the (Kim et al., 2009). To induce the NIDDM state in the mice,
effects of A. vera against coccidiosis, a parasitic infection. Results they were fed a high fat diet for 21 weeks, followed by the
showed that pulp from the leaves stimulated both humoral and treatment of different doses of PAG for 8 weeks whilst
cellular immune responses in the chickens (Akhtar et al., 2011). continuing the high fat diet (Kim et al., 2009). After 2 weeks,
Higher antibody activity can hinder the development of the the hypoglycemic effects were apparent: the fasting blood
parasites in the intestines, and it is stipulated that the glucose levels of the diet-induced obesity (DIO) mice were not
anthraquinones, saponins, and sterols of the plant may have significantly different from those of regular diet-fed mice (Kim
inhibited the multiplication of the parasites as well (Akhtar et al., et al., 2009). In addition to a decrease in blood glucose and
2011). It has potential to be used as a low cost alternative to insulin levels, improved blood glucose homeostasis was
allopathic medicines to control coccidiosis. observed; that is, when given high doses of glucose, the mice
that had been treated with PAG showed high tolerance and a
faster return to homeostasis than the control mice (Kim et al.,
Hepatoprotective effects 2009). While there have been other reports that indicate that
In investigating how to remedy the improper handling of aloe may actually increase plasma glucose levels, it is
petroleum products that leads to possible hepatotoxicity and speculated that this may be due to the parts of the plant used,
carcinogenic effects, researchers found that mice treated with as well as the difference in animal models – the mouse model
A. vera gel exhibited reduced γ-glutamyl transferase (γGT) reasonably models NIDDM in humans (Kim et al., 2009).
Another study was conducted to determine the constituents of susceptible (Im et al., 2010). The mice that were given PAG
A. vera that normalize hyperglycemia in a mouse that has been had significantly reduced renal strain, though the mechanisms
induced into the NIDDM state. Fresh Aloe vera gel was divided could not be indentified (Im et al., 2010).
into five separate extracts and administered separately to the
mice (Tanaka et al., 2006). Only one of the five extracts, T1,
significantly reduced blood glucose levels of the mice, and was Clinical Studies
further divided into fractions until five phytosterols were Periodontal Effects
isolated via chromatography and detailed C-NMR
spectroscopy, which allows for the identification and In a study conducted by the Jaipur Dental College in India, 15
elucidation of chemical structures (Tanaka et al., 2006). subjects were evaluated for periodontitis and treated by applying
Phytosterols are structurally similar to cholesterol, and in the Aloe vera gel to periodontal pockets (Bhat, Kudva, & Dodwad,
1950s it was recognized that plant sterols lower the serum 2011). After three months, subjects showed a significant
concentrations of cholesterol (Tanaka et al., 2006). Mice that reduction in pocket depths as compared to the control group, as
were treated with the five phytosterols showed decreases in well as a reduction in gingival index, which is attributed to the
both fasting blood glucose levels and random blood glucose anti-inflammatory and antibacterial effects of A. vera (Bhat et al.,
samples (Tanaka et al., 2006). 2011). Improved healing was attributed to increased oxygenation
because of the A. vera, as well as the presence of vitamins A, C, E,
B12 and folic acid (Bhat et al., 2011). Vitamin C especially dilates
Burn care blood vessels, thus increasing oxygen concentration. No adverse
effects were found, though a longer study time and larger sample
While aloe is generally regarded as beneficial in the treatment size is necessary (Bhat et al., 2011). These promising results, as
of minor burns, a study in 2008 found that the application of well as the ease of application and low cost of Aloe vera show the
Aloe vera to the burn wound of a large white juvenile pig was potential for its use as a means to improve periodontal conditions.
no more beneficial than the control group in terms of re-
epithelialisation, cosmetic appearance or histology of the scar
(Cuttle et al., 2008). The aloe did, however, decrease the Anti-hyperglycemic/Anti-hypercholesterolemic effects (Anti-
subdermal temperature of the wound, indicating possible diabetic)
cooling and soothing purposes, which cannot be overlooked
(Cuttle et al., 2008). In a randomized double-blind placebo-controlled clinical trial at
the Research Institute of Medicinal Plants in Karaj, Iran, aloe leaf
gel powder was prepared was evaluated for efficacy in the
Immunomodulatory activity treatment of patients with type II diabetes. Just as in the mouse
model trial described above, the aloe gel was treated to remove
To test the immunomodulatory activity of processed Aloe vera aloin and other anthraquinones, known to have laxative effects
gel (PAG) in a diabetic mouse model, the mice were infected (Huseini, Kianbakht, Hajiaghaee, & Dabaghian, 2012). The gel was
with Candida albicans, to which the kidney is particularly then freeze-dried and made into 300 mg capsules (Huseini et al.,
2012). One variant from the mouse model is that the patients Ulcerative colitis
were recommended to decrease their intake of carbohydrates and
Since Aloe vera is known for its anti-inflammatory activity, a
fatty foods, while the mice continued to eat a high-fat diet. The
double blind, randomized trial was used to examine the
results of this study showed that the aloe gel improved glycemic
effectiveness of aloe in the treatment of mild to moderate
control and lowered both total cholesterol and low-density
ulcerative colitis. Subjects took 100mL of A. vera gel orally twice
lipoproteins, but did not effect any other blood lipid levels and did
daily for four weeks and the control group were given a placebo
not seem to have any adverse effects (Huseini et al., 2012). The
(Ke, Yadav, & Ju, 2012). Subjects who had been taking the A. Vera
only bioactive compound that was indentified in this trial was the
gel were nearly four times as likely to show response,
mucopolysaccharide acemannan, but the mechanisms involved in
improvement, or complete clinical remission as compared to
these hypoglycemic and hypocholesterolemic effects were not
those taking the placebo (Ke et al., 2012).
investigated in this study (Huseini et al., 2012).
Contraindications
Burn care
Aloe vera is known to contain compounds that have been
Aloe vera is generally considered safe for topical use
documented to be cytotoxic. In a study by Patna University in
(Maenthaisong, Chaiyakunapruk, Niruntraporn, & Kongkaew,
India, researchers found that while there was not an increase in
2007). In some studies aloe has been shown to reduce healing
structural abnormalities of the chromosomes in the bone marrow
time for burns and other wounds, while other studies have been
of mice injected with the crude leaf extract of aloe, there was a
inconclusive or show that aloe has no great effect on healing
significant increase in chromosome number anomalies and in the
(Maenthaisong et al., 2007). Some studies indicate that the aloe
mitotic index, or proliferation status, of the cells (Verma, Gupta,
may simply be used for its cooling and soothing effects, but it is
Kumar, & Khan, 2012). There have also been reports of
generally agreed upon that 100% aloe is most effective at treating
hepatotoxicity induced by aloe. Patients who had been taking
topical wounds, and anything less than 50% has no effect (Korac
aloe preparations and had been diagnosed with acute hepatitis
& Khambholja, 2011). One study found that application of A. vera
showed the return of liver enzymes to normal levels after the aloe
increased the production of collagen, thus increasing the rate of
use had been discontinued (Yang et al., 2010). Although still
epithelialization (Korac & Khambholja, 2011). In directing the
unclear, there are also some findings that indicate that the
care of outpatient burns, the application of aloe to the affected
compound aloe-emodin induces apoptosis in human kidney-2
area was noted to be successful in treating the pain associated
(HK-2) cells, though these possible toxic effects are unclear and
with superficial wounds or burns (Lloyd, Rodgers, Michener, &
need further research (Zhu et al., 2011). There was clear
Williams, 2012).
evidence of carcinogenic activity in rats from oral consumption of
the whole leaf of the aloe plant, but once again, more research is
needed (Medicine, 2011). Also with the oral use of aloe,
especially as a stimulant laxative, there have been reports of
abdominal cramps and diarrhea, which can further lead to a
decrease in the ability of other drugs to be absorbed (Medicine, medicine regimen, with 77.8% of parents stating that they
2011). Since some compounds in A. vera are known to lower assumed aloe had fewer potential side effects (Dannemann et al.,
blood-glucose levels, people with diabetes are warned to be 2008). It generally accepted that aloe gel is generally regarded as
cautious, as they are generally already prescribed an alternate safe for the treatment of minor burns – there are many topical
glucose-lowering medication (Medicine, 2011). aloe gel treatments available on the market, but anything less
than 100% Aloe vera gel is thought to have little to no efficacy in
treating burns, so one might be best served by having the plant
Current Use in Allopathic and CAM Therapies itself for usage.
Aloe vera supplements are not FDA approved, and thus are used
at the patient’s own risk. There are many people who do choose
to supplement biomedicine with an herbal supplement such as Discussion
aloe, but drug-herb interactions may be overlooked and can lead Aloe vera has been used for its medicinal properties all over the
to serious, sometimes fatal consequences. There is anecdotal world. The gel inside the leaf has been used to treat burns and
evidence of older patients taking aloe preparations for months other minor wounds topically, and it can also be ingested orally;
and developing acute hepatitis that returned to normal after the anthraquinones make it a very effective laxative. Aloe has
discontinuing the use of the oral aloe (Yang et al., 2010). This is also been employed traditionally for its possible abortifacient
discordant with the in vivo study mentioned above that indicates effects, hypoglycemic and hypolipidemic effects, and
hepatoprotective properties in aloe, and it is clear that more hepatoprotective activity. Though many studies have been
clinical trials need to be conducted before people continue to use conducted to determine the efficacy of A. vera in regards to these
A. vera in complementary and alternative medicine without potential beneficial effects, there are enough discrepancies that
consulting a healthcare professional. There is further risk of the results are generally inconclusive, and it is clear that further
using aloe as complementary medicine if it is used in combination studies are required, especially since determining the exact
with antiretroviral drugs for the treatment of HIV, as the mechanism of action could help to identify how the chemical
pharmacokinetic interactions between the antiretrovirals and constituents in aloe help or inhibit certain qualities. Since aloe
herbal medicine is unknown; only antiretrovirals have proven can be cultivated in a wide range of areas it is not in danger of
efficacy in treating HIV (Lamorde, Byakika-Kibwika, & Merry, being overharvested, so more studies can be conducted in the
2012). There were several studies conducted on complementary future without fear of extinction of the species. Aloe vera has the
and alternative medicine usage in Nigeria. In hypertensive potential to have many advantageous medicinal properties, even
patients who visited a tertiary care center, 4.5% used Aloe vera in anticancer activity, and further research will help to solidify
addition to conventional medical treatments (Amira & Okubadejo, findings now that support aloe in the treatment of diabetes
2007). At a multi-specialist hospital in Nigeria, aloe was also mellitus, among other diseases. Since rates of obesity have
found to be used by 28% of patients with osteoarthritis (Obalum increased, rates of diabetes have followed, and finding new,
& Ogo, 2011). In Germany, 7.3% of children with type I diabetes effective treatments that have no adverse effects may prove to be
mellitus are given an aloe supplement as part of a complementary where Aloe vera is needed.
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Ananas comosus (L.) Merr., Bromeliaceae
Anum Dhukani
Introduction
Ananas comosus, otherwise known as the pineapple, belongs
to the family Bromeliaceae. It is also known as the piña by the
Spanish, abacaxi by the Portuguese, ananas by the Dutch and
French, as well as nanas in Southern Asia and the East Indies
(Morton, 1987). While the family Bromeliaceae includes
approximately 2,000 species, the genus Ananas consists of 2
species: A. macrodontes and A. comosus. Of these 2 species, the
more common species is A. comosus (Sanewski 2011) (Figure
1). It is native to Central and South America but is grown in
other areas such as Hawaii, South Africa, China, India, Kenya,
Thailand, Malaysia, and the Philippines (Tochi et al. 2008).
Bromelain is a proteolytic enzyme obtained from the stem of
the pineapple that exhibits therapeutic properties such as
preventing malignant cell growth and platelet aggregation,
thrombus formation, anti-inflammatory and wound-healing
action, and increased permeability of drugs (Maurer 2001).
Other constituents besides stem bromelain include fruit
bromelain, ananain, and comosain (Rowan, Buttle, and Barrett
1990).
Pineapple is indigenous to the tropical and subtropical
regions, especially southern Brazil and Paraguay. It is essential
for the pineapple to grow in these regions due to the favorable
temperatures ranging from 65°F to 95°F; low temperatures Figure 1. The 5 most common pre-Columbian cultivars:
can potentially delay growth as well as cause the fruit to taste ‘Perola’ (A), ‘Queen’ (B), ‘Manzana’ (C), ‘Red Spanish’ (D),
acidic. In addition, high elevations can also induce acidity. The and ‘Cayenne’ (E). (Source: Sanewski 2011).
Volatile compound Aroma epiphytes grow on other plants and objects. The pineapple
4-hydroxy-2,5-dimethyl-3(2H)- Sweet, caramel, fruity, burnt. belongs to the terrestrial branch (Okihiro 2009, 76).
furanone Strawberry and pineapple at
low conc The pineapple plant is an herbaceous perennial ranging from
4-methoxy-2,5-dimethyl-3(2H)- Sweet, caramel, fruity, musty, 2.5 to 5 ft high with a short stem of pointy, waxy green leaves
furanone savoury that are 20 to 72 in. long (Pineapple 1996). The stem begins to
Ethyl 2-methyl butanoate Green, apple, fruity elongate near the apex during blooming time and small purple
Methyl 2-methyl butanoate Fruity, apple or red flowers appear. Known as the “crown” of the pineapple,
Methyl butanoate Fruity, apple this clump of firm, short leaves grows after the stem develops.
Ethyl 3-(methyl thio) Pineapple Developing from the flowers is the cone shaped fruit that is 12
propanoate or more in. in height (Morton 1987).
Methyl 3-(methyl thio) Sulfurous, pinapple
propanoate The pineapple fruit is composed of many small fruitlets, which
Ethyl 2-methyl propanoate Sweet, fruity determine the pineapple’s size. In general, fruit size can be as
Methyl 3-propanoate Fruity, pineapple little as 100 g to as much as 7 kg. Most pineapples range from
Methyl propanoate Fruity, rum-like, apple, banana, yellow to orange skin; however, there are also cream, pink,
strawberry and red skinned pineapples. The yellow, green, and red skin
octalactone Creamy, coconut color is due to carotenoids, remaining chlorophyll, and
decalactone Sweet, coconut, peachy
anthocyanins, respectively. The yellow flesh color is also a
hexalactone Sweet, creamy, coconut,
herbaceous
result of carotenoids similar to the skin. The sweet flavor of
vanillin Vanilla the pineapple is because of the sucrose content. However, it is
1-(E,Z)-3,5-undecatriene Fresh, green, pineapple important to note that the smaller the fruit, the sweeter it is.
octanol Citrus Flesh and skin volatile compounds establish the pineapple’s
Methyl hexanoate Fruity, pineapple distinctive aroma (Sanewski 2011). Table 1 lists some of the
Ethyl hexanoate Fruity, pineapple major compounds that contribute to the pineapple’s aroma
3-methylbutyl acetate Fresh, fruity. Banana and pear and flavor.
at low conc
Table 1. Major compounds in pineapple aroma. This is a The primary pollinator of the pineapple plant is the
list of the compounds that give the pineapple its sense of hummingbird. Hard seeds can be present in the fruit if the
aroma and flavor (Source: Sanewski 2011). flowers are pollinated; however, if they are not, few seeds will
be present (Morton 1987). There are several pests and
plant can be grown on small plots or steep slopes, but since diseases that can infect the pineapple including mealy bugs
the pineapple’s roots are shallow, the land must be prepared and rats. Bud rot, fruit core rot, and heart rot are diseases that
on the surface to avoid damage (Morton 1987). The are also common. Bud rot is rotting of the stem and the
Bromeliaceae family consists of two branches: terrestrial and eventual death of the plant while fruit core rot is seen in fruits
epiphytes. While the terrestrial plants are rooted in soil, the that turn brown in the inside and are smaller in size. Heart rot
is when the leaves begin to redden and the edges become worms. The pineapple root in the form of dried powder was
brown and wilt. To avoid bud rot, the plant should not be cut used to heal edema in Africa while the rind was topically
in a way as to allow fungus to infect it. Controlling mealy bug applied to fractures and hemorrhoids. Even today, compounds
invasion and removing the crown in the rainy season can in the pineapple are commonly used to treat edema as well as
prevent fruit core rot. In addition, proper drainage and to reduce pain and inflammation. In Panama, the leaf juice was
elevation of the plant can ensure safety from heart rot used to promote menstruation, remove worms, and cleanse
(Pineapple: Pests and Diseases 2011). the intestine (Morton 1987).
Five common pineapple cultivars include the ‘Perola’, ‘Queen’,
‘Manzana’, ‘Red Spanish’, and ‘Cayenne’ illustrated in Figure 1
Food uses
(Sanewski 2011). The ‘Perola’ is a yellow, large, and
cylindrical pineapple with no spines and is popular in Pineapples are also commonly used in food. The flesh of the
Venezuela and Columbia. The ‘Queen’ is prevalent in South fruit can be eaten alone, in desserts, salads, pies, cakes,
Africa, Queensland, and the Philippines. It is cone-shaped, puddings, or made into sauces. Malayans add the pineapple in
golden-yellow with more fragrance and flavor than other their curries while the Filipinos use extracted pulp in a dessert
cultivars. However, it matures early, requires thinning, and called nata de piña. The pineapple cannot be frozen because
has a low yield. A minor cultivar in Columbia is the ‘Manzana.’ the flavors are subsequently extinguished. Because pineapples
In addition to these is the popular cultivar in Florida, the West contain a proteolytic enzyme called bromelain, either the
Indies, Venezuela, and Mexico known as the ‘Red Spanish.’ pineapple or the enzyme is commonly used as a meat
Resistant to rotting, it ranges from having orange to red skin tenderizer to break down protein. The canning of pineapples
and represents 85% of commercial planting in Puerto Rico. has significantly increased its demand and made it one of the
Due to its cone-shaped form, orange skin, mildly acidic flavor, leading fruits worldwide. Hawaii alone supplied 70% of the
and canning properties, the ‘Cayenne’ is known worldwide world’s canned pineapple for about a decade starting in 1970
despite its lack of ability to withstand disease (Morton 1987). until the company, Dole, transferred its operation to the
Philippines due to increased production costs (Morton 1987).
Traditional Uses
Ethnobotanical uses
Traditional medicinal uses
Native Americans cultivated the pineapple in Mexico and the
The pineapple has been used traditionally for a variety of
West Indies before the arrival of Christopher Columbus.
ailments particularly in Central and South America (Taussig
Columbus and his crewmembers saw the pineapple for the
and Batkin 1988). The juice was not only consumed as a
first time in 1493 in Guadeloupe. Inhabitants of the Caribbean
diuretic but also gargled for sore throats and to prevent
set pineapples outside their homes to represent friendship
seasickness. Because unripe pineapples are poisonous, it was
and hospitality. As a result, Europeans in Spain and England
traditionally taken for abortion and removal of intestinal
Figure 2. Decorative fruits. The pineapple’s flowers were
commonly used as a source for flower arrangements (Source:
Sanewski 2011). Figure 3. The pineapple as a common ornamental. A
pineapple sits as an ornamental on top of a wall lamp in
illustrated the fruit in carvings on doorways (Morton 1987). George and Martha Washington’s home. (Source: Okihiro
Pineapple ware such as pots, mugs, cups, and bowls were even 2009).
sold in colonial America (Okihiro 2009, 164).
In addition to its medicinal value, the pineapple was used for taken into account. Before the pineapple reaches maturity,
many other applications. The juice was used as a cleanser for starch is converted into sugars in a span of a few days. During
knife blades and scrubbing boat decks (Morton 1987). The the summer, crop is harvested when the skin shows a light
flowers of the plant could be used as an ornamental or flower green color because sugar content and volatile flavors begin to
arrangement illustrated in Figure 2. The fruit itself was also develop. However, the winter crop takes approximately one
used as a means to decorate the home. For example, George month longer to reach maturity; therefore, fruits are
and Martha Washington adorned their wall lamp with a harvested when the base is covered with a light yellow
pineapple on top illustrated in Figure 3 (Okihiro 2009, 166). pigment. In spite of this, winter pineapple is more acidic and
In the Philippines, the natives extract fiber from the leaves in has lower sugar content than summer pineapple. In addition,
order to make fabric (Pineapple: Pests and Pesticides, 2011). if the fruit is overripe, it is not as flavorful and is more likely to
perish. Usually after the stem is cut, a 3% solution of benzoic
acid is applied to the stem in order to protect the fruit from
Harvesting rain and dew. Pineapples should not be stored for more than
Pineapple harvesting requires an enormous amount of six weeks although storage life can be extended by immersing
experience; in addition to size and color, other factors must be the fruit in a wax solution with fungicide (Morton 1987).
inflammatory conditions. They consist of a broad range of
therapeutic effects such as antiedematous, anti-inflammatory,
antithrombotic, and fibrinolytic activities. These proteolytic
enzymes also help regulate immune cells and cytokine
production as well as functions of adhesion molecules on
blood and endothelial cells (Maurer 2001). Table 2 lists the
components found in Ananas comosus.
Figure 4. Structure of bromelain. This illustrates the Biological Activity

complete structure of the 2 oligosaccharides in bromelain.
In vitro
(Source: Ishihara et al. 1979)
Pineapple’s main therapeutic component, bromelain, has been
studied in many in vitro and in vivo studies. In vitro studies
Chemistry and Pharmacology
have found that not only is bromelain degraded in blood
One of the main constituents in the pineapple is a cysteine plasma by protease inhibitors, but oral administration may
protease known as stem bromelain (Figure 4). It is an facilitate bromelain in preserving its proteolytic activity
aqueous extract from the stem and sometimes fruit of (Orsini 2006).
pineapples that is prepared by centrifugation, ultrafiltration,
Researchers stimulated mouse ileum to induce contractions
and lyophilization. This complex process yields a yellow
and then administered bromelain, resulting in the inhibition of
powder. However, when in an aqueous solution, bromelain
contractions. This suggests bromelain inhibits intestinal
can degenerate due to self-digestion; therefore, α2- motility. This discovery could help bromelain become a
macroglobulin, a plasma protein, is added to prevent leading drug in regulating intestinal motility in intestinal
deterioration (Maurer 2001). The majority of research has inflammation as well as diabetes (Borrelli et al. 2011).
been conducted on bromelain and many of the therapeutic Bromelain also hinders tumor growth by 90% in Lewis lung
effects are attributed to it. However, there are also other carcinoma, YC-lymphoma, and MCA-1 ascitic tumor even after
cysteine proteases such as fruit bromelain also known as destruction of the proteolytic activity by heat. This indicates
bromelin, ananain, and comosain. Ananain and comosain are that another factor is responsible for the anticancer effect
found in the stem along with stem bromelain. Bromelain is a observed in pineapple (Taussig and Batkin 1988). Bromelain
proteolytic enzyme comprised of a mixture of components also reduces platelet adhesion to endothelial cells as well as
including peroxidase, acid phosphatase, protease inhibitors, platelet aggregation. In addition, it has the ability to stimulate
and organically bound calcium (Orsini 2006). Used as plasminogen to produce plasmin, which can then cleave fibrin
complementary medication to glucocorticoids, antirheumatics, and decrease fibrin levels (Maurer 2001).
and immunomodulatory agents, proteolytic enzymes’ low
toxicity provides the capability for the treatment of
Components of Ananas comosus
Plant Ethyl proprionate Bromelain also has an antisecretory effect. Diarrhea is caused
2,5-dimethyl-4-hydroxy-3(2H)- Gaba
furanone (1.2 ppm) Gamma-butyrolactone by the activation of the cAMP, cGMP, or calcium-dependent
5-hydroxytryptamine Gamma-caprolactone (.12 ppm) signaling pathways in the large intestine. Using rabbit ileum,
acrylic acid Gamma-octalactone (.3 ppm) researchers found that bromelain prevents changes in these
ananasic acid Hexosans (1000-1500 ppm)
beta-methyl-thiopropionic-acid-ethyl- Indole acetic acid oxidase pathways (Mynott et al. 1997).
ester Isobutanol
beta-methyl-thiopropionic-acid- Isobutyl acetate
methyl-ester Isobutyl formate In vivo
ergosterol peroxide Isocapronic acid
ferulic acid (200-760 ppm) Isopropyl isobutyrate A common question is whether bromelain is absorbed after
p-coumaric acid (330-730 ppm) L-malic acid
stigmast-5-ene-3-beta-7-alpha-diol Malid acid (1000-4700 ppm) oral ingestion; researchers found that 40% of labeled
tetrahydro-alpha-alpha-5-trimethyl- Methanol bromelain is absorbed from the intestine (Maurer 2001).
5-vinylfurfuryl-alc Methyl acetate Bromelain’s anticancer effect was tested in vivo as well in mice
Methyl-beta-acetoxyhexanoate Methyl-
Fruit beta-hydroxybutyrate Methyl-beta- subjected to ultraviolet radiation. Those fed bromelain
Acetic acid (.49 ppm) hydroxyhexanoate Methyl-beta- showed retardation of the growth of lesions (Goldstein et al.
Acetoxyacetone methylthiopropionate Methyl butyrate 1975). Baez et al. also studied a number of tumor lines in vivo
Alpha-linolenic acid (620-4592 ppm) Methyl caproate
Amyl caproate Methyl caprylate (.75 ppm) including P-388 leukemia, sarcoma (S-37), Ehrlich ascitic
Asparagine (1251 ppm) Methyl-cis-4-octenoate (.001 ppm) tumor, Lewis lung carcinoma, MB-F10 melanoma, and ADC-
Biacetyl Methyl isobutyrate 755 mammary adenocarcinoma. All were administered
Bromelain Methyl isocaproate (1.4 ppm)
Bromelin Methyl isovalerate (.6 ppm) bromelain intraperitoneally and all had an increase in survival
Butyl formate Methyl-n-propyl ketone rate besides MB-F10 melanoma (Baez et al. 2007).
Chavicol (.27 ppm) N-valerianic acid
Delta octalactone (.3 ppm) Nitrate (1200 ppm) Bromelain also has the capability of reducing existing edemas
Dimethyl malonate (.06 ppm) Oxalic acid (50-58 ppm) as well as preventing the formation of new edemas (Maurer
Esters (1-250 ppm) P-aminobenzoic acid (1 ppm)
Ethyl acetate (3-120 ppm) P-coumaric acid (330-730 ppm)
2001). Oral bromelain not only reduces swelling and pain but
Ethyl acrylate (.77 ppm) Pentanol also reduces the time it takes to heal by half. Experiments
Ethyl alcohol (60 ppm) Pentosans (3300-4300 ppm) explored the anti-inflammatory effect of bromelain on edemas
Ethyl-beta-acetoxyhexanoate Ethyl- Phosphatase
beta-hydroxyhexanoate Ethyl-beta- Phytosterols (60-444 ppm)
in rats along with eight other drugs, including aspirin, and
methylthiopropionate Ethyl butyrate Propanol found that bromelain was the most effective in terms of a
Ethyl caproate (.77 ppm) Propyl acetate reduction in inflammation (Taussig and Batkin 1988). Further
Ethyl caprylate Propyl formate
Ethyl formate Serotonin (19-60 ppm)
experiments found similar results of bromelain’s potency in
Ethyl isobutyrate Vanillin comparison to other drugs even when applied
Ethyl isovalerate (.39 ppm) Vit-b-6 (.9-6 ppm) intraperitoneally (Smyth, Brennan, and Martin 1962).
Ethyl lactate
Table 2. Components in Ananas comosus (Duke 2010).
Topical bromelain is used for debridement of third degree
burns without removing unburned tissue; a study was done
on rats with experimental burns in which topical bromelain
helped remove damaged tissue with no side effects (Klaue,
Aman, and Romen 1979). Bromelain is especially beneficial
because it prevents bacterial growth, contamination, and
infection to the healthy tissue by removing the burnt tissue
(Rosenberg et al. 2004).
Mechanism of action
Bromelain has a number of therapeutic uses implicating that it
must have multiple mechanisms (Taussig and Batkin 1988).
The anti-platelet and anti-inflammatory effects are related to
bromelain’s proteolytic activity. However, the anticancer and
burn debridement properties are due to some other unknown
factor in bromelain. A possible mechanism of action has been
proposed for the anticancer property of bromelain which
stimulates differentiation of leukemic cells possibly leading to
apoptosis of tumor cells (Maurer 2001).
Bromelain’s mechanism of action is partially due to the
activity of two types of prostaglandins: pro-inflammatory
prostaglandins and anti-inflammatory prostaglandins. Pro-
inflammatory prostaglandins stimulate inflammation, platelet
aggregation, and vasoconstriction. Anti-inflammatory Figure 5. Biosynthesis of prostaglandins and bromelain
prostaglandins have the opposite effect. Bromelain is a pro- effect. This diagram illustrates how bromelain and aspirin
inflammatory prostaglandin inhibitor that is similar to aspirin affect prostaglandins (Source: Taussig and Batkin 1988).
but weaker so it does not promote bleeding. Bromelain
activates plasminogen, which induces plasmin production. AMP. Anti-inflammatory prostaglandins generally lead to
Plasmin subsequently cleaves fibrin, which inhibits pro- increased c-AMP production, inhibited platelet aggregation,
inflammatory prostaglandins. Consequently the ratio between inhibited inflammation, dilated blood vessels and smooth
pro-inflammatory and anti-inflammatory prostaglandins muscles, and increased tissue permeability; this mechanism is
shifts in favor of anti-inflammatory prostaglandins. This leads illustrated in Figure 5 (Taussig and Batkin 1988).
to the activation of adenylyl cyclase and the production of c-
Clinical Studies Cancer
Pain and Inflammation Bromelain is shown to have an anticancer effect; however,
Bromelain demonstrates both analgesic and anti- studies verifying this have primarily been in vivo.
inflammatory properties (Brien et al. 2004). Patients given Nevertheless, its activity was tested in a few clinical studies.
bromelain felt less pain linked to mediolateral epistomy Twelve patients with different tumors were treated with oral
(Zatuchni and Colombi 1967) and bradykinin (Bodi 1966). bromelain and were found to have a decrease in ovarian
Furthermore, bromelain reduces mild knee pain and helps carcinoma, breast cancer, and metastases. Another study
improve general well-being in patients given 200 or 400 mg of found tumor regressions in patients administered high doses
oral bromelain (Walker et al. 2002). It has been widely used of bromelain simultaneously with chemotherapeutic agents
for inflammation ever since its discovery and is commonly such as vincristine. Both studies found that at least 2.4 g per
used for rheumatoid arthritis, thrombophlebitis, hematomas, day of bromelain was necessary and dosages less than 1000
oral inflammations, diabetic ulcers, rectal and perirectal mg were insufficient (Taussig and Batkin 1988).
inflammations, oral and plastic surgery (Taussig and Batkin
1988). Researchers found that patients suffering from
Antibiotics
arthritis with joint swelling when administered bromelain
report reduction in swelling, pain, and soreness (Walker et al. It has been shown that bromelain can enhance the absorption
2002). Previous studies have indicated that bromelain may of antibiotic drugs. It increases tissue permeability yielding
serve as an alternative treatment to NSAIDs for patients enhanced diffusion of the antibiotic after subcutaneous or
suffering from osteoarthritis (Brien et al. 2004). However, the intramuscular application (Maurer 2001). Researchers found
required dosage is unclear; while one study used between 60 that patients treated with bromelain and antibiotics had an
and 160 mg of oral bromelain per day (Cohen and Goldman increase in serum and tissue levels of amoxicillin (Tinozzi and
1964), another study administered 1890 mg of oral bromelain Venegoni 1978). Twenty-three patients with pneumonia,
(Tilwe et al. 2001) per day both of which reported reduced bronchitis, staphylococcus infections, thrombophlebitis, as
pain and swelling. Adverse reactions must also be taken into well as other conditions were administered bromelain with
consideration when assigning dosage. While one study using antibiotic therapy. These patients previously did not react to
945 mg of oral bromelain per day reported gastrointestinal antibiotic therapy but after simultaneous bromelain
problems and subsequent drop-outs (Singer, Singer, and treatment, 22 of the patients responded (Neubauer 1961).
Oberleitner 2001), the previously mentioned study
administering 1890 mg of oral bromelain per day reported no
drop-outs or safety issues (Tilwe et al. 2001). Bromelain’s use Burn debridement
in the treatment of osteoarthritis is promising; however, more One of bromelain’s few topical treatments is its effectiveness
studies must be conducted in order to identify an optimum in the debridement of third degree burns. Patients with
dosage. second and third degree burns were treated with Debridase, a
multienzyme combination containing bromelain. Debridement
of the eschar was achieved after only one to two applications (Maurer 2001). It is important to note that higher doses of
(Rosenberg et al. 2004). Eschar is burnt and traumatized bromelain will lead to a greater likelihood of exhibiting side
tissue that can prevent proper assessment of the burn’s depth effects (Orsini 2006). Since unripe pineapples were used as an
and lead to bacterial growth, contamination, and infection. abortifacient in the past, pregnant women should limit intake
Surgical removal is not only painful and results in significant unless used for that purpose (Morton 1987). Consumption of
bleeding but it also requires frequent doses of anesthesia pineapples can also cause allergic reactions in which
(Tochi et al. 2008). Bromelain can achieve the same end result symptoms include itching, rashes, abdominal pain, vomiting,
with no blood loss and few side effects (Rosenberg et al. and diarrhea (Kabir, Speelman, and Islam 1993). The blood
2004). glucose response in diabetic patients after pineapple
consumption is significantly higher than other fruits such as
mango and chico. Due to the increased glucose response and
Circulation pineapple’s identification as a fruit with a high glycemic index
By inhibiting platelet aggregation, bromelain can serve as an (GI), it is suggested that diabetic patients limit intake to
important treatment in cardiac medicine. Patients with a high moderate amounts (Guevarra and Panlasigui 2000).
platelet count or history of heart attack and stroke were Bromelain can potentially increase bleeding when taken with
treated with oral bromelain leading to a decrease in platelet aspirin and warfarin due to its anticoagulant properties. In
aggregation (Heinecke, Waal, and Yokoyama 1972). addition, there is very little research conducted on the drug
Researchers suggest the activity is due to the activation of safety of bromelain in children; most clinical studies focus on
plasminogen followed by an increase in fibrinolytic activity, adults. Therefore, children should not be given bromelain
therefore blocking fibrin production (Orsini 2006). Bromelain supplements due to the lack of studies in children. There is
also inhibits thrombus formation due to its inhibition of also little information on bromelain’s effects at high doses,
platelet aggregation and decreased fibrin production (Tochi et taken long term, or taken in combination with other
al. 2008). medication (Orsini 2006). More research is needed for
bromelain’s use as an established compound for medicinal
purposes.
Contraindications
According to the U.S. Federal Drug Administration, bromelain
is generally recognized as safe (Orsini 2006). It has low Current Use in Allopathic and CAM Therapies
toxicity and few side effects associated with it (Maurer 2001). Bromelain is an extract that yields a yellow powder (Maurer
Possible adverse effects of bromelain include gastrointestinal 2001) available in the form of a powder, tablet, cream, or
problems, headache, fatigue, dry mouth, skin rash, and allergic capsule (Orsini 2006). Bromelain is also available in
reactions (Orsini 2006). However, these effects are multienzyme combinations in Debridase, Phlogenzym,
uncommon in the general population; a study found a 1.8% Wobenzym, and Traumanase (Orsini 2006) (Figure 6). Other
prevalence of side effects after bromelain administration trade names include Ananase, Bromelain, Resolvit, Extranase,
constituent, bromelain, is not only an anti-tumor agent, but
prevents platelet aggregation and hence thrombus formation.
It is an analgesic as well as an anti-inflammatory agent used in
a number of conditions such as rheumatoid arthritis, oral
inflammations, ulcers, and plastic surgery. Although it can
promote antibiotic drug absorption, one of the most important
capabilities of bromelain is its use in burn debridement of
second and third degree burns. Bromelain is generally
recognized as safe and there are very few if any side effects
due to it, which can possibly occur at very high doses.
However, research is limited in bromelain’s use in children as
Figure 6. Examples of bromelain multienzyme herbal well as the required dosage to view its effects. With more
supplements. (Source: http://www.apomio.de). research, A. comosus can serve as an important plant for the
treatment of dermatological disorders, inflammatory
and Inflamen (Sittig 2007). The German Commission E conditions, as well as cancer treatments in the future.
recommends 80-320 mg of bromelain two to three times per
day. However, if used for arthritis, 500-2000 mg per day
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Klaue, P., G. Aman, and W. Romen. 1979. Chemical debridement of cysteine proteinases of the pineapple plant. Biochemistry
the burn eschar in rats with bromelain combined with journal 266:869-875.
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pharmacodynamie et de therapie 136:230-236 Bromelain reduces mild acute knee pain and improves well-
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Taussig, Steven J., and Stanley Batkin. 1988. Bromelain, the enzyme
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the association of physicians of india 49:621.
Angelica archangelica L., Apiaceae
Jessica Elinburg
Introduction
Known by a variety of names including wild celery, Holy
Ghost, Norwegian angelica, and garden angelica, Angelica
archangelica L., of the Apiaceae (parsley) family is a plant
useful for a vast variety of therapeutic remedies. Sprinkled
throughout the damp soil of Northern Europe and Asia,
angelica was once (and in some cultures still) considered to be
a precious source of holistic medicine as well as a delicious
snack and when dried, a pungent flavoring agent. Historically,
A. archangelica has been used for a plethora of therapies.
From superstitiously wearing the flowers of angelica as
jewelry to instituting the plant as the “official” remedy of the
infamous Plague, society’s awe of angelica’s mysterious
beneficial properties can be traced back to pre-medieval
Europe. The odd towering herb displays antioxidant
properties and possesses anxiolytic (anxiety inhibiting),
hepatoprotective (liver protecting), and anticarcinogenic
(cancer preventing) effects; it also inhibits
acetylcholinesterase, an enzyme that activates acetylcholine, a
neurotransmitter crucial in muscle function and relaxation.
Although only one formal clinical research study has been
performed on A. archangelica, many in vitro and in vivo studies
display promising results for the active compounds in the
plant. Angelica archangelica is truly a diamond in the raw, a
herb largely undiscovered by the Western world that just may
hold the key to obtaining holistic health.
Figure 1. Compound umbel of A. archangelica
http://apps.rhs.org.uk/plantselector/plant?plantid=136
stalks, they may measure up to three inches in length. The
terminal leaflets exist in triads (Figure 2). A. archangelica
produces a green pod-shaped fruit that contains two seeds.
The fragrance of A. archangelica resembles that of celery with
sweet earthy undertones, much like a combination of citrus,
mint, and earth. A. archangelica has an appealing taste and is
thus used in a variety of culinary pursuits.
A. archangelica originated in Europe and Asia, though it has
expanded to many other areas, including the United States, for
agricultural purposes. The herb favors moist environments
near water sources such as marshes, lakes, streams, and even
saltwater bodies (though this is less common). In fact, angelica
favors waterfront cultivation sites to the extent that
domestically cultivating the herb is quite a challenge. A.
archangelica grows best in partial shade (Kowalchik, Hylton,
Carr, & Press, 1987). Surprisingly, insects and parasites rarely
feed on angelica, with the exception of a few species of leaf-
munching worms. Angelica is also a relatively hearty plant,
Figure 2. Leaves of A. archangelica
http://www.mygourmetconnection.com/reading/ingredient-
able to withstand unseasonably cold periods (Bhat, Kumar, &
guides/fresh-herbs-a-to-z-part1.php Shah, 2011).
A. archangelica’s maturation process is unique. In its first year
Botanical Description of growing, only leaves are present among the plant’s thick
stalk. By the second year, the plant has a canopy of serrated
Angelica archangelica L. is a surprisingly tall herb, reaching leaves teaming from its stems. Finally, but not until the third
heights of up to eight feet. The cylindrical, hollow stalk of the or fourth year of existence, does the angelica plant flower and
plant is a dim greyish purple color and eventually branches produce fruit. This rather lengthy cultivation period often
into a globular compound umbel. The umbel may span up to leads to overharvesting and decimation of wild angelica
five inches in width, donning small vibrantly colored flowers populations.
(Figure 1). The color of the flowers exists on a continuum
ranging from vivid yellow green to bright white. At the base of The global demand for A. archangelica is great. However the
the plant, green pinnate leaves extend. Lobes branch from prized plant is becoming rapidly scarcer each year as
both sides of the stem’s axis. The leaves are long, slender, and overgrazing, unfavorable environmental conditions, habitat
ovular, typically serrated down the sides. Hanging from tender degradation, and overharvesting take place over time.
Although angelica is cultivated all over the world, like many
plants, the wild herb is generally more desirable than the prompted the townspeople to propose that perhaps the herbal
domesticated. Angelica populations in Asia are especially at product the peasants were carrying, which happened to be A.
risk for endangerment. Conservation efforts are currently archangelica, somehow had a divine connection or some
being undertaken in hopes that the wild populations of bizarrely idolatrous spiritual significance.
angelica can be replenished. If conservation efforts are
Soon, the reputedly magical plant was cultivated into daily life
successful, not only will exploratory pharmaceutical
in European culture, most commonly being prepared as a type
endeavors may profit, but the ethnobotany of traditional
of Carmelite water. Extracts from the plant were made into an
subartic cultures may be preserved through the continued use
herbal tonic rumored to serve as an effective diuretic, and
of sacred indigenous plants (Bhat, et al., 2011).
more importantly a sweet-tasting treatment for respiratory
and digestive ailments. The herb was commonly used to
Traditional Uses soothe persistent tussis and resultant chest pain. Digestively
speaking, A. archangelica eased digestive upset and lulled
The history of Angelica archangelica L. is rich with gripe. The herb was also interestingly used to treat rabies.
superstitious folk tales and traditional remedies. The herb There have also been reports of using A. archangelica to keep
receives its name from the biblical figure Saint Michael the deafness at bay by pouring juice from the plant directly into
Archangel. Reportedly, the plant bloomed faithfully every year the ear canals.
on May 8, the day of the feast of Saint Michael, a celebration in
Christian tradition. Curiously, today, the plant is more A. archangelica grows mainly in the grasslands and
commonly apt to flower in the early months of summer, June mountainous terrain of sub-arctic Europe. Historically, most of
and July. the arctic population settled in coastal areas, long distances
away from the prized plant, in order to have assured access to
For centuries, A. archangelica has had a pagan association food, travel, and trade. Records indicate the settlers of
with healing powers; the plant was commonly thought to Greenway and Norway would travel cross-country to obtain A.
ward off malevolent spirits and demonic forces. Parents archangelica. On the journey back home to the arctic coast, the
crafted chains of A. archangelica leaves to garb their children sweet plant was eaten raw in rather impressive quantities
with spiritual protection as a sort of precautionary jewelry (Porsild, 1953).
(Bhat, et al., 2011).
Perhaps A. archangelica’s most historically prominent use
A well-known legend that may well have begun A. occurred in the mid-1600s during the time of the infamous
archangelica’s association with the divine originates from a bubonic plague. Legend has it that an English monk
lakeside Latvian town. In the early medieval age, a horde of experienced a vision in which an angel guided him to use A.
Latvian peasants marched into town with the intent of archangelica as a cure for the plague. Once word of the divine
peddling bundles of A. archangelica. As they made their way dream had rounded the community, London’s College of
through the countryside, they chanted ancient mantras that no Physicians included it as an official published treatment for
one, not even they, could understand. This occurrence the plague, boasting it to be “the King’s Majesty’s Excellent
Recipe for the Plague”. The treatment called for the herb to be Chemistry and Pharmacology
heated alongside nutmeg and sugar into a sweet syrup and the
The composition of the essential oils of the fruit seeds of three
syrup be taken orally twice per day. A rather confident
native A. archangelica samples was determined using gas
seventeenth century once wrote than angelica was “the
chromatography and mass spectroscopy by chemical
forefront of all medicinal plants” ((Bhat, et al., 2011).
researchers studying in Lithuania. From the study, sixty seven
By the end of the seventeenth century, widespread use of A. chemical compounds were identified in the essential oil
archangelica in Europe was becoming increasingly rare, other (83.9% to 90.0% of the total constituents) and of the
than for the occasional treatment of acute colic. However, the compounds identified, 63.5% to 76.6% were determined to be
plant was reintroduced into alternative therapies in European monoterpene hydrocarbons. Of the monoterpenes present, β-
medical culture in the early twentieth century when it was phellandrene, an aromatic compound responsible for the
included in the British Pharmaceutical Codex (1934). slightly minty, citrusy scent of the A. archangelica plant, makes
Across the Atlantic, Native Americans had also been using A. up 33.6% to 63.4% of the content. The second most abundant
archangelica, like their European counterparts, for centuries. constituent in angelica’s essential oil is α-pinene (4.2% to
Native Americans had therapies similar to those contrived in 12.8%). This compound is responsible for the characteristic
Europe and Asia. For example, the herb was used for aroma of pine, turpentine, and rosemary; it also contributes
respiratory ailments such as tuberculosis and as a mucous mildly to the unique aroma of angelica. Some of the minor
expectorant. On the digestive spectrum however, instead of terpenoids present in the oil include α-phellandrene (7.4%),
soothing stomach upset, A. archangelica was used in sabinene (3.3%), and germacrene D (3.0%). Although many
concentrated doses as an emetic (Sarker & Nahar, 2004). parts of the plant contain essential oil, the oil if found to be
Interestingly, when combined with Artemisia canadensis L., most concentrated In the roots (Nivinskiene, Butkiene, &
commonly known as Canada wormwood, A. archangelica Mockute, 2005). Monoterpenes serve as important
could be prepared into a topical remedy useful for relieving antioxidants for the body (Xi, Gandhi, Lai, & Kublaoui, 2012).
pain and swelling. Similar to therapies in Europe, the herb was The main chemical compounds responsible for A.
also often incorporated into herbal drinks intended to archangelica’s bioactivity are coumarins and the activity of
replenish the body after illness. those coumarins depends greatly on their concentration
Historically speaking, A. archangelica has also been used as a within the plant, which may vary from seed to root to flower.
flavoring agent in both tobacco and alcoholic beverages such Typically, coumarins concentration is highest in the fruit of
as gin and vermouth. Culinarily, the leaves of plant were used the plant. The two most common types of coumarins found in
in salads and the stems of the leaves candied into a sweet A. archangelica are imperatorin and xanthotoxin. Imperatorin
confection (Sarker & Nahar, 2004). One particularly is approximately three times more abundant within the plant
interesting Scandinavian record reports that angelica was than xanthotoxin. Some other minor coumarins found in the
often used to flavor reindeer milk as a festive beverage (Bhat, plant include osthal, psoralin, bergapten, and angelicin (Patra,
et al., 2011). Ghosh, & Mitra, 1976),
developed no tumors or insignificantly small tumors
compared to unrestrained tumor growth observed in
untreated control mice. Interestingly, the antiproliferative
effects of the A. archangelica leaf extract upon the cancerous
cells could not be attributed to the presence of
furanocoumarins present in the plant, a hypothesis previously
well-accepted (Wojcikowski, Stevenson, Leach, Wohlmuth, &
Gobe, 2007). Further research is being conducted to
determine A. archangelica’s anticarcinogenic activity against
varied cancer cell lines. Also, new proposals for the plant’s
promising bioactivity are being explored after the previously-
Figure 3. Imperatorin and xanthotoxin, important mentioned study concluded that the coumarins present in the
coumarins in A. archangelica. (Source: ChemDraw) plant may not always be responsible for angelica’s bioactivity.
Biological Activity Hepatoprotective effect

Anticarcinogenic effect In vitro studies in mice with ethanol-induced hepatotoxicity
In vitro tests of organic extracts from A. archangelica on were performed to study the potential defensive effect of A.
cancerous pancreatic cell lines proved that angelica displayed archangelica against oxygen free radical formation in the liver.
dose-dependent anticarcinogenic activity towards mutagenic The study found that varying doses (ranging from 10 to 50
cells. The impressively strong bioactivity of the herb was mg/kg) of A. archangelica of “indirectly protected the liver
determined to be sourced from the two main coumarins in from oxidative stress” (Yeh, Liu, Huang, & Huang, 2003).
angelica: imperatorin and xanthotoxin (Figure 3). It should be
noted that the terpenoid content of angelica, although
responsible for the appealing aroma and taste of the plant, Inhibition of acetylcholinesterase
contributed very little, if at all, to the antiproliferative effects A study conducted at the University of Iceland examined the
of the plant extract. acetylcholinsterase inhibition potential of several herbal
In a similar test upon a cancerous Crl cell line, results proved species native to the area. Although many of the plants
that leaf extract from the plant was only mildly effective in displayed little inhibitory activity, ethanolic extracts from the
preventing the proliferation of cancer cells, quite a decrease seeds of A. archangelica contained two primary coumarin
from the aforementioned study. To explain the unexpected compounds that displayed promising behavior: imperatorin
results, in vivo testing in mouse models was performed. and xanthotoxin. Both of these compounds were shown to
However, the in vivo tests proved quite successful: out of inhibit acetylcholinesterase by competing with the compound
eleven test mice treated with extracts of A. archangelica, 82% for nicotine receptors in the body. Of the two coumarins,
xanthotoxin displayed almost twice the activity of models. The study concluded that although each of the
imperatorin. However, it was decided that the total inhibitory individual components of the organic precipitate of A.
activity of A. archangelica could not be solely attributed to the archangelica were effective in reducing anxiety symptoms in
activity of the two primary coumarins. Instead, researchers mice, the anxiolytic activity of the precipitate as a whole was
proposed that synergistic activity between the chemical much more effective, most likely due to synergistic
constituents of the plant most likely occurred when consumed mechanisms of action between the constituents within the
in vivo. Additionally, researchers concluded that optimum body (Dinesh Kumar, Bhat, Kumar, & Shah, 2013) (Sigurdsson
acetylcholinesterase inhibition occurred when extracts from & Gudbjarnason, 2007).
A. archangelica were combined with those of G. sylvaticum, a
vibrantly-hued geranium (Sigurdsson & Gudbjarnason, 2007).
Acetylcholinesterase inhibition is important in promoting Influence on Alzheimer’s patients
relaxation and a stable emotional state within the body, In a small herbal study aimed at understanding the effects of
especially within patients facing mental debilitation (such as bioactive botanicals on Alzheimer’s patients, researchers from
Alzheimer’s or dementia). the Royal Botanical Garden in the United Kingdom compiled
data from a variety of sources to understand the potential
effects of angelica (as well as several dozen more herbs) on
Prophylactic effects on gastric ulcers
patients suffering from dementia. In the study, it was noted
Therapeutic doses of A. archangelica were administered to that A. archangelica increases cerebral blood flow, relaxation,
rats afflicted with gastric ulcers resulting from indomethacin and cognition enhancement. Although no clinical study was
(a non-steroidal anti-inflammatory pain killer known to inflict performed, the British researchers involved in this project
peptic ulcers when given high doses) exposure. Lessened served as a vital catalyst in promoting the further study of an
gastric acid production and heightened secretion of protective angelica not only as an anticarcinogenic agent, but also a
mucins of the stomach were observed. Overall, anti-ulcer cerebral enhancer (Howes, Perry, & Houghton, 2003).
activity was displayed by A. archangelica (Bhat, et al., 2011).
Protection against lead poisoning

Affect on anxiety and anxiety-like conditions
In a study examining the healing potential of A. archangelica
Researchers at the University of Kashmir recently examined on rabbits with induced lead poisoning, it was determined
the cerebral effects of the A. arcangelica A. archangelica was that angelica had an overarching positive effect on the health
extracted with petroleum ether to obtain a solid yellow of the poisoned rabbits. The study orally administered high
precipitate. Within the precipitate, six separate doses of lead to the rabbits for a total of 15 days. Tests to
furanocoumarins were present. The anxiolytic activity of both assure an initial rise of bodily lead levels were undertaken and
the solid yellow precipitate as a whole and each individual it was confirmed that indeed the rabbits had dangerously
component of the precipitate was tested in vivo in mice elevated lead levels. After dosing the test group rabbits with A.
archangelica, it was found that the herb not only prevented in similar moist habitats as those of A. archangelica and has a
premature death in the rabbits, but actually served as a similar appearance (Figure 4). Only those with botanical
healing therapeutic agent, returning the poisoned rabbits’ expertise and experience should scavenge for potent herbs.
bodily lead levels back to a level similar to those of the
unharmed control group of rabbits. Researchers believe that
angelica’s healing properties are resultant of an unknown, yet
potent antioxidative mechanism of action, quite plausibly due
to angelica’s active furocoumarins: imperatorin and
xanthotoxin.
Clinical Studies
So far, only one formal clinical trial has executed to study the
effects of A. archangelica. The recent study examined the
cerebral mood-stabilizing effects of geriatric patients suffering
from dementia:
In a 2011 study by the Japan Geriatrics Society, twenty
patients diagnosed with dementia, ranging in age from 72 to
92, were treated with a therapeutic dose of ferulic acid and A.
archangelica, known as Feru-guard. At the end of four weeks,
95% of patients saw reduced symptoms of dementia
(including delusions, anxiety, and hallucinations, and
Figure 4. Cicuta virosa, a poisonous plant similar in
irritability). Though the outcome of the study was quite
appearance to angelica.
positive, further studies with a larger sample population must
be conducted before any definite conclusions concerning A.
archangelica’s efficacy and safety may be made (Kimura, The U.S. Food and Drug Administration has declared A.
Hayashida, Murata, & Takamatsu, 2011). archangelica to be generally regarded as safe (GRAS), however
this label applies only to the product’s culinary use. Women
who are breastfeeding or pregnant are not encouraged to use
Contraindications
the herb due to the unknown mechanism of action the prime
Caution should be taken by those seeking to collect Angelica constituents in Angelica archangelica undertake when
archangelica L. It is important to beware of other species that consumed in the body. Also, diabetics should exercise caution
appear very similar to the herb. For example, the water when consuming angelica as it tends to raise blood sugar
hemlock, Cicuta virosa L., is a very poisonous plant that grows
levels (as measured by urine analysis) (Bhat, et al., 2011). cough, and the common cold. Angelica’s respiratory activity is
Caution should always be taken when considering any herbal largely due to its activity as an expectorant.
therapeutic remedy.
Stalks and stems

In many European cultures, the stalks and stems of the plant
Angelica archangelica is used widely today in allopathic and may be cooked alongside other vegetables. Chewing on the
complementary alternative medicine. Its uses are endless: stalks and stems of angelica will stimulate one’s immune
distinct cultures seem to utilize the plant in a variety of ways, response and induce a temporary anesthetic effect. Overall,
alluding to the generalized antioxidant activity occurring on use of A. archangelica tends to produce an overarching
the phytochemical level of the plant. Different parts of the antidepressant and emotionally-stabilizing effect on the user,
plant (the roots, seeds, leaves, stalk, flower) may be used for stemming from the strong inhibitory of activity of the plant
different purposes and may be prepared in various manners. towards acetylcholinesterase in the body.
Root Discussion
The oil of the root is commonly used in incense and It’s no wonder than Angelica archangelica was thought to be a
aromatherapy treatments as a relaxant. Roots may be dried, magical plant by early users. The herb, impressive in both
ground, and ingested to relieve digestive problems including stature and remedy, serves traditionally as a digestive and
eating disorders and peptic ulcers. Targeting the female respiratory aid. In current medical culture, the plant’s
reproductive system, angelic is used to relieve painful anticarcinogenic and cerebral enhancement properties are
cramping associated with menstruation and labor pains. The being studied and so far, appear promising. It is interesting to
grounds of the root may be steeped into a tea to relieve note that although there are over thirty species belonging to
flatulence and general stomach upset. The root may also be the Angelica genus, Angelica archangelica is the only species
chewed as a dentifrice to relieve mild tooth pain. considered useful for medicinal purposes (Bhat, et al., 2011).
Conclusions from studies to date imply that instead of having
a solitary active metabolite, the many terpenoids and
Leaves coumarins present in A. archangelica work together in a
The leaves of angelica may be boiled into a tea to be ingested synergistic fashion to produce many wonderful health benefits
after meals to reduce the occurrence of colic. In Chinese for the body. On a more solemn note, as a society, we must
medicine, the plant is used to treat cerebral disorders and remember to be as environmentally responsible as possible.
ailments including anxiety, headaches, and eating disorders Due to a variety of biological factors, the population of the
(D. Kumar, Bhat, & Shah, 2012). Topically applied, the leaves wild A. archangelica is become more at risk everyday. If
are often used to relieve symptoms stemming from bronchitis, research and pharmaceutical development is to be continued
on such a promising plant, we must rethink how we, as Nivinskiene, O., Butkiene, R., & Mockute, D. (2005). Chemical
humans, are interacting with the most precious gift Mother composition of seed (fruit) essential oils of Angelica
Earth has given us: medicinal plants. archangelica L. growing wild in Lithuania. [Article].
LIETUVOJE AUGAN√àI√ò ANGELICA ARCHANGELICA L.
S√ãKL√ò (VAISI√ò) ETERINI√ò ALIEJ√ò CHEMIN√ã
References Cited SUD√ãTIS., 16(3/4), 51-54.
Bhat, Z., Kumar, D., & Shah, M. (2011). Angelica archangelica Linn. is Patra, A., Ghosh, A., & Mitra, A. (1976). Triterpenoids and
an angel on earth for the treatment of diseases. International furocoumarins of the fruits of Angelica archangelica. Ind. J.
Journal of Nutrition, Pharmacology, Neurological Diseases, Chem, 14, 816-817.
1(1), 36. Porsild, A. E. (1953). Edible Plants of the Arctic. Arctic, 6(1), 15-34.
Howes, M.-J. R., Perry, N. S. L., & Houghton, P. J. (2003). Plants with doi: 10.2307/40506558
traditional uses and activities, relevant to the management Sarker, S., & Nahar, L. (2004). Natural medicine: the genus Angelica.
of Alzheimer's disease and other cognitive disorders. Current medicinal chemistry, 11(11), 1479-1500.
Phytotherapy Research, 17(1), 1-18. doi: 10.1002/ptr.1280
Sigurdsson, S., & Gudbjarnason, S. (2007). Inhibition of
Kimura, T., Hayashida, H., Murata, M., & Takamatsu, J. (2011). Effect acetylcholinesterase by extracts and constituents from
of ferulic acid and Angelica archangelica extract on Angelica archangelica and Geranium sylvaticum. Z
behavioral and psychological symptoms of dementia in Naturforsch C, 62(9-10), 689-693.
frontotemporal lobar degeneration and dementia with Lewy
Wojcikowski, K., Stevenson, L., Leach, D., Wohlmuth, H., & Gobe, G.
bodies. Geriatrics & Gerontology International, 11(3), 309-
(2007). Antioxidant capacity of 55 medicinal herbs
314. doi: 10.1111/j.1447-0594.2010.00687.x
traditionally used to treat the urinary system: a comparison
Kowalchik, C., Hylton, W. H., Carr, A., & Press, R. (1987). Rodale's using a sequential three-solvent extraction process. J Altern
illustrated encyclopedia of herbs: Rodale Press, Incorporated. Complement Med, 13(1), 103-109.
Kumar, D., Bhat, Z. A., Kumar, V., & Shah, M. Y. (2013). Coumarins Xi, D., Gandhi, N., Lai, M., & Kublaoui, B. M. (2012). Ablation of Sim1
from Angelica archangelica Linn. and their effects on Neurons Causes Obesity through Hyperphagia and Reduced
anxiety-like behavior. Progress in Neuro- Energy Expenditure. [Article]. PLoS ONE, 7(4), 1-9. doi:
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Yeh, M. L., Liu, C. F., Huang, C. L., & Huang, T. C. (2003).
Kumar, D., Bhat, Z. A., & Shah, M. Y. (2012). Anti-anxiety activity of Hepatoprotective Effect of Angelica archangelica in
successive extracts of Angelica archangelica Linn. on the Chronically Ethanol-Treated Mice. Pharmacology, 68(2), 70-
elevated T-maze and forced swimming tests in rats. J Tradit 73.
Chin Med, 32(3), 423-429.
Arctostaphylos uva-ursi (L.) Spreng., Ericaceae
Marston Jones
Introduction
Arctostaphylos uva-ursi (L.) Spreng. is a well-known plant in
the Ericaceae family. It goes by many names due to its
thorough distribution across the northern hemisphere, and
because it has been widely used from North American and
Canada, through Europe, and into Russia. Kinnikinnick, or
bearberry, as it is most often referred to in the English
language, grows in North America from northern California
stretching up into Alaska, across Canada and the northern U.S.,
and even to New England and Newfoundland. On the western
portion of the states, it follows the Rocky Mountains down
into New Mexico, and can be found throughout the
Appalachian mountains, even as far south as Georgia (Crane,
1991). The berries are a well known food source for bears,
grouse, and deer (Kuhlein and Turner, 1991). This may be
due to the fact that the fruit spoils slowly, so it is available
throughout winter and into spring, which means it can be a
constant food source when others are no longer available. It Figure 1. Arctostaphylos uva-ursi flowers. (Source:
can withstand low summer moisture, salt-spray, and can grow http://calphotos.berkeley.edu/cgi/img_query?enlarge=0000+0000+0506
slowly in semi-shady conditions. In some places it may also be +1197)
a good indicator of areas that are moisture deficient, and
grows rapidly in areas following moderate disturbances
bladder and kidney disorders, and urogenital disorders,
(Crane, 1991).
though since then many more uses have been recorded (Kay,
It was first reported for medicinal use in the thirteenth 1996; Radulovic et al., 2010).
century, and throughout time has made its way into many
pharmacopeias because of its wide range of uses. In 1601, it
had reported use as a hemostatic, and by the time Western Botanical Description
medicine began to flourish, beginning with Spanish and Italian Arctostaphylos uva-ursi is a prostrate, evergreen shrub with
physicians, bearberry found use for calculus complaints, dark green, leathery leaves and twisted trunks. The leaves are
obovate and smooth edged while the bark is thin and reddish
brown. The plant flowers with white-pink urn shaped
clusters, and is followed by red berries (Figures 1 & 2). The
berries themselves are noted to be very dry and mealy when
eaten. The plant can be found at altitudes from 3000 to 9000
feet, and often in open, rocky slopes and sandy areas.
(Kuhnlein and Turner, 1991; Kay, 1996; Crane, 1991)
Bearberry can be confused with both cowberry (Vaccinium
vitis-idaea L., Ericaceae) and box (Buxus sempervirens L.,
Buxaceae), but while box does not share the same
pharmacological constituents as bearberry, cowberry could
potentially be used as a suitable substitution in certain cases
(Radulovic, 2010).
Traditional Uses Figure 2. A. uva-ursi fruits. (Source: http://calphotos.berkeley.edu

Bearberry has been used over time for many different reasons. /cgi/img_query?enlarge=9189+3301+3549+0113)
Much of the information available pertains to its use by Native
Americans of North America, though its use is certainly not leaves was also used by some tribes to attract game and to
limited to one group of indigenous people or a single area. It’s treat earache (Pennachio et al, 2010). Some of its earlier uses
been noted to have appeared in the thirteenth century were based on its astringent properties, and it was used as a
pharmacopoeia of the Welsh, “Physicians of Myddfai”, in wash for sores, to treat kidney pain, and as a tea for cold,
addition to being mentioned by Gerhard in Berlin around chest, and lung conditions (Kay, 1996).
1763 (McKenna et al., 2002). Its use continued to be recorded The fact that the berries of the plant are edible gave way to
in many different locations for a variety of applications. One another simple use: food. In some instances it could be used
of the most widely mentioned uses of A. uva-ursi comes from as an “emergency food” because of its nature of lasting
its leaves. The leaves of the plant were used in smoking through winter, but it was also eaten in general by many
mixtures, either to be mixed in with tobacco to lessen the North American tribes. The berries can be eaten raw, but
harsh taste, or to be toasted in an oven to be smoked alone because of their dry mealy texture, many recorded instances
(Kuhlein and Turner, 1991; Crane, 1991, Duke, 1985). involve individuals roasting and cooking the berries, and even
Another name by which bearberry is known, Kinnikinnick, mixing them with animal grease (Kuhlein and Turner, 1991;
means smoking mixture, but the leaves of A. uva-ursi are Duke, 1985). There are many more advantages of the plant,
generally used in conjunction with other plants and not just such as using the leaves for tanning in Sweden and Russia, and
smoked by themselves (Willard, 1992). The smoke from the using different methods for the treatment of backache,
bladder ailments, bronchitis, diabetes, diarrhea, dysentery,
dysurea, fever, hemorrhoids, hepatitis, nephritis, pancreatitis,
rheumatism, ulcers, urinary disorders and many other issues
(Duke, 1985; McKenna et al. 2002).
Bearberry’s long history of use as an anti-inflammatory and
antiseptic has led to specific application that helps aid in
strengthening the tone of urinary passages in response to
inflammatory diseases. Many different Native American tribes
would prepare an infusion for the urinary tract and also for
venereal disease, with some even using the leaves as a
poultice to for swelling and sprains (McKenna et al., 2002). Its
use has continued up through the 19th and 20th centuries, Figure 3. Structure of arbutin. (Source: http://ntp.niehs.nih.gov/
being used widely now in homeopathic remedies for many of files/Arbutin.pdf)
the aforementioned maladies (Duke, 1985).
which is why, nowadays, the plant is used primarily as a
treatment for urogenital diseases, or at least marketed as
Chemistry and Pharmacology such. Many different things can be natural antioxidants:
phenolic compounds such as flavonoids, phenolic acids, and
Bearberry contains phenols, tanning agents and flavonoids.
tannins, nitrogen containing compounds such as alkaoids,
The flavonoids can be used to chemically differentiate the taxa
chlorophyll derivatives, amino acids, peptides, and also
within the genus, and are may be different depending on the
carotendoids, tocopherols or ascorbic acid and its derviatves.
geographical origin of the plant (McKenna et al., 2002) Its
Epidemiological evidence shows that eating items containing a
main phenolic constituent is arbutin, its most notable
large number of these antioxidant phytonutrients is very
compound (Figure 3), with a content level of about 5-18%. Its
healthy (Amarowicz et al. 2004). Bearberry contains several
main flavonoid is quercetin-3-0-galactoside. A. uva-ursi also
compounds that fall under these categories, but another
contains 6-40% tannin, methyl arbutin, ericinol, ericolin,
pharmacologically active compound of medical importance in
allantoin, isoquercetin, gallic acid, malic acid, quinic acid,
this plant is hydroquinone, which is the result of in vivo
ursolic acid, ursone, ellagic acid, uvaol, hyperin, myricetin,
glucoside cleavage of arbutin (Kenndler, 1990). The
myricitrin, corilagin, and pyroside, to name a few (Kay, 1996;
antimicrobial activity of the plant is dependent on arbutin
Kenndler, 1990; Duke, 1985)
being hydrolysed by β-glucosidase to yield hydroquinone
which is an antiseptic and an astringent (Heinrich et al., 2004).
Biological Activity In a study performed by Radulovic et al. (2010) using GC and
For the current uses of bearberry, arbutin is the chemically GC/MS analyses, 243 different constituents were identified in
active compound of importance. It has antimicrobial activities Arctostaphylos uva-ursi oils. Within the A. uva-ursi, α-
terpineol, linalool, hexdeconioc acid, and (E)-geranyl acetone the leaves of Arctostaphylos uva-ursi as well an extract from
were predominant. There were high levels of terpenoids, in Taraxacum officinale, which provided mild diuretic effects.
addition to fatty acid derived compounds, and fatty acid ester After being given three pills a day for a month of either UVA-E
and carotenoid derived compounds also made up a large or the placebo, there was a significant effect on the recurrence
portion of the oils. The study stressed that the essential oils of cystitis between the two groups. None of the women in the
contained in this plant are vital to the contribution of any UVA-E group experienced a recurrence, whereas 5 of the
medicinal properties, even though they may be found in very women in the placebo group did. The researchers concluded
small amounts. that UVA-E had a significant prophylactic effect on recurrent
A study performed by Dykes et al. (2003) looked at the cystitis, but also noted that it may only act on the most
biological effects of antioxidants extracted from A. uva-ursi on common microorganisms to be isolated in cases of urinary
food-related bacteria. The antioxidant activity in extracts is tract infections.
beneficial to human cells, and will hopefully have the potential While there are not many clinical studies directly relating to
to serve as a natural replacement to synthetic antioxidants for the use of A. uva-ursi, there are studies looking at potential
foodstuffs. Dykes et al notes that ethanolic extracts have effects that arbutin, one of bearberry’s primary constituents
already been found to have “potent antioxidant activity” in has on the human body, and the ways that the two interact. In
model and meat systems, and while this plant has been used a study by Blaut et al (2006), hydroquinone, a mutagenic and
traditionally as antiseptics in European countries, the use as carcinogenic substance that is an aglycone of arbutin, was
an antioxidant in foods will be a new non-medical use for the shown to be present in fecal slurries from several human
plant. The study showed that the extract used affected the subjects. The release of this aglycone due to glycosylation by
hydrophobicity of a very wide variety of bacteria, and intestinal species was determined to pose a potential risk,
hydrophobicity can be associated with increased even though a large majority of arbutin (65-75%) is excreted
pathogenicity and ability to invade human cells. While some in urine. Any potential dangers would also be directly related
bacteria actually increased in hydrophobicity, others, such as to large consumption of foods containing arbutin as well.
S. aureus, saw a substantial decrease. The authors caution
against use of plant extracts as nutraceuticals, but support
that bearberry does show antibiotic effects against various Contraindications
strains of bacteria. If making a tea from the leaves of Arctostaphylos uva-ursi, one
should be careful not to extract using hot water to minimize
the tannin content and avoid upsetting the stomach.
Clinical Studies
Prolonged use is also cautioned against because of the high
In a clinical study performed by Larsson et al (2003), women tannin content and the hydroquinones which can damage the
who had been through multiple bouts of cystitis (at least liver in high doses (Kay, 1996). Very large doses containing
three) before the study were treated with UVA-E or a placebo hydroquinone are oxytoxic and can lead to collapse,
for a month. UVA-E contained a hydroalcoholic extract from convulsion, delirium, nausea, tinnitus and possibly death
(Duke, 1985). For the compounds to have antiseptic
properties on the urinary tract, urine must be alkaline, so
acidic foods should not be consumed during treatment
(Heinrich et al., 2004).
Current Use in Allopathic and CAM therapies

Bearberry is recommended in homeopathy for cystitis,
dysuria, hematuria, incontinence, pyelitis, urethritis, and
urogenital disorders. Because arbutin shows antiseptic affects
on the urinary mucous membrane, it is also used for cervical
ulcerations, cystitis, blennorrhea, enuresis, gallstones,
gonorrhea, gout, and nephritis (Duke, 1985). Willard (1992)
even suggests soaking feet in a strong decoction of the plant
for one hour the night before a long hike or walk to “toughen
up the feet” and to avoid blisters. Other than its advantages in Figure 4. Uva ursi products. (Source: http://www.herbalremedies.
treating urinary tract infections, many of the uses of A. uva- com/uva-ursi-standardized.html ; http://www.herbalremedies.com/176
ursi are yet to be fully investigated scientifically (McKenna et 00.html ; http://www.johnmasters.com/osc.htm)
al. 2002). There are plenty of available products that contain
bearberry ranging from simple supplement and vitamin items continues to be used in homeopathic remedies, and can still be
to skin care products (Figure 4). easily found in many of the regions where it has grown for
years. Some characteristics about the plant, such as its
astringent, anti-inflammatory, and antiseptic properties have
Discussion been well studied, but there is still much to learn, and ways to
make sure its use either as a strictly homeopathic or maybe
For a small shrub, Arctostaphylos uva-ursi has been utilized in even allopathic remedy are safe and viable.
an incredibly large variety of ways for centuries. This is due in
part to its abundance in the northern hemisphere, and as a
result of record keeping of its use throughout history. Its References Cited
many different names are evidence of it widespread influence
Bertil Larsson, Aino Jonasson, and Stefan Fianu. “Prophylactic effect
and use, as well as its efficacy. Other than research showing
of UVA-E in women with recurrent cystitis: A preliminary
its ability to aid against urogenital problems, few studies have report.” Current Therapeutic Research. 53. (1993): 441-443.
been done to verify the many different ways that the plant has
been utilized in the past, but the fact that so many uses exist E. Kenndler, Ch. Schwer, B. Fritsche, and M. Pohm. "Determination of
stands as a testament to the versatility of this plant. It arbutin in uvae-ursi folium (bearberry leaves) by capillary
zone electrophoresis."Journal of Chromatography. 514. Margarita A. Kay, Healing with Plants in the American and Mexican
(1990): 383-388. West. (Tucson: The University of Arizona Press, 1996), 97-
98.
Dennis J. McKenna, Kenneth Jones, Kerry Hughes, and Sheila
Humphrey. Botanical Medicines: The Desk Reference for Michael Blaut, Annett Braune, Sandra Wunderlich, Patrick Sauer,
Major Herbal Supplements (Binghamton, NY: The Haworth Heiko Schneider, and Hansruedi Glatt. “Mutagenicity of
Herbal Press, 2002), 987-1005. arbutin in mammalian cells after activation by human
intestinal bacteria.” Food and Chemical Toxicology. 44.
Gary A. Dykes, Ryszard Amarowicz, and Ronald B. Pegg. "An
(2006): 1940-1947.
antioxidant bearberry (Arctostaphylos uva-ursi) extract
modulates suface hydrophobicity of a wide range of food- Michael Heinrich, Joanne Barnes, Simon Gibbons, and Elizabeth M.
related bacteria: implications for functional food Williamson. Fundamentals of Pharmacognosy and
safety." Food Control. 14. (2003): 515-518. Phytotherapy. (United Kingdom: Churchill Livingstone,
2004), 249-250.
Harriet V. Kuhnlein, and Nancy J. Turner. Traditional Plant Foods of
Canadian Indigenous Peoples. (Gordon and Breach Science Niko Radulovic, Polina Blagojevic, and Palic Radosav. "Comparative
Publishers, (1991), 165-167. Study of the Leaf Volatiles of Arctostaphylos uva-ursi (L.)
Spreng. and Vaccinium vitis idaea L. (Ericaceae)." Molecules.
James A. Duke, CRC Handbook of Medicinal Herbs. (Boca Raton, FL:
12. (2010): 6169-6185.
CRC Press, Inc., 1985), 55-56.
R. Amarowicz, R. B. Pegg, P. Rahimi-Moghaddam, B. Barl, and J.A.
M. F. Crane, 1991. Arctostaphylos uva-ursi. In: Fire Effects
Weil. "Free-radical scavenging capacity and antioxidant
Informations System, [Online]. U.S. Department of
activity of selected plant species from the Canadian
Agriculture, Forest Service, Rocky Mountain research
prairies." Food Chemisty. 84. (2004): 551-562.
Station, Fire Sciences Laboratory (Producer). Available:
http://www.fs.fed.us/database/feis/ (2011, October 15). Terry Willard, Edible and Medicinal Plants of the Rocky Mountains
and Neighboring Territories (Calgary, Alberta: Wild Rose
Marcello Pennacchio, Lara V. Jefferson, and Kayri Havens. Uses and
College of Natural Healing, Ltd., 1992), 164-165.
Abuses of Plant-derived Smoke. (New York: Oxford University
Press, 2010), 24, 46.
Armoracia rusticana G. Gaertn., B. Mey. & Scherb., Brassicaceae
Andrew Mongue
Introduction
Armoracia rusticana, more commonly known as horseradish,
is a member of the Brassicaceae family which includes
broccoli, turnips, and mustard (Sampliner & Miller, 2009). The
name Armoracia comes from Celtic and roughly means “near
the sea.” Another old name, searadish, furthers the idea that
this plant was traditionally found near the coast. The German
for searadish was ‘meerettich’ and it has been proposed that
the name horseradish resulted as a mistranslation confusing
‘meer’ (sea) for ‘mare’ (a female horse) (Courter & Rhodes,
1969). However the common name came to be, it is rather
ironic because horseradish is toxic to horses, pigs, and cattle.
Despite the widespread occurrence of A. rusticana in the
United States however, reports of livestock poisoning are rare,
perhaps do to the pungent taste of the plant (DiTomaso).
This plant derives its famous smell and taste from a class of
compounds known as isothiocyanates, which are also
responsible for much of its biological activity and therefore
important in its medicinal uses (Nedorostova et al., 2011).
These chemicals are natural antibiotics with broad ranging
applications from the treatment of sinus infections to the Figure 1. Whole view of a horseradish plant. Image source:
preservation of food. http://www.finecooking.com/assets/uploads/posts/5645/ING-
The other major class of chemicals is the peroxidase enzyme horseradish-2_sql.jpg
family found in horseradish. These compounds have a range of
uses in both laboratory and industrial settings. They can be
used in everything from waste treatment to chemotherapy For centuries A. rusticana has been recognized as a source of
(Govere et al., 2005; Greco, Folkes, Wardman, Tozer, & Dachs, food and medicine, though its uses have changed through
2000). time. During its history of use the plant we know today was
created through directed selection (commonly known as
propagate on their own (Courter & Rhodes, 1969). Outside of
cultivation it grows best in wet, disturbed areas such as fields
and along roadsides.
A. rusticana, like all members of the Armoracia genus, is a
perennial herb. Horseradish has smaller flowers than other
members of its genus, but like all Armoracia species, its
flowers are four-merous and white in color. Its hairless,
crenulated leaves are arranged in a rosette and grow basally
(Figure 2). Despite continued fruit production, it is unclear
whether this species has retained its non-vegetative
reproductive ability. Since its domestication it has been
Figure 2. Features of A. rusticana (a) compared to the propagated almost exclusively from root cuttings and many A.
closely related A. macrocarpa (b). Note the lack of seeds in rusticana fruits in domestication lack seeds entirely
a-2 compared to b-2 and the increased root size in a-1 (Sampliner & Miller, 2009). One suggested reason for this
compared to b-1. Image adapted from Sampliner & Miller, apparent sterility is the possibility that domestic horseradish
2009. is an interspecific hybrid of two true species. The observation
that chromosome count varies between individuals and even
within an individual plant (leading to partial chromosomal
pairing) supports the hybrid theory (Courter & Rhodes, 1969).
domestication); however its status is now in doubt because of
its apparent inability to produce seeds (Courter & Rhodes, Alternatively, some researchers now believe that horseradish
1969). As discussed below, despite the continued apparent as we know it, A. rusticana, is nothing more than a
success of horseradish as a crop, the method of its cultivation domesticated form of other wild Armoracia species. Evidence
could lead to problems in the future. This cannot be allowed for this is mostly negative, that is to say, despite surveying
given all of the applications botanists are just now discovering efforts no A. rusticana specimens have been recorded in the
for this versatile plant. wild. They can be found only in areas associated with current
or previous human cultivation. Some possible positive
evidence is the relative root size of horseradish in comparison
Botanical Description to other Armoracia species. A. rusticana roots are much larger
Though Armoracia rusticana is now grown on several than those of related herbs, suggesting that this trait may have
continents worldwide, it is believed that horseradish most been cultivated by human rather than natural selection
likely originated in Europe. Wild populations in America (Sampliner & Miller, 2009).
began to grow in Boston in 1840 and were likely the result of The sterility phenomenon was examined by experiments
previously cultivated plants being abandoned and left to conducted on seed production in various American cultivars
of horseradish. Plants from various backgrounds (i.e. or brown glass jars. Anecdotal reports of other plants and
commercial farming and untended “wild” locations) were even wood chips used to pad out the contents of these jars
collected and allowed to flower. In the overwhelming majority speak to a general lack of quality in the condiment market at
of cases the plants could not produce functional pollen grains. the time.
In those that did, no more than 50% of pollen was viable, and
The key then to Heinz’s success was in the way he preserved
those plants were effectively incapable of producing viable
the condiment. By boiling the preserves in clear glass jars in
seeds through self-fertilizing. Outcrossing between the two
salt water after packing he could boast a superior quality that
varieties collected (Bohemian and common) had the greatest
customers could clearly see. Additionally, this sterilizing
success in securing seed but even then only one to two seeds
process meant he could ship goods to more distant markets
were obtained per fruit. When planted, these seeds
and eventually become a national and then international name
successfully germinated and grew, suggesting that there is
brand. Though Heinz today is synonymous with tomatoes and
hope for restoration of sexual reproduction (Weber, 1949).
ketchup it is important to note that it all started with
horseradish (Koehn, 1999).
Traditional Uses In cooking, horseradish has been used as a flavoring
References to Armoracia rusticana by Dioscorides place its condiment on everything from meats to salads. German
first confirmed use to roughly two thousand years ago. While recipes including A. rusticana can be found as early as the
Europe has a long history of using this plant, cultivation in 1500’s (Courter & Rhodes, 1969). The root can be grated
America can only be traced back to 1806. The now robust directly onto food or mixed with ketchup, vinegar, or oil to
agricultural production of horseradish can be specifically form a sauce. In some cases the root is boiled, squeezed,
linked to the Sell and Sass families who immigrated from washed, and mixed with salt and sugar to remove some of the
Germany to Chicago in the 1850’s (Courter & Rhodes, 1969). isothiocyanates which cause its pungent taste.
To this day, the plant is a successful commercial crop and is Leaves and roots of A. rusticana are used in the process of
still grown throughout Illinois (Walters & Wahle, 2010). pickling other vegetables, which allows them to be stored for
Typically, only the taproot is sold commercially while the much longer periods of time. In some places it is still the
smaller offshoot roots are used as propagates for next year’s preferred method of generating a stock of food for the winter.
crop (Courter & Rhodes, 1969). The plant is also fermented to produce a Romanian brandy
The now gigantic condiment business started by Henry Heinz called Tuica (Sampliner & Miller, 2009).
also has its roots with A. rusticana. The would-be condiment Horseradish has a long tradition of ritualistic use as well. It is
king grew up in Pennsylvania, which by this time was one of the traditional plants eaten during Jewish Passover.
recognized as a fertile ground for horseradish. At the
English herbalist John Gerard studied horseradish in the
beginning of his career in the mid-eighteen hundreds, foods
sixteenth century. His medical uses included treatment of colic
like horseradish were either grown by individuals or by small
and sciatica. It was also reported as a diuretic and an
vendors who then bottled and sold preserves locally in green
responsible for the distinct aroma of the plant (Courter &
Rhodes, 1969; Nedorostova et al., 2011).
The peroxidase enzymes found naturally in A. rusticana can be
used to screen for the presence of phenolic compounds in
water samples (Gonzalez-Sanchez, Laurenti, Rubio-Retama,
Valero, & Lopez-Cabarcos, 2011). Additionally peroxidase has
been proposed as part of the treatment for bladder, breast,
and nasoesophageal cancer (Greco et al., 2001).
Three more compounds from horseradish (plastoquinone-9,
see Figure 3; 1,2-dilinolenoly-3-galactosylglycerol; and 6-O-
acyl-β-D-glucosyl-β-sitosterol) have been implicated in cancer
inhibition (M. J. Weil, Y. Zhang, & M. G. Nair, 2005).
Figure 1. Structure of allyl isothiocyanate (top) and Biological Activity

plastiquinone-9 (bottom). Images source:
http://upload.wikimedia.org/wikipedia/commons/9/98/Allyl-
Enzymes in the peroxidase family have a range of applications
isothiocyanate-2D-skeletal.png and as oxidizing agents and can be efficiently recovered (up to
http://upload.wikimedia.org/wikipedia/commons/3/3b/Plastoqui 72% yield) from relatively simple extraction and purification
none.png methods applied to Armoracia rusticana roots (Lavery et al.,
2010). There have also been studies showing that certain
genetically modified moth larva can be made to produce
aphrodisiac. A. rusticana was also used to kill parasitic worms peroxidase, thus providing an alternative source with
in children and promote the expulsion of afterbirth (Courter & similarly high yields (Romero, Targovnik, Wolman, Cascone, &
Rhodes, 1969). While its agricultural uses have remained Miranda, 2011).
largely unchanged, today’s medical uses are quite different One example of horseradish peroxidase use is in the farm
from those described above. industry. Here it has been proven effective as a deodorant
when added to livestock manure. It removes malodorous
Chemistry and Pharmacology phenolics for up to three days per application (Govere et al.,
2005).
The essential oils of Armoracia rusticana consist almost
entirely (i.e. nearly 98%) of allyl isothiocyanate (Chen, Allyl isothiocyanate (Figure 3), an essential oil of A. rusticana,
Akinkurolere, & Zhang, 2011). This compound, along with has shown promise as a natural fumigant that is lethal to at
butyl isothiocyanate and phenylethyl isothiocyanate are least two common crop pests, weevils and meal moths. It has
been proposed that this gaseous compound suffocates insects
by blocking their spiracles and thus preventing oxygen from use of plants to deal with environmental contamination
reaching their internal tissues. This hypothesis is supported (Kotyza, Soudek, Kafka, & Vanek, 2010).
by the observation that allyl isothiocyanate is effective against
The aforementioned anti-cancer potential of horseradish
adult weevils but not to their pupae, which are less permeable
comes from two different mechanisms. First are the inhibitory
to gases due to their structure (Chen et al., 2011).
effects of plastoquinone, sitosterol, and galactosylglycerol on
Essential oils from A. rusticana, composed of allyl the cyclooxygenase-1 (COX-1) enzyme in cancer cells. When
isothiocyanate along with the related phenylethyl purified, these compounds showed 50 to 75% inhibition of the
isothiocyanate, were tested as gaseous antibiotics in an in COX-1 enzyme and growth inhibition in both lung and colon
vitro study alongside extracts from several other plants, cancer cell lines (Marvin J. Weil, Yanjun Zhang, &
including garlic. Researchers found the isothiocyanates to be Muraleedharan G. Nair, 2005).
the most effective oils tested (as determined by the minimum
The second approach to cancer treatment uses the nascent
inhibitory concentration), effective against even MRSA
technique of gene therapy. Researchers found that by
Staphylococcus aureus. As such, it could have applications as a
inserting the gene for the already discussed peroxidase
nontoxic disinfectant spray pending clinical trials
enzyme, also known as horseradish peroxidase (HRP), into
(Nedorostova et al., 2011).
bladder cancer cells, these cells became susceptible to the
Finally with regard to isothiocyanates, there is some evidence otherwise harmless plant hormone indole-3-acetic acid (IAA).
that these phytochemicals may have applications as a Cancer cell DNA became condensed and fragmented,
preservative. One study found that adding no more than 300 ultimately leading to cell death (Greco, Dachs, Tozer, &
parts per million of isothiocyanates, distilled from A. rusticana Kanthou, 2002). This treatment shows promise because IAA is
root, to commercial grade tofu was enough to significantly a long lasting chemical that can cross cell membranes, but it is
decrease bacterial growth and increase shelf life of the not inherently toxic. Thus it would not produce the
product (Shin et al., 2010). This idea is particularly appealing deleterious side effects of many chemotherapies (Greco et al.,
since isothiocyanates are organic and nontoxic to humans at 2000).
such concentrations.
A follow up study expanded the treatment using HRP to treat
Laboratory studies suggest that the roots of A. rusticana are two other cancer cell lines, with more promising results. This
quite effective at removing harmful substances from the soil. study also noted that successful treatment could be obtained
By adding phosphate to soil containing uranium, the roots through proportionally low successful integration of the target
were able to absorb 98% of the heavy metal and even without gene. Even when only 5% of cells expressed HRP, up to 90% of
the phosphate assistance the plants removed more than 80% cancer cells were killed by IAA treatment. Additionally,
of the uranium (Soudek, Petrova, Benesova, & Vanek, 2011). In researchers found that by modifying IAA slightly, they could
another experiment, horseradish root completely depleted achieve better results, indicating great potential for this
soil concentrations of the pharmaceutical acetaminophen, treatment. Like most gene therapies however, HRP therapy is
making it a good candidate for use in phytoremediation, the
not yet in clinical trials and has to undergo more testing Since Hasumura et al.’s study found no other side effects and
before reaching public use (Greco et al., 2001). the dosages were much higher than the dosages in Albrecht et
al.’s study, the results of the Hasumura study should not be
seen as evidence against the therapeutic use of A. rusticana
Clinical Studies taken at typical or traditional quantities.
A double blind study in Germany examined the use of Of note for the cancer inhibition research, the same scientists
Armoracia rusticana as an ingredient in an herbal treatment who found cancer inhibiting effects also found that another
for urinary tract infections. Participants took two doses a day horseradish compound, desulfosinigrin, actually promoted
for a three month period. At the end of the study it was found proliferation of colon and lung cancer cells (Weil, Zhang, &
that patients on the A. rusticana derived treatment, marketed Nair, 2004). As mentioned in their later study with COX-1
as Anti-Infekt N, had a significantly lower recurrence of inhibitory enzymes, A. rusticana possesses cancer inhibiting
urinary tract infections with no adverse side effects thus chemicals as well. The authors suggest that in typical culinary
making it a safe and effective treatment option (Albrecht, use these two effects balance each other out and result in no
Goos, & Schneider, 2007). effect on cancer risks (M. J. Weil et al., 2005).
Another study using the same drug, Anti-Infekt N, and a much Finally, as a culinary and supplement note, like most members
larger pool of participants also found it to be as safe and of the Brassicacae family, horseradish has been classified as a
effective in treating sinusitis and bronchitis as traditional goitrogen. Consumption of raw goitrogens leads to decreased
antibiotic regiments. That is, both treatment groups saw thyroid function which can cause goiters over a period of time
comparable reductions in symptoms (around 80% in both (Robbins, 2007). The chemical culprits here are the abundant
treatments) at the end of the study (Goos, Albrecht, & isothiocyanates which are part of a broader class of known
Schneider, 2006). It is worth noting that both the respiratory goitrogens: thiocyanates (Keshteli, Hashemipour, Siavash, &
and urinary tract infection treatments are traditional Amini, 2010). Additionally as discussed with relation to the
applications as well, demonstrating that traditional origin of the common name, horseradish is toxic to some
knowledge has much to offer modern medicine. domestic animals and should thus be separated from livestock
if grown in their presence (DiTomaso).
Contraindications
While the human trials above showed no harmful side effects, Current Uses in Allopathic and CAM Therapies
in vitro studies involving rats suggest that consuming more Armoracia rusticana has both internal and external historical
than eight milligrams per kilogram of the isothiocyanates use as a remedy and continues to be used as such in some
found in Amoracia rusticana on a regular basis can cause European countries. For rheumatic pain and headache, grated
bladder lesions (Hasumura et al., 2011). horseradish roots or leaves are wrapped in cloth and applied
to the skin at the site of pain. The same preparation is used in
treating sinusitis with the cloth being placed on the throat. For As mentioned above, the apparent decrease in fecundity in
internal use it is often mixed with other ingredients like honey Armoracia rusticana may be a result of a drastic loss of genetic
or vinegar and sugar and ingested to treat cough or high blood diversity. In cultivation, this problem is circumvented by root
pressure, respectively. In some countries, like Romania, it is propagation with great success (Sampliner & Miller, 2009);
common to eat a teaspoon of A rusticana daily prophylactically however, it should be noted that this method essentially
(Sampliner & Miller, 2009). creates clones of the main plant and can only ideally preserve
As a western dietary supplement, horseradish is sometimes or more realistically decrease, but not increase, genetic
sold as a powder or pill, made by grinding up roots which can diversity. From an evolutionary point of view, this implies that
sell for over seventy dollars per pound. It is marketed in much as an agricultural crop horseradish is highly vulnerable to
the same ways it has been historically used. It is a purported disease since any disease able to infect one plant would
to be beneficial to the lungs and sinuses as well as kidneys and necessarily be adapted to infect all the plants propagated from
bladder. In addition, A. rusticana supplements are said to that plant. Indeed there are reports that this is the case; some
increase blood flow to extremities. Warnings attached to this estimates claim effectively 100% of one A. rusticana variety is
product include specific mention that individuals with thyroid susceptible to mosaic viruses. It follows that increased efforts
problems should not take horseradish supplements (Plus, to use sexually produced plants (i.e. those from seeds rather
2011). As a liquid extract horseradish root is dissolved in than root cuttings) would lead to greater disease resistance
water and alcohol; it can sell for seven dollars per ounce and is and benefit the farming industry (Weber, 1949) , but given the
marketed as a treatment for urinary and respiratory tract current state of the species, this method of farming would not
infections. Additional claims include relief from gout, be profitable for some time.
indigestion, rheumatism, and influenza (Creek). With less variation now it may be harder to select for
preferable medicinal or culinary traits. Luckily, the plant in its
current state already has a wide range of applications from
Discussion food preparation to pain relief. Up until now, horseradish has
Human domestication of plants like Armoracia rusticana has been grown largely for food and minor remedies. However
significantly altered them, both phenotypically and recent research shows that it has great untapped potential.
genotypically. Most immediately obvious is the increase in size The essential oils in A. rusticana may become another useful
of consumable plant parts like flowers, fruits, leaves, or roots tool in the arsenal used to fight drug resistant bacteria and
depending on the plant (compare the roots of the now insects. This idea is particularly appealing because the extract
predominantly if not exclusively domestic A. rusticana with of A. rusticana is topically nontoxic, making it well suited for
the still wild A. macrocarpa in Figure 2), but domestication use in situations where it could come into contact with people.
also has the effect of bottlenecking the gene pool for the Isothiocyanate sprays could be used as hospital disinfectants
targeted species. Domesticated crops show a decrease in and organic pesticides on food crops in the field. After harvest,
genetic diversity compared to wild plants (Doebley, Gaut, & perishables could be treated with isothiocyanates to increase
Smith, 2006). their shelf life, leading to greater distribution possibilities and
potentially less wasted food. The issue of thyroid suppression recurrent lower urinary tract infections. [Randomized
linked to thiocyanates means that the isothiocyanate products Controlled Trial Research Support, Non-U.S. Gov't Review].
would have to be regulated and monitored but their potential Curr Med Res Opin, 23(10), 2415-2422. doi:
should not be left unexplored. 10.1185/030079907X233089
Chen, H. L., Akinkurolere, R. O., & Zhang, H. Y. (2011). Fumigant
The live plant itself has proven to be a versatile clean-up tool,
activity of plant essential oil from Armoracia rusticana (L.)
absorbing heavy metals and pharmaceuticals from the soil.
on Plodia interpunctella (Lepidoptera: Pyralidae) and
Given this, horseradish could be introduced in industrial Sitophilus zeamais (Coleoptera: Curculionidae). [Article].
accident sites to help dispose of contaminants. In addition, it African Journal of Biotechnology, 10(7), 1200-1205.
could be planted downstream from medical facilities to limit
the spread of antibiotics and therefore antibiotic resistance to Courter, J. W., & Rhodes, A. M. (1969). HISTORICAL NOTES ON
HORSERADISH. [Article]. Economic Botany, 23(2), 156-&.
the surrounding ecosystem. The odor blocking activity of the
doi: 10.1007/bf02860621
peroxidases combined with the antibiotic properties of the
isothiocyanates make A. rusticana a good choice for managing Creek, T. Teeter Creek Horseradish Tincture, 2012, from
animal waste in farm settings. While it is true that horseradish http://www.amazon.com/Teeter-Creek-Horseradish-
is toxic to some farm animals, using it in a cleaning capacity Tincture-
oz/dp/B000SOMM1S/ref=sr_1_1?s=hpc&ie=UTF8&qid=133
would be safe as long as the animals were kept away from the
4550299&sr=1-1
waste treatment, which they should be anyway.
Davis, E. International Horseradish Festival, from
There is no doubt that horseradish will continue to enjoy http://www.horseradishfestival.net/
popularity as a condiment; see, for instance, the twenty five
year history of the International Horseradish Festival (Davis). DiTomaso, J. List of plants reported to be poisonous to animals in
the United States. In D. University of California (Ed.), Cornell
Additionally, as mentioned above, it has yet unexploited uses
University, Department of Soil, Crop, and Atmospheric
that could benefit a variety of fields, both medicinally and Sciences. Ithaca, New York 14853.
agriculturally. For both of these reasons it is important that
this plant is maintained as a viable species, with enough Doebley, J. F., Gaut, B. S., & Smith, B. D. (2006). The molecular
genetic variation to reproduce on its own and survive attacks genetics of crop domestication. [Review]. Cell, 127(7), 1309-
1321. doi: 10.1016/j.cell.2006.12.006
from disease and changing environmental conditions.
Gonzalez-Sanchez, M. I., Laurenti, M., Rubio-Retama, J., Valero, E., &
Lopez-Cabarcos, E. (2011). Fluorescence decrease of
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product containing Tropaeoli majoris herba (Nasturtium) 10.1021/bm200091m
and Armoraciae rusticanae radix (Horseradish) for the
prophylactic treatment of patients with chronically
Goos, K. H., Albrecht, U., & Schneider, B. (2006). [Efficacy and safety Keshteli, A. H., Hashemipour, M., Siavash, M., & Amini, M. (2010).
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treatments in the daily practice/results of a prospective 10.1007/s12519-010-0236-6
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combination for gene therapy of cancer: horseradish Urban, J., . . . Stolcova, M. (2011). Antibacterial effect of
peroxidase/indole-3-acetic acid. [Research Support, Non- essential oil vapours against different strains of
U.S. Gov't]. Cancer Gene Ther, 7(11), 1414-1420. doi: Staphylococcus aureus, including MRSA. [Article]. Flavour
10.1038/sj.cgt.7700258 and Fragrance Journal, 26(6), 403-407. doi:
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G. M., & Dachs, G. U. (2001). Horseradish peroxidase- Plus, H. E. (2011). Horseradish Root Herbal Supplement from
mediated gene therapy: choice of prodrugs in oxic and Herbal Extracts Plus, from
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Mol Cancer Ther, 1(2), 151-160.
Robbins, S., Kumar, V. (2007). Robbins basic pathology. Philadelphia.
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Romero, L. V., Targovnik, A. M., Wolman, F. J., Cascone, O., &
& Ogawa, K. (2011). Toxic effects of a horseradish extract
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Weil, M. J., Zhang, Y., & Nair, M. G. (2004). Colon cancer proliferating
Their Native Ranges. [Article]. Economic Botany, 63(3), 303-
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Shin, I. S., Han, J. S., Choi, K. D., Chung, D. H., Choi, G. P., & Ahn, J. 10.1207/s15327914nc4802_11
(2010). Effect of isothiocyanates from horseradish
Weil, M. J., Zhang, Y., & Nair, M. G. (2005). Tumor cell proliferation
(Armoracia rusticana) on the quality and shelf life of tofu.
and cyclooxygenase inhibitory constituents in horseradish
[Article]. Food Control, 21(8), 1081-1086. doi:
(Armoracia rusticana) and Wasabi (Wasabia japonica). J
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Weil, M. J., Zhang, Y., & Nair, M. G. (2005). Tumor Cell Proliferation
uptake and stress responses of in vitro cultivated hairy root
and Cyclooxygenase Inhibitory Constituents in Horseradish
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Illinois. [Review]. Horttechnology, 20(2), 267-276.
Artemisia absinthium L., Asteraceae
Michael Clanahan
Introduction
Artemisia absinthium L., commonly known as wormwood,
green ginger, or wermot, has been used for thousands of years
in a variety of fashions. Although most famous for its role in
the production of the alcoholic drink Absinthe, wormwood has
played a major part in traditional medical practices in multiple
cultures. A few main components of the plant that have been
isolated include thujone, absinthin, caffeoylquinic acids,
phenols, and select flavonoids, all of which have different
physiological effects and in some cases, beneficial health
properties.
Traditionally, this plant has been used to treat many different
ailments from diabetes to stomachaches to tuberculosis. Used
all over the world, this powerful plant has faded in and out of
popularity, but continues to have significant medicinal value
in many areas.
Figure 1. Characteristics sheen of Artemesia absintium L.
leaves. (Source: http://www.flowertropes.com/index/tag/kevin-kline)
Morphologically, wormwood is very similar to other plants in between the months of July and October. (Grieve, 2011).
the Asteraceae family. This herb has a perennial root system, Unlike many other plants of the Asteraceae family, the small
and has characteristic firm, branched stems that are woody at wormwood fruits do not contain a crown of hairs, also called
the base (Grieve, 2011). Typically, the plant reaches no more “pappus” (Grieve, 2011). Although the leaves and flowers of
than two to three feet, as it is found mainly in arid climates the plant taste very bitter, the roots have a characteristic
(Arnold, 1989). The leaves of the plant are whitish on both aromatic taste. The flowers smell of thujone, an important
sides, but also contain silvery gray sheen due to short, fine compound with medicinal values will be discussed. (Grieve,
hairs on the indented outside. This sheen can be seen in 2011).
Figure 1. Wormwood is a flowering plant, identifiable by its Closely related plants include Roman wormwood (Artemisia
small globular flower bundles of greenish-yellow tint, mainly pontica), A. judaica, Sea Wormwood (A. maritima), as well as
the herb Tarragon (A. dracunculus) which is also known Wormwood was utilized by other cultures, such as traditional
commonly as dragon’s-wort (Grieve, 2011). Tarragon is found practices in modern day Turkey. In the Kirklareli Province,
in many spice gardens, and Southernwood (A. abrotanum) is wormwood is known locally by many names, including
found primarily in border habitats between fields. The entire pelinotu and pelin. People in this particular area would use
family is characterized not just by physical likeness, but most almost all of the parts of the plant to treat different ailments.
importantly the intense bitterness contained in all parts of the For example, the arial parts, when prepared as an infusion
plant (Grieve, 2011). could be used as an abortifacient, a cure for stomach ache, and
appetizer, or a blood depurative. However, when prepared as
a decoction and consumed 1-2 times a day for 7-8 days, it
Traditional Uses could be used to treat diabetes, uterine cysts, and tuberculosis.
Wormwood is one of the oldest known herbs to be used in Also, by cutting the shoots into small pieces and eaten two
traditional medicine, with evidence tracing its usage back to times a day for 8 days, it is believed to treat malaria (Kültür,
ancient Egyptians. Wormwood’s appearance in the Ebers 2007). In traditional Caribbean medicine, the plant is used
Papyrus dating from 1550 B.C. support this claim and indicate primarily for women’s health. This includes treatment for
not only medicinal value, but also religious significance menstrual cramps and vaginitis (Lans, 2007). Wormwood
(Arnold, 1989). Another important historical medical even plays a part in traditional Chinese medicine (TCM) as a
document, Historia Naturalis, written by Pliny in the first treatment for bacillary dysentery (Zhang, 2005).
century A.D. mentions wormwood in a medical context that Wormwood is traditionally most famous for its role in the
shines light on the common name of the plant. The production of the alcoholic beverage, absinthe. Although used
encyclopedia describes wormwood extract as having powerful medicinally all over the world for centuries, its narcotic effects
effects on gastrointestinal worms, often ridding the human of did not become significant until around 1790 in Switzerland.
a large part of the parasitic load (Arnold, 1989). Dioscorides’ Pierre Ordinaire, a French refugee and physician, created an
De Materia Medica, completed around 65 A.D., also mentioned extract of wormwood for use as a stomach tonic. Due to its
wormwood’s anthelmintic properties, but included many characteristic green tint and reported hallucinogenic
more applications. These include applications such as a properties, the drink quickly became known as La Fée Verte,
natural insect repellant and a natural antidote to poisoning by or The Green Fairy (Lainer, 1995). Early in the 19th century,
hemlock and toadstools (Grieve, 2011). The leaves were the drink recipe was acquired by a Frenchmen named Major
commonly dried and stored with garments and furs to protect Dubied and his son-in-law, Henry-Louis Pernod. Pernod would
them from moths (Arnold, 1989). De Materia Medica’s eventually take over the company, and his name became
authority for over 1500 years is illustrated by the fact that historically attached to absinthe (Lainer, 1995). At this point,
John Gerard, a highly revered Elizabethan herbalist in the the drink became associated more with social functions than
1500s, mentions in his book Herball that “wormewood the medical world. Because of its high price originally, only
voideth away the wormes of the guts” (Mann, 2009). those in certain circles could afford it, and this included the
world of the artists (Lainer, 1995). A few artists known to
have partaken in the consumption of absinthe were
Baudelaire, Rimbaud, Picasso, and most famously, Vincent Van
Gogh (Ashcraft, 2011). Van Gogh may have been addicted to
absinthe in his lifetime. Evidence also suggests that this
addiction aggravated his psychosis and that the hallucinations
he witnessed stemming from thujone may have caused him to
commit suicide (Arnold, 1989). Other artists couldn’t get
enough. Oscar Wilde once wrote, “What difference is there
between a glass of absinthe and a sunset?” (Ashcraft, 2011).
Figure 2. Chemical structure of thujone. (Source:
As the drink became more accessible, the general public began http://www.rdchemicals.com/chemicals.php?mode=details&mol_id=8286)
to take part. The French public consumed an estimated
700,000 liters of absinthe in 1874. However, due to increased
popularity and a severely decreased wine-grape harvest (Lanier, 1995). Although the fear of alcoholism and absinthism
(phylloxera infestation), by 1900, the number of liters was greatest in France, several countries banned absinthe
consumed surpassed 36 million (Ashcraft, 2011). before France, including Switzerland in 1908, The United
States in 1912, and Italy in 1913 (Lanier, 1995).
Absinthism emerged as a serious disease around this time due
to excessive public consumption. Characterized by dazed In 2007, the effective ban was lifted when the Alcohol and
victims, as well as incredibly vivid hallucinations, absinthism Tobacco Tax and Trade Bureau (TTB) redefined the
became a serious problem towards the end of the 19th century, restrictions on the drink. Today, one can buy absinthe in
and also became a point of attack for those opposing the liquor stores, but with one major difference: it is thujone-free.
absinthe business (Arnold, 1989). Some suggested raising the The FDA requires that all thujone be filtered out of the final
taxes on absinthe to reduce addictions within the population. product before distribution to the public. In order for absinthe
When this proposal failed, another bill was brought forward to be “thujone-free,” it must test for lower than 10ppm (CFR,
and ultimately passed in 1908 that increased the amount of 2007).
alcohol in absinthe. The explanation for this was that absinthe
with a higher degree of alcohol was healthier and that the
requirement for higher alcohol content would eliminate those
producers who used artificial essences with lower standards Wormwood has a rich variety of present compounds. The
of purity,” as this was thought to be the reason for some of the major constituent is thujone (absinthol), a terpene, which is
addictions (Lanier, 1995). It would not be for another 6 years toxic if ingested in sufficient quantities. Thujone,
until the sale absinthe was banned on August 16th, 1914. This characterized by its menthol-like odor, is commonly credited
was done as an “emergency measure” to stem alcoholism, but with causing the convulsion episodes anecdotally reported to
absinthe continued to circulate in the public. In January 1915, be associated with Absinthe consumption. The structure of
a presidential decree was issued, explicitly banning absinthe thujone can be seen in Figure 2.
Wormwood also contains important compounds called
phenols, which have been linked to antioxidant activities.
According to Mahmoudi group, wormwood contains 194.9 ±
9.7 mg gallic acid equivalent/g of extract. Polyphenols, or
more specifically flavonoids, have also been shown to exhibit
antioxidant activities. Total flavonoid levels in A. absinthium
are 12.4 ± 0.6 mg quercetin equivalent/g of extract, a
promising value (Mahmoudi, 2009). It is thought that the
antioxidant properties of many phenols and flavonoids may
decrease incidence of certain human diseases when the
Figure 3. Chemical Structure of 5-caffeoylquinic acid. consumption of foods rich in these compounds is increased
(Source: http://www.39kf.com/cooperate/qk/American-Society-for- (Mahmoudi, 2009).
Nutrition/037804/2008-12-28-551072.shtml)
Caffeoylquinic acids contained within wormwood are a
relatively new discovery in the scientific community. 5-
Wormwood’s overpowering bitter taste can be directly caffeoylquinic acid is one of the most abundant within A.
attributed to its absinthin content. This sesquiterpene lactone absinthium, and also goes by the name of chlorogenic acid
has a bitterness threshold of one part per 70,000. In other (Fiamegos, 2011). Figure 3 depicts the structure of 5-
words, a single ounce can be detected in 524 gallons of water caffeoylquinic acid. Studies suggest 5-caffeoylquinic acid is a
(Arnold, 1989). Interestingly, the King James Bible mentions potent antimicrobial compound, as well as an effective biofilm
the bitterness of wormwood a few times. This occurs a few reducer (Fiamegos, 2011).
times in the Old Testament, most notably in the book of
Proverbs: “But her end is bitter as wormwood, sharp as a two-
edged sword” (AV Prov.5:4). Wormwood is again specifically Biological Activity
mentioned by name in The Book of Revelations as part of the Thujone may be the most important, as well as controversial
rapture: “And the third angel sounded, and there fell a great compound contained within wormwood. Its method of action
star from heaven, burning as it were a lamp, and it fell upon is thought to be a reduction of GABAA receptor activity,
the third part of the rivers, and upon the fountains of waters; thereby reducing serotonergic responses (Deiml, 2004).
And the name of the star is called Wormwood: and the third Because thujone reduces GABAA receptor activity, neuron-
part of the waters became wormwood; and many men died of firing inhibition is reduced, allowing neurons to fire more
the waters, because they were made bitter” (AV Apoc. 8:10- frequently. This is thought to cause the convulsions
11). Although the biblical source is accurate in depicting anecdotally and scientifically reported (Höld, 2000). As stated
wormwood’s intrinsic bitterness, there is no evidence to before, wormwood was traditionally used as an anathematic.
support its lethality. Thujone is the compound responsible for this anti-parasitic
activity. Although thujone is a toxic substance, and can be
lethal as high doses, ethanol appears to protect against lethal
effects of thujone, which may have implications for thujone
content in the popular drink, Absinthe (Höld, 2000).
As discussed before, the phenolic and flavonoidic contents of
A. absinthium exhibit important antioxidant properties.
Oxidizing compounds, such as H2O2 (hydrogen peroxide) and
NO (nitric oxide), can cause severe damage within the human
body due to the propagation of free radicals. Although not
fully understood, flavonoids exhibited strong reducing
potential. When compared to a known reducing (antioxidant)
compound, in this case Vitamin C, a methonalic extraction of
wormwood flavonoids showed no significant difference in Figure 4. Chemical structure of quercetin. (Source:
http://www.worldofmolecules.com/antioxidants/quercetin.htm)
absorbance levels (Mahmoudi, 2009).
Phenolics, including quercetin, may have a direct effect on ultimately this analgesia was less potent overall (Ahmad,
H2O2 scavenging, thereby resulting in the termination of the 1992). This same group then studied anti-inflammatory
free radical chain reaction (Mahmoudi, 2009). The structure of effects of the methanolic extract to conclude that it was
quercetin, a polyphenolic, is shown in Figure 4. Quercetin effective, but also dosage-dependent. The 1000 mg/kg dose
showed high antioxidant activity, or high H202 scavenging was tested using the hind paw edema method in a mouse
activity, as its IC50 was 17.01 ± 0.03µg/ml. Hydrogen peroxide model, and again exhibited significant activity. Results showed
as a compound does not have a high rate of activity, but can a peak activity at 3 hours after administration, and a resulting
sometimes create hydroxyl radicals within the body 41% inhibition in increased paw volume (Ahmad, 1992).
(Mahmoudi, 2009). Wormwood phenolics were also extremely Again, however, this activity was much less intense and lasted
effective in chelating Fe2+, a transition metal capable of free a shorter period of time, as well as a delayed response in anti-
radical generation from peroxides, with an IC50 value of 419 ± inflammation (Ahmad, 1992). Although these effects were
20.95µg/ml (Mahmoudi, 2009). exhibited, the exact compounds responsible for the medicinal
actions are unknown.
A study from the Ahmad group showed that methanolic
wormwood extractions exhibited strong analgesic properties A method of action is unknown for the methanolic wormwood
using the tail immersion method in mouse model. Analgesic extraction resulting in antidepressant effects in the mouse
properties were detectable in all three tested dose levels (300, model. For this experiment, a forced swimming test (FST) was
500, and 1000 mg/kg), of which the results were dose used. The results showed a remarkable decrease in duration
dependent (Ahmad, 1992). When compared to the standard of immobility, and were dose dependent (Mahmoudi, 2009).
acetylsalicylic dose of 300 mg/kg, the wormwood extract These results can be seen in Table 1. The results for the 1000
showed a significantly faster onset of analgesic effects, but mg/kg wormwood extraction dose are very similar to the 5
Clinical Studies
One of the most interesting clinical studies conducted on
wormwood involves its usage in treating Crohn’s Disease. This
disease, characterized by intense abdominal pain and frequent
diarrhea, is thought to be an autoimmune disorder, but there
is existing evidence pointing towards a viral cause (Smith,
1993). Wormwood extracts contain caffeoyl and
dicaffeoylquinic acids that have been shown in vitro to inhibit
HIV-1 integrase. HIV-1 integrase is responsible for the
integration of reversibly transcribed viral DNA into the host
genome (Fiamegos, 2011). Another study conducted by Karim
et al. (1996), produced evidence suggesting that aqueous
extracts of A. absinthium are capable of protecting cells against
Table 1. Effect of methanol extract of Artemisia absinthium L. herpes virus (Karim, 1996). The Omer group (2007)
on the duration of immobility during forced swimming test conducted a study administering wormwood capsules to
and tail suspension test (Mahmoudi, 2009). Crohn’s Disease patients being regularly treated with 5-
aminosalicylates and select steroids. For standardization, the
mg/kg dose of the antidepressant imipramine, a known wormwood capsules contained 250mg wormwood powder,
seratonin (HT-5) and norepinephrin reuptake inhibitor and a filler consisting of 100mg rose, 40mg cardamom, and
(Mahmoudi, 2009). 10mg mastic resin, whereas the placebo capsule only
As mentioned before, A. absinthium extracts contain a contained the filler (Omer, 2007). The results showed that at
significant amount of 5-caffeoylquinic acid (5-CQA). Recent week 10, 65% of the test group exhibited little to no
developments in antimicrobial studies have pointed towards symptoms of the disease. Even more interesting is that these
bacterial efflux pumps. Efflux pump inhibitors (EPIs) patients did not need to restart steroid treatment, as there is
effectively stop bacteria from expelling antibiotics taken up no remission of the disease (Omer, 2007). Another interesting
from the surroundings, therefore effectively allowing the point is that those patients that benefited from the treatment
antibiotics to kill the bacteria. Although the effective also experienced a higher quality of life and better mood than
compounds from A. absinthium extracts have not been those who didn’t, according to Hamilton’s Depression Scale
completely identified, 5-CQA plays a key part in the (Omer, 2007).
antimicrobial actions as an EPI by docking with the efflux
pump and changing its conformation, effectively cutting off
any flow (Fiamegos, 2011). Contraindications
As stated before, because thujone reduces GABAA receptor
activity, neuron-firing inhibition is reduced, allowing neurons
to fire more frequently. This is thought to cause the Currently, wormwood’s promise in treating Crohn’s Disease
convulsions anecdotally and scientifically reported (Höld, and other viral diseases is attracting the attention of the
2000). These convulsions were also reported in other sources, scientific community. As stated previously, A. absinthium
along with a possible connection to kidney failure (Ashcraft, contains large amounts of 5-caffeoylquinic acid (5-CQA),
2005). Another source reported thujone as hepatotoxic, as which is being investigated as a compliment to antibiotics.
well as damaging to the brain. Other reported side effects This may have larger implications in the medical community’s
include anxiety and sleeplessness (Naser, 2005). Thujone’s struggle to keep up with antibiotic-resistant strains of
interactions with other drugs has not been well documented. bacteria. If 5-CQA is investigated further in its mechanism and
effectiveness against bacteria, it may grant the medical
community more time to develop stronger antibiotics.
Artemisia absinthium is not used currently in allopathic
medicine the United States. However, it is commonly used in References Cited
CAM therapies as a tea or tincture, and there are claims that it Adams, Jad. Hideous Absinthe: a History of the Devil in a Bottle.
aids in many common ailments, including appetite promotion, London: I.B. Tauris, 2004. Print.
anti-anxiety, as well as hastening the child birthing process. Ahmad, Fayyaz, Rafeeq Khan, and Shahid Rasheed. "Study of
Wormwood has even been reported as an effective agent in Analgesic and Anti Inflammatory Activity from Plant
treating dropsy, as it is believed to be a powerful diuretic Extracts of Lactuca Scariola and Artemisia absinthium."
(Grieve, 2011). However, because of the negative aura Journal of Islamic Academy of Sciences 5.2 (1992): 111-14.
surrounding wormwood from previous centuries, natural Print.
supplements and use is relatively low. Arnold, Wilfred Niels. "Absinthe." Scientific American 260.6 (1989):
112-17. Print.
Discussion Ashcraft, Brian. "Wired 13.11: The Mystery of the Green Menace."
Wired.com. Nov. 2005. Web. 15 Sept. 2011.
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used for thousands of years for its medical benefits, abused for ml>.
its hallucinogenic and euphoric properties, and in modern "Code of Federal Regulations, Title 21, Chapter I, Part 172, Section
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disease. Although in past centuries it was abused and to Food for Human Consumption". US Food and Drug
consequently received negative light, current applications of Administration.
incredibly important compounds contained within Deiml T, Haseneder R, Zieglgänsberger W, Rammes G, Eisensamer B,
wormwood (phenols, flavonoids, caffeoylquinic acids, etc.) Rupprecht R, Hapfelmeier G (Feb 2004). "Alpha-thujone
show a promising future for the plant. reduces 5-HT3 receptor activity by an effect on the agonist-
reduced desensitization". Neuropharmacology 46 (2): 192–
201. reproductive problems.” J Ethnobiol Ethnomed. 2007 ; 3:13.
Fiamegos YC, Kastritis PL, Exarchou V, Han H, Bonvin AMJJ, et al. Lomovskaya O, Watkins W. “Inhibition of efflux pumps as a novel
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M. Nabavi. "Antidepressant and Antioxidant Activities of
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Sept. 2011. of Medicine 8.24 (2009): 7170-175. Print.
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Höld KM, Sirisoma NS, Ikeda T, Narahashi T, Casida JE (April 2000). Print.
"Alpha-thujone (the active component of absinthe): gamma-
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Lans C . “Ethnomedicines used in Trinidad and Tobago for
Asparagus officinalis L., Asparagaceae
Sandy Jiang
Introduction
The genus Asparagus contains more than 200 species, of
which Asparagus officinalis L., (Figure 1) is the most well-
known; it can be found both at the supermarket and on our
dinner tables. Asparagus belongs to the Asparagaceae family.
“Asparagus” is supposedly of Persian origin (Hexamer, 1901),
and it is believed to have originated in the eastern
Mediterranean region, but can now be found growing in many
parts of Europe. Naturalized in the Americas and even New
Zealand, it is now a common crop grown for its young edible
shoots that resemble spears. The lower fibrous parts of the
plant are usually peeled off, leaving the tips to be consumed
(Grubben, 2004). A. officinalis is high in nutrients, particularly
carotenoids and sulfur containing compounds which both give
the plant its distinctive taste. A. officinalis is also high in
saponins, which have been shown to have antifungal,
antioxidant, hypolipidaemic, hypoglycemic, and
hepatoprotective properties. Recent studies have shown that Figure 1. A. officinalis. Image Source: http://2.bp.blogspot.com/-
compared to the stem, the often discarded bases actually wchTZKfSOHY/T-
contain more bioactive compounds. More research is being odkzJN9tI/AAAAAAAAIVo/p8qaIvATDUI/s1600/asparagus+draw.j
conducted on this exciting aspect. pg
branches while the false leaves, termed cladolia, are actually

Botanical Description the same as modified branches (Hexamer 1901). The flowers
The asparagus plant (Figure 2) is a dioecious perennial herb are unisexual, small, greenish-yellow and differ in size
with erect stems up to 2 meters tall. The thick stalks have bud depending on of the gender of the plant. The fruit produced
clusters with leaves that resemble prickly brownish scales. are red berries up to 1 cm in diameter that produce black,
The true leaves usually become spines at the base of the round, and flattened-on-one side shaped seeds (Grubben
2004).
Asparagus germination is slow even at optimum temperatures
of 25-30°C. Flowering, which relies on insect pollination, is
continuous and begins in the plant’s first year of life. An
adequate amount of nutrients is necessary, and fertilizers are
usually administered annually to these crops. Good balance of
fertilizers and appropriate water drainage systems can
protect the plant against certain Fusarium infections which
can cause devastating results to crops. Most diseases that
attack asparagus are fungi including Stemphylium botryosum,
Cercospora asparagi, and Phoma asparagi (Grubben 2004).
In warmer climates, the asparagus plant is green throughout
the year, but in temperate climates, it senesces during autumn
and resumes growth during spring. The seeds are usually
grown in situ within a green house rather than directly sown
into the field. The choice of the asparagus species is crucial as
it is a long-term plant (Grubben 2004). The soil must be well-
drained, sandy, naturally fertile, silicious, and deep so that the
roots can penetrate deeply and absorbed all the nutrients
from that soil (Ilot 1901). Older asparagus roots become
hollow over time as young roots form above them. Thus,
asparagus plants gradually rise above the original soil level
and it is often necessary to cover up the exposed crowns with
additional soil (Ilot, 1901).
Traditional Uses
History
It is believed that asparagus was first cultivated by the
Figure 2. A. officinalis plant structure. Image Source: Egyptians or Greeks. In his book De Re Rustica, Cato lauded the
http://www.mdidea.com/products/proper/asparagus- plant as a valuable garden vegetable for the Romans.
officinalis.jpg Cultivated asparagus went back to being wild after the fall of
the Roman Empire before it was brought back into the Chinese pharmacists save the best asparagus roots for their
monastic gardens of the Middle Ages. It has been said that the close friends and families, believing it will promote feelings of
Italians cultivated the finest asparagus, and therefore many compassion and love. A. officinalis roots have been used as a
societies compared their asparagus to that of the Italians’. remedy for schistosomiasis, tuberculosis, dropsy, and cardiac
Also, the French Huguenot refugees brought asparagus to medicine in these societies as well as Western medicine (Negi
England, improving the delicious but not as robust English et al., 2010).
variety. The English colonists then brought asparagus to North
America, where it became a commercial crop in the 19th
century (Chiffolo & Hesse, 2006). Food uses
Asparagus is usually eaten cooked. The tips are usually eaten,
with chefs cutting off most of the base. Asparagus can also be
Traditional medicinal uses
eaten raw, though thinner stalks are preferred as they tend to
The Romans prized the asparagus highly and it was one of be tenderer compared to the fibrous thicker stalks Fresh
their oldest and most valued medicines. The fresh roots were asparagus must be consumed immediately as asparagus have
used as a diuretic and as a sedative while syrups made from high respiration rates and will become hard and more fibrous
the young shoots and extract of the roots were used as a and thus, not consumable. Asparagus can be bottled, canned,
sedative for heart problems. Mixtures of asparagus, celery, or frozen. The seeds have been reported to be used to make a
parsley, holly, and fennel were used for the treatment of coffee like beverage while germinating seedlings have been
dropsy and gravel. Also, a liniment of asparagus and oil was used as vegetables (Ong, 2008). Asparagus, because of its
believed to protect the user from bee stings, and the root was buttery taste can be used in casseroles and almost any other
used for tooth aches (Hexamer 1901). dish including cream of asparagus soups, fried dishes, broths,
Since A. officinalis is a cultivated plant, most traditional uses in and stir fries (Shulman,2010). A. officinalis is usually
medicine came from Asparagus racemosus Willd as it was the recognized for two varieities, green and white. The white
wild variety. A. racemosus was used in traditional Indian asparagus is grown by covering the plant in dirt to keep it
medicine to increase fertility and to cure bodyaches. Women growing in the dark. This process, termed “etiolation” gives it
would take half a cup of root extract early in the morning for a more bitter taste, but a tender, fiberless, soft, and more
seven days to increase fertility and conception while tribal delicate flavor than the green variety.
ladies took the root powder orally to cure bodyaches and
leucorrhea. A. officinalis was used to increase sexual potency
Ethnobotanical Uses
for both men and women (Jain et al., 2004).
Asparagus are high in saponins which give it its characteristic
The asparagus species has been used in India and China for its
taste. Saponins have been shown to have spermicidic and
diuretic properties as it flushes the kidneys and helps prevent
antifungal properties. In India, asparagus has been used for its
formation of kidney stones. An interesting folk belief is that
medicinal purposes for centuries, and it is believed that
Harvesting
Asparagus is perennial plant and can be harvested annually. It
is typically not economical to harvest asparagus plants that
are over 10-15 years of age, but asparagus plants over a
hundred years of age have been located in western Europe.
Figure 3. Thiols are also known as mercaptans which give The spears of the plant are the most marketable and require
asparagus its famous odor. high nutrition to ensure quality, meaning that there must be
sufficient nutrients in the base of the plant to fuel its growth.
Thus, most asparagus are not harvested until two years after
saponins are the main active ingredients behind these
planting to ensure proper nutrition for the plant. The spears
physiological activities. The bottom parts that are usually
are cut and washed before being sorted and packed for
chopped off and discarded are found to actually possess high
marketing. Asparagus have high respiration rates and will
amounts of saponins (Shimoyamada et al., 1990).
shrivel without water. Thus, they have short shelf lives and
must be kept under high humidity conditions (Grubben 2004).
Pest Control/ Cultivation
The common asparagus beetle Crioceris asparagi was a huge Chemistry and Pharmacology
pest in the early United States in both its larval and adult
Like many plants, asparagus is high in many allelochemicals
forms (Ilot 1901). The insect preys on the soft parts of the
and other nutritious chemicals, including minerals and
asparagus plant rendering it unfit for human consumption.
carotenoids. A. officinalis also contains sulfur compounds,
The insect however was very susceptible to sudden changes in
which are responsible for its distinctive taste and smell.
temperature and had a wide variety of predators. Chickens
and ducks were efficient predators employed by farmers to Both the green and white varieties of A. officinalis are edible,
curb disease. Prominent asparagus farmers used to cut down though the green variety is more abundant in micronutrients.
all plants in early spring to force the beetles to lay eggs on new The characteristic odor of asparagus is derived from dimethyl
shoots which were cut before the eggs could hatch. Other sulphide, which is formed from the degradation of the amino
stalks were designated as sacrificial to lure the beetles before acid S-methyl methionine (Grubben, 2004). Sulphur
air slacked lime was dusted on the plants in the early morning containing compounds are known as thiols or mercaptans
to kill the pests (Hexamer 1901). Paraffin and soap were (Figure 3). The pungent urinary odor produced by many
described by Charles Ilot to be efficient insecticides. It is individuals after the consumption of asparagus has been
interesting that such organic methods kept the shoots still safe shown to be due to six mercaptans: methanethiol, dimethyl
to consume while efficiently removing the pests compared to sulphide, dimethyl disulphide, bismethyl methane, dimethyl
modern chemicals. sulphoxide, and dimethyl sulphone (Waring, Mitchell,
Nutrient n=100g sample Percentage of 100g the leftover tough roots release hytotoxic compounds and may
sample have Fusarium oxysporum (FOA) infections (Grubben, 2004).
Water 75 g 75% Asparagus plants and their decaying root tissues have been
Energy 25 kcal - shown to release allelochemicals such as autotoxins, which
Protein 2.9 g 2.9% can make the plants more susceptible to FOA infections or
Fat 0.6 g 0.6% exacerbate pre-existing FOA infections (Nair et al., 1990).
Carbohydrate 2g 2.0%
Fiber 1.7g 1.7% Of the two varieties, the white asparagus is grown by covering
Calcium 27 mg 0.027g% the plant in dirt to keep it growing in the dark. This process,
Magnesium 13 mg 0.013% termed “etiolation” gives it a more bitter taste, but tender,
Phosphorus 72 mg 0.072% fiberless, soft, and more delicate flavor than the green variety.
Iron 0.7 mg 0.0007% Saponins are primarily responsible for the asparagus’s bitter
Zinc 0.7mg 0.0007% taste. In 2012, Hofmann and Dawid isolated five other
Carotene 315 μg 0.000315% compounds that contribute to the bitter taste. Table 2 lists the
Riboflavin 0.06 mg 0.00006% names and the human taste thresholds for these compounds.
Niacin 1 mg 0.001% Hofman and Dawid also found that asparagus plants have a
Vitamin C 12 mg 0.012% buttery mouth-coating effect that was attributed to the two
Table 1. Breakdown of nutrient components of Asparagus 1,2-dithiolan-4-carboxylic acid 6-D-glucopyranose esters.
officinalis. Source: Grubben, J.G.H., (Ed.)(2004). Vegetables:
plant resources of tropical Africa. (Vol.2). Wageningen,
Netherlands: PROTA foundation/Backhuys Publishers. Biological Activity
The edible portions have been shown to possess antifungal,
Fenwick, 1987). A. officinalis also contains a wide variety of antioxidant, hypolipidaemic, hypoglycemic, and
nutrients, including calcium, phosphorus, and protein (Table hepatoprotective activies. During the industrial processing of
1). A. officinalis, around 30-40% of the spear is discarded as
A. officinalis is high in carotenoids, especially in its fruits. The waste which wastes food and leads to significant environment
ripe fruits contain large amounts of capsanthin, β-carotene, pollution. However, it has recently been shown that the base is
and zeaxanthin and small amounts of capsorubin, rich in bioactive phytochemicals such as steroids, and in
cryptoxanthin, cryptocapsin, antheraxanthin, violaxianthin, particular, saponins (Wang et al, 2012). Saponins have a large
and capsanthin isomers. Interestingly, the biosynthesis variety of biological properties including antioxidants,
pathway of carotenoids in A. officinalis was found to be similar immunostimulants, antihepatotoxic, antibacterial, therapy for
to that in paprika (Deli, Matus, Tth, (2000). diabetic retinopathy, anticarcinogenic, antidiarrheal,
antiulgerogenic, antioxytocic, and reproductive agents.
It is interesting to note that once old asparagus plants die, the Saponin rich plants, such as A. officinalis have been shown to
field cannot be used to replant new asparagus crops because improve growth, feed efficiency, and health in cattle such as
sheep and cows (Negin et al., 2010). This biological activity Compound Compound Threshold
section explains the in vitro and in vivo studies performed by no. (μmol/L)
1 3-O-[α-L-Rhap-(1→2)-{α-L-rhap-(1→4)}-β- 65.9
various studies on the bioactive properties of A. officinalis.
D-glcp]-26-O-[β-D-glcp]-(25R/S)-22-
Table 3 summarizes the plant parts, isolated compounds, and hydroxyfurost-5-ene-3β,26-diole
the activities of the compounds mentioned before and in this
section. 2 (25R/S)-furost-5-en-3β,22,26-triol-3-O-[α- 10.9
L-rhap-(1→4)-β-D-glcp]-26-O-β-D-glcp
In vitro 3 (25R/S)-furostane-3β,22,26-triol-3-O-[α-L- 25.5

rhap-(1→4)-β-D-glcp]-26-O-β-D-glcp
Proteolytic Properties
4 3-O-[{α-L-Rhap-(1→2)}{α-L-rhap-(1→4)}-β- 70.6
Proteolytic enzymes break down proteins and thus can D-glcp]-(25R/S)-spirost-5-ene-3β-o
tenderize meats for culinary purposes. Ha et al., (2012)
performed a study comparing kiwifruit and asparagus extracts 5 3-O-[{β-D-Glcp-(1→2)}{β-D-xylp-(1→4)}-β- 199.7
D-glcp]-(25S),5β-spirostan-3β-ol
and their proteolytic activities in tenderizing meats. Although
purer cysteine enzyme extracts are needed for further
Table 2. Five saponins found in Asparagus officinalis that
analysis, they found that asparagus had noticeable effects in
give its bitter taste and the human taste recognition
tenderizing meats. Even though asparagus was not as effective
thresholds. Source: Dawid, C., &Hofman, T., (2012). Structural
as kiwifruit, ester hydrolysis in asparagus occurred over the
and sensory characterization of bitter tasting steroidal
entire assay pH range from 2-14 and between temperatures
saponins from asparagus spears (Aspragus officinalis L.).
45-75°C, whereas the same reaction in kiwifruit extracts was
Journal of Agricultral of Food Chemistry.
restricted to a pH range of 5.5-7 and a narrower temperature
range. The asparagus enzyme hydrolyzed myofibrillar
proteins slower than kiwifruit. Although it only targeted caused by the production of cytochrome P-450E1. ADH
myosin heavy chains, after an extended incubation, the metabolizes ethanol to acetaldehyde and then acetaldehyde
myofibrillar proteins, except troponin C were degraded. dehydrogenase (ALDH) before becoming acetate.
Acetaldehyde at high concentrations can cause toxic effects
such as sweating, vomiting, and increase pulse rate and thus,
Alcohol Metabolism there is a need to find an efficient and quick way to remove
Another study was on the alleviation of alcohol hangover in excess alcohols and their metabolites from the body. Kim et
which A.officinalis leaves and shoots extracts increase the al.(2009) demonstrated that the leaves which are usually
activities of two key enzymes that metabolize ethanol, alcohol discarded have the most therapeutic use compared to the
dehydrogenase (ADH) and CYP2E1. Chronic alcohol use can stem for alcohol hangover treatment especially on the HepG2
cause ethanol induced fatty liver as well as oxidative stress cell line. A. officinalis had significant effects on ADH and ALDH
by providing strong antioxidant activity and acting as a potent
Aerial 2-hydroxyasparenyn 4’trans- Inhibitory against including Candida albicans, Crytococcus albidus,
parts 2hydroxy-1methoxy-4- cyclooxygenase -2 Epidermophyton floccosum, Microsporum gypseum, and
5(4methoxyphenoxy)-3-
penten-1-ynyl-benzene
Trichophyton spp but was ineffective against other fungi such
Fruits Capsanthin, capsorubin, Antifungal as Rhizopus and Chaetomium.
capsanthin 5,6 epoxide
3-O-[a-L-rhamnopyranosyl (1- Antitumor Activity

2);] beta-o-
glucopyranosyl](25S)spirost- Cancer occurs when harmful mutated cells experience
5-ene-3beta-ol uncontrolled growth. Cells that experience uncontrolled
Seeds Methyl protodioscin and Cytotoxic growth usually form tumors, but those that mutate and then
protodioscin divide uncontrollably cause cancer. The global burden of
Fruits Spirostanol glycoside Immobilization of human
spermatozoa
cancer has made it necessary to find ways to inhibit the
Roots Sucrose-1-fructosyltransferase Cytotoxic growth of malignant cells. Most cancers can be cured
Roots Sarsasapogenin and nine Cytotoxic surgically before metastasis, but once metastasis has started,
asparagosides A,B,C,D,E,F,G,H, it is almost impossible to treat. Metastasis occurs when
and I malignant cells escape from the original tumor and spread via
Roots Steroids Cytotoxic blood and lymph vessels to other sites. It has been shown by
Leaves Flavonoids and rutin Cytotoxic
Base Saponins Antitumor and anticancer
Wang et al. (2012) that A. officinalis saponins (SSA) inhibit the
Base Saponins Antifungal viability of various cancer cells including breast, colon, and
Table 3. Chemical compounds found in A. officinalis and pancreatic cancer cells in a dose dependent manner. SSA also
their activities. induces cancer cell apoptosis, which is the self destruction of
cancer cells. SSA also inhibits cancer cell migration better than
blocking cancer cell growth. It thus also inhibits cancer cell
catalytic factor to stimulate the enzymatic activities required invasion because migrating cells’ cytoskeletal networks were
to break down alcohol. The amino acid and inorganic mineral seriously disrupted by them. Normal cells are usually round in
content was higher in leaves than in the shoots. shape, but they take on a sword shape after being disrupted;
this shape reduces cell motility. Cell migration is regulated by
Rho GTPases, and it has been shown that SSA targets the Rho
Antifungal Properties
GTPase signaling pathway. Wang et al., argue this potential
Shimoyamada et al.(1990) have isolated saponins that have use of asparagus waste can reduce environmental pollution
antifungal activity from A.officinalis extracts. They have and also potentially be used as anticancer and anti tumor
determined that the antifungal properties of the saponins medicines.
come from the waste products of asparagus processing. The
compound was shown to have antifungal activity against fungi
In vivo with aqueous extracts. Qu et al.(2009) found that the ethanolic
Anti-diabetic Properties (EEA) and aqueous (AEA) extracts of asparagus have strong
hypolipidaemic and hepatoprotective properties that can be
Diabetes occurs when the body cannot efficiently break down used in complementary and alternative medicinal treatments
sugar. This usually occurs when the body does not break in combination with other hypoipidaemic drugs.
down insulin or does not have insulin sensitive receptors, and
thus there is a need to find treatments for this illness.
Metabolism and metabolic studies were conducted by Hafizur Clinical Studies
et al. (2012) that demonstrated A. officinalis extracts can
It has been found that Asparagus officinalis has been used as a
control blood glucose by improving beta cell function in type 2
medicinal plant for the treatment of several diseases. A.
diabetes induced rats. Streptozotocin was injected into rat
officinalis is one of the many plants including broccoli,
pups to induce non obese diabetes. After the thirteenth week,
butterhead lettuce, chickpea, dry beans, and spinach that are
the rats were treated with an extract of A. officinalis seeds
high in folic acid. Folic acid is important for the methylation of
before blood glucose, serum insulin, and total antioxidant
amino acids, DNA and RNA, cell division, differentiation, and
status were measured. It was shown that the treatment with
regulation. It also regulates the central nervous system, mood,
these extracts suppressed the elevated blood glucose level
sleep, and appetite. Women who have folate deficiencies at
that would have been high in diabetic mice without insulin.
child bearing age have a high chance of having neural tube
The efficicacy of this extract depended on the dosage with a
defects and spina bifida in newborn babies (Lester, 2006).
500 mg/kg having higher efficacy than 250 mg/kg. The study
thus shows that A.officinalis extract can have anti-diabetic Besides being consumed for health purposes mentioned
effects by improving insulin secretion and beta cell function before such as fertility, diuretic, and sexual potency, most
and antioxidant status. trials are still in vitro or in vivo for A. officinalis since there has
only been a recent discovery that the usually discarded base
holds more compounds than was suspected.
Hypolipidaemic Effects
Hyperlipidaemia includes hypercholesterolaemia and
Contraindications
hypertriclyceridaemia, and is a major risk factor in the
development of cardiovascular diseases. There has been an Allergies
emphasis on dietary plants that show the potential to lower It has been found that some individuals may be allergic to
cholesterol levels in plasma. A. officinalis has been shown to asparagus. A. officinalis has been shown to cause delayed cell
reduce levels of body weight gain, serum total cholesterol, and mediated reactions and IgE mediated reactions. The most
serum LDL cholesterol in mice with high cholesterol when common allergy is skin contact allergies and only a few IgE
they were administered a daily dose of 200 mg/kg for 8 mediated reactions have been observed. IgE reactions are
weeks. HDL cholesterol levels were increased in mice treated further categorized into food allergy and reactions due to
load comes from the cell cycle, and the other 33 percent come
from diet. Thus, treatment for gout requires a diet that is low
in purines or can break down uric acid better. Products that
are high in purines include animal meats, seafood, and some
plants including asparagus (Gordon, 2005). Individuals with
gout, therefore should not consume asparagus and other high
purine products.

It has been shown that saponins can be used as potential
Figure 7. An LB positive spirostanol glycoside that was
effective spermicidal agents. The methanolic extracts of fruits
shown to have potential spermicidal activity.
of A. officinalis has been shown to have glycosidic activities
that may have such spermicidal activity (Morris et al., 1988).
cutaneous or respiratory exposure with anaphylaxis being the When established methods were used, the extracts caused
most clinical symptom of allergy. Asthma, rhinitis, and 100% immobilization of human spermatozoa at a 1.5% level
uriticaria are other less reported reactions (Tabar et al, 2003). (Figure 4).
Asparagus is usually rarely encountered as a cause of IgE
As stated earlier, A. officinalis is high in saponins which have
mediated disease, as only two reports of allergy to asparagus
been shown to have many biological effects. In
have been published. Usually food allergies are connected to
complementary and alternative medicines, saponin rich
pollen allergies, but the individuals who reported allergies
compounds have been used for a variety of treatments such as
were tested and it was found that it could be an onion specific
being antidiarrheal, antioxytocic, antibacterial,
IgE that leads to the sensitization (Escribana et. al, 1998).
antihepatotoxic, antioxidants, and reproductive agents. It is
Although most responsible allergens are unknown, there is
also used still in India as a sexual potency drug and in Chinese
work being done in isolating the responsible compounds. One
culture it is used for diuretic and kidney stone prevention
of them is 1,2,3-trithiane-5-carboxylic acid, which is a plant
(Negi et al., 2010).
growth inhibitor secreted by asparagus in the early phase of
the season (Hausen&Wolf, 1996). Asparagus is highly recommended to women in child bearing
ages as it is high in folic acid which is important for the central
nervous system, moods, and development of children. In CAM
Gout and food therapy, asparagus is highly promoted with other
Gout is a rheumatic disease that involves chronic high folic acid vegetables such as spinach, brussel sprouts, and
hyperuricemia or the buildup of uric acid from the end broccoli for pregnant women (Lester, 2006).
product of purine metabolism. About 66 percent of the purine
Discussion the densest in the base. A. officinalis holds a bright potential in
A. officinalis is a common vegetable found around households his bioactive compounds as scientists have only begun to
and restaurants that are high in bioactivity. It is found in two realize the bulk of its nutrients, which are in the base that
kinds of varieties including the white and green varieties, with usually requires removing 40% of the stalk, have been
the green variety possessing more micronutrients. It is high in discarded for years and are looking into traditional medicines
folic acid and carotenoids, which are crucial for physiological for clues of its activity.
processes such as neural development and antioxidant
properties. A. officinalis like other asparagus species has a
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Atropa belladonna L., Solanaceae
Kristen Cross
Introduction
Atropa belladonna, commonly know as deadly nightshade,
belladonna, devil’s cherries or death cherries, belongs to the
Solanaceae family, which is also home to other well-known
plants such as tobacco and potatoes (Nicotiana and Solanum,
respectively). As implied by its common names, the toxicology
of this plant is well known and it has been used as a poison as
well as a cosmetic and anesthetic throughout its extended and
interesting tale with the human culture. This ‘femme fatale’
has been incorporated into human history since before the
Middle Ages, making a name for itself as a temptress due to
the neurological and muscarinic effects as conveyed by its
tropane alkaloids scopolamine and atropine. These drugs are
still used today as an antidote for cholinergic crises and have
been implicated in helping those with mental illnesses such as
depression and bipolar disorder. These constituents are also
responsible for the plant’s notorious use a recreational drug in
order to induce hallucinogenic episodes. The fascination with
this plant stems from its alluring appearance as well as the
mystery and taboo surrounding it.
Atropa belladonna is native to Western Europe and North Figure 1. Atropa belladonna in natural habitat. Source:
Africa, where it commonly grows in disturbed woodlands as a www.plants.usda.gov
result of it being a somewhat shade-intolerant species. The
herbaceous perennial is often found cultivating the soil on
nitrophilous and requires a sufficient amount of nitrogen
rocky hillsides and other regions where the soil contains an
present in the soil in order to grow. Due to the plant’s
adequate amount of calcium carbonate. A. belladonna is
importance as an anticholinergic, studies were conducted to
find the ideal growing conditions that produce the highest into their pharmacopeia as a flying ointment known as
concentrations of these alkaloids. They found that an increase ‘sorcerers pomade’. This ointment included nightshade,
in nitrogen in the soil would increase the concentrations of henbane, mandrake and hemlock mixed together and pounded
atropine and scopolamine, especially if water is limiting with bear grease. The ointment was then applied all over the
(Baricevic et al. 1999). This factor could be a large contributor skin and the users claimed to experience hallucinations and
to the fact that A.belladonna is rarely found growing in grass sensations of flying. Divination practices also included the
communities, but rather in largely open and uncultivated consumption of nightshade in small amounts in order to
areas. experience visions that may foretell events to come (Lee
It appears as an erect, weed-like plant, standing 50-200 cm 2007). Many superstitions surround this mystic plant,
high depending on the amount of sunlight available (Figure including the placement of cuttings of the belladonna plant in
1). The stem is densely covered in fine, short hairs while the the household in order to ward off evil spirits. Conversely, the
broad, ovular leaves branch out in unequal pairs starting witches and wizards took a liking to the plant because they
about 25cm from the ground. These leaves are green, smooth believed that it was a favorite of the Devil himself.
and often asymmetric. A single purple flower droops from The practice of using plant extracts (particularly those from
each leaf-axil and in the fall season a smooth, dark purple the Solanaceae family) to dilate the eye in order to enhance
berry is produced (Butcher 1947). It is important to note that physical appeal was first recorded by Matthiolus in 1565
all parts of the plants are poisonous upon ingestion, as the (Matthiolus , Feinsod 2000). This activity was recognized as
alkaloids are ubiquitous throughout. being generally dangerous, but as the doses were relatively
The plant was initially confused with mandrake small, few fatalities were recorded. It was this practice of
(Mandragora), as they are closely related members of the Venetian women that lead to the discovery of the mydriatic
Solanaceae family, but belladonna conveys a higher toxicity effects of atropine, as well as what led Linnaeus to give the
than the former. Dioscorides was the first to recognize that plant its species name, belladonna. This translates to
Atropa was a distinct genus and should not be used in place of “beautiful lady” in Italian, referring to the enhanced
mandrake for medicinal purposes (Lee 2007). appearance of the women after their pupils were dilated by
drops extracted from the plant.
Pre-dating these medieval witches, A. belladonna was included
Traditional Uses in tinctures during the Bacchanalian festivals celebrated by
Atropa belladonna gets its namesake from Atropos, the Fate the Greeks and Romans (Lee 2007). In larger doses, the plant
responsible for cutting the thread of life. This christening was was indicated as a deadly poison and is thought to have made
based on the plant’s dark tie to 11th century black magic, an appearance in The Odyssey as the poison administered to
especially related to its use in love potions and enhancing the the sailors by the lovely yet malicious Circe (Campbell 2007,
appearance of female allure via dilation of the pupils (Müller Lee 2007). Tropane alkaloids have also been used to bolster
1998). Witches and wizards of the olden days incorporated it beers of the ancient world in order to give them more potent
effects upon consumption.
During the Roman and Byzantine empires, the drug began to
lose its tie to religious and prophetic rites and instead became
an important soporific used for medicinal purposes.
(Ramoutsaki et al. 2002). From the mid-nineteenth century
into the 1950s, A. belladonna was incorporated into plasters
and liniments for the treatment of neuralgia, chronic
rheumatism, lumbago, myalgia, pleurisy, pulmonary
tuberculosis and acute mastitis. These plasters were taken off
the market when pharmacists realized that some of them
contained extracts from monkshood (Aconitum napellus),
which produces an alkaloid called aconitine. This alkaloid was
implicated in respiratory and cardiac failures and could be Figure 2. Structures of atropine and hyoscine
used in combination with atropine to poison people (Lee (scopolamine). Source: Lee 2007
2007).
Based on this long history of the plants use for recreational mystic past is what led to the investigation of it for medicinal
purposes, herbalists and apothecaries began to examine the practices.
mechanisms behind its - in some cases deadly - effects on the
body and they found that in lower doses it was useful for
medicinal purposes. Andrew Duncan of the Edinburgh Chemistry and Pharmacology
Dispensatory recommended it as a treatment for the plague as
well as nervous disorders such as epilepsy and mania (Duncan The main chemical constituents of this plant include atropine
1803). He also recorded the first use of mydriatic drugs in and scopolamine (Figure 2). Atropine, a tropane alkaloid, was
ocular surgery by Professor Reimarus, an eye specialist in the first isolated from Atropa belladonna in 1831 by German
1800s. The professor used an infusion of nightshade to dilate pharmacist Mein (Sneader 1985). The compound exists as l-
the pupil while he removed cataracts. hyoscyamine in the plant and is the only active isomer, but it
isomerizes upon extraction into the dextro compound. The
A. belladonna has had a dark and fascinating tie to European racemic mixture of these two isomers is called dl-hyoscyamine
culture ever since its first recorded use in cosmetic or, more commonly, atropine. Its unique tertiary-amine
applications in the 1500s (Matthiolus). It has even worked its structure allows penetration of the central nervous system
way into modern media in Tim Burton’s movie A Nightmare (CNS). It is the important characteristic of its structure that
Before Christmas. The movie featured the dried flowers makes it so potent as an antidote, or in cases of overdose, a
implicated in a potion used for its soporific effects. The lethal poison.
intrigue induced by this plant stems from its use in taboo,
sexual practices as well as the fear of its lethal properties. Hyoscine (also called scopolamine) is another tropane
Though it is dangerous to handle without proper care, this alkaloid that has been isolated from A. belladonna.
of exposure to physostigmine as well as prevent the effects if
given preemptively, of up to two to three times the lethal dose
(Greenblatt and Shader 1973).
The isolation of l-atropine from A. belladonna in the 1830s
also marked an important venture into the study of
neurotransmitters in mammals, specifically the in activity of
Table 1. Average concentrations of chemicals in Atropa acetylcholine and its effects in the body. It was used to map
belladonna. Source: http://www.ars-grin.gov/duke/ this pathway because it allowed for a better understanding of
what effects particular neurotransmitters have on the body
Scopolamine is 10 times more potent than atropine, but it (Lee 2007).
works in the same pathway. The only difference in the Laboratory studies on mice showed that atropine extracted
structure of the two alkaloids is in incorporation of an oxygen from Atropa belladonna has immuno- and gastroprotective
atom into one of the 6-membered rings. Like atropine, effects in the event of stress-induced alterations on behavior.
scopolamine is able to penetrate the central nervous system Although the mechanism of action was not elucidated in this
(CNS) and act on the muscarinic receptors. It is interesting to study, the authors attribute the behavioral inhibition to the
note, however, that these two compounds act only on the “anxiolytic-like effects” of A. belladonna (Cromwell 1943).
muscarinic receptors and not nicotinic receptors.
Studies of the effects of atropine extracted from A. belladonna
The average concentrations of the two compounds found in A. as applied to the eyes of rabbits confirmed the mechanism by
belladonna are reported in Table 1. which atropine is absorbed in the iris and results in dilation of
the pupils. This is achieved by blocking the innervation to the
sphincter pupillae and ciliary (North and Kelly 1987).
Biological Activity Reversal of the mydriasis can take up to 10 days in humans
Atropine has significant effects on the central nervous system. and can also lead to blindness and other complications when
Its properties as a stereotypical anti-muscarinic xenobiotic are dosed inappropriately (Salazar et al. 1976). The effect is
well-known and given in the right dosages, it can be a vital responsible for the plant’s use in the Middle Ages in order to
antidote following exposure to muscarinic agonists, such as dilate the pupils for cosmetic appeal. In humans, the drug
pilocarpine and physostigmine (Wills 1963, Greenblatt and works on the M3 muscarinic receptor on the iris sphincter
Shader 1973). In the 1970s, atropine was recognized as muscle. The effect is almost immediate and it extremely
having the ability to reverse the effects of the cholinergic crisis powerful, lasting for 7 to 10 days depending on the
as it competes with muscarinic agonists and administered dose. This is due to the ease by which it is
acetylcholinesterase inhibitors at both central and peripheral absorbed into the body, showing a systematic absorption of up
muscarinic receptors. This activity was extremely beneficial to 65% in some cases (Howland 2011).
for military personnel, as it could mitigate the cardiac effects
A review of the general effects of atropine was conducted some doctors who misused their access to the drug, but it is
using 250 laboratory mice. Each of the subjects was injected still an important component in opthamalic therapies.
with 10μg of atropine and the resulting behaviors were then
observed. The authors noted that there was an increase in
respiration, a relaxing of the tail and the ears flattened against Clinical Studies
the head. Increased sensitivity to touch and sound was also The most common symptoms of A. belladonna poisoning are
noted, though the animals were fatigued for 2-3 hours after tachycardia and mydriasis, as indicated by the anticholinergic
the injection. After 24 hours, all of the symptoms had ceased effects of the drug. Other observed symptoms include increase
(Haley and McCormick 1957). This study was conducted as a in body temperature, flushing of the face, repressed salivation,
general survey of the effects of atropine in order to potentially bizarre mental state described as manic and paralysis of the
expound upon previous findings and perhaps better detrusor muscle of the bladder, resulting in urine retention
understand the mechanism of action. The results of this study (Lee 2007).
have been used to further investigate the mechanisms of
action behind the atropine-induced behavioral changes. Most studies of the effects of A. belladonna on humans come
from toxicology reports wherein the plant was accidentally
Hyoscine has an anesthetic effect and unlike atropine, it does ingested and the symptoms were severe enough to warrant
not have negative effects on the electrical activity of the brain. medical attention. The amount ingested from eating the
This was used to calm patients with mental illnesses and it berries, which are sometime mistaken for blackberries, was
was later found useful in the treatment of major depressive not enough to kill any of the 23 children in the reported cases.
disorder and anxiety disorders. These were observed in mice Common symptoms of belladonna intoxication include
initially as a having the ability to increase “engagement” and meaningless speech, tachycardia, mydriasis, and flushing. In
awareness of seemingly disinterested mice. Animal studies some cases the anticholinergic effects were so severe that
such as these have been effective in the past in determining physostigmine had to be administered to restore homeostasis
which drugs may act on the receptors of neurotransmitters in (Çaksen et al. 2003).
such a way as to regulate mood and behavior. Hyoscine is
currently undergoing clinical trials in humans with promising Scopolamine was administered transdermally to 16 patients
results (Katz and Hersh 1981, Drevets and Furey 2010). with nausea induced by calorization of the ear in a
randomized, double blind study. Nausea was reduced
The primary uses of atropine and scopolamine involve its significantly compared to the effects of the placebo and it was
potent effects as an anticholinergic. Its ability to work on also noted that introduction of scopolamine into the body 6 to
neurotransmitters has led to recent studies, which are looking 8 hours before exposure to a known motion sickness-
into its ability to alleviate the symptoms of depression as well inducing stimulus will prevent the onset of symptoms. Side
as inhibition of short-term memory recall (Aigner and Mishkin effects were negligible (Pyykkö et al. 1985).
1986, Drevets and Furey 2010). Its use in modern medicine
has been decreased due to the infamous cases of poisoning by One of the most important uses of atropine came about during
the 1930s and 40s when OP insecticides that were later
developed into nerve agents in chemical warfare due to their unique to the effects of this particular plant, but can
ability to inhibit acetylcholinesterase. Upon exposure to these sometimes be confused with other plant poisons in the
agents, one would experience increased levels of Solanaceae family, such as henbane (Hyoscyamus niger).
acetylcholine, as the enzyme to metabolize it was no longer Dilation of the eyes, as induced by atropine, results in
functioning due to inhibition. Atropine was then administered photophobia until the pupils return to their normal
due to its muscarinic antagonist effects and it worked circumference, which is usually no longer than a few hours.
effectively and in small enough doses to be safe (Howland Dryness of the skin, mouth and throat can occur due to
2011). decreased secretion from the mucous membranes.
Few clinical studies have been conducted using these drugs Restlessness, irritability or delirium can also occur, as
due to the well-known cases of poisoning and the generally atropine stimulates the central nervous system. Use of
infamy the plant has earned throughout its long, dark history. atropine for any condition in elderly patients is not
The most recent interest with these muscarinic antagonists recommended, as it can cause confusion and may cause brain
comes in the field of mental health, where a new theory is damage. Fatalities, though rare, can occur upon ingestion of
circulating that Alzheimer’s and dementia may be related to this drug due to depression of circulatory and respiratory
the cholinergic system. Scopolamine has been used to induce functions. This is more dangerous in children than adults, as
short-term memory inhibition in order to help elucidate the the fatal dose in children is 10mg versus 100mg (North and
mechanism by which dementia develops. (Aigner and Mishkin Kelly 1987). 90-130 mg is considered to be a toxic dose (Lee
1986). This new field has shown some promising results and 2007). Death is rare in the modern age because the symptoms
may potentially provide just retribution for atropine and are so well known and a cleansing of the stomach as well as
scopolamine and import and effective treatments in western use of artificial ventilation and diazepam can control
medicine. convulsions and reduce the risk of mortality. In most cases,
atropine is eliminated from the body in 72 to 96 hours
without lasting effects on the patient.
Contraindications When atropine was first isolated and brought to the medical
Allergic reactions to topical application of atropine have been market the medicinal knowledge about the drug’s effects was
described as causing swelling of the eyelids, followed by itchy incomplete. The plasters and eye drops could be incorrectly
and stinging sensations. In patients who are prone to prepared and as a result, many accidental deaths occurred
developing narrow angle glaucoma, application of the drug (Lee 2007, Figure 3). These treatments have since been
can lead to an acute attack, but this risk has been evaluated as banned from the market. Atropine can also be absorbed
minuscule. through the GI tract, so if an animal consumes the berries and
the meat from said animal is ingested by a human, it can cause
‘Hot as a hare, blind as a bat, dry as a bone, red as beet and unusual and sometimes toxic symptoms (Polson et al. 1983).
mad as a hen’ was an aphorism widely used to describe the
symptoms of belladonna poisoning. These symptoms are fairly One of the most notorious incidences of atropine poisoning
was the attempted murder of Mrs. Agutter by her husband in
affected eye (Repka et al. 2005). Atropine can be administered
via oral, inhalation and intramuscular routes and it can last for
24 hours within the body depending on the dose. When given
a 2mg dose via autoinjector, heart rate increased to maximal
level in 16 minutes. These autoinjectors are used as an
immediate response for terrorist attacks, especially when they
involve exposure to nerve gas. The atropine stops muscle
spasms and allows heart rate to return to normal (Howland
2011).
Atropa belladonna is commonly used to combat local
inflammation that, if untreated, can lead to sepsis and death. A
study on the various homeopathic remedies that used A.
Figure 3. Plaster containing atropine that used to be sold belladonna outlines the major drug used in homeopathic
in drug stores. Source: Lee 2007. treatment of infection. These include Belladonna—Injeel®,
Belladonna—Injeel Forte® and Belladonna Homaccord®.
1994. By the 1990s, atropine was only available for the use of Preparations containing A. belladonna constituents were
physicians and nurses, so it was relatively easy for him to effective in regulating what types of cells migrate during the
acquire as he worked in a hospital. Dr. Agutter served his wife inflammatory process. This activity helps lower the presence
a gin and tonic laced with atropine, as the quinine in the tonic of proteolytic enzymes, free radicals and chemical mediators
water disguised the bitter taste. Within five minutes she felt that may infer with the immune processes (Pedalino et al.
an agonizing pain in her throat and she started to experience 2004). Another medicinal use of atropine is to lower blood
hallucinations. It was later found that she had only consumed pressure via competition for the norepinephrine receptor,
50mg of atropine before the symptoms hit and she stopped thus mitigating the effects of hypertension (Abraham et al.
drinking. Due to her husband’s miscalculations, she survived 1981).
and he was found guilty of attempted murder and spent the Hyoscine is currently undergoing clinical trials as a treatment
next twelve years in prison (Lee 2007). for major depressive disorder. Its efficacy in relieving
symptoms of depression relative to the effect of placebo is
promising and the efficacy improves with continuous dosing.
Current Use in Allopathic and CAM Therapies The mechanism of action is currently unknown, but the late
Atropine sulfate drops are one the main therapies prescribed onset of the antidepressant effects (past the time of the
for the treatment of amblyopia, a condition of the eye that can anticholinergic effects) suggest that the drug may work on
lead to vision impairment. A clinical study evaluating the transcription of later onset genes as opposed to working on
efficacy of the atropine drops over a 6-month and two year the muscarinic receptors (Drevets and Furey 2010). This
period showing 49% improvement in the condition of the alkaloid has also been found to alleviate motion sickness
mitigation of mental illnesses and helped to enhance our
understanding of depression and its causes. Ultimately, the
powerful and potent biological activity of Atropa belladonna,
initially only recognized by its ability to poison people or
induce hallucinogenic stupors, is what makes it such a
powerful tool to the future of drug discovery. We have known
about some of the effects of belladonna for centuries, and we
are just now discovering some its new applications. The story
of deadly nightshade is an important tale, as it clearly
illustrates the mercurial temperament of western medicine
and how important it is to understand that we do not yet
know all there is to know about the effect of these compounds
Figure 4. Scopolamine patches used to prevent the onset on the human body.
of motion sickness. Source: pharmacydiscounter.com
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Physiological Optics 7:109-114.
Avena sativa L., Poaceae
Kylee Martens
Introduction
Avena sativa L., commonly known as oat, is a part of the
Poaceae family of grasses. A. sativa is also called avoine in
French, hafer in German, avena in Spanish, and javi or jai in
Hindi (Butt et al., 2008). A. sativa was first discovered in
ancient Egyptian ruins that date back 4,000 years and the first
documented medicinal use of oats was recorded by
Dioscorides in de Materia Medica. Though oat is believed to be
Asiatic in origin, it is now predominately grown in moist,
temperate regions in the United States, Canada, Russia, and
Europe. Oats rank sixth in world cereal production, following
wheat, maize, rice, barley and sorghum (Stevens et al., 2000).
Oats contain high nitrate content largely due to the presence
of phenolic compounds known as avenanthramides, which are
unique to oats. They also contain soluble dietary fiber, in the
form of β-glucans. Both avenanthramides and β-glucans are
responsible for most of the biological and pharmacological
activity of oats. Though oats were first used as food for
animals and scorned for their bland taste, they are now a
valued source of antioxidants and contain anti-inflammatory,
antipruritic, emollient, and anxiolytic properties. The study of Figure 1. Avena sativa, commonly known as oat.
the medicinal value of A. sativa is gaining popularity as more (Source: http://ddr.nal.usda.gov/bitstream/10113/
health benefits of this functional food are being discovered. 3559/1/IND43886716.pdf)
typically grows and matures rapidly during the spring and

summer. Oats are hardy crops that can generally withstand
Avena sativa L. grows in cool, moist regions throughout the the cold (Vavilov, 1992). There are three main cultivated
United States, Canada, Russia, and in the Mediterranean forms of oats that differ based on the number of
countries in Europe (Heywood, 1982). As mentioned above, A. chromosomes, including diploid strigosa-brevis, tetraploid
sativa is in the Poaceae family and is an annual grass that abyssinica, and hexaploid sativa-byzantina-nuda (Heywood,
and tillers can reach a height of up to two or more feet (Butt et
al., 2008). Each tiller terminates in a panicle that bears
spikelets (Figure 2), which contain one to two kernels, also
known as groats, which are small and spindle shaped. When
oat plants mature into a yellow color, the groats are ready to
be harvested and processed to the desired consistency. The
groats are heated and dehulled and can then be processed
further (Sides et al., 2001). Some of the varieties of processed
oats are rolled oats, flaked oats, or steel-cut oats, often heated
and eaten with water in the form of oatmeal. Colloidal
oatmeal, a recognized natural skin product, is prepared
through a fine-mill process, which produces a powder of oats
with concentrated starch and protein (Cerio et al., 2010).
Oats in general have a rather bland taste and a tendency to
spoil (Butt et al., 2008). This occurs because the grinding
process activates a lipolytic enzyme system in oats, which
causes rancid properties (Sides et al., 2001). Ideally, the
heating process stabilizes the oat from spoiling, but doesn’t
affect its antioxidant content. The typical nutty, “oaty” flavor
associated with A. sativa often presents itself after the oats
have been heated.
Oats use self-pollination, in which pollen grains settle on the
Figure 2. Spikelets of varieties of oats, which contain the stigma of the same floret (Thapa, 2007). Pollen advance
oat groat. (Source: occurs from the uppermost floret towards the basal spikelets
http://books.google.com/books?hl=en&lr=&id=h7coAAAAYAAJ&oi in about 10 to 11 days (Rajala & Peltonen-Sainio, 2011).
=fnd&pg=PA1&dq=history+of+oat&ots=4rjyPduEf1&sig=D1i10Ut1 Pollen is most often distributed by wind, but oats also benefit
F1VuVPqJNnPbsM7kilg#v=onepage&q=history%20of%20oat&f=fal from insect pollination (Thapa, 2007).
se)
Traditional Uses
1982). The hexaploid form is the most common type of
subspecies. Use as fodder
A. sativa (Figure 1) consists of leaves and up to thirty tillers, The origins of Avena sativa L. are mostly unclear, but this
or lateral shoots, projecting from each stem. The main stem species is believed to have originated in Asia and may have
spread throughout Europe with barley and wheat and been ancient Greeks and Romans. Medical texts written by Pliny
mistaken as a weed (Vavilov, 1992). Avena most likely comes suggest the topical application of oatmeal for the treatment of
from the Latin word, Aveo, which means to desire (Coffman, a variety of dermatologic conditions (Sur et al., 2008). The
1977). Before oat was desired as a food source for humans, it topical application of oats was used in facial masks and baths
was first used as fodder for animals in central Europe and to relieve itching and irritation, as well as eczema (Aburjai &
west Asia (Pieroni, 2009). Oats are not indigenous to North Natsheh, 2003). Ayurvedic practitioners also used a tincture of
America, but were instead introduced by the Spanish to the oats to cure the opium addiction, and oats were also reputed
southern part of North America in the 16th century as food for to reduce nicotine cravings (Lewis & Elvin-Lewis, 2003). Oats
their horses (Coffman, 1977). The first oats introduced in were most likely selected for this use because of their sedative
northern North America were planted by English colonists in properties and ability to act as a depressant on the central
Jamestown in the early 1600s, primarily as fodder. nervous system. A. sativa has also traditionally been used by
the ancient Greeks and Romans to treat nervous anxiety,
stress, and excitation as well as to promote mental health and
Use as food cognitive function (Abascal & Yarnell, 2004).
A. sativa eventually evolved into a food source for people, The ancient traditional uses of A. sativa for skin disorders
mainly in Ireland and Scotland beginning in the sixteenth have largely remained the same, and much of the knowledge
century. English author Samuel Johnson defined oats as “eaten of the ethnomedicinal uses of oats have come from ancient
by people in Scotland but fit only for horses in England” to medical texts like de Materia Medica. While whole or rolled
which James Boswell responded, “that’s why England has such oats were traditionally used in baths for their soothing
good horses and Scotland has such fine men” (Maunsell, properties, oats are used today in the form of finely ground
2011). Due to their bland taste, oats were not highly reputed colloidal oatmeal (Kurtz & Wallo, 2007). Colloidal oatmeal is
and mainly eaten only in Scotland and Ireland. Oats were even more effective than whole or rolled oats because it is more
thought to be a diseased form of wheat. Today, oats have easily dispersed in bath water, and thereby applied more
evolved from a food for animals to a desired and important thoroughly.
food for humans throughout the world. Processed oats are
now found in many different kinds of foods including oatmeal,
different varieties of cereal and granola, breads, and oat flour. Other uses
Oats are often combined with other food condiments to
The Spanish settlers in the 16th century combined A. sativa
enhance their bland taste. with other materials to make adobe brick buildings (Coffman,
1977). Oats have not only been used as fodder, but also
traditionally used as bedding for animals. Oats also were
Traditional ethnomedicinal uses
distilled for the production of alcohol, which is still a method
Not only were oats used for fodder and for food, but they also used today (Pereira, 1855).
have a long history of use for skin treatment, especially by the
Chemistry and Pharmacology Major Compounds Percent Composition in A.
sativa
Avena sativa contains about 65-85% starch and soluble
Starch 65-85%
polysaccharides, 15-20% proteins, 3-11% lipids, and 5% fiber
Proteins 15-20%
(Table 1) (Sur et al., 2008). Polyphenols, saponin glycosides, • Avenin
flavonoids, and vitamin E represent the remaining compounds • Albumen
found in oats (Heinrich, 2004). The major medicinal chemical
Lipids 3-11%
components of A. sativa are discussed below.
Fiber
• β-glucan 5%
β-glucans Polyphenols
• Avenanthramides A, B, C 0.03%
The dietary fiber in oats mainly consists of the compound β- • Vanillin acid
glucan (Figure 3). β-glucan is a linear-nonbranched • Sinapic acid
polysaccharide with high viscosity, which is responsible for its • Ferulic acid
exceptional nutritional value. Its high viscosity contributes to • Caffeic acid
many of oat’s medicinal properties, including its low glycemic Flavonoids 0.05%
response and its emollient properties. Oat groats contain • Apigenin
about 2.3 to 8.5% β-glucan content, mainly present in the • Luteolin
outer layers of the groat (Butt et al., 2008). • Tricin
Table 1. Major chemical compounds found in A. sativa.
(Source: Sur et al., 2008)
Phenolic Compounds
Oats contain many different forms of phenolic compounds,
such vanillin, sinapic, ferulic, and caffeic acids (Bratt et al.,
2003). Perhaps the most important phenolic components
unique to oats and responsible for their flavor are the low
molecular weight, soluble polyphenolic compounds known as
avenanthramides (Meydani, 2009). Oats contain over twenty
avenanthramides produced by the oat plant in response to Figure 3. Structure of β-glucan, main component of
pathogens. They are present in oats at about 300 parts per soluble fiber in A. sativa
million, or 0.03%, and are available in three major forms: A, B, (Source:
and C (Sur, et al., 2008). http://www.oatsandhealth.org/index.php?option=com_content&vi
ew=article&i d=14&Itemid=38)
Flavonoids avenanthramides appear to be the most medicinally
Three major flavonoids have been identified in oats, apigenin, beneficial, present in highest amounts in the outer layers of
luteolin, and tricin, which also are responsible for A. sativa’s oats.
antioxidant properties and its resistance to the generation of
reactive oxidative species (Cai et al., 2012). Though
An in vitro study using two different tests to determine
avenanthramides have been shown to have greater
antioxidant activity, β-carotene bleaching and DPPH assay,
antioxidant activity than flavonoids, flavonoids are still an
confirmed that avenanthramides have antioxidant properties
important medicinal component to oats.
(Peterson et al., 2002). In vivo, the antioxidant activity of
avenanthramides was also analyzed by feeding rats an
Biological Activity avenanthramide-enriched diet of 0.1g/kg for 50 days (Li Ji et
al., 2003). The results of this study concluded that the rats that
Results of in vitro and in vivo studies have demonstrated that were fed this diet had decreased reductive-oxidative species
Avena sativa has antioxidant, anti-inflammatory, antipruritic, (ROS). Specifically, it was found that avenanthramides
emollient, and anxiolytic properties. increased the level of superoxide dismutase (SOD) and
glutathione peroxidase (GPX). Both SOD and GPX are tissue
antioxidant enzyme systems.
Antioxidant
The antioxidant activity of A. sativa was studied by analyzing
the concentrations of phenolic compounds of oat fractions in Anti-inflammatory and anti-irritant
vitro. The total phenolic content of the pearling fractions, Avenanthramides have also been shown to have anti-
which contain a greater percentage of the outer layers of the inflammatory properties. It was found in an in vitro study that
oat groat, was almost double the total phenolic content in avenanthramides inhibit NF-κB signaling in cells treated with
other oat fractions (Emmons et al., 1999). This suggests that these polyphenols (Sur et al., 2008). NF-κB is an important
the outer layers of the groat, as opposed to the inner content, regulator of expression of pro-inflammatory proteins. By
contain more phenolic compounds, which have been linked to inhibiting this signaling, avenanthramides inhibited the
increased antioxidant activity. Antioxidant activity was production of interleukin-8 and thus prevented inflammation
evaluated by β-carotene bleaching, which showed that the in cells.
cinnamic acids, like ferulic acid and caffeic acid, inhibit low-
density lipoprotein (LDL) oxidation (Emmons et al., 1999). The anti-irritant properties of oats have also been studied and
Avenanthramides have also been analyzed for their attributed to the effects of avenanthramides. Specifically,
antioxidant activity and have been found to have 10-30 times these phytochemicals have been shown to decrease the
the antioxidant activity of the other phenolic compounds ionophore-stimulated liberation of arachidonic acid and can
found in oats (Emmons et al., 1999). Though there are many inhibit prostaglandin biosynthesis (Sur et al., 2008). By
different kinds of phenolic compounds present in oats,
inhibiting these processes, oats can naturally relieve skin 2004). A recent in vivo study was performed on rats to access
irritation through this topical application of A. sativa. the effects of oats on behavioral responses in situations that
would produce anxiety (Schellekens et al., 2009). Rats given
oat extract showed friendly social behavior and less
Antipruritic aggressive behavior in agonistic interactions, supporting the
The antipruritic property of avenanthramides was also claim that oats provide anti-anxiety and calming effects. The
evaluated in an in vivo study in mice. Avenanthramide-treated oat extract showed inhibition of the neurotransmitter
mice scratched 40.7% less than the control mice when metabolizing enzyme monoaminoxidase B and of the cAMP
injected with pro-itch compound 48/80 (Sur et al., 2008). degrading phosphodiesterase 4. These enzymes play a role in
Because avenanthramides can inhibit the production of anxiety and depression, so this inhibition may account for the
interleukin-8, they can thereby inhibit the release of anxiolytic properties of A. sativa.
inflammatory cytokines shown to be elevated in pruritic skin
disorders. Avenanthramides may also inhibit histamine
signaling, which suggests another mechanism for the role of Clinical Studies
these compounds in the treatment of chicken pox and other Various clinical studies have been conducted to study the
pruritic skin diseases (Sur et al., 2008). medicinal benefits of A. sativa in the prevention and treatment
of heart disease, diabetes, skin disorders, gastrointestinal
disorders, and libido.
Emollient
In vitro studies on the effects of β-glucan on the skin have
concluded that this dietary soluble fiber is able to penetrate Heart Disease
the dermis layer of the skin. Pillai et al. concluded that β- Avena sativa has been linked to cholesterol-lowering effects,
glucans interact directly with macrophages to produce which reduce the chance for developing coronary heart
interleukin-1 (IL-1), which promotes the production of disease. In a study conducted to analyze this property of oats,
procollagen (2005). The conversion of procollagen to collagen it was shown that there was an 8.7% reduction in low-density
explains oat’s emollient properties, as well as its cosmetic uses lipoprotein (LDL) cholesterol levels in subjects who ate two
for the reduction of wrinkles in the skin. β-glucan’s high oat-bran muffins a day for a month (Gold & Davidson, 1988).
viscosity also contributes to oat’s emollient and moisturizing Another study demonstrated that there was a similar
properties. reduction of total and LDL cholesterol levels in patients with
an increased coronary heart disease risk (Berg et al., 2002).
Soluble fibers, like β-glucan, are able to bind to bile acids and
Anxiolytic Properties cholesterol, which increases bile acid excretion (Berg et al.,
Oats have also been proven to act as a mild sedative to 2002). This excretion increases lipid excretion and
alleviate anxiety, stress, and excitation (Abascal & Yarnell, upregulates the amount of hepatic cholesterol receptors,
significantly when they followed this diet, suggesting a strong
correlation between β-glucan and lowered blood pressure in
overweight patients. This correlation may be related to insulin
responses, which may have indirectly lowered blood pressure
in these patients, but additional research is necessary to
define the mechanism of lowered blood pressure in response
to the intake of A. sativa.
Hyperglycemia
Oats have been associated with the prevention of diabetes by
lowering blood-glucose levels, which prevents the
development of insulin insensitivity. Specifically, β-glucans in
oats have been studied for their blood-glucose-lowering
capabilities. In one study, blood-glucose levels of both healthy
and type 2 diabetic subjects were reduced after consuming oat
bran as compared to the blood-glucose levels of subjects in the
control group who received no oat products (Wood, 2006).
The primary factor responsible for oat’s low glycemic
Figure 4. Aveeno skin lotion contains 1% colloidal response and reduced blood glucose levels is β-glucan’s high
oatmeal viscosity.
(Source: http://www.aveeno.com/skincare/products/daily-
moisturizing-lotion)
Skin Disorders
which help to clear cholesterol from the blood. In 1997, the A. sativa has been used to treat eczema and repair UVA/UVB
FDA issued a statement that declared that diets low in damaged skin (Aburjai & Natsheh, 2003). Oats have even been
saturated fat and cholesterol that include soluble fiber from evaluated for their efficacy in the reduction of wrinkles. In one
whole oats may reduce the risk of developing heart disease study by Pillai et al., 27 subjects used gel formulations of β-
(Wood, 2006). This statement recognized the beneficial effects glucan twice daily for 8 weeks, applying the gel to the face
of soluble fiber from β-glucans in A. sativa in the prevention of (2005). A significant reduction of wrinkles was observed on
heart disease. There are also a few studies that support the the faces of the subjects, and it was also concluded that β-
blood-pressure lowering effect of β-glucans. Specifically, Maki glucan penetrates the dermis layer of the skin and is able to
et al. studied the effects of a β-glucan diet in obese patients stimulate the production of collagen.
(2007). The blood pressures of these patients dropped
Using the sodium lauryl sulfate irritation model, Vie et al. carcinoma cells (Malkki & Virtanen, 2001). This potential anti-
studied the anti-inflammatory effects of oat extract on the cancer effect is still being reviewed and researched.
upper arms 12 healthy subjects (2002). The oat extract was
able to significantly counteract the inflammation caused by
this irritation model, suggesting the use of oat products in the Libido and impotence
reduction of skin irritation and inflammation. The phrase, “sowing ones wild oats,” was coined in the 16th
Avenanthramides were shown to have these anti- century to describe destructive sexual liaisons. The
inflammatory and anti-irritant effects, which explains the use correlation between sex and oats has been widely marketed in
of oats in the treatment of dermatitis and eczema. the past few years, and oats have been suggested as a
treatment for male erectile dysfunction. However, a few
studies have confirmed its effectiveness in treating erectile
Celiac Disease
dysfunction and promoting libido (Moyad et al., 2004).
Celiac Disease is an autoimmune disease that generates Though oat is a well-known aphrodisiac, more research must
intolerance to gluten. Oats have been studied in patients with be conducted to determine its effectiveness in treating
Celiac disease to determine if they can be tolerated (Butt et al., impotence.
2008). Oats do not contain the intolerable protein gliadin that
is found in wheat, but instead contain the protein avenin. Oats
are safe to eat by those with Celiac disease, but they must be Contraindications
pure because often, processed oats contain some gluten from Avena sativa has no known contraindications, adverse effects,
other grains. Pure oats provide an alternative food source for or interactions (Abascal & Yarnell, 2004). It is generally
celiac patients who follow a gluten-free diet. regarded as safe (GRAS). Colloidal oatmeal is one of the few
natural products that has been recognized and approved by
the FDA in the treatment for dermatologic conditions (Cerio
Gastrointestinal Disorders and Colon Cancer et. al, 2010). In 1997, the FDA also recognized that oats rich in
Soluble dietary fiber in oats, found in the form of β-glucans, soluble fiber may reduce the risk of heart disease (Wood,
has also been shown to have numerous beneficial effects on 2006).
the gastrointestinal system. The high viscosity of β-glucans
have been shown to increase fecal wet-weight, and thereby
relieve constipation (Malkki & Virtanen, 2001). There may Current Use in Allopathic and CAM Therapies
also be a correlation between the soluble fiber in oats and the Avena sativa ranks sixth in world cereal production and has
prevention of colon cancer. This is mainly due to the gained much popularity since they were first used solely as
fermentation of the fiber in the intestine, which stimulates cell fodder. Not only are they eaten, but they are also widely used
proliferation in normal epithelium, but prevents the growth of for their emollient properties. Oats have long been used to
provide antipruritic relief, skin hydration and smoothness. In
signaling and play a similar role as the drug Tranilast, which
could also explain the antipruritic effects of avenanthramides
(Sur et al., 2008).
A. sativa is currently sold as a supplement and is marketed as
an aphrodisiac to improve sexual libido. There are few studies
that confirm these properties of oats, and these herbal
supplements have not yet been proven to be effective. Some
oat extract supplements also claim to improve nervous system
Figure 5. Structure of drug Tranilast compared to an health, though this claim also needs to be further studied.
avenanthramide, polyphenol compound unique to A.
sativa.
(Source: http://onlinelibrary.wiley.com/doi/10.1111/j.1753- Discussion
4887.2009.00256.x/full)
Avena sativa L. has evolved throughout the centuries, since it
was first used in ancient Egypt almost 4,000 years ago.
1945, colloidal oatmeal became available by finely grinding Because of its rich content of avenanthramides and β-glucans,
the oat and extracting the colloidal material (Kurtz & Wallo, oat is a rich source of antioxidants and it contains anti-
2007). Today, colloidal oatmeal is included in shampoos, bath inflammatory, anti-irritant, antipruritic, emollient, and
powders, and in moisturizing creams like Aveeno (Figure 4). anxiolytic properties. The traditional medicinal knowledge of
The use of oats in skin products for cosmetic purposes oats for the skin, discovered over 2,000 years ago by the
provides a cheaper and safer alternative to cosmetic ancient Greeks and Romans, is still valued today, and
procedures. In 2003, the FDA approved colloidal oatmeal as a continued research of oats has helped to discover both CAM
safe and effective skin protectant based on its moisturizing and biomedical treatments for heart disease, diabetes,
and anti-irritant properties (Aburjai & Natsheh, 2003). gastrointestinal ailments, and impotence. A. sativa provides a
Colloidal oatmeal is also commonly used to treat the itching natural prevention to many of the prevalent diseases that
and irritating symptoms of chicken pox, due to its soothing humans are succumbing to throughout the world. Oat is a
and antipruritic effects. It is also currently used to topically cheap and healthy plant that is easily accessible and can be
treat diseases like dermatitis and psoriasis (Cerio et. al, 2010). added to the diet with no known contraindications. For these
Currently in Japan, the synthetic drug Tranilast, with a reasons, the medicinal future of A. sativa appears promising as
structure similar to an avenanthramide, is used as an this plant gains more popularity as a healthful food source,
antihistamine (Meydani, 2009). Both avenathramides and and continued research leads to the discovery of more of the
Tranilast (Figure 5) were discovered to have anti- medicinal benefits of this plant.
proliferative effects on vascular smooth muscle cells, which
could explain the mechanism by which oats reduce the risk of
colon cancer. Avenanthramides may also inhibit histamine
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Heywood, V. H. (1982). Popular Encyclopedia of Plants. New York:
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coronary heart disease risk. A controlled randomized Kurtz, E. S. and W. Wallo (2007). "Colloidal oatmeal: history,
lifestyle intervention study." Ann Nutr Metab 47(6): 306- chemistry and clinical properties." J Drugs Dermatol 6(2):
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Bratt, K., K. Sunnerheim, et al. (2003). "Avenanthramides in Oats Lewis, W. H., and Elvin-Lewis, M. (2003). Medical Botany. Hoboken,
(Avena sativa L.) and Structure, Antioxidant Activity New Jersey: John Wiley & Sons, Inc.
Relationships." Journal of Agricultural and Food Chemistry Li Ji, L., D. Lay, et al. (2003). "Effects of avenanthramides on oxidant
51(3): 594-600. generation and antioxidant enzyme activity in exercised
Butt, M., M. Tahir-Nadeem, et al. (2008). "Oat: unique among the rats." Nutrition research 23(11): 1579-1590.
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Antioxidant Activities of Subfractions from Oats (Avena 786-795.
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507-513. bran and oat gum - A review." Lebensmittel-Wissenschaft
Cerio, R., M. Dohil, et al. (2010). "Mechanism of action and clinical Und-Technologie-Food Science and Technology 34(6): 337-
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Emmons, C. L., D. M. Peterson, et al. (1999). "Antioxidant capacity of of oats." Nutr Rev 67(12): 731-735.
oat (Avena sativa L.) extracts. 2. In vitro antioxidant activity Moyad, M. A., J. H. Barada, et al. (2004). "Prevention and treatment
and contents of phenolic and tocol antioxidants." Journal of of erectile
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Pereira, J. and F. B. Kilmer (1855). The elements of materia Medica Stevens, E., K. Armstrong, et al. (2004). "Fodder oats: an overview."
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exhibit antioxidant activities in vitro." Food Chemistry 79(4): Sur, R., A. Nigam, et al. (2008). "Avenanthramides, polyphenols from
473-478. oats, exhibit antiinflammatory and anti-itch activity." Arch
Dermatol Res 300(10): 569-574.
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traditional knowledge of gastronomic and medicinal plants Thapa, R. (2007). "Honeybees and other insect pollinators of
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from wild green oat improves rat behaviour." Phytotherapy
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Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton, Malpighiaceae
David Nardo
Introduction
The term ayahuasca refers to a hallucinogenic brew used in
many of the healing practices and religious rituals of the
natives of the Amazon Basin region. The word stems from
Quechua and means “vine of the souls” (aya = spirit or ghost,
huasca = vine or rope). The hallucinogenic brew is composed
of a myriad of plants and varies in recipe from person to
person, the only constant being the use of Banisteriopsis caapi.
B. caapi is known colloquially by many names, among them
are ayahuasca, yaje (also yage), caapi, and huasca (Dobkin de
Rios, 1971; Rivier & Lindgren, 1972). Banisteriopsis caapi
(Figure 1), of the Malpighiaceae family, is a vine that has been
the source of several political arguments over the last few
decades as it has made its way from the heart of the Amazon
into ‘civilized’ areas and has been exploited by thrill seekers
under the pretext of achieving a higher state of mind and a
more personal relationship with god. Figure 1. Botanical drawing of Banisteriosis caapi (Image
source: http://jornadasdamente.blogspot.com/p/ayahuasca.html)
Although little is known about the origins of its use, the role of
the plant in indigenous cultures dates back to ancient times. and religious practices of the native, including the
There is an abundant body of archeological evidence affirming consumption of ayahuasca. It is also because of these groups
its use as early as 1500, although much of this archeological that the plants used to concoct ayahuasca have made it into
evidence seems to attest more to the use of other pants, like mainstream culture. Despite the cultural roots of the beverage,
tobacco and coca, rather than ayahuasca (Dennis J, 2004). however, it seems likely that the use of ayahuasca will fade
Knowledge of the plant and its use have been passed down from society, namely because of people who use the cover of
through generations, from shaman to shaman, and continues religion to partake in the use of ayahuasca. As more and more
to take part in many of the practices today. Non-natives that people join religious communities, like the Santo Daime, for
also use the brew in their religious practices are the UDV, the sole purpose of usingthe drug, the public opinion will over
Barquinia and Santo Daime sects in Brazil. These, although not time become worse and most likely, the plants that are used in
part of native tribes, have partaken in many of the customs making ayahuasca will be banned from every country.
Figure 2. B. caapi vine. (Image source: Figure 3. Young leaves of B. caapi. (Image source:
http://interactivetimeline.com/824/timeline-of-entheogen- http://en.wikipedia.org/wiki/File:Caapi.jpg)
use/57.php?w=580)
as it reaches maturity, the vine becomes long and woody and
Botanical Description branches significantly. The woody stems of the vine can reach
Banisteriopsis caapi (Figure 2) is endemic to the entire several inches in diameter, giving the appearance of thin trees
Amazon basin area and can be found anywhere from Brazil, to or tree branches. In adult vines, the leaves are green and
Peru, to Ecuador (Tupper, 2008). The plant grows naturally in appear only on the smaller branches. The leaves have an
the moist climate of South America but can also be cultivated oblong shape that points at the ends and can reach about 7
through the cuttings: the cuttings are allowed to sit in water inches in length. On the more distal branches grow the
until they develop roots, at which point they can be inflorescence holding the flowers, which are white or pale
transplanted to soil (Luna, 1984). It should be noted, however, pink and reach about a half inch in length (Figure 4).
that most of the plants used in making the ayahuasca brew are Polinators include bees and other forest insects that help
taken from the wild and not cultivated (De Alvarez De Toledo, carry pollen (Dennis J, 2004; Rätsch, 2005). The seeds, due to
1960; Dobkin de Rios, 1971; Flores & Lewis, 1978; Kjellgren, their “helicopter shape” (see Figure 5) are able to travel great
Eriksson, & Norlander, 2009). distances being carried by the wind.
The ayahuasca plant takes the shape of a large vine and grows With pertinence to the plant’s use in making the ayahuasca
only in moist tropical climates. In its early stages, the plant brew it should be noted that two varieties that have been
stems are green and the leaves are small (Figure 3). However, distinguished, B. caapi var. caupari and var. tukonaka. The
latter of these two is the better known one, which has a
Figure 5. “Helicopter-shape” seeds of B. caapi. (Image source:
http://www.shamanic-extracts.com/xcart/shamanic-
products/banisteriopsis-caapi-seeds.html)
(Dobkin de Rios, 1971; Flores & Lewis, 1978; Kjellgren et al.,

2009; Luna, 1984; Reichel-Dolmatoff, 1987). The plant is used
for spiritual, rather than physical healing. Although it does not
Figure 4. Flowers of B. caapi. (Image source: produce physical healing, B. caapi is believed to confer a sense
http://upload.wikimedia.org/wikipedia/commons/f/f6/Banisteriopis-
caapi-flowers-lg.jpg)
of completeness and a connection with the spiritual. It is used
by shamans as a guide when they are trying to find answers to
problems, and it is used by laymen in trying to resolve
smooth stem. The former, said to be more potent, has knotty conflicts.
stems (Gates, 1982; Kjellgren et al., 2009; Rätsch, 2005). Aside
from the differences in stem shapes and in chemical In preparing the ayahuasca brew, the stems, bark and leaves
concentrations, there seem to be no other notable differences of the vine can be employed, although the stems are used in
in the varieties. most cases (Figures 6 and 7) (De Alvarez De Toledo, 1960).
The stems of the plant are taken and crushed and placed in a
vessel and other plants, such as P. viridis. The vessel is the
Traditional uses filled with water and the mixture is boiled for at least one
hour, after which the brew can be strained and allowed to cool
Although the plant leaves are sometimes smoked, caapi is (Rivier & Lindgren, 1972).
most commonly consumed in a brew. The shamans believe
that, while other plants are responsible for visions, it is B. On her treatise of the plant, Dr. de Alvarez de Toledo mentions
caapi that allows them to connect to the spirit world and to that the plant is used by Peruvian natives ‘when a person is in
escape their corporeal forms. They consider the plant to be a love and the family knows that the other person is bad for
connector to the realm of the spirits where they can them and they take them to a healer’. It is believed that the
communicate with the dead, or with the spirits of the forest, plant can help a person find out another person who has
from whom they can derive knowledge on healing, etc wronged you and can also work to make you confess to
Figure 7. Preparation of Ayahuasca. (Image source:
http://fbgamestipsandtricks.com/wp-includes/Text/ayawaska-
buy)
rather she perceived but mild pseudohalucinations. Finally,

Figure 6. Ayahuasca vine. (Image source: she adds that the natives of the High Amazon use the plant in
http://upload.wikimedia.org/wikipedia/commons/5/51/Banisteriopsis-
the treatment of mental illnesses, although she was unable,
caapi-vine2.jpg)
herself, to presence any of these (De Alvarez De Toledo, 1960).
wrongdoing. The natives also mentioned that, while under the

influence of ayahuasca, a healer can also make a person Chemistry (pharmacology and toxicology)
commit crimes. Upon taking the beverage, the first symptoms
Despite what one might assume, none of the chemicals in B.
felt are usually nausea and vomiting. Once these started, it was
caapi are responsible for causing hallucinations in humans.
only necessary to open one’s eyes and see, by focusing the
Instead, B. caapi contains high amounts of β-carboline MAOIs
mind, what it was that one wanted to see, whether it was
(uses discussed later), namely banisteriopside A and B,
those who wished us ill, or a dead person’s spirit. The overall
harmine, tetrahydroharmine, harmaline, harmol and
experience described by de Alvarez de Toledo, however, is
harmamol (also called h-carbolines) (Riba et al., 2003). The
extremely disappointing since, according to her, the
stems of the plant contain up to .83 percent of these alkaloids,
experience was not at all what the natives described and
Plant Part Yield,a Compounds Quantified (Content, %)
% 1 2 3 4 5 6 7 8 9
Fresh leaves 0.49 0.002 0.0004 0.0004 0.000 0.004 0.0001 0.002 0.021 0.002
Fresh leavesb 5.28 0.072 0.015 0.011 0.003 0.114 0.002 0.042 0.333 0.090
Dried leaves 10.06 0.166 0.027 0.005 0.005 0.101 0.004 0.031 0.070 0.030
Fresh young stem 0.85 0.009 0.002 0.0004 0.0003 0.005 0.0003 0.001 0.002 0.002
Fresh young stemb 11.70 0.129 0.032 0.007 0.005 0.055 0.005 0.020 0.070 0.070
Dried matured stem 12.74 0.270 0.572 0.004 0.003 0.148 0.042 0.233 0.166 0.624
Dried matured stemb 9.27 0.075 0.046 0.002 0.003 0.030 0.005 0.007 0.195 0.185
Fresh bark of matured stem 2.16 0.085 0.198 0.005 0.004 0.012 0.005 0.089 0.151 0.093
Dried bark of matured stem 14.29 0.314 0.809 0.019 0.014 0.041 0.017 0.280 0.672 0.486
Fresh debarked young stem 2.67 0.087 0.058 0.001 0.002 0.107 0.015 0.063 0.112 0.096
Dried debarked young stem 9.76 0.267 0.188 0.007 0.002 0.340 0.058 0.226 0.527 0.703
Fresh leaves 0.60 0.005 0.001 0.001 0.0002 0.010 ---- 0.003 0.014 0.005
Fresh young stem 0.80 0.005 0.002 0.002 0.001 0.006 ---- 0.002 0.011 0.002
Fresh bark of large branchd 3.0 0.117 0.322 0.003 0.007 0.020 0.004 0.098 0.051 0.018
Dried bark of large branchd 18.1 0.711 1.926 0.018 0.040 0.103 0.029 0.672 0.434 0.163
Fresh debarked large branchd 5.2 0.120 0.279 0.002 0.010 0.089 0.018 0.177 0.062 0.036
Dried debarked large branchd 7.6 0.154 0.378 0.002 0.010 0.103 0.020 0.229 0.205 0.114
Fresh leaves 3.71 0.080 0.049 0.007 0.003 0.126 0.007 0.062 0.063 0.056
Fresh young stem 2.50 0.027 0.041 0.005 0.001 0.016 0.004 0.040 0.008 0.010
Dried young stem 8.20 0.158 0.125 0.003 0.007 0.157 0.030 0.103 0.098 0.148
Fresh leaves 2.17 0.018 0.007 0.004 0.002 0.039 ---- 0.011 0.254 0.156
Dried leaves 8.33 0.107 0.021 0.008 0.006 0.147 ---- 0.025 0.017 0.025
Fresh matured stem 2.9 0.062 0.103 0.002 0.003 0.050 0.010 0.075 0.078 0.099
Dried matured stem 9.56 0.210 0.382 0.004 0.008 0.207 0.046 0.350 0.057 0.115
Dried matured stem
15.43 0.150 0.074 0.002 0.006 0.103 0.017 0.043 0.046 0.031
(BCEx-1)
Dried matured stem
9.80 0.170 0.153 0.002 0.008 0.159 0.024 0.133 0.245 0.382
(BCEx-4)
aYield of the aqueous plant extract measured by weight.
bExtracted with water by automated ASE-200 extractor.
cPlants from this collection are 3 years old.
dLarge branches: diameter: 3-8 cm. NT = Not tested. NA = No antioxidant activity up to 31.25 μg/mL.
Table 1. Quantification of markers banistenoside A (1), banistenoside B (2), harmol (3), THNH (4), THH (5), harmaline (6),
harmine (7), epicatechin (8) and procyanidin B2 (9) of various extracts of B. caapi. Adapted from:
http://ukpmc.ac.uk/articles/PMC2878139?table=T1/.
Biological activity
The procyanidins mentioned in the previous section,
epicatechin and procyanidin 2B, belong to the flavonoid class
of compounds. Flavonoids have the distinct ability that they
are able to rid the body of reactive oxygen species (ROS). ROS
are oxygen containing compounds that can be found in the
body as a response to pathogens, as a result of oxidative
phosphorylation, or simply due to intake in certain foods.
These compounds contain unpaired electrons with extremely
high levels of energy that cause them to react with nearby
molecules, resulting in damage to tissues and potentially
Figure 8. DMT, found in Ayahuasca brew (derived from causing cancer. Flavonoids, as do other antioxidants, interact
other species – not B. caapi). (Image source: with these ROSs and absorb the damage, thus preventing any
http://www.erowid.org/chemicals/dmt/dmt_chemistry.shtml) harm to the body. Because of the composition of these
compounds, they are able to deal with the stress created by
while the branches contain up to .37, the leaves up to .70 and ROS much better than say, DNA or cell phospholipids.
the roots contain up to 1.95 percent (Table 1) (Riba, Anderer, Drinking ayahuasca has also been linked with improved
Jane, Saletu, & Barbanoj, 2004; Riba & Barbanoj, 2005; Riba et immunity and several of the β-carbolines have shown
al., 2003; Rivier & Lindgren, 1972; Wang et al., 2010; effectiveness in getting rid of protozoal, bacterial and
Winkelman, 2005). Interestingly, in dried plant material, the helminthic pathogens (Dennis J, 2004).
concentration of these chemicals does not seem to diminish, For the making of the brew, however, it is the β-carboline
but rather increases, indicating that they are not lost due to MAOIs that prove useful. One key aspect of digestion is the
evaporation. ability to break down nitrogen containing compounds. One
In addition to the great variety and quantity of β-carboline class of nitrogen containing compounds are monoamines,
MAOIs found in B. caapi, there are also two compounds containing a single nitrogen atom. Via a process
proanthrocyanidins, epicatechin and procyanidin 2B, which called monoamine oxidation, spearheaded by molecules called
exhibit a great deal of antioxidant activity. There are also monoamine oxidases (MAOs), single-nitrogen containing
several other compounds in the plants that have yet to be molecules are broken down by the body. This results in the
classified, but exist in very small amounts (Wang et al., 2010). formation of a complex carbohydrate and an ammonia
It should be noted that several sources indicate that DMT molecule, which is then expelled along with other wastes. The
(discussed later) is present in B. caapi. According to all the β-carbolines found in B. caapi, such as harmaline, act as
literature cited here, this is not the case. While DMT (Figure monoamine oxidase inhibitors (MAOIs). By performing this
8) is present in the ayahuasca brew, it does not come from B. duty, MAOIs are able to prevent the breakdown of single-
caapi, but rather from other sources. nitrogen containing molecules (MB & PF, 2004).
One of the uses of MAOIs has been in the treatment of in the field. However, when taken orally, DMT is broken down
depression. Depression is caused by a low level of serotonin in and procures no reaction (de Araujo et al., 2011).
the brain. Serotonin is normally released from one neuron to
By combining B. caapi with other plants that contain DMT the
the next and is reabsorbed from the neuronal synapse. As a
stomach is unable to break down DMT and it can be absorbed
monoamine, however, serotonin is sometimes broken down
into the bloodstream and make its way to the brain. What
by MAO and the resulting drop in serotonin levels eventually
makes ayahuasca so interesting is that it provides such a finely
leads to depression. Later studies also found that in patients
balanced mixture of chemicals, coming from a people who
with Parkinson’s disease, who are also afflicted by low levels
haven’t the slightest knowledge of chemical. The ayahuasca
of serotonin, MAOIs have a significantly positive effect, which
brew exemplifies the complexity and the knowledge of the
has led to research on the use of MAOIs for this condition (MB
natives of South America (Morton, 1931; Riba et al., 2004;
& PF, 2004). MAOIs also affect the concentrations of
Riba et al., 2003; Rivier & Lindgren, 1972; Wang et al., 2010).
epinephrine and norepinephrine in the body. Like serotonin,
these two molecules are monoamines and can be up-regulated
by administering MAOIs. This can help regulate several Contraindications
conditions that are dependent of these neurotransmitters
(Dennis J, 2004). B. caapi alone seems to confer the MAOI effect in the brew.
When an extract of the vine is used alone, it produces mood-
Indeed the happy feeling of those who take ayahuasca is likely enhancing and sedative properties, however, the β-carbolines
due to the effects of MAOIs in the brew (Dennis J, 2004). in the plant can induce nausea and vomiting (Dobkin de Rios,
However, what makes B. caapi so interesting is the interaction 1971; Luna, 1984; Rivier & Lindgren, 1972). Aside from the
that it has with another chemical present in the brew. The nauseating feelings caused by ayahuasca consumption, the
compound in the ayahuasca brew that produces hallucinations brew also seems to have other side effects. Among the more
N,N-Dimethyltryptamine (DMT), a monoamine that is not significant ones is an increase of diastolic pressure. According
actually found in B. caapi, but in Psychotria viridis, Diplopterys to several studies, however, this might actually be caused by
cabrerana and the other plants used in the ayahuasca brew. DMT and not by any of the chemicals found in B. caapi itself
Upon oral ingestion, a drug has to go through the stomach (Riba et al., 2003).
where it is broken down and eventually absorved in the Several studies seeking to test the potentially adverse effects
intestine, this is also true of DMT. However, upon reaching the of the plants showed no adverse side effects in pregnant
stomach DMT is broken down by monoamine oxidases and it women, or their children (dos Santos, 2010; Labate, 2011).
is unable to reach the brain, where it causes its hallucinogenic There is also no evidence to suggest that consumption of the
effects. DMT acts by interacting with serotonin and dopamine plant has negative effects on teenagers (Doering-Silveira et al.,
receptors in the brain, which lead to the euphoric and 2005). Frequent use of the plant seems to have a higher rate of
hallucinogenic properties of the chemical. When inhaled or illicit drug use, although ayahuasca itself does not seem to
injected, DMT can act on the body to induce these properties
and it abilities have been properly documented by researches
have any particularly harmful or addictive properties
(Fábregas et al., 2010).
In interesting case mentioned by McKenna is that the β-
carbolines in B. caapi can induce epileptic form seizures in rat
and in chickens homozygous for the epileptic gene. In
addition, rats fed with B. caapi extract showed decreased
fertility (Dennis J, 2004).
Current Uses in Allopathic and CAM Therapies

Most studies performed on B. caapi focus on trying to
determine whether the plant is safe to use, or not. Some
research has been done regarding its potential use in treating
substance abuse, alcoholism, serotonin deficiency, as well as
immunity enhancing, but these studies have been uncertain
and have ahd difficulty progressing, often because of legal
issues with the plant (Dennis J, 2004). Figure 9. Ayahuasca vision art. (Image source:
http://inyectamemas.blogspot.com/)
Today, B. caapi is still used by South American natives in
pretty much the same manner that it has always been used. In
addition, several groups throughout the world use the plant in are often seen in the paintings as well as other images that are
their so called religious practices. Among these are the UDV, imbedded in the psyche of the drinker (Shanon, 2010).
Barquinia and Santo Daime sects in Brazil, who use the plant
in religious rituals in trying to become enlightened, but have
Legal Status
been in part responsible for bringing the attention of
authorities to the plant (Dennis J, 2004). During the twentieth century, media and government
attention was brought to ayahuasca. This was due in part to
Another important aspect of ayahuasca use is the artistic
the previously mentioned religious groups, many of which
visions it produces. Several artists, like Peruvian native Pablo
have a negative light in the public’s eye. These religious
Amaringo and New Yorker Robert Venosa, have helped
groups, like Santo Daime are based on syncretic beliefs, taking
popularize ayahuasca through awing portrayals of their
from African, Native American and European Judeo-Christian
visions (Figure 9). These paintings range from simplistic
cultures. Their goal in using ayahuasca is to achieve a
geometric patterns to very complex symbolist imagery of the
connection with God. As these groups have made their way
spiritual ideas associated with ayahuasca. Vines and serpents
out of Brazil into Europe and the United States, they have
gained popularity among those who wish to “acheive made all of the ingredients in ayahuasca illegal to use or
enlightenment”. In addition to those who seek enlightenment, possess.
there are many who have learned to use ayahuasca as a
recreational drug. This has brought the plants used in the
brew, B. caapi included, to be questioned by politicians and Discussion
mass media (Kjellgren et al., 2009; Winkelman, 2005). Ayahuasca’s healing properties exist for those who believe in
In the United States and in most other countries, DMT is a them. The natives continue to use the plant for healing rituals
Schedule I drug. However, the right to use plants containing that focus on healing the soul and the mind. In those cases
DMT varies from country to country and there are no where they use the plant to search for lost causes to illnesses,
international laws prohibiting the growth and sale of these the healer, or the “patient”, interprets the hallucinations
plants by the public (Bullis, 2008; Dennis J, 2004; Winkelman, created by the plant to discover a cause or cure. Again this
2005). This means that those who wish to purchase B. caapi or requires a great deal of belief in the spiritual something that is
P. viridis can do so freely in most countries and they can do not found in many “civilized cultures.” As far as Western
with these plants as they desire. medicine is concerned, ayahuasca conveys no actual medicinal
purpose and like many other plants used by indigenous
In the Unites States, those who believe the plant is harmful
people, its useful for nothing other than sooth saying and
and those who use it in their spiritual practices are debating
spiritual psychobabble. What little evidence is reported on the
the use of plants containing DMT. The law currently allows for
potential use of the plant in treating diseases is unconvincing
the importation of many of the plants used to make ayahuasca
and the current legal issues regarding the plant make it barely
for the purpose of religious ceremonies. Brazil has had similar
worth the effort.
issues since the 1980s; they have concluded that so long as the
plant is being used for religious purposes, then the While the Native Americans who use ayahuasca do so in order
consumption of the plants is allowed. However, the Brazilian to heal, whether the mind or some physical state through
government bans the use of ayahuasca for recreational spiritual means, the newer groups that have spread ayahuasca
purposes. The legal status in the Netherlands is a bit more to the rest of the world propagate it as purely religious plant.
permissive, as people are allowed to buy the plants needed for In the religious ceremonies of groups like Santo Daime,
the brew as they please (Bullis, 2008; Dennis J, 2004). ayahuasca takes the brew to connect with God. This has led
thrill seekers to join these religions for the sheer purpose of
Conversely, in France and the UK the law forbids the sale and
“getting high”. What is worse, people have started to use it for
use of any plant containing DMT. Several public articles online
recreational purposes. Since the spread of Santo Daime, drug
explain how a French supreme court ruling in 2005 allowed
tourism has caused a negative light to be shed on ayahuasca
the use of ayahuasca plants so long as no extractions were
(Bullis, 2008).
performed on these to obtain pure DMT. This decision was
overturned four months later because of another case that In reality, the brew seems to convey little harm to those who
take it, yet many countries, like France, have chosen to ban the
plants used to make ayahuasca. Because of the exploitation of Research Part B: Developmental and Reproductive Toxicology,
the plant by tourists and by those who have close constant 89(6), 533-535. doi: 10.1002/bdrb.20272
with natives, as well as by natives themselves, who choose to Fábregas, J. M., González, D., Fondevila, S., Cutchet, M., Fernández, X.,
sell their knowledge for monetary gain, the banning of the Barbosa, P. C. R., . . . Bouso, J. C. (2010). Assessment of
ayahuasca plants from public opinion is imminent. Looking at addiction severity among ritual users of ayahuasca. Drug
the history of plants like cannabis, it seems inevitable that and Alcohol Dependence, 111(3), 257-261. doi:
ayahuasca will eventually become one of the many plants that 10.1016/j.drugalcdep.2010.03.024
are controlled by government regulations globally. Flores, F. A., & Lewis, W. H. (1978). Drinking the South American
Hallucinogenic Ayahuasca. Economic Botany, 32(2), 154-
156.
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Calendula officinalis Linn. Asteraceae
Paula Tyler
Introduction
The Common Marigold or Pot Marigold, is formally known as
Calendula officinalis Linn. of the Asteraceae family (formerly
Compositae) (Gilman & Howe, 1999). This small and
unassuming but brightly colored herb is also known as the
Bride of the Sun, Mejorana or flaminquillo in Spanish, fior
d’orgni in Italian, gauche-fer or souci des champs in French,
goldblume or Ringelblume in German, and the golden flower
of Mary (Basch et al., 2006). Native to Europe and parts of
Asia, C.officinalis has been cultivated since the 12th century for
medicinal use as an antiseptic, anti-inflammatory, cicatrizing
agent, and antibacterial (Khalid & da Silva). C.officinalis is also
used for culinary purposes, and for ethnoveterinary medicine.
It contains many types of secondary metabolites, including
terpenoids, flavonoids, carotenoids, volatile oils, quinones,
lipids, and coumarins. Many of these compounds have potent
Figure 1. Calendula officinalis. Note the characteristic
pharmacological and biological activities that support its
yellow-orange color and the ovate leaves. (Image Source:
history of ethnomedicinal use. http://pharmacology.georgetown.edu/urbanherbs/calendula.htm)
Botanical Description Traditional Uses

Calendula officinalis is a hardy cool season annual herb. Its Ethnomedical
habit is round, with single or double showy white, orange, or Bangladesh
yellow flowers (Figure 1). It grows 12-18 inches in height and From an ethnomedicinal survey of the Kavirajes of the Kushtia
width, and it is dense with simple ovate green leaves. It grows District of Bangladesh, Calendula officinalis is known as Ganda.
in full sun in acidic clay or sand and is known to attract The leaf juice is applied topically for ear aches, skin infections,
butterflies (Gilman & Howe, 1999). C. officinalis is indigenous and insect bites (Rahmatullah et al., 2009).
to Europe, and is cultivated in North America, Europe and the
Balkans, and India (Khan et al., 2011).
India is used to treat oedema of the leg and painful veins. A tea is
For medicinal uses in India, Calendula officinalis cream is often also prepared as a vermifuge (Jarić et al., 2007).
combined with other herbs to treat hemorrhoids, burns, and
abrasions. The florets in particular are made into ointments
United Kingdom
for wounds, herpes, ulcers, and other skin damage. Varicose
In the UK, psoriasis, leprosy, measles, and smallpox were
veins are treated with an infusion of the leaves. Other
treated with a decoction of Calendula officinalis flowers, while
ethnobotanical applications include the use of dried flowers
the juice could be used for jaundice, constipation, and
as an insect repellent (Khalid & da Silva).
menstrual flow suppression (Khalid & da Silva).
Italy
United States of America
In a phytotherapy study conducted in the Peninsula
Similar to the Portuguese ethnomedicinal use, Calendula
Sorrentina of southern Italy, Calendula officinalis was a
officinalis was used in the US for ulcers, liver problems,
constituent of mixtures used for the treatment of unspecified
wounds, and conjunctivitis in the 19th century (Khalid & da
varices. It is known locally as Calendula or sciure’e Silva).
Sant’antonio (De Feo et al., 1992). C.officinalis teas are also
used for eye infections, throat inflammation or pharyngitis,
gingivostomatitis, and inflammatory skin conditions (Khalid & Ethnobotanical
da Silva).
Culinary
Portugal As an alternative to saffron, C.officinalis is occasionally used in

Trás-os-Montes is a small area in Northern Portugal. Calendula India as a colorant and for flavoring. (Khalid & da Silva).
officinalis is known there as Calêndula, Mariana, or Maravilha.
The dry flowers are popularly used for problems with anxiety Veterinary
(nervousness and insomnia), the liver (jaundice), the eye In a survey of the Lower Mainland of Canada,
(inflammation), digestion (ulcers), the skin (callus and warts), Thompson/Okanagan Region and South Vancouver Island of
and incontinence (Neves et al., 2009). British Columbia, livestock farmers reported using the flower
oil of Calendula officinalis for wounds on their ruminants. The
Serbia farmers specified that it is not generally used for deep wounds
Calendula officinalis is locally known as Neven in the Kopaonik because the cicatrizing action of the herb can close the wound
Mountian area of central Serbia. An ointment of the plant is too quickly and seal infection inside. C.officinalis is also
used for foot fungus, wounds, burns, and frostbite. Flowers are combined with Plantago spp., Urtica dioica and Symphytum
combined with boiled fat and then filtered after 24 hours. This officinale for diarrhea and a tea is given orally for the relief of
a sore stomach (Lans et al., 2007).
Chemistry & Pharmacology
The flowers of Calendula officinalis contain various terpenoids,
volatile oils, 15 amino acids, and fatty acids. Inflorescences
contain carbohydrates, coumarins, and flavonoids. Terpenoids
are found in the roots, while the leaves and stems contain
carotenoids. Pollens and petals also contain carotenoids.
Quinones are found in the leaves, cellular chloroplasts, and
mitochondria. Seeds contain many neutral lipids in addition to
various fatty acids. Loliolide is a main bitter constituent. Other
compounds include calendulin, and n-paraffins (Muley et al.,
2009). Table 1 contains an adapted summary of the chemical
classes, names, and locations of these chemical compounds.
Flavonoids and carotenoids are powerful antioxidants, while
triterpenoids are efficacious anti-inflammatory agents. The
structures of some of these terpenoids are demonstrated in
Figure 2.
Figure 2. A summary of the structures of anti-
inflammatory triterpenoids in Calendula officinalis. (Image
Biological Activity Source: Neukirch et al., 2005)
In Vivo Studies
Spasmolytic and Spasmogenic guinea-pig ileum. The mechanism may be an interference of
calcium release or influx.
The use of Calendula officinalis for gastrointestinal problems is
less documented than some other uses, but there are The dichloromethane extract contained more spasmolytic
spasmolytic and spasmogenic constituents in the flowers that constituents than the ethyl acetate or aqueous extracts.
could elucidate the plants effect on cramps and constipation. However, the aqueous extract had a dose-dependent
Fresh flowers were powdered and extracted in distilled water, spasmogenic effect on the guinea-pig ileum at 1-10 mg/mL
dichloromethane, and ethyl acetate. The spasmolytic and but was partially blocked with pretreatment of atropine. This
spasmogenic activity was analyzed in 2 cm long segments of suggests that the spasmogenic mechanism as potentially
rabbit jejunum or guinea pig ileum, respectively. As a similar to acetylcholine, which is important for regulation of
spasmolytic, C.officinalis inhibited the contraction of free Ca++ peristalsis. By acting as a calcium channel blocker or
induced jejunum contraction in a dose-dependent fashion. A cholinergic, C.officinalis is capable of either relaxant or
pretreatment dose of 0.3 mg/mL exhibited 80-90% inhibition stimulant actions (Bashir et al ., 2006).
against acetylcholine and histamine induced contraction in the
Chemical Compounds Plant Part Activities violaxanthins,
Class luteoxanthin,
1) Sitosterols, stigmasterols, antheraxanthin,
Terpenoids diol diesters, taraxasterol 1) Flowers Antioedematous mutatoxanthins, luteins,
monoesters, erythrodiol, 2) Roots Anti- cryptoxanthins, and β-
brien, ursadiol, faradiol inflammatory carotene
esters, arnidiol esters, alanine, arginine, aspartic acid,
calenduladiol esters, Amino Acids asparigine, valine, histidine, Flowers
oleanolic acid saponins, glutamic acid, leucine, lysine,
calendulosides, proline, serine, tyrosine,
calendulaglycosides, threonine, methionine, and
glucuronides, and phenylanlanine
cornulacic acid Polysaccharides and
2) Oleanolic acid glucosides Carbohydrat monosaccharides Inflorescence
Quercetin, isorhamnetin, es
Flavanoids isoquercitin, narcissin, Inflorescence Proteolytic 1) Neutral lipids:
calendoflaside, Enzyme Lipids phospholipids, glycolipids 1) seeds
calendoflavoside, Inhibition and Fatty acids: 2) flowers
calendoflavobioside, rutin, Antiviral conjugated trienic acid 3) seed oil
isoquercetirin, and dimorphecolic acid
neoheperididosides, and 2) Fatty acids: lauric,
isohamnetin and quercetin myristic, palmitic, stearic,
rutinosides oleic, and linoleic monols,
Scoplotetin, umbelliferone, sterol esters, 3-
Coumarins esculetin Inflorescence monoestersm and 3-
1) Plastoquinone, monoester diols
Quinones phylloquinone 1) Leaves 3) oxygenated fatty acid
2) α-tocepherol 2) Chloropl Loliolide
3) Ubiquinone, asts Other Calendulin Bitter
phylloquinone, α- 3) Mitocho n-paraffins constituents
tocepherol ndria Table 1: Summary of Phytochemical Constituents of Calendula
Monoterpenes and
Volatile Oil sesquiterpenes: α-thujene, α- Flowers Allergen officinalis L. (Asteraceae) and examples of known bioactivity
pinene, limonene, 1,8- cineol, (adapted from Muley et al., 2009).
geraniol,
Essential oil: α-cadinene, α-
cadinol, tmuurolol, lionene, Antidiabetic & Antihyperlipidaemic
and 1,8-cineol
1) neoxanthins, The search for natural products efficacious in the treatment of
Carotenoids violaxanthins, 1) Pollens Anti- diabetes mellitus is worth pursuing because synthetic and
luteoxanthins, and inflammatory
auroxanthin, favoxanthin, Petals Choleretic- semi-synthetic drug products can have undesirable side
luteins, cryptoxanthins, 2) Leaves Cholagogue effects. Chakraborthy et al. (2011) examined the ability of
lycopene, α-carotene, β- and Antioxidant
Calendula officinalis to affect the metabolism of glucose and
carotene Stems Increase Tumor
2) neoxanthins, Latency lipid peroxidation in rats with induced diabetes. The study
used an 8.7 % extract of the leaves in ethanol and water. responsible for the anti-inflammatory and choleretic-
Alloxan and glucose were administered intraperitoneally to cholagogue activity (Rusu et al., 2005).
induce diabetes in rats, and 36 rats with a resulting blood
glucose range of 200-270 mg/dL after two weeks were given Antioxidant
either 2 mL saline as a control, 25 mg/kg, 50 mg/kg, or 100
Oxidative stress, resulting from an excess of free radicals and
mg/kg of C.officinalis, or 6 U/kg of insulin orally for 42 days.
lack of antioxidant action can result in damage to lipids,
Blood glucose and urine sugar were measured at 2 weeks, 4 proteins, and DNA. The carotenoid and polyphenol content of
weeks, and 6 weeks. The response of blood glucose and urine
Calendula officinalis is considered high and indicative of
sugar to C.officinalis extract was determined to be dose
antioxidant activity, so Frankič et al. (2009) explored the
dependent. The 100 mg/kg dose actually restored the blood effectiveness of C.officinalis extract for protection against DNA
glucose/urine sugar to normal levels, while the 25 and 50
damage and lipid peroxidation in pigs. The extract was
mg/kg dose still significantly lowered these indicators. There
prepared from flower tops or petals in propylene glycol and
was an overall significant increase in haemoglobin and body experimental groups received either 3mL/day of petal extract
weight when given C.officinalis. The lipid levels in blood serum
or 3 mL/day of flower top extract in the feed. Oxidative DNA
were also lowered. The proposed mechanism of the extract is
damage was induced by high polyunsaturated fatty acids
the activation of increased insulin secretion from the
(PUFA) in the feed, and both C.officinalis extracts significantly
pancreas. Because the effects of the extract are so similar to decreased the amount of DNA damage. High PUFA content
that of administered insulin, the potential of C.officinalis for also raises the marker of lipid peroxidation in urine, but the
antidiabetic and antihyperlipidaemic use at 100 mg/kg body amount of C.officinalis extract was not sufficient enough to
weight (BW) should be explored further for human reduce the lipid peroxidation in this study. In summary, these
application (Chakraborthy et al., 2011). therapeutic amounts of C. officinalis are considered efficacious
enough in antioxidant activity for the protection of DNA, but
Hepatoprotective are not sufficient for inhibiting lipid peroxidation (Frankič et
Potential hepatoprotective properties of Calendula officinalis al., 2009).
were examined using induced hepatic toxicosis in rats. Carbon
tetrachloride (CCl4) produces the free radical CCl3, which
affects lipid peroxidation and enzyme activity. CCl4 was given Anticancer
to induce the toxicosis, and the animals were treated with an Calendula officinalis contains lutein, which is a potent
ethanol extract of powdered flowers every 24 hours for 7 days carotenoid antioxidant. High levels of lutein have previously
beginning 30 minutes after intoxication. C.officinalis showed a been shown to correlate with survival rates and the
positive effect by decreasing hepatocytolysis by 28.5% and expression of estrogen receptors in breast cancer cells. In
reducing enzyme and steatosis changes. The carotenoids, order to examine the potential of low dietary lutein as an
flavones, saponins, and phenylpropanoids are believed to be inhibitor of mammary cancer cells, a murine mammary tumor
cell culture was prepared and infused into female mice. After
the amount required to induce 65% tumor incidence was used to measure the size of the ear canal in both ears of each
determined, 30 mice were given a semi-synthetic diet with animal were removed and the difference in plug weight
0.002, 0.02, and 0.4% extract from C.officinalis and inoculated indicated the amount of swelling. Faradiol-3-myristic acid
with the tumor cells after two weeks. At 70 days post- ester and Faradiol-3-palmitic acid ester exhibited 50%
inoculation the solid tumors were excised and lipid oedema inhibition at 240 µg/cm2 and 65-66% at 480µg/cm2.
peroxidation activity was determined. Mice fed 0.02 and 0.4% On a molar basis, 21 µmol/cm2 of ᵠ- taraxasterol is needed to
lutein had a tumor incidence of only 20-37% compared to achieve the same effect. It was proposed that the limited
70% in non-supplemented mice, and final tumor incidence activity at higher doses may be due to the difficulty of
was greater at day 70 for the untreated mice. Mice fed 0.002% lipophilic compounds moving through the epidermis. It was
had a tumor latency of about 50 days, while the tumor latency concluded that Faradiol was as effective as Indomethacin and
was delayed by 15 days with other concentrations. Lipid more active than the esters or ᵠ- taraxasterol (Zitterl-Eglseer
peroxidation was not dose dependent on lutein. Though lutein et al., 1997).
from C.officinalis did not prevent tumor growth, it may
prevent the initial establishment of tumor cells as indicated by
the increased tumor latency. The proposed mechanism of Anti-inflammatory
action is the antioxidant activity of lutein by quenching singlet Reducing inflammation is perhaps the best known activity of
oxygen and possibly additional immunomodulation, cell-cell Calendual officinalis and most common ethnomedicinal
communication, and prostaglandin production (Park, Chew, & application, so Preethi et al (2009) studied this particular
Wong, 1998). property in a multi-pronged study. Similar to the
antioedematous activity, the combination of caratenoids,
flavanoids, and triterpenoids in C. officinalis was found to
Antioedemous mediate acute and chronic inflammation in mice by cytokine
Three of the most powerful compounds in Calendula officinalis and macrophage inhibition, and free radical scavenging.
include the tripterpenoid alcohols faradiol-3-myristic acid Flower tops were extracted with ethyl alcohol to a yield of 1.1
ester, faradiol-3-palmitic acid ester and ᵠ- taraxasterol. Their g/100 mL, dried, and dissolved in distilled water for
efficacy as antioedemic agents was investigated by Zitterl et al. experimental use, and 8 groups of 6 mice received an injection
(1997). The compounds were extracted from the powdered of carrageenan and Dextran in the right paw to model acute
flower heads with dichloromethane. The irritant, Croton oil, inflammation. The control groups orally received only
was applied to the right inner ear surface of mice and the left carageenan, distilled water, Dextran, or Diclofenac. The
ear was left untreated for comparison. Experimental mice experimental groups orally received either 250 or 500 mg/kg
received a mixture of Faradiol monoesters, Faradiol-3- BW of Calendula officinalis extract. Caliper measurements of
myristic acid ester, Faradiol-3-palmitic acid ester, ᵠ- the paw thickness were taken before and after injection and
taraxasterol, and Faradiol, or the control Indomethacin while every hour. Conversely, Formalin was used to model chronic
control groups only received the irritant. After 6 hours, plugs inflammation in 4 groups of 6 mice. These groups received no
treatment, 250 or 500 mg/kg BW of extract, or Diclofenac 1 Cutaneous Wound Healing
hour before an injection of Formalin and for 6 days afterward.
Calendula officinalis has long been used in topical applications
Calipers were used to measure the paw every day. The extract
for wound healing because of its anti-inflammatory,
significantly reduced acute and chronic edema with 50.6-
cicatrizing action, and anti-microbial properties. The effect of
65.9% and 62.3% inhibition, respectively.
a gel containing C. officinalis on collagen production and
The effect of Calendula officinalis on TNF-α, a tumor necrosis wound healing in rats was studied by Naeini et al. (2012). The
factor from macrophages, was also examined in this study. oily product was extracted from fresh flower tops with ethyl
Macrophages were induced by sodium caesinate in alcohol, dried, and a 5%, 7%, and 10% gel were created. The
experimental groups of mice. The mice were treated with the rats received a square 2x2 cm surgical skin incision under
extract alone at 100 or 250 mg/kg BW or with anesthesia, and the gel was applied daily for 14 days. Control
lipopolysaccharide (LPS) + extract at 100 or 250 mg/kg BW rats received no gel or a gel base placebo, and experimental
for 5 days. LPS was injected on the 5th day and after 6 hours rats received 5% gel, 7% gel, or 10% gel and they were
the macrophages were collected for the TNF-α activity observed daily. The wounds were investigated by biopsy at
assessment. Treatment with the extract resulted in minimal days 14, 21, and 45. At day 21, the collagen and
macrophage cytotoxicity and normal cell growth. hydroxyproline content were higher for the 7% and 10%
The extract’s effect on proinflammatory cytokines was groups, but on days 14 and 45 the 7% group was the highest.
determined by treatment of mice with LPS, or 50, 100, or 250 It was concluded from statistical evaluation that the 7% gel
mg/kg BW LPS and Calendula officinalis. The LPS was was more effective that the other concentrations because it
administered after 5 days, and the levels of cytokines were showed significant collagen synthesis. Furthermore, the
determined after 6 hours. The cytokinase level in response to C.officinalis gel was most effective at day 14 (Naeini et al.,
inflammation was also inhibited by C.officinalis. 2012).
Inflammation was also induced by LPS after 5 days of

receiving 100 or 250 mg/kg BW of extract to determine the In Vitro Studies
expression of the cyclooxygenase-2 gene. RNA was isolated
Antimicrobial& Antifungal
from the spleen, and cDNA was prepared by RT-PCR and
One aspect of Calendula officinalis wound healing action may
amplified. Band intensity of the Cox-2 gene was lower in
be the antimicrobial and antifungal properties of the plant.
C.officinalis treated animals, indicating expression inhibition.
These activities were studied by Efstratiou et al (2012). Petals
In summary, the proposed mechanism for the anti- from the flowers were isolated, dried, and extracted in
inflammatory action of the extract is the modulation of methanol or ethanol. Each extract was tested against Bacillus
cytokines and Cox-2 gene inhibition in addition to antioxidant subtilis, B. cereus, B. pumilis, Pseudomonas aeruginosa, three
action against activated macrophages (Preethi, Kuttan, & strains of Escherichia coli and ampicillin-resistant E.coli,
Kuttan, 2009). Staphylococcus aureus, Klebsiella aerogenes, Enterococcus
faecalis, two strains of Candida albicans, C. krusei, C. glabrata,
C. parapsilos, Aspergillus flavus, A. fumigates, A. niger, and extract, which also inhibited HIV-1 mediated cell fusion and
Exophiala dermatiditis. The extracts were dissolved to 300 delayed cell death up to 24 hours. The organic extract also
mg/mL in their respective solvents, and 15 µL were used to reduced HIV-1 reverse transcriptase activity dose-
soak paper discs. Bacterial controls were Ciprofloxacin and dependently. The mechanism is proposed to be some action of
solvents. 10 mg/mL extracts were used for the fungal test and the flavonoids blocking virus adsorption, potentially by
the controls were Fluconazole and the solvents. The interfering with binding sites on the membrane of the cell or
antimicrobial activity, indicated by growth inhibition, was virus (Kalvatchev, Walder, & Garzaro, 1997).
observed by disc diffusion. C.officinalis was comparable
against both Gram-positive and Gram-negative samples, and
methanol was generally more effective. However, S. aureus Inhibition of Proteolytic Enzymes
and E. faecalis were more susceptible to the ethanol extract. In addition to the anti-inflammatory triterpenoids,
Both methanol and ethanol extracts were comparable in carotenoids and antioxidants, Calendula officinalis contains
antifungal activity to Flucanazole (Efstratiou et al., 2012). the flavonoid quercetin, which can inhibit proteolytic enzymes
like matrix metalloproteinases (MMPs). MMPs are expressed
by fibroblasts and are implicated in periodontal disease. The
Immunomodulatory
efficacy of C.officinalis was tested against collagen degradation
It is possible that Calendula officinalis regulates inflammation and MMP activity from human gingival fibroblasts (HGF). The
by regulating the immune response on a cellular level. To test fibroblasts were incubated with either C.officinalis or
this hypothesis, Amirghofran et al (2000) prepared ethanol quercetin in ethanol or aqueous Doxycycline, and the assay
extracts of C.officinalis and other herbs. Human lymphocytes did not indicate statistically significant cytotoxicity. Collagen
and thymocytes were isolated and assayed with the extract. degradation was completely inhibited by C.officinalis, but
Proliferation was significantly inhibited by C.officinalis and dose-dependently inhibited by quercetin alone. In regards to
dose-dependent. The potential mechanism is through MMP activity, C.officinalis exhibited 86% and 98% inhibition
interaction with growth factors or cell surface molecules at 1.0% and 1.5% concentrations, and complete inhibition at
(Amirghofran, Azadbakht, & Karimi, 2000). 2.0% and 3.0% concentration. The extract containing
quercetin was more efficacious than quercetin alone,
suggesting that there are other active compounds acting on
Antiviral the proteolytic enzymes. In conclusion, 1-3% C.officinalis was
Calendula officinalis was investigated for antiviral activity by not cytotoxic to fibroblasts, and prevented collagen
Kalvatchev et al (1997). The dried flowers were extracted as degradation completely by mediation of MMPs (Saini et al.,
organic and aqueous stock solutions. The aqueous extract did 2012).
not show inhibition of HIV-1 replication in infected cells, but
the organic extract was an effective inhibitor at 10-30 µg/mL.
Again, the aqueous extract was less effective than the organic
Clinical Studies Radiation Dermatitis
Mouth Rinse Postoperative irradiation for breast cancer can often induce
The use of mouth rinse as a complement to daily brushing and dermatitis of varied severity. It is usually treated with topical
flossing for the prevention or elimination of plaque biofilm corticosteroids, Aloe vera gel, or Trolamine. A Phase III
could be instrumental to oral health, and the active randomized trial of a commercialized Calendula officinalis
components of some botanicals like Calendula officinalis have extract ointment manufactured by Boiron Ltd in comparison
been shown in vivo to exhibit antigingivitis and antimicrobial to Trolamine was conducted between 1999 and 2001 on
properties. One prepared mouth rinse containing 0.67% women aged 18-75 who were undergoing postoperative
melaleuca oil (Melaleuca alternifolia), 0.33% manuka oil radiotherapy for non-metastatic breast adenocarcinoma in
(Leptospermum scoparium), 1% Calendula officinalis flower France. This particular ointment was known to be well-
extract, 0.5% Camellia sinensis extract, and 12.8% ethanol in tolerated for the management of second and third- degree
water was subjected to a Phase II double blind randomized burns compared to a proteolytic ointment or petroleum jelly.
placebo-controlled study against 12.8% ethanol. Twice a day, C.officinalis was randomly assigned to 126 while the
participants rinsed with 15 mL of their assigned liquid for 30 remaining 128 were assigned Trolamine. The assigned
seconds. Each tooth was examined at baseline, 6 weeks, and ointment was applied topically twice a day or as needed after
12 weeks for Gingival and Plaque Index, and plaque samples the onset of radiotherapy. Once a week the acute dermal
were collected along with vitals and blood for monitoring. toxicity, pain, and reactions to the ointment of each patient
Genomic DNA from the plaque samples was used to determine were recorded. Patient treatment with C.officinalis was only
the abundance of Actinobacillus actinomycetemcomitans and interrupted once with no allergic reactions compared to 15
Taneralla forythensis. Two women reported adverse events interruptions and 4 allergic reactions with Trolamine. The
and withdrew from the trial, and others left the study for acute skin toxicity of grades 2-3 occurred in 41% of
unrelated reasons for a final total of 17 out of 20 original C.officinalis patients compared to 63% of Trolamine patients.
subjects. Statistical analysis did not show a significant Less pain and more overall satisfaction with erythema
reduction in average Plaque Index, Gingival Index, or prevention and pain was reported for the C.officinalis group
abundance of A. actinomycetemcomitans or T. forsythensis, but than the Trolamine group. However, C.officinalis was
this small scale study did support the safety of the product considered difficult to apply by 30% of patients. C.officinalis
and warranted further study of efficacy. Limitations cited ointment was significantly superior to Trolamine by statistical
were the aqueous nature of the rinse (due to solubility issues) analyses for the prevention of acute skin toxicity above grade
and the less than optimal concentrations of the ingredients. 2 as well as incidence of allergic reactions, treatment
However, great interest is shown in botanical agents like interruption, pain relief, and patient satisfaction. Based on the
C.officinalis for oral health applications and potential for results of this study, C.officinalis ointment can be proposed as
further trials. (Lauten et al., 2005). an alternative preventative treatment for irradiation induced
dermatitis after surgery for breast cancer (Pommier et al.,
2004).
Contraindications
Allergy & Topical/Cosmetic Use
Since Calendula officinalis is a member of the daisy family,
Asteraceae (Compositae), individuals with known allergies to
other members of this family should avoid the using this herb.
The Asteraceae family contains sesquiterpene lactones that
may trigger acute allergic reactions or delayed
hypersensitivity. This hypersensitivity may manifest as either
chronic or gradually progressive reactions. Barring known
allergy incidence, C. officinalis is generally recognized as safe
for culinary use and does not raise concern as a cosmetic Figure 3. Traumeel® offers a range of anti-inflammatory
ingredient (Reider et al., 2001). products containing Calendula officinalis extract as one of
the active ingredients. (Image source:
http://www.traumeel.us/)
Reproductive
There have been no reports of reproductive or developmental effects when administered with hypoglycemic drugs,
toxicity from Calendula officinalis itself. However, further antihyperlipidaemic drugs or herbs, or insulin (Basch et al.,
study may be warranted because similar compounds are 2006).
found in coriander oil, which one study found to decrease rat
litter size in high doses. (Reider et al., 2001) Additionally, in
vitro studies reported mild uterotonic effects and the safety of Current Use
use during pregnancy and lactation is unknown (Basch et al., In addition to the biological activities under current study,
2006). research is ongoing for the applications of Calendula officinalis
in allopathic medicine. The terpenoids responsible for anti-
inflammatory activity are of particular interest, and more
Additive Effects effective synthetic derivatives are in development. The
Some in vivo studies that administered high doses of Calendula addition of polar groups to ᵠ- taxarenes strengthened the anti-
officinalis resulted in sedative and hypotensive effects, so inflammatory action, and may serve as a springboard for
there may be reason for concern regarding additive effects further modification (Neukirch et al., 2005). Current use is
when used alongside sedative or antihypertensive agents. As most prevalent in complementary and alternative medicine as
implicated by the aforementioned antidiabetic study by there are many topical products available as tinctures, lotions
Chakraborthy et al. (2011), C. officinalis may have additive or creams, and also teas for internal use. Products like
Traumeel® for musculoskeletal injuries and Otikon Otic or References Cited
NHED eardrops for otitis media are compounded solutions
Amirghofran, Z., Azadbakht, M., & Karimi, M. H. (2000).
that contain C. officinalis. Traumeel® ointment contains
Evaluation of the immunomodulatory effects of five
450mg/100g C. officinalis and has undergone extensive
herbal plants. Journal of Ethnopharmacology, 72(1–2),
clinical trials (Figure 3). It is well tolerated and available as an
167-172. doi: http://dx.doi.org/10.1016/S0378-
ointment, tablet, or injection. It is a viable anti-inflammatory
8741(00)00234-8
and analgesic alternative to NSAIDs (Schneider, 2011).
Studies of Otikon Otic eardrops suggest that they are well Basch, E., Bent, S., Foppa, I., Haskmi, S., Kroll, D., Mele, M., . . .
tolerated and may be efficacious alternatives after further Yong, S. (2006). Marigold (Calendula officinalis L.): An
study (Basch et al., 2006). With such a wide range of biological Evidence-Based Systematic Review by the Natural
activity, the potential conventional medicinal uses of C. Standard Research Collaboration. Journal of Herbal
officinalis are still being explored. Pharmacotherapy, 6(3/4), 135-159. doi:
10.1300/J157v06n03-08
Bashir, S., Janbaz, K. H., Jabeen, Q., & Gilani, A. H. (2006).
Discussion
Studies on spasmogenic and spasmolytic activities of
It is little wonder that Calendula officinalis has such a long and Calendula officinalis flowers. Phytotherapy Research,
varied history of use. Its biological activity includes 20(10), 906-910. doi: 10.1002/ptr.1980
antimicrobial, antiviral, anti-inflammatory, antioedematous,
Chakraborthy, G., Arora, R., & Majee, C. (2011). ANTIDIABETIC
immunomodulatory, spasmolytic, spasmogenic, antidiabetic,
AND ANTIHYPERLIPIDAEMIC EFFECT OF HYDRO-
antihyperlipidaemic, antitumor, antioxidant, and
ALCOHOLIC EXTRACT OF CALENDULA OFFICINALIS.
hepatoprotective mechanisms that are just beginning to be
International Research Journal of Pharmacy, 2.
understood. These activities support its traditional use as a
wound healing agent, for treatment of liver problems, for De Feo, V., Aquino, R., Menghini, A., Ramundo, E., & Senatore, F.
relief of cramping and diarrhea, and as an analgesic. (1992). Traditional phytotherapy in the Peninsula
C.officinalis is generally well tolerated and popular in CAM Sorrentina, Campania, Southern Italy. Journal of
therapeutic remedies. It has potential for incorporation into Ethnopharmacology, 36(2), 113-125. doi:
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healing in particular. The future of research for this “golden Efstratiou, E., Hussain, A. I., Nigam, P. S., Moore, J. E., Ayub, M.
child” of an herb includes safety and long term toxicity studies, A., & Rao, J. R. (2012). Antimicrobial activity of
standardization of dosages for various treatments, isolation Calendula officinalis petal extracts against fungi, as well
and/or modification of specific compounds and combinations as Gram-negative and Gram-positive clinical pathogens.
for drug development, and further determination of Complementary Therapies in Clinical Practice, 18(3),
mechanisms of action. 173-176. doi:
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Frankič, T., Salobir, K., & Salobir, J. (2009). The comparison of Phytotherapy Research, 19(11), 951-957. doi:
in vivo antigenotoxic and antioxidative capacity of two 10.1002/ptr.1763
propylene glycol extracts of Calendula officinalis
Muley, B., Khadabadi, S., & Banarase, N. (2009). Phytochemical
(marigold) and vitamin E in young growing pigs.
constituents and pharmacological activities of
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Naeini, A., Miri, R., Shafiei, N., Tabandeh, M., Oryan, A., & Nazifi,
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Mijatović, M., Karadžić, B., . . . Pavlović, P. (2007). An officinalis gel on collagen and hydroxyproline content
ethnobotanical study on the usage of wild medicinal of skin in rats. Comparative Clinical Pathology, 21(3),
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Kalvatchev, Z., Walder, R., & Garzaro, D. (1997). Anti-HIV Activity of Three New Terpenoids Derived, by
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Lauten, J. D., Boyd, L., Hanson, M. B., Lillie, D., Gullion, C., &
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Camellia sinensis (L.) Kuntze, Theaceae
Nina Patel
Introduction are wilted in the sun, bruised a bit, and then finally fermented.
The scientific name for tea is Camellia sinensis, and it belongs However, if the wilted leaves are fermented, black tea is
to the Theaceae family ("Tropicos," 2012). It is one of the produced instead (Ferrara et al., 2001).
oldest drinks in the world, and only water surpasses it in Tea is composed of three main constituents: caffeine,
consumption (Chow & Hakim, 2011). Other common names of catechins, and theanine (Saberi, 2010). Tea also contains other
tea used by different cultures include thee, cha, chai, shai, and compounds, such as volatile oils, vitamins, and minerals. The
O cha (Saberi, 2010). Archaeological evidence suggests that active compounds in tea are the polyphenols, mainly
the origins of tea date back to China over 5,000 years ago, and epigallocatechin, gallic acid, and bioflavonoids. These
from there it diffused into India, Japan, Thailand, Korea, and catechins may help to fight various types of cancers, such as
Sri Lanka (Meltzer, Monk, & Tewari, 2009). Tea was native to skin, esophageal, stomach and colon cancer. Tea can also be
the ancient kingdoms of Shu, which was located in the “four used as a topical agent to help control bleeding that has
rivers” and the neighboring kingdom of Ba in China. The resulted from cuts and scrapes. C. sinensis can also be used to
Chinese book Chajin by Daoist Lu Yü, is the first book written relieve insect bites and help control blood sugar and insulin
that discusses tea, and it dates back to 780 CE (Steeped in levels (Ferrara et al., 2001). Overall, tea has many medicinal
history : the art of tea / Beatrice Hohenegger, editor ; with uses.
essays by Terese Tse Bartholomew ... [et al.], 2009). The
Apart from its medicinal uses, it is also a historically,
medicinal use of tea was also discussed in the ancient Chinese
economically, and culturally significant plant. For example,
pharmacopoeia “Ben Cao Gang Mo” (Lin, Tsai, Tsay, & Lin,
one of the reasons that the colonization of India occurred was
2003).
to control the tea trade (Steeped in history : the art of tea /
There are three main types of tea originating from the same Beatrice Hohenegger, editor ; with essays by Terese Tse
plant: green, oolong, and black (Ferrara, Montesano, & Bartholomew ... [et al.], 2009). C. sinensis is an important
Senatore, 2001) . Green tea is consumed mostly in China, botanical plant that still continues to have relevance 5,000
Japan, India, some North African and Middle Eastern countries years after it was first discovered.
whereas black tea is consumed mostly in Asian and Western
countries (Cooper, Morre, & Morre, 2005). Green tea is
prepared from fresh leaves and buds that are heated by pan Botanical Description
frying or steaming to inactivate the enzymes and stabilize the Camellia sinensis is grown in thirty countries (Cooper et al.,
monomeric catechins, and then these leaves are dried (Ferrara 2005). It is grown 1,000-7,000 feet above sea level, in
et al., 2001); (Hara, 2011). To produce oolong tea, fresh leaves temperatures between 50-85ºF, and in areas with annual
Tea can reach a height of 10-15 meters when grown in the
wild, and 0.6-1.5 meters when cultivated. The leaves are
green, short stalked, coriaceous, alternate, lanceolate, serrate
margin, glabrous or pubescent beneath, and vary in length
from 5-30 cm and are 4 cm in width. Mature tea leaves are
bright green, smooth, and leathery whereas the young tea
leaves are pubescent. The flowers are white fragrant and
range from 2.5-4 cm in diameter. The flowers either occur by
themselves, or they can occur in clusters of two or four. They
have stamens with yellow anthers, and they make brownish
red capsules. The fruit is a flattened, smooth, round trigonous
three celled capsule, and there are seeds the size of a small nut
in each fruit (Mahmood et al., 2010). The seeds ripen on the
plant, and then they germinate in damp sand pits. When the
seed shell opens, the seeds are planted in either nurseries or
Figure 1. Camellia sinensis. Source (Hamilton, 2010) in fields. Proper shading is crucial for tea bushes. The tea
plants are prevented from developing into trees by pruning
rainfall between 80 to 90 inches (Saberi, 2010). It is grown and hand-picking (Shalleck, 1972). A picture of the plant can
best in humid climates (Cooper et al., 2005). The ideal be seen in Figure 1. Tea is a self-sterile and cross-pollinating
geographical area for tea to be grown ranges from Java in the crop (Abrol & Abrol, 2012).
south to Japan in the east and the north and India to the west.
This area also includes Formosa, China, Sumatra and outer There are four varieties of plants: the Assam (Indian) plant;
neighboring countries. It is grown best on terraced hillsides the Chinese plant (Bohea); a relative of the Indian plant which
and open fields (Shalleck, 1972). It can be grown as a tree or a is grown in Ceylon, Java, and Sumatra; and a relative of the
shrub (Mahmood, Akhtar, & Khan, 2010). It is an evergreen, Chinese plant which is cultivated in Formosa and Japan
perennial plant (Mondal, Bhattacharya, Laxmikumaran, & (Saberi, 2010). These types are mainly distinguished by their
Singh Ahuja, 2004). leaves (Mondal et al., 2004). Bohea is a small and stunted bush
that is compactly branched containing small stiff leaves and
For tea growth, warm weather with an even distribution of purple leaf buds (Saberi, 2010). The relative of Bohea is
rainfall throughout growing season is needed. The leaves will similar in appearance, but it is larger and contains bigger
grow more if the weather is wetter and the rainy season is leaves. Assam tea can reach up to a tree height of thirty feet
longer. The colder the weather, the slower the growth of the when grown in its wild state. This Indian tea plant contains
tea bushes, which will result in fine tea with small supple, huge leaves and few flowers. The relative of Assam is similar,
leaves. However, frost will blacken the leaves thereby marring but it is composed of smaller, thicker, and more precisely
the tea (Shalleck, 1972). serrated flowers (Shalleck, 1972). The Chinese plant can live
for hundreds of years whereas the Assam variety can live for apothecaries and Daoist healers. These healers worked with
about 40 years (Saberi, 2010). chefs of noble houses to infuse tea into healthy recipes and
tasty dishes. It was a bitter herb that was used in cooking and
took on many forms: fresh leaves, pulp, pastes, and gels in
Traditional Uses season, dried loose leaves or “bricks” of compresses leaves,
Traditional Medicinal Applications and “wafers” and “cake” of dried paste (Steeped in history : the
art of tea / Beatrice Hohenegger, editor ; with essays by Terese
Tea has been used an ethnomedical remedy for centuries. For Tse Bartholomew ... [et al.], 2009)
example, in the Chinese book Kissa Yojoki (ca 1191), tea was
described as a medicine to help control bleeding, heal wounds, Many of these ancient uses still have relevance in modern
regulate blood sugar, help with digestion, and regulate body CAM applications as well as modern day traditional medicines.
temperature (Meltzer et al., 2009). During the Zhou dynasty in Powerful infusions of tea are used often for bathing the feet
China, tea was used as a stimulant to promote positive moods. and to treat fungoid infections. Tea (in the drinking form) can
Tea was consumed to calm and clear the mind, sharpen be used as cleanser for the face to help get rid of pimples and
mental acuity, and relax smooth muscles. It was also used as a skin rashes. In rural China, strong tea is used as a mild
diuretic, antitoxin, mild disinfectant, and as an efficacious disinfectant for new skin lacerations. Hair can become soft
rinse to soothe strained, tired eyes and to alleviate skin and glossy when washed with tea. It is also used for halitosis
ailments (Steeped in history : the art of tea / Beatrice in the leaf form by placing the leaves in the mouth. In North
Hohenegger, editor ; with essays by Terese Tse Bartholomew ... China, individuals rinse their mouths with green tea after
[et al.], 2009). The remedy used to treat many of these eating. Toothaches can be relieved by chewing tea leaves
discussed problems was drunk as a bitter medicinal drink. (Blofeld, 1985). Green tea is consumed between meals or after
This drink was prepared by infusing tea leaves in hot water. meals in Japan and Asian countries (Lee et al., 1997). In Japan,
Salt was often added (Saberi, 2010). When rinsed in the tea can be found in foods, such as kanten (tea jelly) and a
mouth, tea cleansed the palate and since it contains trace green tea ice cream called matcha. It is also found in O-
minerals like fluoride, it promoted dental health and aided chazuke, which is a rice dish (Saberi, 2010)
digestion (Steeped in history : the art of tea / Beatrice Oolong tea has hypocholesteromic properties that become
Hohenegger, editor ; with essays by Terese Tse Bartholomew ... active after a fatty meal, and this can help with hypertension
[et al.], 2009). In the ancient world, tea was thought to and arterial disease by being an anti-clot agent. Black tea has a
increase blood flow, act as an immunostimulant, speed up high content of tannins, which can help with diarrhea and
metabolism, help with anemia, fight the effects of summer headaches. Damp black tea bags can help with tired, red eyes
heat, and increase the number of years a person lived (Blofeld, as well and relieve itching and redness caused by insect bites
1985). (Ferrara et al., 2001). Many of the ancient day uses of tea still
For the Daoists, tea was thought to promote health and apply today.
increase life span. It was prescribed as a tonic and remedy by
Tea Drinking middle, and lower classes in Great Britain. Although today this
Around the world, many forms of drinking tea occur, and this tradition has declined, tearooms can be found across Great
is intricately tied into the cultures of many societies. In Central Britain, and they are very popular placaces (Saberi, 2010).
Asia and Tibet, the oldest form of tea drinking still remains.
This ancient practice consists of boiled tea that is made with
The Economics and History of Tea
compressed tea, which is either shaved off a brick or broken
off a cake. Then, it is boiled with water and usually other Camellia sinensis is a historically important plant and is closely
ingredients. Indian chai is made in a similar manner. During interlaced with the histories and economies of China, India,
the Song Dynasty (960-1279), whisked tea arose in China and and Britain. China used to dominate the international tea
diffused into Japan, where it was integrated into ceremonial trade till the mid-nineteenth century. China lost control
practices. Whisked tea is made from leaves that are grounded because Great Britain started to compete with them, as they
into a fine powder, and then whipped with bamboo sticks and were eager to make their own tea. To do this, Britain turned to
hot water in separate bowls. Steeped tea, in which tea leaves other regions. For example, the colonialization of India started
are steeped in the tea pot, became a common practice during in 1757 in part because the British wanted to make their own
the Ming dynasty in China (1368-1644). It was steeped tea tea, and India presented the perfect opportunity with its huge
that maritime traders introduced into Europe (Steeped in population of peasant cultivators. As in other British islands,
history : the art of tea / Beatrice Hohenegger, editor ; with the indenture system was eventually established in India. This
essays by Terese Tse Bartholomew ... [et al.], 2009). system recruited and constrained laborers to tea plantations
under a penal system. Indian indentured laborers also
Tea drinking is intricately tied into the Japanese culture as it
supported the British plantation economy in other places
has influenced the fine arts, including garden design, flower
besides India, such as Fiji and East Africa and the lives of these
arrangement, architecture, calligraphy, painting, lacquer, and
laborers were like those of the African slaves. This indenture
ceramic arts. The tea ceremony in Japan is called chado, ‘The
system eventually caused Indian tea to surpass Chinese tea in
Way of Tea,’ and it was originally a Buddhist ritual. This tea
the global market (Steeped in history : the art of tea / Beatrice
ceremony still continues on today in Japan (Saberi, 2010).
Hohenegger, editor ; with essays by Terese Tse Bartholomew ...
In Korea, nconsumption of tea is tied with the Panyaro Seon [et al.], 2009).
(Zen) of tea. Tea ceremonies are seen as a spiritual activity
The history of tea is also closely interlaced with the history of
that results in inner awakening and even total enlightenment.
sugar because sweetened tea was a common beverage. Both
Temples in Korea also serve tea to visitors (Saberi, 2010).
tea and sugar entered the British market as rare and
In England in the 1850s, tea began to become the focus of expensive items during the mid-seventeenth century that only
social visits. It was served with sandwiches, biscuits, cakes, the elite could afford. Two hundred years later, sweet tea
and pastries. Fancy silver or fine bone china tea-ware arose to replaced both beer and malt liquor as the top beverage. The
accommodate this important social event. Afternoon tea United Kingdom drank 40 percent of the tea worldwide by
became a unique event. It became common among the high, 1900. This was due to industrialization—it helped the new
industrial workers meet their caloric needs and helped to
keep them awake by acting as a stimulant—and the growth of
the British Empire. In the British Caribbean colonies, over a
million African slaves worked under arduous conditions to
produce sugar. These workers were overworked,
malnourished, and disease ridden and their death rate far
exceeded their birth rate. This cheap land and labor increased Epicatechin Epigallocatechin
the demand for tea by making it cheap and readily accessible
to the lower classes in Britain (Steeped in history : the art of
tea / Beatrice Hohenegger, editor ; with essays by Terese Tse
Bartholomew ... [et al.], 2009).
Tea has a rich history that was tied to the exploitation of
native populations. It has changed the world, and it still is
relevant today. As a highly consumed beverage, tea is still an
economically significant commodity. For example, in the
United Kingdom, around 165 million cups of tea are consumed
daily (Saberi, 2010). Also, 2/3rd of the world population
consumes tea daily as a morning drink, and about 2.2 millions
tones of it are produced annually (Mondal et al., 2004). Epicatechin-3-gallate Epigallocatechin-3-gallate
Figure 2. Chemical structures of the four major catechins
found in Camellia sinensis. These catechins are EC
Chemistry and Pharmacology (epicatechin), EGC (epigallocatechin), ECG (epicaetchin-3-
The constituents of tea possess biological properties that are gallate), and EGCG (epigallocatechin-3-gallate). Source
beneficial for one’s health as they have been shown to be (Kim et al., 2010)
possess antiallergenic, antioxidant, antimutagenic, anticancer,
antiartherosclerotic, and antibacterial properties (Ferrara et
al., 2001). Many of these biological activities can be traced acts to suppress the stimulant activity of caffeine (Saberi,
back to the three main components of tea: caffeine, catechins, 2010).
and theanine. Catechins are polyphenolic flavonoids (tannins), Catechins are made by the tea plant/shrub during the day and
and they are responsible for the briskness and astringent stored in cell vacuoles in the shoot of the plant. As the
flavor of tea. Caffeine, a mild stimulant, also brings about the temperature gets higher, the rate of production of these
bitter flavor of tea. In contrast to caffeine, theanine is an catechins increases These catechins may be useful secondary
amino acid that is responsible for the sweetness of tea, and it metabolites that may serve to protect leaves from bacteria,
viruses, fungi, and vermin bites. Catechin oxidation forms
Active Ingredient Content (g/kg dry leaves) Components Green Tea Black Tea
Caffeine 36 Catechins 30-42 3-10
Catechins Ravanols 5-10 6-8
Epicatechingallate 15.2 Other flavonoids 2-4 -
Epigallocatechin 46.0 Theogallin 2-3 -
Epigallocatechin gallate 129 Ascorbic acid 1-2 -
Epicatechin 0.9 Gallic acid 0.5 -
Major catechins 191 Quinic acid 2 -
Flavonols Other organic acids 4-5 -
Myricetin 0.8 Theanine 4-6 -
Quercetin 1.8 Other amino acids 4-6 13-15
Kaempherol 2.6 Methyxanthines 7-9 8-11
Table 1. Major constituents of green tea by g/kg of weight. Carbohydrates 10-15 15
Source (Perva-Uzunalic et al., 2006) Minerals 6-8 10
Volatiles 0.02 <0.1
Theaflavins - 3-6
dimers and polymers named theaflavins and thearubigins, Thearubigins - 12-18
which retain many of the properties of catechins. Catechin Caffeine 3-4 3-4
oxidation is the main chemical reaction involved in the Table 2. Major constituents of green and black tea by
synthesis of black tea (Shalleck, 1972). weight % of extract solids. Source (Chow & Hakim, 2011).
Catechins comprise 30% of the dry weight of tea leaves (Chyu
et al., 2004). They can be categorized as either free catechins of tea; proteins constitute 15% of tea; chlorophyll constitutes
or galloyl catechins. The free catechins include (+)-catechin 0.5% of tea; the polyphenols, such as EGCG and EGC constitute
(+C), (+) galocatechin (+GC), (-) epicatechin (EC) and (--) 25-35% of tea. A cup of green tea can contain anywhere from
epigallocatechin (EGC). Galloyl catechins include (-) 300-400 mg of polyphenols or 10-30 mg of EGCG The
epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG), polyphenolic compounds present in tea are essentially
and (-)-galoocatechin gallate (GCG) (Hara, 2011). EGCG is also colorless (Meltzer et al., 2009). Table 1 shows the percent
the main antioxidant catechin found in tea, and is responsible composition of the constituents of tea as present in green and
for many of the attributed health effects of tea (Chyu et al., black tea.
2004). The structures of some of these major catechins are
Table 2 shows the content by weight of active ingredients in
shown in Figure 2. They consist of polyphenolic aromatic
dry tea leaves. Caffeine weighs 36g/kg; the major catechins
rings that contain hydroxyl groups (Hara, 2011).
weigh 191 g/kg; the flavonols weight 5.2 g/kg (Perva-Uzunalic
In a cup of tea, the following percentages of compounds are et al., 2006).
found: caffeine constitutes 2-4% tea; amino acid constitute 4%
Among the three different types of tea, there is also a
of tea; lignins constitute 6.5%; organic acids constitute 1.5%
difference in chemical content as the they undergo different
levels of fermentation. Green tea has the most antioxidant with PBS treatment (P<0.05). Also, the sizes of the plaques
content due to a higher EGCG content with black tea having were the same in both day 42 and day 21 treated mice that
the least EGCG content (Cheng, 2006). Black tea has the most had been administered EGCG. This suggests that treatment
caffeine content, and green tea has the least (Lin et al., 2003). may halt the development of these lesions. EGCG treatment
did not reduce established lesions in the aortic sinuses or the
rest of the aorta. EGCG injections may have reduced evolving
Biological Activity lesions because it increased antioxidant capacity in local
Many of the health benefits of tea can be attributed to its EGCG vascular tissue as well as systemic circulation. It also
content. EGCG has strong antioxidant properties, and it also decreased vascular smooth muscle cell proliferation and redox
accounts for more than 65% of the catechin content of tea and sensitive gene activation (Chyu et al., 2004).
more than 10% of the extract dry weight of tea (Kaedei et al.,
2012).
Diabetes
Hyperglycemia can lead to diabetic complications, such as
In Vivo neuropathy, retinopathy and nephropathy in diabetes
Atherosclerosis mellitus. This study investigated the effect of oral
administration of green tea (GT) on kidney tubules of diabetic
Many of the potential protective effects of catechins found in rats, and it found that diabetic rats treated with green tea
Camellia sinensis may not work once a disease or illness is well showed a reduction in serum levels of glucose, glycosylated
established. For example, many of the human clinical trials proteins, creatinine, and blood urea nitrogen levels in
that administer antioxidants may fail because the therapy comparison to untreated diabetic rats. Glucose, protein, urea
begins long after atherosclerosis is already established in the nitrogen and creatinine excreted in the urine of GT treated
patients. In contrast, the positive results seen in laboratory diabetic rats also decreased. A decreased number of glycogen-
animals may occur because the early initiation of antioxidant filled proximal tubules were also seen in diabetic rats treated
therapy occurs when atherosclerosis is still developing. with GT, which means that GT has a positive effect on renal
This study investigated the preventive potential of tea histochemical parameters. Overall, GT was found to improve
catechins in hypercholesterolemia apolipoprotein E-null mice. serum levels and urine excretions as well as reduce glycogen
Mice with either evolving or established atherosclerotic levels in the kidneys (Renno, Abdeen, Alkhalaf, & Asfar, 2008).
lesions were injected daily with either intraperitoneal
injections of EGCG (10 mg/kg) or PBS. These lesions were
produced by periadventitial cuff injury to carotid arteries. In Vitro
Results were taken after 21 and 42 days of treatment. It was ECGC and motility of Sperm In Vitro
found that this therapy decreased evolving atherosclerosis
plaque sizes at 21 days by 55% and 42 days by 73% compared Catechins can inhibit some of the effects of ROS (reactive
oxygen species), hydrogen peroxide, hydroxyl radicals, and
nitric oxide. They have also been shown to have higher breast cells. EC, ECG, EGC, and EGCG are some of the main
antioxidant properties than both vitamin C and E (Kaedei et catechins found in green tea. It was shown that EC decreased
al., 2012; Zhao, Li, He, Cheng, & Xin, 1989). cell proliferation and apoptosis at 100 µg/mol. ECG, EGC, and
For motility, sperm require the production of ATP. The EGCG decreased cell viability and proliferation and increased
synthesis of ATP in the mitochondria results in the formation cell apoptosis. EGCG was more toxic than EGC, which was
of ROS, which can decrease the motility of sperm. In this study, more toxic than ECG, which was more toxic than EC. GTCs
it was found that the motility and penetrability of boar have preventive activity as they were shown to suppress
spermatozoa improved with co-incubation of 50 and 100 µMs chronic cellular carcinogenesis from exposure to
of EGCG. EGCG could potentially protect spermatozoa from environmental carcinogens (Rathore, Choudhary, Odoi, &
oxidative stress and improve energy production, which would Wang, 2012).
result in improved sperm movement (Kaedei et al., 2012).
Melanoma
Breast Cancer This study tested whether a physiological concentration of
A long-term exposure to low doses of environmental EGCG at .1-1µM inhibited human metastatic melanoma cell
carcinogens may cause most human cancers. For example, lines, 1205Lu and HS294Y, and they found that it did in a dose
short term exposure to low doses of NNK (4- dependent manner. The research group showed that EGCG
(methylnitrosamino)-1-(3-pyridyl)-1-butanone) and B[a]P depresses NF-kB activation in a dose dependent manner. IL-
(benzo[a]pyrene) results in higher levels of ROS (reactive 1beta signaling led to activation of NF-kB. The secretion of IL-
oxygen species). NNK is a potent lung carcinogen in tobacco 1 beta also decreased because NLRP1 (a part of the
products and B[a]P is an environmental, dietary, and tobacco inflammasomes) was suppressed and this led to subsequent
carcinogen. This study looked at the preventive aspects of capase-1 activation depression. They also found that turning
catechins found in Camellia sinensis in preventing breast off NLPR1, an inflammasome that may be involved in tumor
cancer. inhibition, reversed these results (Ellis et al., 2011).
Immortalized, non-cancerous human breast epithelial

MCF10A cells in culture were exposed to 100pmol/l of NNK Mechanism of Action
and B[a]P. This exposure resulted in carcinogenesis of human
EGCG is involved in several cellular pathways (Figures 3 and
breast epithelial cells due to an increase in ROS levels, which
4) that result in inhibition of apoptosis, cell cycle arrest,
activated the Raf-independent extracellular signal-regulated
growth inhibition, inflammation, antiangiogenesis, and
kinase (ERK) pathway and led to successive cell growth and
inhibition of metastasis. EGCG inhibits receptor tyrosine
DNA damage.
kinases, such as epidermal growth factor receptors (EGFRs),
Green tea catechins (GTCs) stopped ROS elevation, ERK insulin-like growth factor-I receptor and vascular endothelial
activation, cell growth, and DNA damage in non-cancerous growth factor (VEGF) receptor (VEGFR), and some of their
Figure 3. Some of the cellular pathways that EGCG targets.
Source (Kim et al., 2010) Figure 4. Some of the cellular pathways that EGCG targets.
Source (Singh, Shankar, & Srivastava, 2011)
downstream effectors, such as pAkt and pERK by preventing signal transducer and activator of transcription 3 (Kim, Amin,
ligand binding and phosphorylation/activation of the receptor & Shin, 2010).
tyrosine kinases. It also inhibits cytoplasmic signaling In the atherosclerosis study already mentioned, in vitro
molecules, such as Akt, extracellular signal-related kinase studies showed that treatment with EGCG 30 µmol/L reduced
(ERK) ½, and mitogen-activated protein kinase or ERK kinase the activation of redox-sensitive transcription factor AP-1 and
(MEK). EGCG inhibits intracellular signaling pathways , such TNF-a induced iNOS expression. iNOS is a source of reactive
as phosphoinositide 3-kinase/Akt/mammalian target of oxygen species and is a part of the tissue proliferative repair
rapamycin (mTOR), Janus-activated kinase (JAK)/signal process (Chyu et al., 2004).
transducer and activator of transcription (STAT),
RAF/mitogen activated protein kinase or ERK kinase
(MEK)/ERK/AP-1, and Akt/NF-kb. NF-kB is involved in DNA Clinical Studies
transcription of genes, and these genes are involved in
inflammation, immunity, and carcinogenesis. ECGC also Obesity
activates p53 and its downstream targets p21, p57, and Bax, In this clinical study, AR25, which is a green tea extract, was
which results in cell death and G0-G1 arrest. It also inhibits the found to inhibit lipases and at the same time stimulate
binding of effector transcription factors—NF-kb, AP-1, and the thermogenesis and fat oxidation. AR25 is an 80% ethanolic
dry extract that is standardized at 25% EGCG catechins. This individuals. There were no significant side effects. This study
study involved seventy patients aged between 20 to 69 years shows that GTCs are both safe and effective as a preventive
that were given an AR25 extract. During the course of the therapy for the development of CaP. These capsules also
study, a decrease of 4.6% in mean body weight and a reduced lower urinary tract symptoms associated with benign
reduction of waist circumference by 4.48% was observed. prostate hyperplasia (Bettuzzi et al., 2006).
After three months of treatment, no significant decreases in
A study examined the chemopreventive effects of green tea
plasma cholesterol levels or reduction in blood pressure was
among cigarette smokers of 52 healthy male aged 20-51 years
seen. The increased thermogenesis and fat oxidation was not
of age. Smoking increases the frequency of sister-chromatid
linked to a heart rate increase. This is promising since obese
exchange (SCE) in mitogen stimulated peripheral lymphocytes
patients tend to have underlying cardiovascular problems and
by 35%. This increase may be due to smoking-induced DNA
hypertension. This extract can influence both body weight and
damage. It was found that the frequency of SCE in smokers
composition by influencing body energy expenditure and the
who consumed green tea (3 cups a day for 6 months) was
utilization of various substrates in the body (Chantre & Lairon,
similar to that of non-smokers suggesting that consumption of
2002).
green tea may help to prevent lung cancer (Lee et al., 1997).
Cancers
Contradictions
Recent research shows that 30% of men with high-grade
Camellia sinensis should be avoided if on anticoagulants, such
prostate intraepithelial neoplasia (HG-PIN) develop prostate
as Warfarin as it decreases the anticoagulant effect through an
cancer (CaP) within a year after repeated biopsy. Several
antagonism mechanism. Warfarin inhibits the production of
epidemiological studies have shown that Asian countries
vitamin-K dependent clotting factors. Green tea contains
where green tea is a popular beverage have a lower incidence
vitamin K, and therefore acts in opposition to the drug (Izzo,
of CaP, and that when these Asian immigrants migrate to the
Di Carlo, Borrelli, & Ernst, 2005).
United States and adopt new dietary habits, the prevalence of
CaP increases. The green tea catechins capsules used in this Products containing green tea have been found to be
clinical trial consisted of 5.5% (--)-epigallocatechin, 12.24% (- hepatotoxic. A study examining this found that no chronic
-)-epicatechin, 51.88% epigallocatechin-3-gallate, and 6.12% liver damage occurred. All of the patients recovered within 4
(--)-epicatechin-3-gallate. Less than 1% caffeine was used. months after stopping to use supplements containing C.
Sixty male volunteers with HG-PN underwent this double sinensis (Bonkovsky, 2006).
blind, placebo-controlled trial, and they were given three daily Tea herbal supplements should also be checked for their
green tea catechin (GTCs) capsules, 200 mg each for one year. caffeine content. Caffeine levels can reach a high level in these
The incidence rate of tumors among the 30 GTCs-treated men products and may cause thermogenic, cardiovascular, and
was 3% (1 person developed a tunor), and it was 30% (9 other health effects in humans (Seeram et al., 2006). Too much
individuals developed tumors) among the 30 placebo treated
consumption of tea may also result in insomnia, and this may of the drug ("Veregen: a botanical for treatment of genital
be due to the caffeine content of tea (Izzo et al., 2005). warts," 2008).
Since EGCG and polyphenols in green tea may be proteasome A 0.5 cm strand of Veregen ointment should be dabbed on
inhibitors, they should not be taken with other proteasome each wart, covering it with a complete layer, 3 times each day.
inhibitors, such as boranic acid-based inhibitors or Treatment should continue until the warts completely
Bortezomib. If taken in conjunction with these drugs, then disappear, but should not last longer than 16 weeks
tumor cell death may not occur thereby preventing these ("Veregen: a botanical for treatment of genital warts," 2008).
drugs from working (Shord, Shah, & Lukose, 2009).
The catechins in Camellia sinensis are metabolized by
CAM Therapies/ Modern Day Products
catechol-O-methyltransferase, and therefore should not be
taken in conjunction with monoamine oxidase inhibitors or Camellia sinensis is found in many herbal supplements on the
dopamimmetic drugs due to a potential adverse interaction market (Seeram et al., 2006). For example, EXOLISE® is a
(Shord et al., 2009). capsule containing 375mg of green tea extract AR25, and it
has been found to have anti-obesity properties (Chantre &
Lairon, 2002). Many of these other supplements are available
Current Use in Allopathic and CAM Therapies in capsule form with a recommended dosage of 100mg to
Allopathic Medicine 150mg a day (Shord et al., 2009).
The green tea sinecatechin, Polyphenon E (Veregen) ointment C. sinensis is also available in iced and brewed teas, and no
is the first FDA approved botanical drug. Polyphenol E is more than 2.25g of tea per 6 ounces of water is recommended
administered for the treatment of anogenital warts because of per serving (Shord et al., 2009). Many skin care products sold
its antiviral, immunostimulatory, and antioxidant properties by corporations, such as Avon Products Inc, Estee Lauder Inc,
(Meltzer et al., 2009). It is sold as a 15% ointment. Each gram Elizabeth Arden, L’Oreal, Carter-Wallace Inc, Aubrey Organics,
of ointment is composed of 150 mg of sinecatechins and Schwartzkopf & Dep Corp. contain green tea. These
("Veregen: a botanical for treatment of genital warts," 2008). merchandises include toothpastes, shampoos, depilatory
Over 85% of this drug consists of catechins that are derived creams, facial cleansing lotions, moisturizing creams,
from a partially purified fraction of water extract of green tea moisturizing lotions, scented sprays, body lotions, and bath
leaves from Camellia sinensis (Meltzer et al., 2009). The tea and shower gels. Due to the presence of catechins, these
leaves are extracted with water followed by ethyl acetate. The products may have anticarcinogenic, antioxidant, and anti-
resulting product undergoes column chromatography using inflammatory activity. Clinical trials should be conducted to
water/alcohol to elute the catechins. The resulting catechin investigate these potential biological activities (Katiyar,
powder has the following composition: EGCG>65%, EC<10%, Ahmad, & Mukhtar, 2000).
EGC<10% and other trace catechin derivatives (Hara, 2011). Apart from being used in supplements and skin care products,
Gallic acid, caffeine, and theobromine compose another 2.5 % C. sinensis has been found to be incorporated into the
treatments of patients suffering from illnesses and chronic production / Dharam P. Abrol. Dordrecht: Dordrecht :
diseases. For example, a study conducted in Jordan found that Springer Science+Business Media B.V.
20.5% percent of diabetes patients used some form of C. Bettuzzi, S., Brausi, M., Rizzi, F., Castagnetti, G., Peracchia, G., & Corti,
sinensis in their treatment. Most of these patients used this A. (2006). Chemoprevention of human prostate cancer by
plant to relieve the symptoms (Wazaify, Afifi, El-Khateeb, & oral administration of green tea catechins in volunteers with
Ajlouni, 2011). In another study, it was found that some high-grade prostate intraepithelial neoplasia: a preliminary
cancer patients undergoing radiation therapy for various report from a one-year proof-of-principle study. Cancer Res,
neoplasms at rural cancer centers used green tea. Of the 153 66(2), 1234-1240. doi: 66/2/1234 [pii]
patients surveyed at these rural centers, 23 people or roughly 10.1158/0008-5472.CAN-05-1145
15% reported using green tea (Rausch et al., 2011).
Blofeld, J. (1985). The Chinese Art of Tea. London: George Allen &
Unwin Ltd.
Discussion Bonkovsky, H. L. (2006). Hepatotoxicity associated with
supplements containing Chinese green tea (Camellia
The origins of Camellia sinensis began in China, but today it sinensis). Ann Intern Med, 144(1), 68-71. doi: 144/1/68 [pii]
has diffused into all regions of the world. It is a culturally,
historically, and economically relevant botanical plant. For Chantre, P., & Lairon, D. (2002). Recent findings of green tea extract
AR25 (Exolise) and its activity for the treatment of obesity.
example, the plant is used in food, cosmetics, tea ceremonies,
Phytomedicine, 9(1), 3-8.
and traditional and allopathic medicinal therapies. Many of
the biological and clinical studies discussed in this paper Cheng, T. O. (2006). All teas are not created equal: the Chinese green
focused on the preventive aspects of tea in preventing cancer, tea and cardiovascular health. Int J Cardiol, 108(3), 301-308.
diabetes, obesity, and atherosclerosis. Many of these activities doi: S0167-5273(05)00768-0 [pii]
are due to the major catechin found in tea, which is EGCG. 10.1016/j.ijcard.2005.05.038
EGCG has numerous cellular targets, and therefore may be an Chow, H. H., & Hakim, I. A. (2011). Pharmacokinetic and
effective product to consume to prevent diseases and chemoprevention studies on tea in humans. Pharmacol Res,
illnesses. EGCG is also a rich source of antioxidants. The first 64(2), 105-112. doi: S1043-6618(11)00143-5 [pii]
FDA approved botanical drug was also derived from tea
Chyu, K. Y., Babbidge, S. M., Zhao, X., Dandillaya, R., Rietveld, A. G.,
catechins. Due to its relevance in many diverse areas, C. Yano, J., . . . Shah, P. K. (2004). Differential effects of green
sinensis will continue to play an important role in human tea-derived catechin on developing versus established
history. atherosclerosis in apolipoprotein E-null mice. Circulation,
109(20), 2448-2453. doi:
10.1161/01.CIR.0000128034.70732.C2
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Cannabis sativa L., Cannabaceae
Anh-Phuong Pham
Introduction
Cannabis sativa, the most popular plant in the Cannabaceae
family (Linnaeus, 1753), grows annually in warm climates
(Figure 1). There are two species closely related to C. sativa:
Cannabis indica and Cannabis ruderalis. However, taxonomists
continuously argue over whether or not these plants may just
be the subspecies of C. sativa or the same species adapted to
different environments. C. sativa is more commonly known as
marijuana, pot, weed, ganja, and hundreds of other nicknames
among alternative cultures. Marijuana is a mind-altering
hallucinogen that contains hundreds of chemicals.
Cannabinoids, the main class of chemicals found in marijuana,
are unique to the plant. The main cannabinoid found in
marijuana is Δ-9-tetrahydrocannabinol (tetrahydrocannabinol,
Δ-9-THC, or THC), which contributes to most of the
psychoactive behavior of the drug. Two other active
cannabinoids in marijuana are cannabidiol (CBD) and
cannabinol (CBN). CBD makes up about 40% of marijuana Figure 1: Cannabis sativa flowers grow hairs that produce
extracts and has been found to have a wide scope of medicinal psychoactive cannabinoids. (Source:
properties, while CBN is a metabolite of THC and a http://psychotropia.co/?attachment_id=3623).
psychoactive agent in C. sativa. Marijuana can be cultivated in
many ways depending on its use, which include industrial, under the Controlled Substances Act (CSA) in the USA,
recreational, medicinal, and spiritual purposes. The seeds are meaning it is an illicit drug that is not federally accepted for
most commonly used to make oil or food, while the flowers medical treatment (ElSohly & Slade, 2005).
are where the psychoactive compounds are found. The
flowers and leaves can be dried or made into resin or oil. The
main methods of marijuana use consumption through Botanical Description
inhalation, mixed with foods, or in tea (Booth, 2003).
Cannabis sativa is an herb that blooms in the spring and
Currently, marijuana is considered a Schedule I substance
summer. Of all the plants in the Cannabis genus, C. sativa is the
Figure 3. A chunk of Lebanese resin, also known as
Figure 2. The flowers of male Cannabis sativa plants are “hashish” (Source:
much smaller than the flowers of their female http://www.erowid.org/plants/show_image.php?i=cannabis/
counterparts (Source: hashish_chunk__i2006e1398_disp.jpg).
http://life.nthu.edu.tw/~g864204/hemphist.html).
plants. The female plants are able to produce a sticky resin
most widespread, capable of growing up to 6 m in height. This and flowers even if it has not been pollenated. The resulting
plant is very adaptable; it can be cultivated up to 8000 ft in plants are called sin semillas (“seedless” in Spanish) and are
altitude, in poor soils, and with only a small amount of water. popular among marijuana cultivators today for the
However, direct sunlight, open ground, loamy soils, and tropic psychoactive properties provided by the high amount of THC
or temperate areas are best for the plant to thrive. Originally produced from the continually growing buds. Successful
cultivated in central Asia, C. sativa has since spread to many pollination of C. sativa in the wild depends on wind strength
other areas of the world, including India, northern Europe, and air currents. The flowers of the male plants are small, and
and the Americas (Booth, 2003). can be shades of green, yellow, and purple. They grow in
dense bunches and wither and die after they release their
Marijuana plants are usually either male or female, but
pollen. The female flowers are more complex, consisting of a
monoecious plants are not completely unknown. The male
pair of white stigmas which join an ovule a small green pod
plants, which produce the pollen, are taller than the female
formed by bracts and bracteoles (Figure 2). The hairs on the
anthers of the male stamens and the perianths of the female
flowers produce an amber-colored resin (Figure 3). The resin
has also been speculated to help seeds from suffering from
water loss during transpiration, protect seeds from ultraviolet
radiation, or to trap pollen, but no primary function has been
verified (Booth, 2003). Females tend to grow more hairs than
males, with three distinct types: bulbous, capitate-sessile, and
capitate-stalked. These three glandular hairs vary in their
developing bracts, and although not much research has been
done on the glands, there exists a direct correlation between
the amount of glands and THC in the plants (Hammond &
Mahlberg, 1973). The stalks from cannabis plants have been
used for centuries as a natural fiber because of their incredible Figure 4. A drawing of hemp and hemp after cultivation,
strength. Cannabis seeds enclose oils that contain many harvesting, and cutting (Source:
unsaturated fatty acids that are rich in nutrients and can also http://www.madehow.com/Volume-6/Industrial-
be used to make lamp fuel, soap, varnish, and paint (Booth, Hemp.html).
2003).
Within the C. sativa plant species are two subspecies: Cannabis Traditional Uses
sativa L. ssp. indica and Cannabis sativa L. ssp. sativa (USDA).
While THC is the main cannabinoid found in all cannabis Hemp fiber
plants, CBD is the next most common. The var. indica plant Hemp fibers are tall, grow in warm climates, and contain very
appears to have a higher CBD to THC content ratio than its little psychoactive properties. The extremely strong fiber is
close relative. The wide difference between members of the C. made from the stalks of C. sativa plants (Figure 4).
sativa species has resulted in some taxonomists speculating Domestication of Cannabis sativa as hemp began in China
that the different subspecies and varieties may just be around 4500 BP, and was the only fiber available at that time.
botanically adaptable versions of the same plant (Graham, Historical evidence of hemp fabrics can be found in Anatolian,
1976). The specific chemotype of individual cannabis plants Sarmatian, Scythian, and Russian cultures (Zohary, Hopf, &
and observable distinctions, differentiated by the amount of Weiss, 2012). Before silk was discovered and woven, hemp
THC they produce may be more important when comparing cloths were very popular because of their enduring nature.
plants than focusing on taxonomic classification. The “drug Pottery shards with pieces of impressed hemp cord from the
type” contains high concentrations of THC and no CBD, the Tapenkeng culture in Taiwan, dating back to between 10000
“intermediate type” has moderately high concentrations of and 3000 BC, are one of the earliest recorded records of the
THC and CBD, and the “hemp type” has low THC and low CBD usage of C. sativa as a fiber. The extraction process begins with
concentrations (Lewis & Elvin-Lewis, 2003). soaking the stems in water until they break down and cause
Hemp Seed Macrocomposition from nylon or cotton today, but some ropes made from hemp
Components Results (% w/w) fiber are still available (Earleywine, 2002).
Fatty Acids
Linoleic Acid (18:2ω6) 52-62
α-Lineoleic Acid (18:3ω3) 12-23 Hempseed oil
Oleic Acid (18:1ω9) 8-13 Seeds produced by Cannabis sativa have a wide array of uses,
Palmitic Acid (16:0) 5-7 including food for animals and humans, bait for fishermen,
Stearic Acid (18:0) 1-2 and as a source of oil (Graham, 1976). The seeds have great
γ-Linoleic Acid (18:3ω6) 3-4 nutritional value, including minerals, vitamins, amino acids,
Eicosanoic Acid (20:0) 0.39-0.79 unsaturated fats, and protein. Most of the fatty acids in
Eicosenoic Acid (20:1) 0.51 hempseed oil are linoleic, α-linolenic, and oleic acids (Table
Eicosadienoic Acid (20:2) 0.00 1). The presence of α-linoleic acid is effective in preventing
Natural Products coronary heart disease and cancer, while γ-linolenic acid is
Cannabidiol 10 mg/kg known for its effects against inflammation. Hempseed oil is
Δ9-tetrahydrocannabinol not detectable also associated with a reduction of serum cholesterol and
Myrcene 160 mg/L heart diseases (Oomah, Busson, Godfrey, & Drover, 2002).
ß-Caryophyllene 740 mg/L Vegetable oil can be extracted from hempseed, which can then
ß-Sitosterol 100-148 g/L be turned into diesel fuel, flammable fuel oil, or non-viscous
α-Tocopherol trace amounts lubricant. Hempseed oil can be used as a cheaper alternative
γ-Tocopherol 468 mg/L to almond, coconut, and olive oils in cosmetics as an emollient.
Methyl salicylate trace amounts However, the US government requires sterilization of hemp
Table 1. Cannabis sativa plants are rich in fatty acids, products before they are put on the market, which greatly
making them high in nutritional value for human reduces their important properties (Booth, 2003).
consumption. Table adapted from (Leizer, Ribnicky, Poulev,
Dushenkov, & Raskin, 2000)
Psychoactive properties
the non-fibrous tissue to fall off. Afterwards, the fibers can be Historically, Cannabis sativa has been used for its psychoactive
separated for use by bending the stems (Booth, 2003). properties recreationally, medicinally, and spiritually in many
England began importing hemp from Russia in the early societies. C. sativa grown as a psychoactive agent can be
1600s, eventually demanding the American colonies to prepared herbally, as cannabis resin, or in the form of hashish
cultivate the plant. Hemp became an important crop in oil. Herbal cannabis is prepared by drying the flowers and
America in its early days, but production decreased after laws leaves, cannabis resin requires separating the hairs from the
were implemented against the plant. Most ropes are made plant, and hashish oil requires a sophisticated, hot extraction
process, but is the most potent (Oomah et al., 2002). Long
after being cultivated as a fiber, C. sativa began being used marijuana use through inhalation, study and acceptance of
medicinally around 2737 B.C. in China. The emperor, Shen other religions and philosophies, and psychedelic films and
Neng, used cannabis, ephedra, camellia sinensis, and ginseng books. Many accounts of marijuana use still exist today,
for their medicinal properties (Earleywine, 2002). Shen despite its illicitness (Earleywine, 2002).
Neng's book, Pen Ts’ao Ching is the earliest known Chinese
pharmacopoeia and lists hundreds of herbs he tasted with
grade and rarity ratings. In particular, marijuana was noted as India
an anti-inflammatory agent and painkiller (Li, 1975). Shen Traditional herbal medicine passed down orally from
Neng would advise patients to drink a ‘hemp elixir’ made of generation to generation is the most important form of
cannabis leaves and flowers to treat many different types of healthcare for rural populations living in India. Today, the
ailments including gout and malaria (Booth, 2003). Marijuana Monpa group in Arunachal Pradesh still use Cannabis sativa to
was also considered a holy plant in the Atharvaveda, a Hindu cure dysentery and diarrhea in cattle and goat (Namsa,
text; ancient Indian healers prescribed C. sativa for asthma, Mandal, Tangjang, & Mandal, 2011) while the Khetawas in the
congestion, fevers, or inflammation in the mucuous Jhajjar district of Haryana use it to treat coughs (Panghal,
membranes. These medicines were most commonly consumed Arya, Yadav, Kumar, & Yadav, 2010). For both of these
as a tea. Other known applications include easing pain during cultures, C. sativa is consumed orally.
childbirth and alleviating postpartum depression. Reports of
early use of marijuana as an intoxicant are not as prevalent as Indians also use cannabis for recreational purposes. Hindus in
its other purposes. While China’s Taoist movement first north Indian use three different forms of cannabis. Bhang
condemned recreational cannabis use, it was eventually used refers to the dried leaves of the herb, charas are the hashish
in religious rituals by the Taoists. A group of writers in the form, and ganja is what they call the flowering tops. Bhang is
19th century known as the Hashish Club used marijuana orally usually eaten or used as a drink called thundai, while ganja
and through inhalation for its creative elements. Baudelaire, a and charas are smoked through pipes. Hindu castes do not
member of this club, documented changes in thoughts, condemn cannabis; it is sometimes used in religious rituals,
sensations, euphoric and dysphonic reactions, and ceremonies, and festivals (Hasan, 1975).
intoxication that resulted from marijuana use. C. sativa as an
intoxicant continued to spread, and finally reached the
Jamaica
Americas in the 16th century. However, laws against cannabis
arose in the United States in the early 1900s, most likely due The hemp plant has been present in Jamaica since the late
to discrimination against certain minority ethnic groups eighteenth century, but it became a popular smoking
including African and Mexican immigrants who were the most commodity among the working class around the mid-
common marijuana users of that time. Its popularity quickly nineteenth century. When Indian indentured laborers came to
increased again in the 1960s. This time, the enthusiasts were the West Indies, they introduced cannabis and “the ganja
“hippies” and college students. The alternative culture soon complex.” This consisted of cultural beliefs about Cannabis
spread throughout the Western world, promoting social
Classes of Chemical Compounds in C. sativa Rastafarians. They advocate a "back to Africa" movement and
Classes Amount Known worship Haile Selassie I, the emperor of Ethiopia from 1930-
Cannabinoids 61 1974. Rastafarians consider marijuana a biblical weed and use
Nitrogenous compounds 20 the herb while chanting hymns during religious ceremonies
Amino acids 18 (Rubin & Comitas, 1976).
Proteins, glycoproteins, & enzymes 9
Sugars & related compounds 34
Hydrocarbons 50 Nepal
Simple Alcohols 7 Cannabis sativa has been used traditionally in Nepal for
Simple Aldehydes 12 centuries for ritual, social, and medicinal purposes. Ayurvedic
Simple Ketones 13 medical systems use cannabis orally to treat a variety of
Simple acids 20 physiological and psychosomatic conditions. One treatment
Fatty acids 12 uses cannabis with around 15 other ingredients to treat
Simple esters & lactones 13 diarrhea. Cannabis can also be used as a tranquilizer to put
Steroids 11 children to sleep. Another common cannabis practice is
Terpenes 103 recreational use and pain relief among older people (Fisher,
Non-cannabinoid phenols 16 1975). Since the majority of the population lives in areas
Flavanoidglycosides 19 where health care facilities are lacking, traditional healing
Vitamins 1 systems are responsible for passing down knowledge about
Pigments 2 medicinal plants. The people of the Manang district in central
Table 2. There are hundreds of compounds that are found Nepal continue to cultivate many medicinal plants in the
in Cannabis sativa. Some of these constituents have never Ayurvedic tradition, including C. sativa. Many parts of the
been isolated, while others, especially cannabinoids, have plants are used medicinally and can be made into powders,
been gone through many research analyses. Table adapted pastes, decoctions, and infusions. Powders and decoctions are
from (Turner, Elsohly, & Boeren, 1980) the most popular forms used by the Nepalese and are most
often prepared by dissolving in hot and cold water, but milk,
sativa, methods and preparation, and Hindu names that are honey, oil, and ghee can also be used (Bhattarai, Chaudhary, &
still common terms for Jamaicans today. Jamaicans use ganja Taylor, 2006).
to treat all their maladies. This culture still exists in Jamaica
today, where children begin smoking the drug recreationally
at around 8 years old. While use is most predominant in the Chemistry and Pharmacology
lower class, it has spread to the middle class, which focuses Currently, there are over 420 known compounds in Cannabis
more on psychoactive reactions. One well known group of sativa (Table 2), which is considered a psychoactive drug.
cannabis smokers in Jamaica are a religious group called the Psychoactive agents are either psychotropic or
Figure 5.Chemical structure of Δ-9-THC, the most active
isomer of THC, a psychoactive compound found in
Cannabis sativa (Source:
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=160
78).
Figure 6. CBD is a major cannabinoid found in the plant.

psychotomimetic. C. sativa falls under the latter category, but Although it is a psychoactive compound, it is not intoxicating
rather than containing alkaloids like other hallucinogens, its and has a wide range of medical applications (Source:
psychoactive properties are attributed to the presence of http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid
cannabinoids, which are unique to the plant. The most =136351015&loc=es_rss).
common cannabinoid is THC (Figure 5), but CBD (Figure 6) is
also very active, and CBN is present in the resin (Booth, 2003).
9-THC), which may be almost three times as potent. The
Cannabinoids are found in both male and female parts of
cannabis plants, but are most concentrated in the female tops. cannabinoid composition in marijuana leaves may be different
Besides cannabinoids, there have also been reports of than in the smoke. Over 60% of the original THC content
terpenes, phenols, sugars, flavonoids, trans-cinnamic acid, appears in the smoke after normal smoking conditions, but
choline, trigonelline, piperidine, alkaloids, and cannabamines with a negative side effect of containing 70% more
found in cannabis plants. The interactions between these benzopyrene (Figure 7) than tobacco smoke (Petersen, 1980).
compounds and the cannabinoids may enhance or decrease
the psychotomimetic effects of cannabis. The full
pharmacological activity of C. sativa is still unknown because Biological Activity
most cannabis research focuses on the effects of THC (Graham, The active cannabinoids in Cannabis sativa act on specific
1976). Researchers attribute most of cannabis’ effects to Δ-9- cannabinoid receptor sites. Two receptors have been cloned,
THC because of its abundance in the plant. When it reaches the CB1 and CB2, and more receptors are suspected to exist. The
liver, it is broken down into 11-OH- Δ -9-THC (11-hydroxy- Δ- CB1 receptors are found on C-fibers and are expressed in
species including mollusks, protozoa, and many mammals,
which suggests they play important functional roles in the
body. Human and rodent cannabinoid receptors are very
similar which is helpful in applying animal study results to
people. Overall, there is definitive evidence that CB1 receptors
are involved with memory and motor control, while CB2
receptors are associated with the immune system
(Earleywine, 2002).
Structural MRI and post mortem examinations of the brain
have been used in in vivo studies of human patients to
investigate the relationship between cannabis use and brain
Figure 7. Benzopyrene is an organic compound that can morphology. Cannabis use in these studies showed a decrease
be found in coal tar, after volcanic eruptions, in cigarette in specific brain structures in psychosis or at-risk for
and wood smoke, and in burnt foods. Inhalation, psychosis patients. Brain regions rich in CB1 receptors, and
ingestion, and dermal contact of benzo(a)pyrene are patients with mental illness were the most affected (Rapp,
related to lung cancer (Source: http://wtt-pro.nist.gov/wtt- Bugra, Riecher-Rossler, Tamagni, & Borgwardt, 2012).
pro/index.html?cmp=benzo~a~pyrene).
Interest in the consequences of prolonged C. sativa use can be
attributed to its popularity in parts of the world, especially
neurons found in the nervous system, while CB2 receptors are lower socioeconomic groups. In vivo and in vitro studies were
found in non-neuronal tissues. Animal studies have led to the conducted to investigate the cytogenetic effects of C. sativa.
belief that the main role of the endocannabinoid system is to The in vitro studies consisted of rat embryonic fibroblasts
suppress pain. In this case, the cannabinoids found in treated with cannabis resin and colcemid (Ciba) after 4-14
marijuana are able to act as neurotransmitters. CB1 receptor days of culture, processed, and then examined for
agonists have been observed to produce antinociception in chromosomal irregularities, and the addition of cannabis resin
response to acute pain through peripheral nervous system, to the blood of rat and human subjects. The in vivo studies
spinal cord, or brain injection, or through the usage of crude were comprised of pregnant rats that had daily injections of
marijuana extract. Other studies suggest that cannabinoids cannabis resin for the six days of gestation. The embryos were
can diffuse from stimulated cells to act as presynaptic neuron then removed from each rat on days 11-13 and homogenized
receptors. Furthermore, two natural cannabinoids in the body, in cell suspension. After 3-6 days of culturing, the cells were
anandamide and methanandamide are able to activate processed for chromosomal examination. Blood was also
vanilloid receptors expressed in kidney cells (Calixto, Scheidt, taken from the pregnant rats when they were killed and
Otuki, & Santos, 2001). These compounds are less potent and cultured for two days to examine the chromosomes. Another
short-lived than THC, but imitate some of its effects. in vivo experimental group involved chronic cannabis users,
Cannabinoid receptors can also be found in a variety of other who had been smoking at least three "spliffs" a day for at least
10 years. These individuals were admitted to a hospital for reduction of 2.74 points on the Ashworth scale, and an
five days of clinical study, and had peripheral blood drawn the average of 5.28 points in reduction in pain scores on a visual
first morning of admission. The blood was cultured for two analogue scale was also seen in the experimental group
days for chromosomal examination. Unlike the other (Corey-Bloom et al., 2012).
experimental groups, there was no treatment for these
Smoked cannabis also seems to be effective in relieving pain
cultures. The control groups for this study received a Tween-
and improving sleep and mood according to patients with
saline solution instead of cannabis resin (Martin, Thorburn, &
chronic neuropathic pain. The pain is usually a result of
Bryant, 1974).
pharmacotherapy and not many treatment options are known.
Cannabis resin given to the experimental groups in the in vitro One randomized controlled trial concluded that inhaling 25
studies resulted in a lowered mitotic rate. Higher mg of 9.4% THC three times a day for five days effectively and
concentrations of cannabis showed a relation to greater tolerably reduces pain and improves sleep (Ware et al., 2010).
mitotic depression, with 200 µg/mL of resin resulting in
Epidemiological studies in Sweden, New Zealand, The
complete inhibition. However, because cells that received
Netherlands, and Israel show that cannabis abusers have an
cannabis resin in vivo did not show any mitotic inhibition,
increased likelihood to developing schizophrenia. Other
there is no confirmed evidence that exposure to cannabis
studies suggest that the cannabis use precedes the onset of
resin is related to chromosome abnormalities. It may be
symptoms of schizophrenia in subjects with cannabis use
possible that very high concentrations of C. sativa in frequent
disorders (CUD). However, no significant association was
users may inhibit the proliferation of embryonic and germ
found between the onset of schizophrenia and CUD in subjects
cells. If a large amount of the drug passes through the
in a study that controlled demographic and clinical variables
placenta, mitotic arrest can occur, interfering with normal
(Sevy et al., 2010).
embryonic development (Martin et al., 1974).
Contraindications
Clinical Studies
Cannabis sativa is the most commonly used illegal drug. About
Multiple sclerosis (MS) is an inflammatory disease that results
a third of all Americans have used marijuana at least once, but
in demyelination, scarring, and many poorly controlled
less than 5% report using it at least once a week. It is difficult
symptoms. Spasticity is common in individuals suffering from
to truly measure the extent of marijuana use because some
MS, and many of these individuals respond adversely to anti-
users lie due to its legal status or forget about their use.
spasticity medication. Evidence that cannabinoid receptors
Marijuana addiction is also difficult to measure because there
may be able to control spasticity led to the belief that Cannabis
is no universal definition. To some, addiction refers to a
sativa could be used as an effective treatment against
physical or biological process, whereas dependence is a
neurological conditions. One randomized, placebo-controlled
collection of three of the following symptoms: tolerance,
trial examined the effects of smoking cannabis on spasticity.
withdrawal symptoms, use exceeding initial intention, failed
Patients that received cannabis instead of a placebo had a
attempts to decrease use/constant desire for the drug, loss of least 50% of the THC is lost while smoking (Earleywine,
time related to use, reduced activities because of drug use, and 2002).
continued use despite problems. A small portion of frequent
While there are no recorded documents of fatal marijuana
cannabis users also appear to suffer from marijuana substance
overdose, it is well known that cannabis users often ingest
abuse. The current diagnosis requires one of the following
other illegal drugs. These drugs may be detrimental to their
symptoms: interference with major obligations, intoxication in
health, as well as having adverse interactions with C. sativa.
unsafe situations, legal problems, and continued use despite
This common practice among drug users has prompted
problems. Overall, only about 6-23% of cannabis users report
researchers to conduct experiments on both animals and
difficulties with marijuana use (Earleywine, 2002).
humans on the consequences of combining C. sativa with other
The toxicity of cannabinoids, cannabis, and cannabis products drugs, especially alcohol which is most commonly combined
are varied because many different compounds exist in the with cannabis. Acute depressant effects due to cannabis and
plant and resin. In one study, two comparable male subjects alcohol combination in animal models appear to be greater
smoked cannabis, with the experienced user enjoying himself, than the use of either drug alone. THC also appeared to
and the less experienced user becoming disoriented and enhance the impairing subhypnotic effects of ethanol. The
suffering adverse side effects, including dizziness, tremors, effects of these two drugs appeared to be additive, resulting in
and muscular rigidity. Immediate toxic effects of ingested or greater body temperature, depressed heart rate, and impaired
smoked marijuana include nausea, vomiting, thirst, and rotarod performance. Similar results were also found in
dryness of the mouth. Nevertheless, these symptoms are studies done on human subjects -- reduced standing
comparable to the effects of tobacco smoke and may not be steadiness, reaction speed, and cognitive performance.
due the active compounds of Cannabis sativa. Other side Besides their mental and psychomotor effects, combining
effects that have been reported include ataxia, cold marijuana and ethanol also increases pulse rate and
extremities, and precordial pain due to shortness of breath. conjunctival reddening. Cannabis also appears to enhance the
Typically, a single administration of smoked or swallowed depressant effects of sedatives and hypnotics in both animals
cannabis is not very toxic, but intravenous injection done by and people (Petersen, 1980).
misguided persons have resulted in disastrous effects,
including tachycardia, peripheral circulatory failure, vomiting,
diarrhea, enlargement of the liver and spleen and pulmonary Current Use in Allopathic and CAM Therapies
edema. However, because cannabinoids are insoluble in water, Despite several US states passing legislation for medical
these effects are most likely due to the act of intravenous marijuana and two states passing legislation for recreational
administration. The development of an allergy a C. sativa use, possession of cannabis in the United States, even as a
constituent is another possible method leading to toxicity medicinal agent, is still a federal offense. However, medical
(Graham, 1976). In general, a lethal dosage of THC requires marijuana usage rates are still high. There is evidence from
125 mg of the drug per kilogram of body weight. Most controlled studies that suggest the cannabinoids found in
marijuana cigarettes only contain about 20 mg of THC, and at Cannabis sativa are effective in reducing pain and vomiting,
Figure 9. Cesamet is the trade name for a synthetic
cannabinoid called nabilone that is used for the treatment
Figure 8. Canasol eye drops are used all around the world of nausea and vomiting due to chemotherapy in cancer
for treating eye pressure in glaucoma patients (Source: patients (Source: http://www.cesamet.com/patient-about-
http://www.hambaarst.ee/artiklid/702/). cesamet.asp).
promoting weight gain and appetite, decreasing eye pressure psychoactive ones. Canasol is also compatible with other
in individuals with glaucoma, and minimizing spasticity and topical treatments for glaucoma (Earleywine, 2002).
involuntary movements. Other therapeutic effects were also Dronabinol, a synthetic version of THC, is still on the market
found for individuals with asthma, insomnia, anxiety, seizures, today under the name, Marinol. It is usually suspended in
tumors, menstrual cramps and PMS, Crohn’s disease, and sesame oil and ingested orally, and it can be used to enhance
other medical and psychological disorder(Earleywine, 2002). appetite and reduce nausea and vomiting. Other studies
Since 1987, a cannabis derivative has been marketed by suggest its effectiveness as treatment for spasticity in MS
researchers in the West Indies for reducing intraocular patients and disturbed behavior in Alzheimer’s patients
pressure in glaucoma patients. Canasol eye drops (Figure 8) (Earleywine, 2002). Furthermore, more recent research has
have been used in many parts of the world to manage shown statistically significant reductions in hair-pulling in
glaucoma, especially in the Caribbeans. These eye drops can individuals diagnosed with trichotillomania that were given
lower pressures up to 50% in 15 minutes or less. They are dronabinol (Grant, Odlaug, Chamberlain, & Kim, 2011) and
also inexpensive and have little to no side effects, including increases in food intake and improved mood and sleep in HIV-
positive marijuana smokers (Haney et al., 2007). However,
Marinol has been argued to be less effective than smoked
marijuana. Some of these arguments criticize that the oral
ingestion of Marinol may be difficult for patients who find
swallowing difficult due to their nausea. Also, the effects do
not appear as quickly as smoked marijuana. The pills are
extremely expensive as well; some patients may have to spend
up to $1000 on the pills in one month. To put this into
perspective, a 10 mg pill of dronabinol costs as much as $13 or
$8 a pill if bought in bulk, whereas the same amount of THC
can be found in half a marijuana cigarette, which can be
purchased for less than $5 if bought in bulk illegally
(Earleywine, 2002).
Nabilone, marketed as Cesamet (Figure 9), is another example
of synthetic THC that is available in some countries today. It is
an orally ingested drug available that has been approved for
Figure 10. Sativex is a new drug developed by GW
treating nausea and vomiting during chemotherapy since
Pharmaceuticals for treating spasticity in multiple
1985 (Skrabek, Galimova, Ethans, & Perry, 2008). Nabilone is
sclerosis patients (Source:
typically administer in single doses ranging from 1 to 5 mg.
http://clarkfrench.wordpress.com/2011/06/06/access-
and the effects can take between 1 and 1.5 hr to become
sativex/).
evident and continue for up to 12 hr (Lemberger & Rowe,
1975).
individuals. Overall, THC can act as an analgesic, muscle
The newest cannabis inspired drug on the market is called
relaxant, and appetite stimulant. Patients are often advised to
Sativex (Figure 10), which is the trade name for Nabiximols.
deliver small doses throughout the day in order to avoid the
Sativex is currently the only non-synthetic cannabinoid
intolerable side effects while still being effectively treated for
pharmaceutical product. Currently, it is used as an oromucosal
whatever pain they may be experiencing (Barnes, 2006).
spray for MS patients suffering from spasticity. There is
definitive evidence that continual use of Sativex results in
long-term improvement of spasticity (Notcutt, Langford, Discussion
Davies, Ratcliffe, & Potts, 2012). Currently, it is also going
under research as a possible treatment for cancer patients There is a lot of evidence from clinical, in vivo and in vitro
experiencing chronic pain (Portenoy et al., 2012). studies that the active ingredients in Cannabis sativa are
effective in a variety of treatments including spasticity and
When administering THC to patients, it is important to control chronic pain. The cannabinoids in marijuana have also been
dosage because the therapeutic dose is variable in different found to be effective bronchodilators, which makes it a good
alternative treatment for asthma and allergies (Ziment & the Western world were more willing to accept it as a possible
Tashkin, 2000). The US Drug Enforcement Administration alternative medicine rather than a forbidden drug, more
(DEA) currently lists marijuana as a Schedule I drug under the treatments for cancer, HIV, and other chronic diseases could
CSA. Schedule I drugs, which also include heroin and LSD. be researched and marketed. Medical marijuana is a strongly
Schedule I drugs are considered to have a high potential for debated topic, and will probably remain in the dark until it is
abuse and no accepted medical purposes. They are the most finally accepted by governments.
dangerous group of drugs under the CSA because of the
potential dependence. Since it has been outlawed in the USA
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Capsicum annuum L., Solanaceae
Ezinne Nwankwo
Introduction
Capsicum annuum L. is also known by a variety of names. The
numerous subspecies include bell peppers, chili peppers,
paprika, and banana peppers to name a few. It is a member of
the nightshade family, Solanaceae (Andrews, 1995). These
peppers are native to Central and South America but have
been cultivated worldwide and are essential members of
many cultural cuisines. Other members of this family are the
tomato and Atropa belladonna, or deadly nightshade
(Andrews, 1995).
The fruit of this plant is rich in vitamins A, B complex C, E, and
a.
P. Additionally; it serves as a source of polyphenols. The
chemical constituent, capsaicin, gives the fruit its well-known
pungent characteristic (Andrews, 1995) and confers many of
its medicinal properties. Capsaicin is anti-carcinogenic and
anti-inflammatory (Surh, 2002), (Reddy, Ravinder, Prasad, &
Kanjilal, 2011). Peppers have been used to combat diseases as
diverse as inflammation, diabetes, and evil eye (Aggarwal,
Surh, & Shishodia, 2007), (Ishtiaq, Hanif, Khan, Ashraf, & Butt,
2007). C. annuum varieties have other uses also. They have
been used as a coloring agent for processed food, drugs, and
cosmetics.
b.
Botanical Description Figure 1 a and b. Flowering C. annuum
(Source: http://www.g6csy.net/chile/var-ann.html)
Capsicum annuum is herbaceous when young and woodier
with age. The woodiness only occurs in areas that do not
freeze when grown as a perennial. There is dichotomous leaves branching off of the same main stem. There are also
branching, with the main stem ending in a flower with several two or three more stems branching off of the first, main stem
honey bees, who are attracted to the scentless nectar. The
nectar is secreted and accumulates at the base of the lobes of
the corolla and eventually presents at the surface of the petals.
Other insects such as aphids, butterflies, and ants also transfer
pollen (Andrews, 1995).
The fruit formation depends on genetic factors (size and
shape) as well as environmental factors (growth). The apex of
the fruit can be sunken and lobed with a depression, as in the
boxy bell peppers. In other varieties it can be pointed or blunt.
The base of the pod, the attachment point to the peduncle or
stalk, may bulge or be nonbulged. In domesticated versions, a
hard to detach stem is present. This feature was selected on
the basis of ease of storage. Wild versions have a deciduous or
Figure 2. C. annuum fruits
(Source:
easily detachable stem. Many cultivators prefer this version to
http://www.beautifulbotany.com/STOCK%20C/Capsicum%20annu use with machine harvesting and to decrease the amount of
um%20'Garda%20Tricolor'.jpg) waste generated. The pericarp, or fruit wall, ranges in
thickness from thin to thick. This has an impact on
preservation technique. The fruit with a thin pericarp can be
that also end in flowers. The height of the plant varies with the dried readily but those with thicker pericarps must be pickled,
variety. It can be tall and erect, compact, or prostrate. The canned, or smoked. The placenta and vein of the plant are also
leaves vary in shape and texture. They can be smooth or included in the pericarp and contain the active ingredient,
wrinkled. The colors of the leaves range from green to purple capsaicin. The color of the fruits is usually green when unripe
to white. The roots can be deep or shallow depending on the but is known to be yellow-green, yellow, orange, bright or
variety. deep purple (Figure 2). When the fruits reach maturity, the
The corolla of the plant (all of the petals of the flower) tapers colors range from yellow, orange, and red or brownish red.
to a point. This means that they are acuminate. On average the Red, however, is the most common color. (Andrews, 1995)
corolla is five lobed but this number can also change. There
are three veins in each lobe. The color of the corolla can be
anything from cream to purple to greenish white (Figure 1a Traditional Uses
and 1b). There are also some varieties with greenish yellow Traditional Medical Uses
spots. The pistil can be longer than the stamens, which is
characteristic of more primitive plants, or shorter than the West Indians use a mixture of ground bird peppers combined
stamens. The shorter variety is more favorable for self- with onions, cucumber, lemon juice and Madiera as a
fertilization. Sexual reproducing plants are frequented by stomachic, or stomach strengthener (Andrews, 1995). The
people of the Samahni valley in Pakistan use Capsicum Paprika is a ground mixture of many capsicum varieties. It has
annuum as a rubefacient as well as sore throat, dyspepsia, a characteristic red coloring and can be mild or more pungent.
yellow fever and snake bites. It is treated by moving three, Sweet paprika contains mostly fruit wall with the seeds
five, or seven chilies over the head. These same chilies are removed. The hotter versions contain more of the placenta,
then burned in a fire. Chili smoke is also used as a ghost seeds and stalks. Interestingly, there is a Hungarian version
repellent in the treatment of giant. Giant is a cultural disease that is very pungent and uses the long, dried pods. Conversely,
in the middle east (Ishtiaq et al., 2007). the Spanish version contains a more tomato shaped pepper.
The Mayans used chilies for similar ailments that include sore Morocco and Bulgaria are two other countries that have their
throats, asthma, cough and respiratory disorders. They also own versions of paprika. Many Balkan growers brought
used the peppers topically to heal infected gums. Swedes use a paprika seeds to South Carolina after World War II and
salve made from Chiltepine peppers to sooth sore muscles. In California is one of the leading producers of paprika. This
Germany, the peppers are an ingredient in a warming bandage increase in the United States industry may be due to the
used for muscle pain (Andrews, 1995). decline of the Soviet Union, which caused a decrease in the
European paprika industry. (Andrews, 1995)
Many cultures use peppers for other medicinal purposes. C.
annuum has been used as an aphrodisiac, carminative, central Pepper sauce is another way that C. annuum is consumed. The
nervous system stimulant, and a tonic. Interestingly, it has peppers are either pickled whole in brine or vinegar or
been used to treat gonorrhea (Dr. Duke Ethnobotanical Uses). mashed to make the sauce. The sauce is then used to flavor
other foods. Chili peppers are the variety used in this method.
Peppers can also be canned or processed to make dips and
Food Uses sauces. (Andrews, 1995)
The use of Capsicum annuum as a condiment and spice is
spread worldwide. It is a constituent of Indian curry powder Use as a Coloring Agent
and Texan chili powder. The dried, crushed peppers of the red
and cayenne varieties are used in America and Turkey. The The peppers have been used by Central and Southern
ground form of cayenne pepper is grown and used in Africa, Americans to enhance the color of a bland diet. They are also
India, Japan, and Louisiana as a flavoring. Red peppers are used to replace red coloring lost in food preparation.
grown in the southern and western regions of the United Carotenoids from the peppers are also used to color drugs and
States as well as Turkey. Other pepper varieties are used in cosmetics (Andrews, 1995).
the whole from, either dried or fresh. This form is popular in C. annuum has been used extensively in the food industry.
Central and South America as well as southern North America. Foods from sausages to salad dressings to gelatin are colored
(Andrews, 1995) with the extractable colors of capsicums. The waste from
pimento pepper processing is used to influence the color of
egg yolks. The capsanthin present in the pimento waste gets
deposited in the egg yolk and gives it a dark reddish yellow
color. The color of the chicken itself is also influenced, with the
addition of pimento assuring a yellow skin color in the body of
the chicken. An unintentional influence is that the hatched
chicks are stronger and offspring of pimento fed chicken have
a higher rate of hatchability. This “improved” color is also
manifested in faded pink flamingos and trout that are fed
pimento waste. (Andrews, 1995)
Figure 3. Capsaicin structure
Other Uses
mucous production in the mouth from ingestion protects
Italians in the high Molise region of central-southern Italy use stomach ulcers from harsh stomach acids (Andrews, 1995).
a pungent variety of Capsicum annuum to protect food
Mammals are unique in that they have a specific capsaicin
products from parasites (Guarrera, Lucchese, & Medori,
receptor on their sensory neurons called the vanilloid
2008).
receptor-1 (VR1) or the transient receptor potential of
vanilloid 1 (TRPV1). Administration of CAPS to peripheral
Chemistry and Pharmacology nerve endings results in an initial reaction of pain and
neurogenic inflammation. However, desensitization occurs
Capsicum annuum contains a large variety of chemicals that with repeated application of CAPS to the same nerve endings
have a huge impact on its pharmacology. It is to be noted that may have indications for its use as an analgesic for many
there are multiple varieties of this species that differ in their painful neuralgic conditions. The nerve desensitization from
chemical makeup. The major difference in these varieties is CAPS is most likely from the effect on the neuropeptide
the amount of capsaicin. More pungent varieties such as the Substance P. Substance P is involved in pain transmission to
red chili pepper have more capsaicin content that less the brain and is inhibited by CAPS. The inhibition with
pungent varieties like bell peppers with have a minimum increased, repeated exposure to CAPS has the effect of
amount of capsaicin (Andrews, 1995). moderating pain (Aggarwal et al., 2007).
Capsaicin or CAPS is the major pungent ingredient in C. As shown above, C. annuum has effects on the nervous system.
annuum. CAPS is a homovanillic acid derivative (see Figure 3) Similar to other members of the Solanaceae family, more
(Aggarwal et al., 2007). It has effects on many organ systems pungent varieties of C. annuum can alter the conscious state,
in humans. For example, it causes peristalsis in the stomach albeit momentarily. The effect of C. annuum differs from other
stimulating the mucous membranes. This movement aids in members of the Solanaceae family in that it is nonhallucinogic
digestion. Stomach acid secretions are increased with C. and nonaddictive. It is also generally safe for consumption
annuum consumption. These increased secretions also
increase appetite along with aiding digestion. The increased
although. annuum has stimulant activities that can activate the antioxidant activity in vitro (Lee et al., 2009), (Materska &
vagal reflex and cause vomiting (Andrews, 1995). Perucka, 2005).
In hot climates, C. annuum can cause psychological gustatory A study was conducted on effect of Indian spices on
sweating. This is a form of thermoregulation that is confined esophageal squamous carcinoma cells. In the study, an
to the face and scalp. Evaporation of this sweat can facilitate a aqueous chili pepper extract induced a 88% apoptotic cell
cooling effect. Cooling the body can relieve this gustatory demise and cell death within 24 hours of exposure (Dwivedi,
sweating from consuming the peppers (Andrews, 1995). Shrivastava, Hussain, Ganguly, & Bharadwaj, 2011).
Other chemicals in C. annuum include many nutrients, In a similar vein, a study was done on human umbilical vein
including Vitamins A (beta-carotene) and C (ascorbic acid). endothelial cells in which extracts from Capsicum species and
They also contain capsanthin and many capsianosides. capsaicin were assessed for cytotoxicity to the endothelial
Carotenoids and phenolic acid compounds are also found in cells and protection from lipopolysaccharide (LPS) induced
these peppers. Minerals, amino acids and sugars occur in cellular apoptosis (Chularojmontri, Suwatronnakorn, &
abundance in C. annuum fruits (Dr. Duke Phythochemical and Wattanapitayakul, 2010). It was shown that the extracts and
Ethnobotanical Database). capsaicin improved endothelial cell function and conferred
protection against the LPS induced apoptosis. It was also
shown that the extracts where not cytotoxic to the endothelial
Biological Activity cells. This protection indicates that consumption of the fruits
In vitro of Capsicum annuum species could promote endothelial health
(Chularojmontri et al., 2010).
It has been found that the CaBtf3 NAC subunit in Capsicum
annuum is involved in the hypersensitive response of plants to In addition to promotion of cellular health, C. annuum may be
viral infection (Huh, Kim, & Paek, 2012). The hypersensitive a potential antibacterial agent. A Japanese study showed that a
response facilitates plant cell death after viral infection. Plants methanol extract of capsaicin inhibited cholera toxin
use it as a strategy for preventing viral movement and gaining production in Vibrio cholera. (Chatterjee et al., 2010) This
systemic acquired resistance against further viral infection discovery may have implications for the use of natural
(Huh et al., 2012). It is not known whether this is a compounds to combat increasingly antibiotic resistant
transcription factor but knowledge of its involvement in the bacterial pathogens (Chatterjee et al., 2010).
plant viral response could have implications for potential
therapies. In 2011, researchers isolated 28 polyphenols from
three C. annuum bell pepper varieties and determined that In Vivo
these compounds had both anticancer and antioxidant effects Many rat and mice studies have been conducted on the effects
in vitro (Jeong et al., 2011). Many studies conducted of capsaicin on pain reduction, weight reduction, and cancer
confirmed that the polyphenols found in C. annuum do exhibit treatment and prevention along with a host of other topics. In
one study it was shown that capsaicin may confer protection
from autoimmune diabetes. This study was conducted by As stated above, capsaicin can decrease sensation of sensory
researchers at the University of Connecticut School of neurons. One study measured the effects of capsaicin
Medicine. The vanilloid receptor 1 or VR1 is present on mediation denervation on bone metabolism in adult rats
sensory neurons as well as immune cells (Nevius, Srivastava, (Ding, Arai, Kondo, & Togari, 2010). It was shown that high
& Basu, 2012). This receptor can regulate gut events in doses of capsaicin decreased trabecular bone volume because
response to its ligand, capsaicin. In mice, when capsaicin is of increased bone resorption. This increase in bone resorption
administered orally it stops the growth and activation of led to weaker bones in the rats. The study concluded that
autoreactive T cells, which attack the cells of the body. This sensory innervation of bone helps to maintain trabecular bone
attenuation is specific to lymph nodes in the pancreas, which volume by inhibiting bone resorption (Ding et al., 2010).
is the area of insulin production. The attenuation is how the There was no indication of whether the amount of capsaicin
protection from type 1 diabetes is conferred (Nevius et al., administered to the rats was comparable to levels commonly
2012) because capsaicin prevents the autoreactive T cells consumed by humans.
from attacking the insulin producing cells. The researchers
Several in vivo studies have shown that capsaicin has an effect
also found that the binding of capsaicin to the VR1 receptor
on weight. One such study focused on rabbits (Yu et al., 2012).
activates pancreatic macrophages that express anti-
It was shown that the capsaicin specific receptor, TRPV1, was
inflammatory factors (Nevius et al., 2012). The influencing of
expressed in many organs. The organs were the brain,
nutrient-immune interactions by VR1 through inhibiting the
kidneys, spleen and adrenal gland. The rabbit TRPV1 receptor
autoreactive T cells and activating anti-inflammatory
amino acid sequence was more similar to humans than to rats,
macrophages could have implications on gut-mediated
which makes the rabbit a great model system for the effects of
immune tolerance (Nevius et al., 2012).
capsaicin on humans. In the study, two groups of rabbits were
Capsaicin has been implicated as an anti-carcinogenic. Female fed a high fat diet. One group’s high fat diet also included 1%
mice treated topically with capsaicin exhibited lowered hot pepper. This group had a significantly lower body weight
multiplicity of VC-induced skin tumors (Aggarwal et al., 2007). than the high fat control group. This study concluded that
When CAPS was applied prior to induced mutagenesis there capsaicin could potentially decrease diet-induced obesity (Yu
was less skin tumor formation in the treated mice (Aggarwal et al., 2012).
et al., 2007). Several studies conducted showed that capsaicin
Another study fed a spice cocktail including ginger, curcumin,
inhibited metabolic activation of carcinogens via various
piperine and capsaicin to high fat rats to measure the
mechanisms. One such mechanism was the modulation of
influence on bile secretion and fat digestion (absorption of
CYP-dependent monooxygenase activities (Aggarwal et al.,
dietary fat) in the rats (Prakash & Srinivasan, 2011). This
2007). Specifically, a rat study showed that capsaicin inhibited
study found that fat digestion was enhanced by the spice
the activity of epidermal arylhydrocarbon hydroxylase. This
cocktail because of increased secretion of bile salts and
inhibition blocked the activation and binding of the
stimulation of other pancreatic enzymes. It was also found
carcinogen benzopyrene to DNA which prevented it from
that the spice cocktail increased energy expenditure in the
mutagenizing the DNA (Aggarwal et al., 2007).
rats, which prevented the accumulation of the digested fats
(Prakash & Srinivasan, 2011). This study differs from the first supplementation, 45 minutes before the repeated sprint test
in that it shows a mechanism of action for the capsaicin and immediately after the repeated sprint test. Several
induced weight loss. perceived symptoms were also recorded which included
perceive exertion, gastrointestinal distress, and muscle
soreness. This data was collected one minute before the test,
Clinical Studies during the test, and one minute after the test. Muscle soreness
Many of the in vivo studies about energy expenditure and was also measured three days after the test. The capsaicin
weight control effects of Capsicum annuum focused on increased the amount of gastrointestinal symptoms 6-fold. It
capsaicin. A clinical study showed that capsinoids, which are did not influence performance on the sprint test. The study
non-pungent capsaicin analogs, activate brown adipose tissue concluded that capsaicin should not be recommended for
in humans. This activation increases energy expenditure, athletes involved in repeated sprints (Opheim & Rankin,
which could have implications in the use of capsaicin as a 2012).
weight loss aid (Yoneshiro, Aita, Kawai, Iwanaga, & Saito, Another recent study tested the tolerability of a capsaicin
2012). In this same study, participants ingested an oral dose of patch on human patients for treatment of neuropathic pain. In
the capsinoids under warm conditions. The energy this case, three other topical anesthetics were used as a
expenditure was measured under both warm and cold pretreatment in the patients. It was generally safe and well
conditions. The subjects in the negative control and placebo tolerated in the patients (Webster et al., 2011). Two clinical
group did not show the same amount of energy expenditure trials also conducted in 2011 compared Qutenza, a new high
(Yoneshiro et al., 2012). potency capsaicin patch, to existing capsaicin patches (Jones,
Capsaicin has demonstrated anti-carcinogenic activity in both Moore, & Peterson, 2011). It was found that the Qutenza patch
in vitro and in vivo studies. One study completed in 2002 reduced the numeric pain rating scale (NPRS) score at higher
showed that the vanilloid compounds that make up capsaicin rates than the control capsaicin patch (Jones et al., 2011).
induce oxidative stress and contributes to the death of tumor However, the Qutenza must be administered under a doctor’s
cells from human cutaneous squamous cell carcinoma, which care and comes with a risk of application site pain and
is a form of skin cancer (Surh, 2002). erythema (Jones et al., 2011).
A crossover placebo controlled study was conducted that
included nineteen health male athletes with experience Contraindications
(Opheim & Rankin, 2012). The purpose of the study was to
assess the influence of capsaicin on inflammation and exercise The contraindications found in Capsicum annum other than
performance. The same group was used for two trials, a the risks of application site pain and erythema associated with
placebo study and a capsaicin study. After each the Qutenza pain patch (Jones et al., 2011). C. annuum is also
supplementation period, the subjects completed repeated an emetic (Andrews, 1995). Further research into this area
sprint tests. Additionally, blood was drawn before may prove otherwise.
many members of the Solanaceae family as well as other
brightly colored fruits contain polyphenols, which have
antioxidant properties. The fruits have a rich plant chemistry
that contributed a promising drug in capsaicin. Interestingly,
this fruit has been used for similar reasons in different
cultures across the globe. This is a nod to the knowledge of
indigenous peoples that embrace the natural world. Though it
is consumed primarily as a food source, there may be other
traditional medical uses for it. For example, my mother and
Figure 4. Capsaicin Pain Cream many other West Africans use a pepper soup as a normal food
(Source: http://drugster.info/drug/medicament/4073/) as well as a treatment for colds and respiratory ailments. This
plant is very influential worldwide and deserves to be the
subject of more ethnobotanical research.
Current Use in Allopathic and CAM Therapies References Cited
Topical capsaicin in complementary and alternative medicine Aggarwal, B. B., Surh, Y.-J., & Shishodia, S. (2007). The molecular
is used in the treatment of various ailments like rheumatoid targets and therapeutic uses of curcumin in health and
arthritis (Richards, Whittle, & Buchbinder, 2012) and disease Advances in experimental medicine and biology v 595
peripheral neuralgia (Webster, Peppin, Murphy, Tobias, & (pp. 1 online resource (xxi, 489 p.)). Retrieved from
http://getitatduke.library.duke.edu/?sid=sersol&SS_jc=TC0
Vanhove, 2012). It can come in a cream form or as a patch
000204969&title=The%20molecular%20targets%20and%
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2011). h%20and%20disease
Andrews, J. (1995). Peppers : the domesticated Capsicums (New ed.).
Discussion Austin: University of Texas Press.
Capsicum annuum L. is a very diverse species. There are many Chatterjee, S., Asakura, M., Chowdhury, N., Neogi, S. B., Sugimoto, N.,
Haldar, S., . . . Yamasaki, S. (2010). Capsaicin, a potential
varieties under the C. annuum umbrella that have many
inhibitor of cholera toxin production in Vibrio cholerae.
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not a lot of scientific studies that describe the ethnobotanical
uses of C. annuum as it relates to specific cultures and uses. Chularojmontri, L., Suwatronnakorn, M., & Wattanapitayakul, S. K.
(2010). Influence of capsicum extract and capsaicin on
The peppers included under this umbrella are widely used as
endothelial health. J Med Assoc Thai, 93 Suppl 2, S92-101.
a food and flavoring source worldwide, even though they are
native to South America. There is evidence that C. annuum, like Ding, Y., Arai, M., Kondo, H., & Togari, A. (2010). Effects of capsaicin-
induced sensory denervation on bone metabolism in adult
rats. Bone, 46(6), 1591-1596. doi: S8756-3282(10)00482-5 (Capsicum annuum L.) and their antioxidant effects.
[pii]10.1016/j.bone.2010.02.022 [Research Support, Non-U.S. Gov't]. Arch Pharm Res, 32(10),
1345-1349. doi: 10.1007/s12272-009-2001-8
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(2011). Cytotoxic potential of Indian spices (extracts) Materska, M., & Perucka, I. (2005). Antioxidant activity of the main
against esophageal squamous carcinoma cells. Asian Pac J phenolic compounds isolated from hot pepper fruit
Cancer Prev, 12(8), 2069-2073. (Capsicum annuum L). J Agric Food Chem, 53(5), 1750-1756.
doi: 10.1021/jf035331k
Guarrera, P. M., Lucchese, F., & Medori, S. (2008).
Ethnophytotherapeutical research in the high Molise region Nevius, E., Srivastava, P. K., & Basu, S. (2012). Oral ingestion of
(Central-Southern Italy). [Comparative Study]. J Ethnobiol Capsaicin, the pungent component of chili pepper, enhances
Ethnomed, 4, 7. doi: 10.1186/1746-4269-4-7 a discreet population of macrophages and confers
protection from autoimmune diabetes. Mucosal Immunol,
Huh, S. U., Kim, K. J., & Paek, K. H. (2012). Capsicum annuum basic
5(1), 76-86. doi: 10.1038/mi.2011.50
transcription factor 3 (CaBtf3) regulates transcription of
pathogenesis-related genes during hypersensitive response Opheim, M. N., & Rankin, J. W. (2012). Effect of capsaicin
upon Tobacco mosaic virus infection. [Research Support, supplementation on repeated sprinting performance. J
Non-U.S. Gov't]. Biochem Biophys Res Commun, 417(2), 910- Strength Cond Res, 26(2), 319-326. doi:
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Ishtiaq, M., Hanif, W., Khan, M. A., Ashraf, M., & Butt, A. M. (2007). An Prakash, U. N., & Srinivasan, K. (2011). Fat digestion and absorption
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Capsicum annuum L. (bell pepper) varieties using high-
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J. K., & Vanhove, G. F. (2011). Tolerability of NGX-4010, a
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herpetic neuralgia. BMC Anesthesiol, 11, 25. doi: Nonpungent capsaicin analogs (capsinoids) increase energy
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Webster, L. R., Peppin, J. F., Murphy, F. T., Tobias, J. K., & Vanhove, G.
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10.2147/JPR.S25272 012-1592-1
Carica papaya L., Caricaceae
Apollonia Wenting Kang
Introduction
Carica papaya, an arboreal, herbaceous, and monosexual plant
from the small Caricaceae family, is of Central America origin
(Doughari, Elmahmood, & Manzara, 2007). Of the four species
within the Carica genus, Carica papaya L. is the most
commonly cultivated species among others (Krishna,
Paridhavi & Patel, 2008). Other names of papaya include
papali in India, tepaya used by Kadazan Dusun community in
Malaysia, betik in Peninsular Malaysia, pawpaw in Sri Lanka,
lechosa in Venezuela, Ibebe in Yoruba-Nigeria, or Okroegbe in
Igbo-Nigeria, all speaking volumes of its widespread
availability in a diversity of regions worldwide (Anuar, Zahari,
Taib & Rahman, 2008). Although it originates from Central
America, specifically, Costa Rica, Mexico and Panama,
nowadays it grows and is cultivated in almost all tropical and
sub-tropical regions around the world.
Major chemical compounds responsible for papaya remedies
include vitamins, minerals, polysaccharides, proteolytic
enzymes, citric acid, alkaloids, flavonoids, and proteins like
chemopapain, papain, and carpain. Different concentrations of
those bioactive compounds render different parts of papaya a
wide spectrum of medicinal uses. It has been widely
cultivated and consumed as a fruit containing a wide array of
nutrients, and is also commonly used in daily diets as
vegetable. Its medicinal properties have been exploited in
therapeutic remedies, both traditionally and currently, mainly Figure 1. Carica papaya L. trees (source:
because it is thought to contain some antimicrobial, immune- http://www.henriettesherbal.com/pictures/p03/pages/carica-
stimulating and anti-oxidant agents that are beneficial for papaya-2.htm)
wound healing (Canini, Alesiani, D’Arcangelo, & Tagliatesta,
2007). In a related vein, immature fruits and roots are famous transparent aril (Figure 2). Usually only trees younger than
for their abortifacient properties (Cherian, 2000); 18 months old inoculate. Papain-containing milky juice will
consequently, its seeds are now strong candidates for anti- leak out if leaves and unripe fruit are cut. C. papaya plants are
fertility drugs with great efficacy and negligible side effects omnipresent in tropical and subtropical regions worldwide,
(Lohiya et al., 2000). The latex and the seeds are also used in after being distributed from Central America to Malaysia,
the treatment of gastrointestinal nematode infections called India, China, Sri Lanka, and Africa. Papaya is commonly grown
Heligmosomoides polygyrus, because of its anthelmintic for commercial purposes, but it is grown in home gardens as
activity (Doughari, Elmahmood, & Manzara, 2007). The leaves well.
relieve gastrointestinal upsets, serving as an expectorant.
Papaya leaves also dispel asthma, fever, and amoebic
dysentery. Methanolic leaf extracts demonstrated vasodilatory
and anti-oxidant effects, lowering cardiovascular risks
(Runnie et al., 2004).
C. papaya is a popular choice of edible fruit because of its
palatable, juicy taste, nutritive value and easy digestion (Monti
et al., 2004). Its physical appearance resembles palm trees.
The height of its tree may range from 3 to10 meters (Krishna
et al., 2008). A scar marks every spot where leaves have fallen
off on the fleshy stem. On the top of the tree there stands a
canopy made of long petioles with leaves and five to seven
lobes (Figure 1). Male flowers are fragrant, trimorphic, and
unisexually dioecious, with tips of pendulous, hollow rachis
covered by dense pubescent cymes (Krishna et al., 2008). By
contrast, nurturing large berries in various sizes, female
flowers are large, solitary, and shaped in few racemes with a
short thick rachis (Krishna et al., 2008). It is worth pointing
out that the polygamous attribute of papaya seeds pose a
challenge to identify whether a plant is male, female or
hermaphrodite. The racemes extend to form a globular
structure with a large cavity in the middle, where the black Figure 2. Flowers and fruits with seeds of Carica papaya L.
seeds of papaya are lumped together and enfolded in a (Source: http://botanical.com/botanical/mgmh/p/papaw-02.html)
Traditional Uses Contraceptives and abortifacient agents
Dietary supplements Papaya seed extracts have been traditionally used as a
Given their richness of nutrients and anti-oxidative promising male contraceptive in various parts of Assam in
components, papaya leaves also serve culinary functions as a northern India (Tiwari et al., 1982). The Kadazan Dusun
vegetable. Papaya leaves are also popular as medicinal drinks community in east Malaysia uses the decoction of papaya root
in manufacture of teas and infusions (Canini et al., 2007). The as an effective tool of birth control by stopping menstruation
black seeds are known for a spicy, sharply bitter taste, to the (Fasihuddin & Ghazally, 2003). Indians use papaya roots
extent that sometimes they replace black pepper in cooking in assuredly because papaya fruits work effectively without
India (Krishna et al., 2008). In south Asia, the young, green known effect on the reproductive tract morphology (Bitto et
leaves of papaya are steamed and consumed like other al., 2006).
vegetables (Krishna et al., 2008). Indian traditional beliefs dictate that unripe fruits of plants
such as papaya, banana and pineapple are “hot, fiery” food
that promotes rapid blood flow in uterus and thus inducing
Chronic diseases miscarriages (Tiwari et al., 1982). In India and Assam, the
Aborigines from Central America are aware of the anti-oxidant combination of C. papaya and resin from Ferula narthex are
properties effective in preventing several chronic diseases used in abortive procedures (Tiwari et al., 1982).
such as cardiovascular disease, cancer, and diabetes
(Murakami et al., 1994). Researchers agreed with this
traditional use of papaya, because they found out that unripe Skin diseases and infections
pulp of C. papaya treats congestive heart failure effectively In Cambodia, Laos and Vietnam, C. papaya latex is used to
due to its abundant carbohydrate and starch (Oloyede, 2005). treat genital wounds, eczema and psoriasis (Amenta et al.,
2000). Topical application is the most common traditional use
of C. papaya (Gurung & Basnet., 2009). Ethnobotanical
Expectorant and antibacterial agents practitioners mention that fully mature but unripe fruit of
The immature fruit and seeds are known to inhibit growth of papaya contains more latex than that in ripe papaya, thus
human enteric pathogens, hence unripe papaya fruits are containing more wound-healing constituents (Krishna et al.,
often remedies for gastrointestinal upset in tropical regions 2008).
(Osato et al., 1993). Moreover, Africans also recognized the
bacteriostatic activity of papaya, so African hospitals use
unripe fruit to cure skin trauma and burns (Starley et al., Respiratory and intestinal complications
1999). Carica papaya L. is used for the treatment of bronchitis in the
Atlantic Forest coastal region in Brazil (Figueiredo, Leitao-
Filho, & Begossi, 1997). In Ayurvedic medicine, different parts
of papaya are utilized frequently to treat constipation, benzylglucosinolate
diarrhea, and gonorrhea (see Table 1). Leaves Flavonols (kaempferol and Young leaves as vegetable,
quercetin), caffeic acid, jaundice, urinary
Part Main Bioactive Medicinal Uses
alkaloids carpain, complaints & gonorrhea
Compounds
pseudocarpin and (infusion), dressing
Fruits Protein (papain etc.), fat, Ripe fruits: digestive, dehydrocarpain I and II, wounds (fresh leaves),
fiber, polysaccharides, stomachic, carminative, carposide, vitamin C and E antimicrobial activity,
minerals (calcium, diuretic, dysentery and vermifuge, in colic, fever,
phosphorous, iron), chronic diarrhea, beriberi, abortion
vitamins A and C, carotene, expectorant, sedative and (infusion), ashma (smoke)
riboflavin, thiamine, amino tonic, obesity-relieving,
Flowers Not known Jaundice, emmenagogue,
acids, citric and malic bleeding piles, febrifuge and pectoral
acids, volatile compounds urinogenital wounds,
properties
(linalool, ringworm and skin
Stem β-sitosterol, glucose, Jaundice, anti-haemolytic
benzylisothiocyanate), infections, psoriasis
Bark fructose, sucrose, galatose activity, sore teeth (inner
alkaloid, carpaine, bezyl-β- Unripe fruits: Laxative,
bark), antifungal activity,
D-glucoside diuretic, dried fruit
STD
reduces enlarged spleen
and liver, antidote for Latex Proteolytic enzymes Anthelmintic, relieves
snakebite, abortifacient, (papain, chemopapain, dyspepsia, cures diarrhea,
anti-impalantation activity glycyl endopeptidase and pain of burns and topical
and antibacterial activity caricain), chinitase, use, bleeding
linamarase, chymopapains haemorrhoids, stomathic,
Juice N-butyric, n-hexanoic and Seed juice treats bleeding
A, B and C, peptidase A and whooping cough
n=octanoic acids, lipids; piles and enlarged liver
B and lysozymes
myristic, palmitic, stearic, and spleen
linoleic, linolenic and oleic
acids Table 1. Chemical constituents in different parts of Carica
Seeds Fatty acid, crude protein, Carminative, papaya L. and their corresponding therapeutic uses
crude fiber, papaya oil, emmenagogue, vermifuge, (adapted from table 2 and 3 in Krishna, Paridhavi and Patel, 2008)
carpaine, carpsemine, abortifacient, counter
benzylisothiocyanate, irritant, as paste in the Miscellany
myrosin, caricin, β- treatment of ringworm
sitosterol and psoriasis, male In Kelantan, a province of Malaysia, the latex of unripe fruit of
contraceptives papaya is used as a poison for criminal purposes (Wiart,
Roots Carposide, myrosin, Abortifacient, diuretic, 2006). However, C. papaya juice is traditionally known as an
saponins, tannins, antifungal, checking antidote (Wiart, 2006). In India, papain, a prominent
alkaloids, glycosides, bleeding from the uterus compound extracted from fruit and stem latex is used in
phenols, and piles
brewing and fermentation of wine, and in the textile and calming agent to the heart, thus lower risks of cardiovascular
tanning industries (Krishna et al., 2008). Generally, fermented disease (Canini et al., 2007).
papaya acquire antioxidant properties related to both
hydroxyl scavenging and iron chelating properties targeting at
superoxide and hydroxyl radicals (Imao et al., 1998). Seed Latex
juice treats bleeding piles, enlarged liver and spleen (Imao et The papaya latex is famous for providing four cysteine
al., 1998). Stem bark relieves sore teeth (Krishna et al., 2008). endopeptidases, namely papain (see Figure 3), chemopapain,
For more uses, please refer to Table 1. glycyl endopeptidase and caricain (Azarkan et al., 2003).
Chemopapain in latex after purification has shown
immunological properties (Krishna et al., 2008). The latex
from unripe papaya fruits contains a mixture of antifungal
A considerable amount of chemical compounds and chinitases, protease inhibitors, linamarase, and proteins
biochemical activities in Carica papaya were identified, but without known functions (Azarkan et al., 2004).
very little has been published on the percentages of the
chemical compositions of different compounds in papaya. As
alluded to previously, different structures of papaya contain
different bioactive components (Table 1).
Leaves
Phytochemical analysis identified secondary metabolites,
particularly phenolic compounds, from the leaves of C. papaya,
using the technique of gas chromatography-mass
spectrometry (Canini et al., 2007). The majority of the free
phenolics are flavonols, such as kaempferol and quercetin,
which have shown anti-oxidant and anti-carcinogenic
activities. Caffeic acid, also one type of phenolic acids, is the
most abundant of all the identified compounds. Figure 3. Molecular structure of papain (source:
http://linus.chem.ku.edu/hewlett/Chem188/Enzyme/enzyme_bac
kground.htm)
Seeds
Alkaloids like carpain and carpsemine, which render papaya Roots
seeds a bitter taste, have been reported as a depressant,
The phytochemical analysis of root extracts of C. papaya is Anti-amoebic. The diarrhea-causing intestinal ameobiasis is
indicative of the presence of the following phytoconstituents: now a dangerous disease in tropical regions. Fully mature
saponins, alkaloids, tannins, glycosides, and phenols papaya seeds macerated in aqueous solutions exhibited anti-
(Doughari et al., 2007). amoebic activity against Entamoeba histolytica (Tona, Kumbu,
Ngimbi, Cimanga, & Vietinck, 1998).
Biological Activity Anti-malarial. The petroleum ether extract of the rink of raw
papaya fruit has shown noteworthy antimalarial property. The
In vitro rinds of papaya are normally discarded after consumption as
Antimicrobial. The agar cup plate method showed that the waste; if the rinds can be exploited for antimalarial activity,
seed and pulp of both ripe and unripe papaya effectively kill there may be impressive commercial and health benefits
parasitic enteropathogens such as Bacillus subtilis, Escherichia (Bhat & Surolia, 2001).
coli, Salmonella typhi, Staphylococcus aureus, Proteus vulgaris Antifungal. Partnered with Fluconazole, papaya latex
and Pseudomonas aeruginosa (Krishna et al., 2008). Gram- demonstrated synergic actions in the suppression of Candida
negative bacteria were more susceptible to the extracts, yet albicans growth by degrading fungal cell wall (Giordani,
both gram-negative and gram-positive bacteria, including E. Siepaio, Moulin-Traffort, & Regli, 1991). The fungistatic effect
coli, S. aureus, B. cereus and S. pyogenase, were inhibited by C. is accomplished by breaking down the polysaccharides
papaya root extracts (Doughari et al., 2007). This result does components of the outmost wall of defense in fungal cells and
not only validate the topical use of C. papaya extracts in forcing cell debris into the culture medium. Another
traditional treatment of ailments, but also gives rise to advantage is that only minimal protein concentration is
possibilities of developing therapeutic substances against required for papaya latex to be antifungal (Giordani et al.,
multidrug-resistant organisms. 1991).
Anthelmintic. The air-dried papaya seeds, cheap, natural, Antioxidant. The contribution of L-ascorbic acid (AA), a
easily accessible, and generally regarded as safe, significantly measure of antioxidant capacity, to the scavenger hunt of free
eliminate harmful human intestinal parasites. radicals was 48% in solo papaya and 62.3% in foot long
Benzylisothiocyanate, a main component in seeds, plays a key papaya, indicating the extraordinary potential in slowing
role in determining its anthelmintic properties. Ethanol down cell aging and cellular damage due to oxidation (Leong
extracts of papaya possess a promising potential of anti- & Shui, 2002).
parasitic action, directly impacting eggs, infective larvae and
adult Haemonchus contortus (Hounzangbe-Adote, Paolini, Immunomodulatory. Fermented papaya preparation exerted
Fourastel, Moutairon, & Hoste, 2005). Organic extracts were immunomodulatory actions on the macrophage cell line called
more effective than aqueous extracts in defending against RAW 264, which initiates the damaging actions of macrophage
drug resistance, because the active components dissolve cells, thereby intensifying nitric oxide synthesis and TNF-
better in organic solvents (Olafsdottir et al., 2002). alpha secretion to benefit the growth and repair of the
organism (Rimbach et el., 2000).
consecutive days (Lohiya, Mishra, Pathak, & Maniyannan,
In vivo 1999). Chloroform extracts of papaya seeds are extremely
anti-fertile, because they selectively target new-born germ
Antimicrobial. Papaya seeds demonstrably have bacteriostatic cells; in other words, prolonged treatment can develop into
actions on both Gram-positive and Gram-negative organisms, azoospermia and reversible sterility (Lohiya, Goyal,
which may potentially become a valid treatment of chronic Jayaprakash, Ansari, & Sharma, 1994). Toxicological
skin ulcers (Krishna et al., 2008). In diabetic rats, the aqueous assessments of papaya seed extracts have reached consistent
extract of fruit still exhibited antimicrobial activity and conclusions: the drug was free of adverse side effects (Lohiya,
enhanced wound healing process (Nayak, Pereira, Pinto, & Pathak, Mishra, & Maniyannan, 2000). Papaya seed extract
Maharaj, 2007). also changes the biochemical operations and the contractile
Abortifacient. Varying doses of papaya latex extract pattern of vas deferens, thus even a short term administration
differentially strengthened the uterotonic contractile activity of an aqueous extract of papaya seed yielded a shortage of
in rats during the proestrus and estrus stages of the estrous androgen, leading to anti-fertility effects (Chinoy & George,
cycles, eliciting prolonged uterine contraction and thus 1983).
facilitating parturient delivery, due to the harm induced by In terms of female antifertility, papaya root extract has been
benzylisothiocyanate on the myometrium (Adebiyi, Ganesan, suggested as containing bioactive compounds in the induction
& Prasad, 2003). of morphological changes in the endometrial surface
Contraceptive. Speaking of male antifertility properties of epithelium in albino rat uterus (Sharma & Mahanta, 2000).
papaya, the pronounced hypertrophy and hyperplasia of The disorientation of cells and diminishing microvilli on
pituitary gonadotrophs have been identified in papaya seed epithelium account for the anti-fertile properties of the root.
extracts. Genital epithelium cells were degenerated post- Additionally, the organic and aqueous extracts of papaya
treatment, leading to confirmation of the antifertility activity seeds restrain ovulation in female rabbits (Kapoor, Garg, &
of papaya seeds (Uche-N, Ezeokoli, Adogwa, & Offiah, 2001). Mathur, 1974). Aqueous seed extract exhibited abortifacient
Besides, after 3 weeks of treatment, the cavities of the actions on female Sprague Dawley rats, whereas interestingly
seminiferous tubules were significantly emptier in the the extracts were shown to have neither anti-zygotic nor anti-
experimental mice, indicating ceased spermatogenesis (Uche- implantation activities on female rabbits (Bodhankar, Garg, &
N et al., 2001). The benzene chromatographic portion of the Mathur, 1974).
chloroform extracts from the seeds elicits revocable male Anthelmintic. Heligmosomoides polygyrus was inhibited by the
contraceptive possibility without apparent toxicity, by anthelmintic latex of papaya in experimentally infected mice,
immobilizing sperms, diluting sperm concentration and proposing a potential anthelmintic agency against stubborn
lowing viability of sperms in male langur monkeys, male adult intestinal nematodes in most mammalian hosts (Satrija,
rabbits and male albino rats (Lohiya, Manivannan, Goyal, & Nansen, Murtini & He, 1995). Papaya latex has also shown
Ansari, 2008). The sharp decline in numbers of sperm is called 100% anthelmintic efficacy against a common infection of
oligospermia, which can be reached after treatment of 75 Ascaris suum found in pigs (Satrija, Nansen, Bjorn, Murtini &
He, 1994). Papaya extracts also possess does-dependent, ring contractions (Runnie, Salleh, Mohamed, Head, &
anthelmintic activity on the egg, larvae and adult worms of Abeywardena, 2004).
Triochostrongylus colubriformis (Hounzangbe-Adote,
Wound healing. Wound healing entails three phases in
Fouraste, Moutairou & Hoste, 2005).
sequence: inflammation, proliferation and maturation
Diuretic. The root extract of papaya has shown potent efficacy (Diegelmann & Evans, 2004). C. papaya latex aids all three
in treating dysuria because it exerts diuresis in treated rats phases. Extracts of green papaya accelerated healing of
(Spripanidkulchai et al., 2001). Orally taken extracts of papaya wounds in mice, due to the antimicrobial and antioxidant
root yielded increased frequency of urination in rats properties (which reduce any potential oxidative damage to
(Bungorn, Varima, Pisamai, Jamsai & Dusit, 2001). the tissues) from the proteolytic enzymes, chymopapain and
Antioxidant: As free-radical scavengers, fermented papaya papain in the epicarp (Osato et al., 1993). Mahmood et al
preparation is able to repair oxidative DNA damage due to (2005) replicated the same results that the extracts speeded
hydrogen peroxide in rat cells (Marotta, Yoshida, Barreto, up wound-healing process in rats. Papaya latex significantly
Naito, & Packer, 2007). It may also facilitate the reversal of increased collagen synthesis, as indicated by incremental
inflammation in cirrhosis due to oxidation by hepatitis C. virus hydroxyproline content (Gurung & Basnet, 2009). Growth in
(Marotta et al., 2007). By and large, yeast fermented papaya hydroxyproline content suggests faster collagen synthesis
may have a potentially supportive role in regulating any turnover, thus promoting more rapid wound healing. Wound
neurological diseases that involve the damages caused by free contraction, another variable measuring wound healing
radicals (Imao, Wang, Komatsu, & Hiramatsu, 1998). process, was more intense and frequent, after the application
of papaya latex (Dawkins, Hewitt, Wint, Obiefuna, & Wint,
Hepatoprotective. The ethanol extracts of papaya fruit 2003). Higher levels of wound contractions indicate that the
significantly alleviate induced hepatotoxicity, but the tissues have acquired greater reparative properties to shrink
mechanism of action remains unknown (Krishna et al., 2008). the wound more quickly. The epithelialization time, the third
Muscle relaxant and antihypertensive. Ethanol extract of parameter quantifying wound healing, was largely reduced
papaya seeds have dose-dependent, irreversible deactivation than that in untreated groups (Dawkins et al., 2003).
of jejunal shrinks in rabbits (Adebiyi & Adaikan, 2005).
Moreover, pentane extract of papaya seeds were found to
have muscle-weakening effects on the carotid arteries of dogs Clinical Studies
(Wilson, Kwan, Kwan, & Sorger, 2002). Ethanol extract of Systematic studies evaluating the pharmacological and
unripe papaya fruit bears a calming effect on arterial pressure, therapeutic properties of C. papaya are limited. Unripe papaya
much stronger than that of hydralazine in rats with extracts were shown to have antisickling activity that puts off
hypertension. Hence, fruit juice of papaya potentially involves the sickling of hemoglobin on sickle cell patients (Oduola et al.,
antihypertensive components (Abeywardena et al., 2000). 2006). Oral ingestion of C. papaya extracts during different
Papaya leaves also afford potent depressant actions on aortic stages of pregnancy exerted various effects on embryonic
development, such as anti-implantation activity, increased
post-implantation loss and embryotoxicity (Oderinde et al., papaya could be dangerous in pregnancy (Adebiyi et al.,
2002). In terms of wound-healing, topical treatment of mush 2002).
pulp of C. papaya containing papain and chemopapain on
Of note, papaya should be used with caution in the treatment
human skin facilitates desloughing of necrotic tissue,
of urinogenital disorder like trichomoniasis to avoid overdose
granulation and healing, and reduces odor in chronic skin
toxicity. Higher concentration of papaya seed extracts is
ulcers (Hewitt et al., 2000). The mechanism of action may
cytotoxic, given the increased membrane permeability to
include proteolytic enzymes such as chemopapain and papain
calcium ions (2+; Wilson, Kwan, Kwan, & Sorger, 2002).
exerting antimicrobial activities (Starley, Mohammed,
Schneider, & Bickler, 1999). Most importantly, C. papaya
demonstrated purported potential in improving immunity. In
fact, C. papaya seed extract enhanced the phytohemagglutinin
responsiveness of lymphocytes in vitro, indicating the Current Use in Allopathic and CAM Therapies
immunostimulatory actions (Mojica-Henshaw et al., 2003). Burns and trauma wounds are common in both developing
Nevertheless, researchers have yet to replicate this finding on and developed countries. But because of the heavy financial
humans. burden on citizens of developing countries, burn wounds
impose a bigger challenge to local healthcare systems (Gurung
& Basnet, 2009). The promising wound shrinking capacity of
Contraindications papaya offers people in developing countries an economical
Bioactive compounds such as papain and chymopapain lead to approach to relieve financial burdens.
intense uterine contractions, accounting for the abortifacient Papaya is praised for its nutritional value as it is low in
properties of papaya. However, papaya latex only causes such calories and rich in natural vitamins and minerals (Krishna et
voluntary uterine contractions if other enzymes or alkaloids al., 2008). Papaya is ranked in the top tiers among all fruits for
have induced increased estrogen levels (Cherian, 2000). Crude vitamin C, vitamin A, riboflavin, folate, calcium, thiamine, iron,
papaya latex may play a similar role as oxytocin in causing niacin, potassium and fiber (Krishna et al., 2008). Papaya
spasmodic contraction of the uterine muscles via the notably increases iron absorption in rice meals. Ripe papaya
suppression of progesterone. Progesterone is crucial because fruit is highly recommended for obese people on diet due to
it affirms that the fertilized ovum will not be dislodged and its relatively low concentration of calories (32 kcal/100g;
that no more ova will be released. However, Schmidt (1995) Krishna et al., 2008). Papaya has high carotene content in
suggested that pure papain itself up to a dose of 800 mg/kg (in comparison with other common fruits such as organs, apples,
rats) neither intoxicated the maternal organism nor guavas and plantains, lending hands to its excellence at
jeopardized the embryonic development. Due to the different stopping free radicals from oxidizing body tissues. Unripe
chemical contents between the ripe and the unripe, green papaya differs in nutritive contents from ripe papaya
reasonable intake of ripe papaya during pregnancy should not the most in terms of the lack of carotene. As a popular choice
impose any hazardous consequence, whereas the unripe of vegetable in salads, juices, pies and confections, green
unripe papaya ensures sufficient supply of vitamins to chronic skin ulcers patients who have developed drug
maintain good eyesight. Papaya is rich in a diversity of resistance against most lab-synthesized drugs because its
enzymes with papain being the major one. Papain, vegetable chemically diverse compounds make bacteria and parasites
pepsin, works well under different pH environments (acidic, more susceptible to antibiotics.
alkaline, or neutral). Papain comforts the digestive system and
slows down bowel movement. Adding raw papaya to recipes
with meat prevents people from dyspepsia. It also stretches Discussion
people’s tolerance of certain proteins which would not be Although Carica papaya L. is commonly recognized for its
digested without treatment of crude papain (Krishna et al., edible and nutraceutical values throughout the world, its
2008). Papaya, if fermented, becomes a more powerful medicinal and therapeutic properties should not be taken
antioxidant. Another enzyme in papaya, the papaya lipase, acts lightly. Traditionally, people have been exploiting various
like a biocatalyst that hydrolyzes the water insoluble portion ethnopharmacological functions of the different structures of
of crude papain to build up a protective trench against aging papaya (see Table 1). Primarily, papaya extracts are
oxidants in elderly patients. responsible for desloughing necrotic tissue, prevention of
Bionormalizer, an effective antioxidant health food from Japan infection, and the antimicrobial and antioxidant properties
that is mostly consisted of fermented papaya, enhances the associated with hydroxyl scavenging and iron chelating. The
haemorrheology in alcoholics either by direct activation of the reliance on ethnobotanical remedies such as papaya reduces
lipoperoxidation and xanthine oxidase system, or by the financial burden of people in developing countries where
alternating red blood cell membrane characteristics. It also insurance and healthcare systems are not sophisticated.
displays therapeutic actions against several pathological Besides, papaya is also frequently used in relieving
disorders, such as tumors and immunodeficiency, achieved by gastrointestinal upset, and even as “birth control pills” in
free radical scavenging as well as stabilization of an traditional medicine.
organism’s superoxide level. Bionormalizer normalizes In the modern era, attention has been drawn to its capacity in
superoxide level via the inhibition of the ferrous ions, which weakening drug resistance. The search for alternative sources
wither organisms. Currently, papaya seed extracts are of antibiotics encompasses a wide array of challenges, among
propelled as a nutritional supplement pertaining to revitalize which drug resistance remains the most burdensome.
the body (Mojica-Henshaw, Francisco, De Guzman, & Tingo, Infectious diseases cost us 50,000 deaths every day
2003). worldwide (Ahmad & Beg, 2011). The development of
Moreover, papaya fruit extracts are contained in the topical multidrug resistance further worsened the situation.
ulcer ointment used by nurses in the Spanish Town Hospital, Researchers thus turn to plants in the quest of new resources
Kinston Public Hospital, as well as the University Hospital of of antibiotic drugs with greater efficacy. Plants contain more
the West Indies in Jamaica, for its desloughing, granulating complex bioactive constituents that are unlikely to be
and healing properties (Hewitt, Whittle, Lopez, Bailey, & synthesized in lab. In addition, chemical compounds in plants
Weaver, 2002). It is especially effective and cost-efficient for have been attached to valuable functions throughout the long
course of evolution. People in Asia, Latin America and Africa healing and during pregnancy. Food and Chemical
use natural plants as primary health remedies. Papaya seems Toxicology, 46, 2384-2389
to be a strong candidate for an alternative source of antibiotic Ballot, D., Baynes, R. D., Bothwell, T. H., Gillooly, M., Macfarlane, J.,
to fight off multidrug resistance. MacPhail, A. P., ... & Bothwell, J. E. (1987). The effects of fruit
juices and fruits on the absorption of iron from a rice meal.
Taken together, C. papaya contributes a significant amount to
British Journal of Nutrition, 57(03), 331-343.
maintain overall human health, by enriching daily diets, curing
infections, combatting against drug resistance, garnering free Bhattacharjee, S. K. (2000). Handbook of medicinal plants. Aavishkar
radicals, and rejuvenating our bodies. Researchers have Publishers, pp. 1-71.
replicated findings consistently on a diversity of animals in Bhat, G. P., & Surolia, N. (2001). In vitro antimalarial activity of
vivo, all suggesting the effectiveness of C. papaya chemicals. extracts of three plants used in the traditional medicine of
Going forward, more human clinical trials should be India. The American journal of tropical medicine and
implemented to investigate if the same effects hold for hygiene, 65(4), 304-308.
humans. I suggest future clinical studies on human subjects Bodhankar, S. L., Garg, S. K., & Mathur, V. S. (1974). Antifertility
focus on the following aspects: antibacterial activity against screening of plants. Part IX. Effect of five indigenous plants
skin diseases, birth control efficacy on humans, multidrug on early pregnancy in female albino rats. The Indian journal
resistance on various bacteria, antihypertensive properties in of medical research, 62(6), 831.
preventing cardiovascular diseases, and anti-carcinogenic Bungorn, S.,Varima, W., Pisamai, L., Jamsai, S., and Dusit, J. (2001)
activities treating cancer. Diuretic effect of selected Thai Indigenous medicinal plants
in rats. Journal of Ethanopharmacology, 75, 185-190.
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Castanea sativa Mill., Fagaceae
Sam Anderson
Introduction
Castanea sativa Mill., also known as sweet chestnut, belongs to
the Fagaceae family. Additionally known by the common
names of marron, European chestnut, Spanish chestnut, and
Portuguese chestnut, C. sativa fruits are a popular food item
on nearly every continent (De Vasconcelos, Bennett, Rosa, &
Ferreira-Cardoso, 2010). A mid-sized tree that originated in
the Mediterranean areas of Europe over ninety million years
ago, C. sativa has spread throughout the rest of the continent
and into parts of western Asia and northern Africa (Lim,
2012). Archeological evidence indicates that the sativa species
surfaced in Asia Minor where it was first domesticated. The
advent of the Roman Empire shortly thereafter greatly
expanded the species’ range into areas of western and
northern Europe where it became a prominent food source for
rural populations (De Vasconcelos et al., 2010; Ketenoglu, Tug,
& Kurt, 2010). Thus, European populations have relied on
sweet chestnut for their nutritional value for nearly 3,000
years, and its popularity has migrated across oceans and over
mountains to both Asia and America where high consumption
occurs. Although edible, chestnuts are infrequently eaten raw,
and most often the nuts are cooked, boiled or baked in order
to enhance the taste, modify the texture, and increase
nutritional value (De Vasconcelos et al., 2010).
Despite this widespread use as a food source, sweet chestnut
also harbors several medicinal properties that greatly benefit
human health. As early as the first century, C. sativa was used Figure 1. C. sativa Catkins Hanging from Elliptical Leaves.
for its astringent and antitoxic capabilities evidenced in the The jagged edges of elliptical leaves hanging down form a
works of an early pharmacologist, Pedanius Dioscorides (De tomentose arrangement of leaves. Yellow catkins sit on top of
Vasconcelos et al., 2010). Since antiquity, all parts of the sweet the leaves and extend upwards ("Photo Gallery," 2013).
chestnut plant—the bark, wood, leaves, fruits—have been
used in the Mediterranean and other areas of Europe to treat a
wide range of illnesses, including respiratory problems, skin
and soft tissue infections, inflammation, vascular problems,
diarrhea, wounds, and rheumatism among others (Budriesi et
al., 2010; Chiarini et al., 2013; Jarić et al., 2007; Quave, Plano,
& Bennett, 2011; Zlatanov, Antova, Angelova-Romova, &
Teneva, 2013). Recent studies have not only confirmed and
justified many of these traditional applications of C. sativa, but
they have also found new medicinal uses and potential
applications of various parts of the plant. Due to high
concentrations of phenolic compounds in nearly every part of
the plant, C. sativa leaves, bark, fruit, spines and wood have
demonstrated significant antioxidant activity and thus can be
used to prevent photo-aging, cancer, diabetes,
neurodegenerative diseases and other oxidative stress-
associated diseases (Grdovic et al., 2012). In addition to
widespread antioxidant activity, individual components of C.
sativa have demonstrated other significant disease-reducing
capabilities; various extracts have shown cardioprotective,
anti-quorum sensing, antispasmodic, anticancer, anthelmintic, Figure 2. Spiny Burrs Surrounding Chestnut Fruit.
and antibacterial activities (Bahuaud et al., 2006; Basile et al., The red-brown chestnut fruit is protected by spiny burrs of
2000; Budriesi et al., 2010; Chiarini et al., 2013; Frederich et female cupules or flowers lacking pedals ("Photo Gallery,"
al., 2009; Jedinak, Valachova, Maliar, & Sturdik, 2010; Quave et 2013).
al., 2011). Coupling its rich medicinal properties with its
excellent taste, C. sativa is a superb medicinal food and leaves with jagged edges seen in Figure 1 that it loses and
promising candidate for pharmaceutical development (De regrows seasonally. These pastel-green leaves generally reach
Vasconcelos et al., 2010). lengths between fourteen and twenty-eight centimeters and
widths of anywhere between five and nine centimeters
(Ketenoglu et al., 2010; Lim, 2012). The crown of C. sativa
Botanical Description expands significantly past the diameter of the trunk, and the
Castanea sativa is a mid-sized tree that reaches a maximum branches lay compressed over one another in a tomentose
height of 40 meters and a diameter of 2 meters. As a fashion. C. sativa catkins are either entirely male or
deciduous tree, sweet chestnut has narrow, oval-shaped androgynous with a few female flowers present as well. These
catkins hang down loosely and are pale blond (Lim, 2012). studies have found a large range of traditional uses, some of
Both male and female flowers lack petals, and the female which are unique to certain cultures and others that are
flowers take the form of light green, spiny cupules shown in shared across different societies. Throughout the
Figure 2. The fruit of sweet chestnut boasts a red-brown color Mediterranean, the leaves of C. sativa are ground and
and possess a diameter between 1.3 and 2.5 centimeters. (Lim, dissolved in boiling water to create a decoction to treat
2012). asthma, coughs, colds and other respiratory diseases (Chiarini
Native to the European regions surrounding the et al., 2013). In southern and eastern regions of Europe, the
Mediterranean, sweet chestnut is now found throughout fruit is used for pain relief, inflammation, vascular disorders
Europe, northern Africa and the Middle East (Lim, 2012). Due and burns (Zlatanov et al., 2013). Additionally, in southern
to its preference of locations that receive between 750 and Italy, the leaves are applied to the skin surrounding varicose
1200 mm of precipitation, C. sativa thrives in Mediterranean veins to diminish swelling (Quave et al., 2011). In northern
climates (Ketenoglu et al., 2010; Lim, 2012). With an extensive areas of Europe such as France, sweet chestnut leaves are
root system, sweet chestnut favors faintly acidic and loamy dissolved into a tea that alleviates diarrheal symptoms
soils that are well drained and allow its roots to penetrate (Budriesi et al., 2010). In regions of Turkey, the honey is used
deep into the earth. Although it prefers sunlight, the tree as an antibacterial to cover wounds, burns and ulcers of the
survives in shaded areas as well and has been found in regions skin (De Vasconcelos et al., 2010). The use of sweet chestnut
with altitudes ranging from sea level to 1500 m (Alía., 2003.; in traditional Slovak medicine in the Carpathian mountains is
Lim, 2012). Pollinated by both insects and wind, the recorded but no specific ailment or method of use is found
lightweight chestnut pollen can be carried up to 100 km from (Jedinak et al., 2010). The most detailed record of use of C.
its parent tree. Due to its wide distribution and expanding sativa is from an ethnobotanical study on the usage of wild
crown, C. sativa is a notable tree (Alía., 2003.; Lim, 2012). medicinal plants in central Serbia. In the area surrounding the
Kopaonik Mountain, the fruit of sweet chestnut is chopped
and dissolved in plum-brandy for six weeks and then
Traditional Uses internally taken as an astringent that lessens coughing and
relieves varicose vein pain (Jarić et al., 2007). Thus, Castanea
Ethnomedical Uses sativa has a wealth of traditional medicinal uses in various
Sweet chestnut has a wide range of traditional uses in areas of parts of Europe and the Mediterranean.
the Mediterranean and neighboring regions. During the
Roman Empire, Pedanius Dioscorides, a Greek physician and
author of a major pharmaceutical guide, recorded the use of Nonmedical uses
sweet chestnut for its astringent and antitoxic properties. In addition to the numerous medicinal applications of sweet
Throughout the Middle Ages, the uncooked chestnut seeds chestnut, the plant is also used for many other reasons. The
were used to treat cardiovascular problems in several areas of dependency of Europe’s rural, mountainous populations on C.
Europe (Lim, 2012). More recent ethnopharmacological sativa as a source of nutrition cannot be overstated; the highly
nutritious content of sweet chestnut fruits was so saturated fatty acid. Polyunsaturated and monounsaturated
fundamental to their survival that historians deem these fatty acids demonstrate anticancer properties, and decrease
societies as chestnut civilizations (Conedera, Krebs, Tinner, risks for cardiovascular disease. Specifically, polyunsaturated
Pradella, & Torriani, 2004). The popularity of sweet chestnut fatty acids have demonstrated hypolipidemic activity by
fruit persists to this day, and chestnuts are ingredients in decreasing blood lipid concentration, antithrombotic activity
many food items. Often processed via boiling, roasting, or by mitigating the thickening of arteries, and anti-arrhythmic
frying to improve taste, the nuts are often added to desert activity by eliminating abnormal heart rhythms (Das,
items such as chocolate and cakes. As well, chestnuts are used Bhaumik, Raychaudhuri, & Chakraborty, 2012). High amounts
to create flour, Corsican porridge and beer (Lim, 2012). of these beneficial fatty acids and low amounts of saturated
However, chestnut fruits are not the only product used non- fatty acids promote general human health by reducing
medicinally. During Roman times, sweet chestnut wood was cardiovascular disease.
used as timber due to its numerous applications for use, and
In addition to the high amounts of beneficial fatty acids, sweet
the use of chestnut for construction purposes continues to this
chestnut yields high amounts of antioxidant vitamins,
day (Conedera et al., 2004; Lim, 2012). In addition to the use
vitamins E and C (De Vasconcelos et al., 2010). In the sweet
of the wood for construction, it is also used to tan hides and
chestnut fruit, vitamin E or ϒ-tocopherol was found at an
skins due to the high tannin concentration. Other products
average concentration of 1.9mg/100g fruit. Vitamin E is a
obtained from C. sativa include a dye extracted from the
lipid-soluble antioxidant that protects lipid components of the
leaves, and a shampoo from the fruit husk and leaves (Lim,
cell—membranes, fatty acids—from peroxidation by free
2012). C. sativa has numerous medical and nonmedical
radicals (De Vasconcelos et al., 2010). Vitamin E’s antioxidant
traditional uses, some of which persist to this day.
activity is generated by its donation of a hydrogen atom to a
singlet oxygen molecule, therefore preventing the oxidation of
Chemistry and Pharmacology lipids by the singlet and damage to the cell (Das et al., 2012).
Vitamin C or ascorbic acid is found at a concentration of
Sweet chestnut boasts a wide variety of biologically active 15.6mg/100g chestnut fruit (De Vasconcelos et al., 2010).
chemicals that vary in their concentration depending on the Vitamin C acts as an antioxidant in the mitochondria of colon
part of the plant. Chestnut fruits have been extensively cells by donating a hydrogen atom to lipid radicals and singlet
analyzed for nutritious and thus chemical content due to their oxygen radicals; thus it responds to and prevents oxidative-
popular consumption. Analysis of chestnut fruit composition stress induced damage (Das et al., 2012; De Vasconcelos et al.,
revealed that water claimed 53% w/w, followed by 2010). Additionally, vitamins E and C act synergistically to
carbohydrates with 42%, crude protein with 2.7%, and crude eliminate reactive oxidative species. The elimination of
fat with 0.7% (Barreira et al., 2012). The lipid composition of reactive oxygen species and the mitigation of oxidative
the fruits was thus found to be low, but it contained high damage stalls the development of many diseases and
amounts of polyunsaturated fatty acids at 42% w/w of the conditions such as cancer, stroke and heart attack (Das et al.,
lipid fraction, 38.7% monounsaturated fatty acids and 19.4% 2012). The high levels of antioxidant vitamins E and C
Compound mg/g phenolic content and antioxidant activity (Grdovic et al.,
Ellagic acid 84.1 2012). Phenolic compounds prevent oxidative damage to cells
Valoneic acid dilactone, methyl ester 73.7 by many methods; the phenolic compounds in C. sativa
Methyl gallate 30.8 demonstrate antioxidant activity due to their scavenging of
Gallic acid derivative 22.5 peroxyl, hydroxyl, and superoxide radicals (Grdovic et al.,
p-Methoxycinnamic acid 20.5 2012). These phenolic compounds in C. sativa are responsible
Ellagitannin 16.3 for much of the plant’s antioxidant activity.
Flavogallonic acid 9.3
Kaempferol 7.4 Tannins, another class of phenolics, are found in relatively
Dehydrodigallic acid, dimethyl ester 6.3 high amounts in Castanea sativa. In sweet chestnut, there are
Isorhamnetin 4.0 high amounts of ellagitannins, a type of hydrolysable tannin.
Flavogallonic acid 3.5 Ellagitannins are responsible for anti-inflammatory and
Protocatechuic acid 2.7 antioxidant activity (Chiarini et al., 2013). Another subset of
Tryptophan 0.0695 tannins present in C. sativa are condensed tannins or
p-Hydroxybenzoic acid 0.0338 proanthocyanidines. Proanthocyanadines are responsible for
Table 1. Compounds from the Antioxidant and Phenolic- reducing cardiovascular disease due to relaxation of
Rich C. sativa Spiny Burr Extract. High amounts of phenolic endothelium cells (Chiarini et al., 2013). Due to these high
compounds were found in this extract that displayed high concentrations of both hydrolysable tannins and condensed
antioxidant activity due to the elimination of reactive oxygen tannins, sweet chestnut exhibits numerous medicinal
species. (Grdovic et al., 2012) properties.
promote health by preventing and mitigating damage caused

Biological Activity
by reactive oxygen species.
Antioxidant Activity
Despite the beneficial effects of vitamins and fatty acids,
phenolic compounds are responsible for the majority of sweet Castanea sativa extracts have demonstrated incredible
chestnut’s medicinal properties. Phenolic compounds, antioxidant activities. Oxidative damage leads to many severe,
composed of a benzene ring with a hydroxyl group(s) debilitating conditions such as cancer, neurodegenerative
attached, display antioxidant, anti-microbial, anti- diseases, diabetes, heart disease, and several more. Reactive
inflammatory and cardioprotective capabilities (Das et al., oxygen species wreak havoc on cells by oxidizing cell
2012). The major phenolic compounds found within C. sativa components; antioxidants can prevent oxidative damage by
extracts are ellagic acid and its derivatives at 100.4mg/g dry eliminating reactive oxygen species or by improving the cell’s
extract, gallic acid and its derivatives at 59.6 mg/g, and response to reactive oxygen species by increasing enzyme
flavonoids at 24.1mg/100g; these compounds are listed in activity (Grdovic et al., 2012). The antioxidant properties of C.
Table 1. Studies have found a correlation between total plant sativa have been examined in several studies, both in vitro and
in vivo, and in several different types of cells. One study the extent and mechanism of antioxidant activity in C. sativa
examined the formation of reactive oxygen species and cell (Grdovic et al., 2012).
survivorship in cultured neonatal rat cardiomyocites treated
Free radical scavenging, reducing power, hydrogen peroxide
with a methanol extract of sweet chestnut bark. Following
scavenging, and nitric oxide radical scavenging determine
exposure to the C. sativa extract for 24 hours, the cells were
whether an antioxidant eliminates reactive oxygen species.
exposed to hydrogen peroxide for half an hour, and the levels
Free radicals are reactive oxygen species that cause oxidative
of cellular reactive oxygen species were determined.
damage; free radical scavenging is an antioxidant property
Cardiomyocites treated with 100μg/mL of extract produced
that reduces cell damage (Grdovic et al., 2012). Scavenging
only twenty percent of the control group’s level of reactive
was measured by the reduction in absorbance of 2,2-diphenyl-
oxidative species. In other words, treatment with this
1-picrylahydrazyl (DPPH). The C. sativa extract dramatically
concentration reduced reactive oxygen species formation by
decreased DPPH absorbance and thus increased levels of free
80% (Chiarini et al., 2013). Cell viability following exposure to
radical scavenging. Total reducing power—a measure of
hydrogen peroxide likewise increased with increasing extract
antioxidant activity—was measured by absorbance as well.
concentration. Cardiomyocites treated with 100μg/mL of the
The reducing power of the extract was likewise very high; it
extract survived roughly thirty percent more than control cells
matched the reducing power of the control, vitamin C or
(Chiarini et al., 2013). Thus, the methanol extract of sweet
ascorbic acid at a concentration of 0.5 mg/mL. Hydrogen
chestnut bark decreased the formation of reactive oxygen
peroxide-scavenging activity, another indicator of antioxidant
species and improved cell viability following exposure to
activity, was found by measuring the absorbance of hydrogen
hydrogen peroxide. Thus, C. sativa exhibits significant
peroxide solution. Again, the sweet chestnut extract exhibited
antioxidant activity in neonatal rat cardiomyocites.
total hydrogen peroxide scavenging ability at 0.75 mg/mL, a
Considering oxidative stress’ role in diabetes, another study concentration lower than that of the control, ascorbic acid. C.
examined the influence of C. sativa spiny bur extracts on sativa additionally showed impressive scavenging ability of
pancreatic cell death following oxidative stress. Pancreatic β- nitric oxide, a reactive species; the extract completely
cell death due to oxidative stress induces diabetes in humans scavenged nitric oxide at 1 mg/mL, which again was lower
(Grdovic et al., 2012). To mimic the immune system’s than the concentration of the control molecule curcumin. As
destruction of pancreatic β-cells that leads to reactive species well, lipid peroxidation, a result of oxidative damage, was 2.4
formation, rat pancreatic β-cells were treated with times greater in cells not treated with the sweet chestnut
streptozotocin (STZ). Following cell exposure to STZ, the extract (Grdovic et al., 2012). Thus, C. sativa’s antioxidant
pancreatic cells were treated with differing concentrations of activity is due to its elimination of reactive oxygen species.
chestnut extract, and afterwards, levels of free radical
Examining cell survival, DNA damage, and antioxidant enzyme
scavenging, total reducing power, hydrogen peroxide-
activities demonstrate how the removal of these reactive
scavenging activity, nitric oxide radical scavenging, cell
oxygen species benefits the cell. When treated with the
viability, DNA damage, lipid peroxidation, and antioxidant
extract, β-cell survivorship increased by 19% and DNA
enzyme activity were examined. These measurements reveal
damage was significantly reduced as well (Grdovic et al.,
2012). In order to determine whether these extracts malondialdehyde decreased by roughly fifty percent
influenced the cells’ antioxidant enzymes’ responses to STZ, compared to the pigs fed the n-3 PUFA diet and no extract. As
the activity of superoxide dismutases and catalase were well, the measure of total antioxidant status did not differ
examined. β-cells treated with the extract showed a 28% among any group regardless of n-3 PUFA or C. sativa extract
decrease in catalase activity, and two out of three superoxide treatment. However, levels of DNA damage were reduced to
dismutases’ activity levels returned to activity levels of control levels of control diet pigs. As well, levels of oxidative stress
cells not treated with STZ. The decrease in these enzymes’ were reduced to those of the control (Frankic & Salobir,
activity levels signifies that the extract does not stimulate the 2011). Thus, the C. sativa extract showed significant in vivo
cell’s response to oxidative stress; it reveals that sweet antioxidant activity in several tests that measure different
chestnut antioxidants prevent oxidative damage and reduce oxidative stress outcomes. Additionally, liver toxicity wrought
the cell’s burden to quell oxidative stress (Grdovic et al., by the sweet chestnut extract was determined by measuring
2012). Thus, the sweet chestnut spine extract demonstrated the activity of liver enzymes aminotransferase, alanine
antioxidant activities through the elimination of several aminotransferase and glutamyl-transferase. The three
reactive oxygen species that lessened damage to DNA, lowered enzymes’ activity levels in the experimental group treated
cell morality, and decreased the activity of the cell’s with the extract mirrored those of the control, signifying that
antioxidant enzymes. Therefore, C. sativa extracts possess the extract is not hepatotoxic (Frankic & Salobir, 2011). This
high antioxidant capabilities in vitro due to elimination of in vivo study shows that C. sativa extracts demonstrate safe in
reactive oxygen species, and this elimination improves cell vivo antioxidant activity in animals and warrants further study
outcomes. Additionally, the high phenolic chemical for potential use in humans.
composition of this fraction was analyzed and displayed in
Table 1.
Cardioprotective Activity
In addition to in vitro studies of cell outcomes, in vivo studies
of C. sativa extracts’ antioxidant activity in animals have C. sativa not only is an excellent antioxidant, but it also
revealed that sweet chestnut exhibits antioxidant activity in exhibits cardioprotective activity. To examine the
animals. In a study determining the antioxidant activity of C. cardioprotective activities of C. sativa, one study examined the
sativa in living organisms, pigs were fed a diet of n-3 response of guinea pig right and left atria along with the left
polyunsaturated fatty acids (n-3 PUFA) to increase their papillary muscle to agonists and antagonists when treated
vulnerability to lipid peroxidation and then orally given a C. with the sweet chestnut bark extract high in hydrolysable
sativa wood extract with high amounts (73%) of hydrolysable tannins (Chiarini et al., 2013). As well, the response of guinea
tannins. Antioxidant activity was then measured by pig aortic strips to potassium ions and noradrenaline was
determining levels of lipid peroxidation, DNA damage, and examined. Atria treated with C. sativa showed positive
oxidative stress (Frankic & Salobir, 2011). Lipid peroxidation inotropic effects and negative chronotropic effects; thus, it
levels were measured by two peroxidation products, slowed the heart rate and increased the potency of the heart
malondialdehyde and F2-isoprostanes; only levels of muscle’s contractions. Likewise, C. sativa lessened the
contraction of aortic strips (Chiarini et al., 2013). Thus, C. effects on intestinal tissues, signifying possible therapeutic
sativa exhibits cardioprotective activity by regulating heart use for the treatment of diarrhea (Budriesi et al., 2010).
rate and contraction strength.
Anticancer Activity
Quorum Sensing Inhibition
C. sativa also displays strong anticancer activity against at
In addition to its antioxidant and cardioprotective activities, least three human cancer lines. In one study, the ethyl acetate
an ethanol C. sativa leaf extract inhibits quorum sensing in bark extract of sweet chestnut was applied to LoVo colon
Staphylococcus aureus bacteria. Quorum sensing allows cancer cells, PC3 prostate cancer cells, and U373 glioblastoma
bacterial cells to coordinate the release of toxins once a cancer cells. The C. sativa extract eliminated 50% of the
certain number of bacteria are present in a host. Preventing cancerous cells at 25 µg/mL for the colon cancer, 31 µg/mL
quorum sensing reduces the ability of bacteria to release these for the prostate cancer cells, and 24 µg/mL for the
toxins and harm host cells (Quave et al., 2011). The ethanol glioblastoma cells (Frederich et al., 2009). Earlier studies
leaf extract was applied to S. aureus bacteria, and quorum showed that the cytotoxic activity was due to polysaccharides,
sensing was measured by quantifying the production of δ- but analysis of this extract showed little polysaccharides
toxin. Following treatment with 125 μg/mL of C. sativa extract, present (Frederich et al., 2009). Thus, Castanea sativa is an
δ-toxin production decreased by 90% (Quave et al., 2011). excellent in vitro anticancer agent for multiple cancer types
Thus, the sweet chestnut leaf extract shows promising and deserves further study in animal models to determine its
quorum sensing inhibition that could hinder bacteria’s mechanism of action.
capability to infect a host.
Antibacterial Activity
Antispasmodic Activity
C. sativa shows potent antibacterial activity. An ethyl acetate
Not only does C. sativa weaken bacteria, but it also induces fraction demonstrated effective antibacterial activity against
muscle relaxation. In order to characterize the C. sativa wood both gram-positive and gram-negative bacteria. Further
extract’s antispasmodic effects, guinea pig ileum and proximal analysis of the active fraction showed that the chemicals rutin,
colon tissues were exposed to spasmodic agents such as hesperidin, quercetin, apigenin, morin naringin, galangin and
carbachol, histamine, potassium chloride, and barium chloride kaempferol were present in high amounts. These chemicals
and then were treated with the sweet chestnut extract were then individually applied to bacteria, and quercetin,
(Budriesi et al., 2010). Determining the extent of rutin and apigenin demonstrated the highest antibacterial
antispasmodic activity was performed by quantifying the activity. Some reactivity was lost upon dividing the fraction,
reduction in the spasmodic response. Treatment with the suggesting a synergistic mechanism. Thus, C. sativa exhibits
extract significantly reduced the spasmodic effects of the high antibacterial activity against both types of bacteria, and
agents in the tissues. Thus, C. sativa exhibits antispasmodic
the individual compounds within the fraction mirrored that reached over 90% at 500 µg/mL (Almeida et al., 2008). Thus,
same reactivity (Basile et al., 2000). the study demonstrated that the leaf extract of C. sativa is safe
and its efficacy is maintained in vivo.
Anthelmintic Activity
In addition to its antibacterial activity, C. sativa also targets Contraindications
other small organisms such as parasitic nematodes. Earlier Castanea sativa does not present many contraindications;
studies have demonstrated that plants high in tannins exert however oral allergy syndrome can be induced by plant-oral
anti-parasitic effects against nematodes, and C. sativa contains mucosa contact. The allergy generally occurs in individuals
significant concentrations of tannins, some of which are listed with allergies to certain pollens (Antico). Additionally, very
in Table 1. One study examined the effect of a C. sativa fruit high levels of phenolic consumption and ingestion are
extract on the exsheathment or transition of the nematode unhealthy, and the precise effects of phenolic compounds on
from its final larval stage to full parasite. Exposing nematode health are not entirely understood (Das et al., 2012).
larvae to the extract for fifty minutes inhibited 100% of the Moreover, cytotoxic levels of extract use have been recorded
worms’ exsheathment. Thus, C. sativa exhibits extraordinary for concentrations above 100 µg/mL whereas some extracts
anthelmintic and anti-parasitic activity. only exhibited effective activity at concentrations above 100
µg/mL. Thus, there is potential for a narrow margin between
the therapeutic and toxic doses of extracts (Almeida et al.,
Clinical Studies 2008; Chiarini et al., 2013).
Antioxidant Activity
To determine whether a C. sativa extract could be used as a Current Use in Allopathic and CAM Therapies
topical antioxidant to prevent photo-aging and other oxidative
stress diseases, an extract of C. sativa leaves was applied Castanea sativa is used throughout Mediterranean regions to
topically to the skin of twenty volunteers to determine treat a wide range of illnesses in accordance with traditional
whether the use of the extract would induce any unpleasant medicine practices. As mentioned earlier, these illnesses and
effects such as allergic reactions or dermatitis and to conditions include varicose veins, vascular problems, diarrhea
determine whether efficacy was maintained in vivo. The and multiple others (Budriesi et al., 2010; Quave et al., 2011;
extract used contained 238 mg of phenolic compounds/g Zlatanov et al., 2013). No articles on contemporary medicinal
extract, and contained cholorogenic acid, ellagic acid, rutin, uses other than the continuation of traditional practices were
isoquercitrin and hyperoside in high amounts. The extract was found. However, chestnut food products can be used as a
determined to be safe for use due to little or no dermatitis or substitute for gluten-containing foods for individuals who
allergic reactions. As well, analysis of the skin cells showed suffer from coeliac disease and cannot digest gluten. Chestnut
that DPPH scavenging activity surpassed 80% at 50 µg/mL, does not contain gluten; thus, it can be used to make flower
and iron chelating activity—another antioxidant activity— that substitutes for the many food items that contain gluten.
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Catharanthus roseus (L.) G.Don, Apocynaceae
MyKeya Henderson
Introduction
Catharanthus roseus, whose common name is Madagascar
periwinkle or just periwinkle, belongs to the Apocynaceae.
Although C. roseus is the accepted scientific name, this plant
was once referred to as Vinca rosea in the West Indies from its
association with folk medicine (Lewis and Elvin-Lewis 2003).
Probably one of the most important pharmacological
properties of C.roseus is its production of vinca alkaloids or
bisindole alkaloids (Shams, et al. 2009). This is a native plant
of the Island of Madagascar, hence the common name
“Madagascar.” This plant has been widely cultivated and used
in traditional medicine for thousands of years. Not only was
this an important plant in Europe for medicinal purposes such
as treatment of diabetes, but it has also been used in several
other countries such as China and the Caribbean for a variety
of health conditions and diseases ranging from cough
suppressants and eye infections to Hodgkin’s disease and even Figure 2. Catharanthus roseus, commonly known as
cancer (Quave 2011). Aside from its medicinal use, Madagascar Periwinkle. (Source: http://digilander.libero.it/
Madagascar Periwinkle is also grown for its beautiful felrig/photos/catharanthus_roseus.htm).
botanical appearance as an ornamental plant.
and have a corolla tube that is a 1 inch long. This slender tube
Description can expand to be 1 ½ inches wide. The leaves are not glossy
and are about 2 to 3 inches wide with rigid-like stems. The
If you have ever seen any vivid beds of flowers or visited a plant is typically small and grows to be anywhere from 2 to 3
botanical garden, you have probably seen the plant feet tall. The fruit are classified as follicles and are anywhere
Catharanthus roseus, as shown in Figure 1. C. roseus is an from 2 to 4 centimeters long. Madagascar periwinkle grows
annual evergreen perennial shrub. It usually has five petals. best in frost-free environments. Although this plant is native
The flowers are typically rose pink in color, but sometimes to Madagascar, it grows world-wide, but mostly in the tropics,
red, purple, white, and pink. The flowers are tubular in shape subtropics, and the southern parts of the United States. It is
also grown in Australia, Africa, India, and southern Europe for Islands who used 18 leaves boiled in a pot a water, different
commercial use (Afolayan and Sunmonu 2010). Even with its variations were practiced (Nammi, et al. 2003). The extracts
pharmaceutical interest, this plant can be found often times in were also used in India for treatment of wasp stings. During
the wild. The type of conditions that Madagascar periwinkle the medieval period, Europeans also believed that this plant
grows best in is one with full sunlight exposure or partial could ward off evil spirits” and thought of it as a “magical
shade with well-drained soil. Growth is inhibited when the soil plant,” while the French believed it to be “the violet of
is too fertile or moist. A unique characteristic about this sorcerers” (Lewis and Elvin-Lewis 2003).
perennial is that the flowers fall off after blooming and the
plant reseeds itself under favorable conditions. Madagascar
periwinkle can even withstand hot conditions, unlike other Chinese Usage
periwinkle plants. This plant also produces “milky latex” like The Chinese, on the other hand, used Madagascar periwinkle
sap from its stem (Floridata 2010). Madagascar periwinkle is as an astringent and cough remedy, as well as for its diuretic
closely related to the class of true periwinkles, Vinca, which properties (Lewis and Elvin-Lewis 2003). These forms of
also belongs to the family Apocynaceae. The difference in the treatment were made using extracts from the plant.
two is that Madagascar periwinkles can endure hot conditions,
but true periwinkles cannot; the leaves of true periwinkles
tend to curl until the temperature returns to normal (Floridata Caribbean Usage
2010).
The traditional use for this plant in the Caribbean was for eye
infections and diabetes (Lewis and Elvin-Lewis 2003).
Traditional Uses However, using extracts of the whole plant, the plant was used
for treating asthma and flatulence in the Bahamas. Among the
As mentioned before, Madagascar periwinkle is found often as other islands such as Cuba, Puerto Rico, and Jamaica, the
an ornamental plant in flower pots or bedding of flowers; flower of the plant was used as general eye wash (Mishra
however, it also has a variety of other uses. The usage is 2009). Although there is very limited research; Madagascar
specific to the area and culture in which it is cultivated. periwinkle has also been used to treat “unspecific male
problems” such as those related to reproduction issues in
Trinidad and Tobago (Lans 2007).
European Usage
In Europe, the primary pharmaceutical interest is for the
treatment of diabetes. They sometimes used the pant to treat Other Usage
headaches too. Herbalists would use the juice from the leaves Recently, the pharmaceutical properties of Madagascar
as a household remedy. In India, about 7 flowers or leaves periwinkle have drawn interest for the treatment of cancers
were used each time, but in other countries such as the West such as lung or leukemia (Ueda, et al. 2002). There are several
Indies who used the roots along with whiskey, and the Cook other usages for this plant such as for the treatment of Malaria
cause a noticeable effect on bone marrow and the white blood
cell count. About 2 years later, Robert Noble and an organic
chemist joined forces and began to isolate and characterize
vinca alkaloids. These alkaloids soon became one of the most
important drugs to cancer chemotherapy (Wright 2002).
C. roseus is the source of two important chemical compounds
that are also classified as anticancer agents. The compounds
vinblastine and vincristine, whose chemical structure is
shown in Figure 2, are well known vinca alkaloids that are
derived from this plant (Roepke, et al. 2010). Vinblastine,
Figure 3. Chemical structure of vinblastine (Source: which is marketed as by Eli Lily, is used to treat lymphoma,
http://www.thefullwiki.org /Alkaloid). advanced breast and testicular cancer, Hodgkin’s disease, and
Kaposi’s sarcoma. Likewise, vincristine is marketed as
in Vietnam, a remedy for sore throat in South America, for Oncovin and is used to treat acute leukemia, Hodgkin’s
controlling hypertension in Curacao in Bermuda, controlling disease, as well as other types of lymphomas (Lewis and Elvin-
bleeding in patients in Hawaii, for treatment of dyspepsia and Lewis 2003).
indigestion in Mauritius and for treatment of dysmenorrheal
The fractions and percentages of the alkaloids are shown in
in Indo-Chinese (Mishra 2009). Other indications of the plant’s
Table 1. Although vinblastine and vincristine are the primary
usefulness in medicine include treatment of hypertension and
alkaloids, a study by The Phytochemistry Department in
tuberculosis and for regulation of menstruation. (Nazif, et al.
Europe showed another alkaloid, catharanthine, to be present
2009) Because of the wide-variety of medicinal purposes that
(Shams, et al. 2009). These alkaloids were discovered over a
Madagascar periwinkle has, it has become of the most
course of five different methods.
interesting plants in the pharmaceutical industry.
Biological Activity
Vinca alkaloids of the plant Catharanthus roseus are sone of
For several years, Catharanthus roseus had been studied for its
the most widely studied anti-mitotic drugs because of their
anti-diabetic properties, which was influenced by folk
biological activity as it relates to treating certain forms of
medicine. The discovery of vinca alkaloids was by Robert
cancer. The alkaloids act by disrupting the microtubules in
Laing Noble (Wright 2002). Noble had obtained some leaves
cells. First, they bind to tubulin monomers. At low
of the Madagascar periwinkle plant from his brother, Clark
concentrations of the alkaloids, the formation of microtubules
Noble, who is best known for his studies on insulin. Robert
is inhibited. If the concentration of the alkaloids is high
Noble then tested leaf extracts and discovered that there were
enough, they can cause the protofilaments of the microtubule
little effects on blood glucose levels. However, the extracts did
Table 1. Alkaloids and the percentage present in Catharanthus roseus.
walls to peel. If the microtubules fail to form, the assembly of involved in the biosynthesis of terpenoid indole alkaloids”
the mitotic spindle cannot take place, which therefore blocks (Rishcer, et al. 2006). The results are important for
mitosis (Jordan, Himes and Wilson 1985). Once mitosis is understanding the metabolic rate and mechanism within the
blocked, the affected cells begin to die. plant.
Over the past few years, there have been lots of studies There have been several innovating studies conducted
regarding the biological activity of C. roseus. One study concerning Catharanthus roseus and its medicinal
explored the chemical composition and activity that occurs contribution. In a study by the Department of Pharmaceutical
through the leaf. The results showed indications of the leaf Sciences at the Andhra University, results indicated there are
secreting varying amounts of catharanthine (Roepke, et al. notable juices produced by the plant the exhibits
2010). This is an important feature because catharanthine has hypoglycemic activity. These juices showed a significant
antifungal and antiseptic properties, among others. In fact, the decrease in blood glucose of normal and diabetic rabbits
complexity of the leaf is so dynamic that the monoterpenoid (Nammi, et al. 2003). These results thus support the belief of
indole alkaloids (MIAs) regulate the transport mechanism and traditional herbalists who used the plant a remedy for
the rate of biosynthesis within the plant (Roepke, et al. 2010). diabetes.
Another study explored the vast gene-to-metabolite networks Another study showed the healing power of C. roseus. This
that are inhibited by the alkaloids. The results showed the experiment was conducted on lab rats, rather than rabbits as
varying branches and metabolic pathways within the planet. in the previously mentioned study. Results showed that
According to the review, the purpose of the networks is to extracts from the plant “increased the wound breaking
“identify a select number of genes and metabolite likely to be strength in the incision wound model” (Nayak and Pinto
Pereira 2006). This study, too, supports the beliefs studies, vinflunine is most noted for its antitumor activity
incorporated from traditional medicine that C. roseus can be (Kruczynski 2001).
used as an antiseptic.
In addition to the ongoing clinical trials has begun approval of
One other study focused on the biochemical specialization of some vinca alkaloids and their derivatives. For instance,
the plant. The plant is composed of several classes of vincristine has been approved and is available as an injection
metabolites. Among that was about different types of cells as by prescription only (Drugs.com n.d.). Something interesting
well as numerous genes and gene networks (Murata, et al. to note about this drug is that although it has received
2008). All of these components contribute to the plants ability approval, the mechanism of action is still under investigation.
to multifunction for different medicinal purposes.
Contraindications
Clinical Studies
As with any medicinal plant or drug, there are always cautions
Aside from the in vivo studies, there have also been clinical associated with the usage. Catharanthus roseus has displayed
studies conducted. One study focused on the treatment of toxic effects when exposed to cattle (Lewis and Elvin-Lewis
Hodgkin’s lymphoma with BEACOPP. BEACOPP is a regimen 2003). For humans, it should not be taken by mouth because
composed of the vinca alkaloid, vincristine, and a host of other the vinca alkaloids present can be highly poisonous. Some
drugs such as bleomycin, etoposide, doxorubicin, common side effects associated with consumption include
cyclophosphamide, procarbazine, and prednisone. A random nausea and vomiting, the loss of hearing, as well as liver
selection of patients that had untreated Hodgkin’s lymphoma damage and death (Lewis and Elvin-Lewis 2003).
were given BEACOPP, while another group were given ABVD.
ABVD is composed of a vinblastine, doxorubicin, bleomycin
and dacarbazine. The study showed that patients with the Current Use in Allopathic & CAM Therapies
regimen that included vincristine (BEACOPP) showed a Currently, there are several studies being conducted to verify
greater progression than the patients who received ABVD the safe usage of the drug as an anticancer agent. However,
(Simonetta, et al. 2011). several semi-synthetic derivatives of the drug are available for
One of the newest vinca alkaloids is vinflunine. It was clinical usage. Aside from Velbe and Oncovin, as mentioned
developed through the process of fluorination. The alkaloid is before, Catharanthus roseus is also marketed as Eldisine to
most studied for its anticancer properties as well. Studies have treat leukemia and lung cancer and as Navelbine to treat
shown that like most vinca alkaloids, vinflunine has “mitotic- ovarian cancer (Lewis and Elvin-Lewis 2003).
arresting and tubulin-interacting properties” (Kruczynski
2001). However, this alkaloid is easily distinguishable from
other vinca alkaloids because it “induced smaller spirals with
a shorter relaxation time” (Kruczynski 2001). In clinical
Discussion Lans, Cheryl. 2007. Ethnomedicines used in Trinidad and Tobago for
reproductive problems. Journal of Ethnobiology and
Catharanthus roseus is a complex plant that has a wide variety Ethnomedicines. 3 (13)
of medicinal uses. Because of the vinca alkaloids that are Lewis, Walter H, and Memory P.F. Elvin-Lewis. 2003. Medical
produced, cancers such as leukemia and lymphomas can be Botany: Plants Affecting Human Health. Hoboken: John Wiley
treated (Lewis and Elvin-Lewis 2003). Minor health & Sons.
conditions such as the common cough can also be treated by Mishra, M.P. Traditional –ethnoherbological and medicinal properties
this plant. C. roseus is so dynamic that is cultivated in of Madagascar periwinkle.
countries across the world to treat anywhere from everyday http://www.ecosensorium.org/2009/09/traditional-
wasp stings to more serious conditions such as diabetes. ethnoherbological-and.html
Extracts of this plant has linkages to traditional medicine Murata, Jun, Jonathon Roepke, Heather Gordon, and Vincenzo De
Luca. 2008. The leaf epidermome of Catharanthus roseus
dating all the way back to folk medicine in the West Indies.
reveals its biochemical specialization. The Plant Cell. 20 (3)
Even today, C. roseus still proved to be an important plant in 524-542.
the pharmaceutical industry. Nammi, Srinivas, Murthy K Boini, Srinivas D Lodagala, and Ravindra
Behara. 2003. The juice of fresh leaves of Catharanthus
roseus Linn reduces blood glucose in norman and alloxan
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Chondrodendron tomentosum Ruiz & Pavón, Menispermaceae
Kimberly Beck
Introduction
Chondrodendron tomentosum Ruiz & Pavón is a member of the
Menispermaceae family, also known as the Moonseed family,
and is found primarily in South American rainforests. The
Moonseed family consists of over 78 genera, mainly woody
vines, and is commonly found in the tropics (Wiart, 2006). C.
tomentosum was first identified by Hippolyto Ruiz and Joseph
Pavón in 1793 after they brought it back from a South
American expedition to be identified and classified. C.
tomentosum is primarily utilized to make curare, a poison
used in hunting and previously in tribal warfare, in the
western Amazon. The root, known as the Pareira brava, is the
primary source of curare from C. tomentosum; however many
times due to shortage the stem of the vine is used as a
substitute (Bentley, 1902). Locally known amongst indigenous
Amazonian tribes as curare, pareira or amphihuasca, the name
amphihuasca comes from the name “ampi” the term for the
macerated bark product used to extract the poison. The
Tikuna tribe of the Peruvian Amazon is generally considered
amongst Amazonian tribes, as well as the outside world, to
produce the highest or best quality of curare poison to be used
on poison darts or arrows. Curare is found throughout the
western Amazon basin, leading to different storage
techniques. Some groups would store the curare in terracotta
pots in the soil while others would store it in dried gourds.
The most influential manner of storage, though, was in
bamboo tubes leading to the name of the derivative
tubocurarine, meaning “tube of curare.” Now curare is stored
Figure 1. Chondrodendron tomentosum leaves, stem, and
in cans or whatever storage containers can be found
fruit.
(Birmingham, 1999). Curare comes from both C. tomentosum,
common to the forest parts of South America in Ecuador and
Peru, and Strychnos toxifera, found in other regional areas. D-
tubocurarine and other muscle relaxants that have
anticholinergic effects at the neuromuscular synapse were
developed from these two plants. C. tomentosum was initially
used as an anesthetic and muscle-relaxant during surgeries in
the 18th century paving the way for increased development in
the field of surgery allowing advancements that would
otherwise not have been possible (Booij, 2000).
Chondrodendron tomentosum is a liana, a strong woody-
stemmed vine that is rooted in the soil and grows to a
thickness of three-quarters of an inch to over two inches,
climbing up trees into the forest canopy in order to reach a
well-lit area. Given the name “Pareira brava”, signifying “wild
vine” in Portuguese, the liana grows slowly and extensively in
the western Amazon region climbing to the peak of high trees.
The bark is generally dark brown or black, thin and loosely
attached with deep furrows and ridges in a longitudinal
pattern as well as diagonal ridges and channels. The wood Figure 2. Twisted Chondrodendron tomentosum vine.
itself is porous, concentrically marked, separated into wedge
portions and is of a yellow or a brown-grey color. The wood is
fibrous when broken; however, when shaved or cut, it has a found in South American rainforests (see Figure 2); it has
waxy consistency (Bentley, 1902). Like other plants of the been specifically used in western Amazonian tribes in Peru
Menispermaceae family, C. tomentosum has large heart- and Brazil (Birmingham, 1999). C. tomentosum has small
shaped three-veined leaves that alternate and typically exhibit flowers, as do all menisperms, with each containing six or
a wiry pulvinar flexion where the leaf connects to the stem more tan or grayish, pubescent hard monocarps (Gentry,
(see Figure 1). The bottoms of the leaves of the C. tomentosum 1996). Fruits spread and radiate from the thick woody
are densely white and tomentose, as well as broadly ovate and gynophores stalk to which they are attached by short stalks.
veined (Gentry, 1996). It is a woody, branchless, twisted vine The fruit are of a purplish black color, measure to nearly one-
inch long and are oblong-ovoid shaped. When fully ripe the
oblong fruit resemble a bunch of grapes in appearance, this
can be seen in Figure 3 (Bentley, 1902).
Traditional Uses
Traditional Uses in Hunting
Chondrodendron tomentosum is the source of curare for
western Amazonian tribes and its origins are rooted in
traditional Tiriós folklore. The story goes that the world began
with one man and three animals; a howler monkey, a yellow-
headed parrot and a yellow-headed vulture. The howler
monkey is really a woman in disguise and through a series of
events the man and her marry. The Tiriós man is then shown a
liana and the recipe for curare by a harpy eagle that tells him
the curare are to help him in his hunting. The Tirió story
demonstrates the power and importance curare is
traditionally believed to possess; as the man gains knowledge
he is too quick to try his newfound weapon and hastily kills all
the howler monkeys in the region including his wife disguised
again as the howler monkey (Plotkin, 1993). This tragedy
serves as a warning to respect the poison and not use it in
excess. The added cultural component of a sacred folk tale
adds to the obvious importance of the tradition of how curare
is prepared and what it is used for. The methods by which
curare is prepared are ritualistic in nature, and of such
importance that its preparation was shrouded in secrecy for
years. It took a long time for ethnobotanists to gain the trust of
Figure 3. Botanical drawing featuring coloring, leaves,
the tribal elders and learn how various tribes prepared curare
stem, vine, flowers, and fruit of Chondrondendron
from C. tomentosum (Plotkin, 1993). Traditionally, “curare” or
tomentosum.
“ampi” is prepared by native Amazonians by crushing and
boiling the roots and stems, adding in other herbaceous plant
or animal venoms, and mixing it until it reaches a light syrup of their darts and arrows by creating grooves with piranha
consistency. They then use this concentrate to poison the tips teeth and then dipping the darts and arrows into the syrupy
substance. (Duke, 1994). Each tribe’s recipe varies by the Chemistry and Pharmacology
different venoms that are added; the one constant ingredient
Chondrodendron tomentosum has several different active
throughout the western Amazon is the base of C. tomentosum
crystalline alkaloid compounds, one of which is d-
(Plotkin, 1993). The storage of the curare also varies; some
Tubocurarine, the alkaloid responsible for inhibiting nerve
tribes store the decoction in bamboo tubes while others store
impulse transmission to muscles. (Panda, 2002) The
it in terracotta pots. The name tubocurarine (an alkaloid
tubocurarine contained in C. tomentosum is that of
derivative of C. tomentosum utilized in modern medicine)
tubocurarine chloride which contains a bisbenzyl isoquinoline
literally comes from the curare stored in the tubes. The usage
structure in a quaternary compound as its principle alkaloid.
of curare derived from C. tomentosum for hunting is consistent
Tubocurarine only occurs naturally in C. tomentosum and acts
throughout the western Amazon, even though indigenous
as a muscle-relaxant utilizing a non-depolarizing mechanism
tribes’ methods of creating the concoction vary. In the western
at the neuro-muscular junction. Muscular paralysis is caused
Amazon region, curare is still used in hunting (Plotkin, 1993).
by a competitive blockade of the post-synaptic nicotinic
acetylcholine receptors. In this respect it is similar to the
Traditional Medicinal Uses alkaloid toxiferine found in the Strychnos species but was
In native Brazilian culture, the root of Chondrodendron found to be less active (Bisset, 1989). It also contains four
tomentosum is used to treat a variety of internal ailments, non-quaternary bases: isochondrodendrine,
including as a febrifuge, an emmenagogue and a diuretic. It is isochondrodendrine dimethyl other, berberine and
common in the treatment of dropsy, madness, bruising, chodrocurine. Berberine is the alkaloid responsible for the
orchitis and kidney stones (Duke, 1994). bitter principle in C. tomentosum (Daniel, 2006). After initially
being used by Benjamin Brodie in a patient with tetanus
In addition, C. tomentosum has been used as a diaphoretic to curare was then used topically as well as in the treatment of a
cure snakebites through rapidly sweating out the venom in variety of ailments including hydrophobia, epilepsy and
Amazonian culture. The root extract affects the mucus cholera (Booij, 2000).
membrane of the genito-urinary organs by acting as an
astringent and sedative upon them, thus, decreasing the
secretion of the ropy mucus during bladder inflammation as Mechanism of Action
well as reducing the inflammation. A decoction is made from
Curare derived from Chondrodendron tomentosum works
adding small pieces of the root to water and filtering the
rapidly to block nerve impulses to the muscles resulting in
mixture to get a dose of 30-100 grams (de Tavera, 1901).
paralysis from flaccid muscles. The muscle paralysis induced
In addition, C. tomentosum has been traditionally used as an by curare is temporary but still has the potential to lead to
antiseptic, anti-inflammatory, in the treatment of rheumatism, death through failure of respiratory muscles to function and,
jaundice, dropsy, and gonorrhea (Gonzalez-Coloma, 2011). thus, asphyxiation (Panda, 2002). In terms of paralysis, curare
first acts on the muscles of the eyes, followed by the nose and
the neck and then the limbs. The diaphragm is the final muscle
to become paralyzed leading to probably asphyxiation and motor function, not sensory function, was affected by curare
death. Curare acts on the motor endplate of a nerve by (Booij, 2000).
depressing the potential of the endplate in the neuromuscular
junction, but does not affect the pre-junctional release of
acetylcholine. Curare competitively inhibits acetylcholine and Chondrodendron tomentosum & Leishmania
also interferes with the feedback control of acetylcholine by Extracts of C. tomentosum were tested to see if it is a possible
occupying the pre-synaptic receptors involved in new treatment for Leishmaniasis, a protozoan parasitic
acetylcholine release. It was demonstrated that between 70% disease with a high associated morbidity and mortality rate
and 95% of acetylcholine receptors must be occupied by that is endemic in 88 countries, and Chagas disease, a tropical
curare to inhibit muscle contraction, this margin is know as parasitic disease. The current treatment for Chagas disease,
the margin of safety of neuromuscular transmission. At 70% nifurtimox and benzinidazole, have severe side effects and
occupation of acetylcholine receptors, muscle contraction their distribution and production are problematic. Current
begins to decrease while at 95% occupation full blockade treatments for both diseases are at extremely high dosages
exists. (Booij, 2000). Curare can be ingested as it is inactive with high potentials for resistance leading to the necessity for
unless injected directly into the bloodstream. This is because the development of a new treatment. After interviewing locals
the compounds are so large and highly charged that they are from the city of Iquitos, Peru on the subject of the most
unable to pass through the digestive tract lining and be powerful traditional medicines, C. tomentosum was selected as
absorbed into the bloodstream (Nasiripourdori, 2011). a possible new treatment for both Leishmaniasis and Chagas
disease. A crude alkoloidal extract was evaporated from C.
tomentosum. 700 g of dry bark extract of C. tomentosum was
Biological Activity macerated with ethanol to yield an extract of 54.6 g (7.8%).
Chondrodendron tomentosum and the Heart After testing C. tomentosum along with other local traditional
medicines it was concluded that C. tomentosum bark is one of
In the early 19th century, Benjamin Brodie used rabbits as a
the most effective of the medicines tested against
model to show the potential for artificial ventilation of the
lungs as a means to maintain life after curare-induced Leishmaniasis as well as Chagas disease. C. tomentosum
paralysis. He observed that curare did not have an effect on exhibited strong anti-parasitic effects exhibiting selective
activity against L. infantum promastigotes. Additionally the
the heart and proceeded to use curare on a human being to
treat tetanus in 1811. Subsequently, in 1850 Claude Bernard Menispermaceae family produced alkaloid extracts that
demonstrated the effect of curare on neuromuscular exhibited antimalarial activity and in vitrotoxicity against the
tumoral cell lines KB-3, KB-V1 and P-38878. The study
transmission utilizing frog nerve-muscles. Through this
continued to subject C. tomentosum to bioassay-guided
experiment he showed that direct muscle stimulation resulted
in muscle contraction while nerve stimulation had no fractionation. Chondrocurine (Figure 4.4), (S,S)-12-O-
methyl(+)-curine (Figure 4.5), and cycleanine (Figure 4.6)
resulting contraction. This proved that curare acts on the
are all bisbenqylisoquinolines that were isolated from C.
nerves rather than on the muscle leading to the discovery that
tubocurarine in vitro. The study was conducted in order to
demonstrate the importance of understanding the differential
paralysis of the laryngeal muscles caused by d-tubocurarine
and the best method by which upper airway obstruction may
be avoided during anesthetic/sedative induction. Cecal
ligation and puncture was used to induce sepsis and educe
panperitonitis in rats in order to record electromyograms and
endplate potentials from the LCA and PCA muscles. It was
noted that in normal rats the PCA muscles are more sensitive
the d-tubocurarine than the LCA muscle. Sepsis is thought to
decrease laryngeal muscle sensitivity to non-depolarizing
neuro-muscular blockers such as d-tubocurarine. Sepsis was
induced in the rats by anesthetizing them with isoflurane and
making an incision mid-abdomen to puncture the cecum filled
with feces. The incisions were then closed and the rats were
injected with saline solution subcutaneously in the back
during the operation in order to resuscitate them. The rats
were observed for two hours post surgery and given free
Figure 4. Bioassay-guided fractionation of C. tomentosum. access to water but deprived of food. 10 to 16 hours post
Chondrocurine (Figure 4, 4), (S,S)-12-O-methyl(+)-curine surgery isoflurane anesthesia was used to kill the rats in order
(Figure 4, 5), and cycleanine (Figure 4, 6). for the larynx and attached recurrent laryngeal nerves could
be dissected. The preparations were maintained in a modified
Kreb’s solution (NaCl, 135; KCl, 5; CaCl2, 2; NaHCO3, 15;
tomentosum. Chondrocurine and (S,S)-12-O-methyl(+)-curine Na2HPO4, 1; glucose, 11: in mmol-1) bubbled with 95% O2 and
exhibited activity against both parasites. It was concluded that 5% CO2 and maintained during oxidation at a pH of 7.40 ±
these compounds are responsible for the activity of C. 0.05. Before beginning the experiment, electromyographic
tomentosum and that C. tomentosum is active against response and visual inspection were used to confirm the
Leishmaniciasis as well as Chagas disease (Gonzalez-Coloma, contraction of the LCA and PCA muscles by supramaximal
2011). stimulation of the recurrent laryngeal nerves. Extracellular
microdes measured the compound action potentials’
amplitudes of the LCA and PCA muscles’ action potentials. In
The Effect of Sepsis on d-Tubocurarine as seen in Rats
order to assess neuromuscular transmission intracellular
The effects of sepsis on the lateral cricoarytenoid (LCA) and microelectrodes recorded the EPPs of the muscles. Currents
posterior cricoarytenoid (PCA) muscles were evaluated as were measured as several concentrations of d-tubocurarine
they underwent the neuro-muscular blocking actions of d- were applied through superfusion into the Kreb’s solution.
The data was then statistically analyzed. The study showed onions, and emotional upset. The study was conducted when
that d-tubocurarine induced neuromuscular blocking was the patient was asymptomatic; ten days after the reaction, a
weakened by sepsis. Sepsis inhibits the reduction of blood sample to determine histamine was drawn. In addition
transmitter release induced by d-tubocurarine in the LCA and to blood samples, direct intradermal tests were conducted on
PCA muscles with the LCA muscles showing more d- the patient’s right forearm of 0.75% d-tubocurarine, 2.5%
tubocurarine resistance. The study indicated that sepsis thiopental, and 0.4% gallamine each injection of 0.05 ml
blocks the neuromuscular transmission by stage-dependently volume. The histamine levels of the patient’s blood were
inhibiting the d-tubocurarine and, thus, depressing action analyzed using a spectrophotometer. The study inferred the
potentials. The study acknowledged that the contraction force histamine response was a result of d-tubocurarine
of the laryngeal muscles is reduced by the inhibition of d- administration. The histamine levels in the patient at the time
tubocurarine as a neuro-muscular block by sepsis. The study of the reaction were nearly twice the patient’s normal value.
concludes that d-tubocurarine induced neuromuscular
blocking is weakened by panperitonitis-induced sepsis in both
the LCA and PCA muscles. It is noted that the differential Various Historical Clinical Studies and Usages
sensitivities of the LCA and PCA muscles to d-tubocurarine Initially, curare derivatives from C. tomentosum were tested
was not significantly influenced by the induced sepsis, the PCA and used as a muscle relaxant to relieve stiff muscles caused
muscle remained more sensitive than the LCA muscle to d- by polio as well as to treat a variety of conditions such as
tubocurarine (Nishikawa, 1999). lockjaw, epilepsy, and chorea (a disorder leading to irregular
and uncontrollable muscle movements). These efforts proved
fruitless as other more effective and safe treatments were
Clinical Studies
found for these ailments. Efforts were successful, however, in
Change in Histamine Levels as a Result of d-Tubocurarine extracting the compound d-tubocurarine from C. tomentosum
Administration and injecting it as a muscle relaxant for use during throat,
As a result of an allergic reaction experienced by a twenty-five rectal and abdominal surgeries in addition to using it to lessen
year old patient undergoing a tendon transfer to his left arm. the burden of tense flexed muscles on the spines of patients
Swelling was noted in the eyelids of the patient immediately receiving shock therapy (Plotkin, 1993).
after tracheal intubation using d-tubocurarine anesthesia.
Other allergic symptoms included swelling of the face and
Contraindications
neck and the appearance of giant hives on most of the body.
The symptoms were so severe that the surgery was postponed The danger associated with the derivative tubocurarine when
and the patient was removed from anesthesia where the it was used as a muscle relaxant during surgery was possible
patient’s symptoms subsided and he was discharged. The asphyxiation; however, this worry was reduced with
patient’s history revealed urticarial reactions as a result of a technological breathing support during surgery. The effects of
variety of things including ingesting strawberries or green tubocurarine as an active constituent are temporary; with
artificial ventilation of the lungs to ensure that the patient is The synthetics include steroidal and benzylquinolone
still breathing the risk of asphyxiation is minimized. derivative classes as well as the drug Fazadinium. These
When prepared in liquid extract to act as a diuretic or tonic, C. synthetic drugs are not as complex or as multi-dimensional as
tomentosum is considerably less powerful. Curare must be C. tomentosum, but they are much safer and more controlled
injected directly into the bloodstream in order to reach its full than the tubocurarine derived from C. tomentosum (Booij,
toxicity; it is not harmful when taken orally in recommended 2000).
doses. This also explains why people of the Amazon are able to
hunt with it and then eat the “poisoned” meat; the animal
Discussion
meat is not poisonous to them due to the nature of the
compounds in curare. The highly charged and large nature of It is amazing that something in nature is potent enough to
the compounds causes them unable to cross through the paralyze a monkey with the prick of one dart. C. tomentosum is
digestive lining in the gut (Booij, 2000). the source of an incredibly powerful drug that enabled
surgery to advance. The development of modern medicine
Allergic reactions to d-tubocurarine have also been
was incredibly impacted by C. tomentosum, muscle relaxants
documented in patients with injection of d-tubocurarine
developed from derivatives like curare and d-tubocurarine
resulting in increased histamine output in the body inducing
allowed surgery to advance in ways that it could not have
swelling and the appearance of hives on the body (Westgate,
otherwise. Although its use has been replaced with synthetics
1961).
such as Fazadinium and other compounds belonging to the
steroidal and benzylquinolone derivative classes, curare holds
Current Use in Allopathic and CAM Therapies an unforgettable place in medical history and can never be
fully recreated in a laboratory (Booij, 2000). The importance
When traditionally prepared in the western Amazon regions of C. tomentosum was only realized through working with
of Brazil and Peru as a diuretic or tonic, the root of C. native Amazonian tribes and having an open mind about a so-
tomentosum is dried and then used to create a liquid extract. called poison; there are always multiple ways of looking at
The powdered root is seeped in boiling water and then a small things and this happened to be more than just a poison.
portion is evaporated to get an approximation of how much of Without innovative minds in the early twentieth century,
the plant was extracted. The liquid is then concentrated until tubocurarine might never have been derived from this
it thirty three and a half percent of it is made up of the notorious poison. Even though C. tomentosum may not play as
extractive. Alcohol is then added to bring it up to dosage. This influential of a role in the future of medicine as it did in the
method is rather ineffective, however, and leads to a product past, it still has potential in many facets of medicine that it has
that lacks potency and produces inconsistent results and not previously been tested in. The tribes of the Amazon
yields (Gadd, 1904). possess knowledge of countless plants and animals in the
There are not currently drugs on the market, as the traditional region and could hold the key to a number of illnesses modern
natural derivatives have been replaced with synthetic drugs. medicine has yet to cure. It is the combination of traditional
medicinal knowledge and innovative and open minds that (Colombia, Ecuador, Peru) with supplementary notes on
truly hold the key to unlocking cures to diseases that plague herbaceous taxa. Chicago, IL: University of Chicago Press.
the world, it is necessary to look into the rich history of González-Coloma, A., Reina, M., Sáenz, C., Lacret, R., Ruiz-Mesia, L.,
traditional medicine and consider the knowledge they can Arán, V. J., ... Martínez-Díaz, R. A. (2012). Antileishmanial,
provide when looking for chemicals and ingredients that can Antitrypanosomal, and Cytotoxic Screening of
truly make all the difference in medicine. Ethnopharmacologically Selected Peruvian Plants.
Parasitology Research, 110(4), 1381-1392. doi:
http://link.springer.com/article/10.1007%2Fs00436-011-
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genera of woody plants of Northwest South America
Cimicifuga racemosa (L.) Nutt., Ranunculaceae
Aerhealle Hampton
Introduction
Native to North America, Cimicifuga racemosa (syn. Actaea
racemosa) has long been a plant of many debated names. Its
common names include black cohosh, black snakeroot,
bugwort, bugbane, rattleweed, and squawroot, though the
latter is also used to refer to the unrelated blue cohosh
(Caulophyllum thalictroides). Of the Ranunculaceae family and
originally recognized by Linnaeus as belonging to the genus
“Actaea,” in 1818, Nuttall re-classified the plant’s genus as
being that of “Cimicifuga.” This was largely accepted until
recent years in which taxonomists have called for the return
to its original genus classification (Compton 1998). To reduce
conflicts with cited literature, however, C. racemosa will here
be used as the recognized scientific name.
Black cohosh has traditionally been used as an herbal remedy
in women’s health as it was believed to ease childbirth and
stimulate menstruation. It continues to be marketed toward
women and sold as a reliever of menopausal symptoms. The Figure 1. Racemes of C. racemosa displaying showy, white
exact method of action is still unknown, but many important flowers. Source: treefrogfarm.com
compounds have been isolated from C. racemosa including
triterpene glycosides and phenolic acids. Antioxidant, anti-
inflammatory, and anti-HIV properties have also been shaded, wooded hillsides that stretch across the mountainous
documented in black cohosh. regions of the midwest to eastern United States and Canada
(Li et al 2002). These wooded areas provide the well drained
soils that allow black cohosh to be an understory plant in
Description deciduous forests (Thomas et al 2007). Since it is an
herbaceous plant, the leaves and stems of black cohosh die
Cimicifuga racemosa is a perennial herbaceous plant that is down at the end of each growing period. During the next
harvested from the wild, almost exclusively (Thomas et al growing period, however, new flowering stalks 1-2.5 meters
2007). It thrives in sunny woodland pastures, as well as
in length grow and produce a crown of large, green, tri-ternate onto affected areas, as in a common treatment for
leaves. Smaller, ovoid leaflets (about 5-8 centimeters wide) rheumatism. Especially important was the use of Cimicifuga
are also produced with doubly serrate edges. Presumably the racemosa in Native American women’s health. The use of this
“black” in C. racemosa’s common names has its origins in the plant by Native American women was so prevalent that
dark brown to black coloring of its rhizome, from which the pioneers designated it with yet another nickname:
flowering stalks sprout (Lloyd and Lloyd 1884). “squawroot,” using the Algonquian word for “woman”. The
C. racemosa begins to bloom in late June and continues females of these native cultures used black cohosh for
throughout August. It is during this time that the large ailments such as painful childbirth and to stimulate
flowering racemes are produced, containing between fifteen menstruation (Sattler 1884).
to twenty flowers (Lloyd and Lloyd 1884). The showy flowers In the 1800s, many doctors began to include C. racemosa in
themselves, shown in Figure 1, are comprised of a small pistil their own reports and materia medica. Benjamin S. Barton
surrounded by multiple stamens, creamy white in color. The (1801) heralded the astringent properties of the root. He
clustered flowers lack noticeable petals and produce abundant noted that the gargling of a strong decoction made from the
pollen as well as a strong, unpleasant odor that attracts rhizome of black cohosh was useful as a treatment for an
pollinators (Wood 2000). The fruiting bodies of C. racemosa, ailment known as “putrid sore throat,” as well as a cure for
which brought about one of the major conflicts in the “the itch.” T.S. Garden later reported in The American Medical
designation of an appropriate genus for the plant, are a little Recorder (1823) that he self-medicated with C. racemosa to
over six millimeters in length, long, dry, oval in nature, and treat what he referred to as “Phthisis pulmonalis.” Though he
covered with thick, leathery sides. When the pod, containing was most likely suffering from what would now be recognized
8-10 brown and angular seeds, dies, it remains on its stalk as a case of bronchitis, Garden still reported that doses of an
throughout the winter and produces a rattling sound when extract from this plant lessened his night sweats, improved his
struck by coming winds, providing insight as to why this plant coughing, and lowered his pulse. In addition to this, he
is sometimes called “rattleweed” and “rattlesnake root” (Lloyd claimed that the black cohosh extract also calmed him with its
and Lloyd 1884). In the following warm season (following a sedative properties and may have even possessed possible
warm-cold-warm seasonal pattern of temperate regions), the vasodilatory properties. Described under the name of
seeds reach ripen and reach maturity (Wood 2000). Botrophis serpentine, C. R. Rafinesque also referred to the use
of C. racemosa as an inducer of both sweat and menstruation,
a treatment for joint pains, as well as a remedy in the
Traditional Uses treatment of hysteria. Rafinesque also mentions veterinary
Traditionally, black cohosh was used as a very important and uses of the plant in which he suggests that the consumption of
popular remedy in Native American cultures. In the instance black cohosh by cattle purged them of worms. Chapman, in
of snakebite, the chewed root was thought to be a sure cure Elements of Therapeutics and Materia Medica (1831), classified
for the onset of the poison when applied directly to the C. racemosa as an expectorant and sited uses of it being used
wound. For other ailments, a decoction of the root was rubbed as a narcotic (in the sense of it being a sedative and analgesic),
appetite, and possibly permanent decrease in brain function in
a matter of months (Young 1832).

Cimicifuga racemosa contains an abundant number of
secondary metabolites and compounds, varying in
composition during the lifecycle of the plant and dependant of
from where a sample is taken. That being said, many of these
compounds remain undiscovered. Due to this heterogeneity,
and lack of uniform results in research, the active components
in black cohosh also remain unknown. An example of two
secondary metabolites that vary greatly throughout the plant
and season are the terpenoids 23-epi-26-deoxyactein and
cimiracemoside A. It was found that about ten times the
amount of 23-epi-26-deoxyactein was found in inflorescence
tissues than the amount found in the rhizome of black cohosh.
The drying of this matter, however, lowers this amount to a
mere fourth of that found in the rhizome (Thomas et al 2007).
A large number of the main major constituents that have been
Figure 2. Major compounds found in Cimicifuga racemosa. identified in C. racemosa are its triterpene glycosides. Of the
Source : http://nutrition.perfectskillset.com/main/dietary- cyclolanostane triterpenes found in C. racemosa, the largest
supplements/supplements-a-c/700-black-cohosh-cimicifuga- group contains cimigenol as an aglycone (Zhou et al 2008).
racemosa-.html Cimicifugosides, cimiracemosides, and actein are also
important compounds in the chemical makeup of this plant.
an antispasmodic, a diaphoretic, and also an emetic when Though a uniform standard for purity markers have not been
taken in large enough doses. Around this time, C. racemosa created for black cohosh, these compounds have been found in
was also a popular treatment for pulmonary ailments, varying levels in liquid extract, powdered extract, and milled
including asthma and what we now know to be tuberculosis, plant material. Phenolic compounds, such as ferulic acid,
as it relieved cough, and reduced fever and heart rate (Sattler isoferulic acid, and caffeic acid, as well as the alkaloid
1884). C. racemosa was also documented as being a useful cImipronidine have also been found in C. racemosa (Li et al
treatment for St. Vitus Dance chorea, a disease believed to 2002). Structures of some of these compounds can be seen in
cause sporadic movement and twitching of the limbs, loss of Figure 2.
Biological Activity was given to male Wistar rats each day for thirty days. Their
liver morphology and other hepatic functions were closely
Though extensive testing has been performed, the method of
action for Cimicifuga racemosa is still unknown (Li et al 2002). watched and samples were taken and examined for damge
and abnormal cells. It was concluded that there was no
A common misconception posited for many years that black
cohosh acted as a phytoestrogen, mimicking the effects of correlation between C. racemosa and liver damage because an
absence of affected liver enzymes were found (Mazzanti et al
estrogen in the body. However, contrary to popular belief,
when tested alongside 7 other extracts from botanical sources 2008). Possible uses of C. racemosa in the treatment of HIV
in vitro for estrogenic activity, C. racemosa exhibited did not have also been pursued in vitro. The compound actein was
exhibit any estrogenic activity (Liu et al 2001). In 2003, tested alongside twelve sapponins has been tested for anti-
Burdette et al tested rhizome extracts from C. racemosa to try HIV activity. By inhibiting the replication of H9 lymphocytes,
to determine the mechanism of action for the alleviation of hot this triterpenoid displayed great effectiveness and anti-HIV in
flashes using ovariectomized Sprague- Dawley rats. The rats experiments (Sakura et al 2003).
were given a 40% propanol extract of black cohosh for two
weeks with and without the presence of the compound
Clinical Studies
estradiol. These researchers looked for clues of estrogenic and
antiestrogenic properties by observing the unterine weight of In a randomized controlled study comparing the effect of
the rats as well as recording their vaginal cellular makeup. exercise in changes on bone mineral density and 10 year risk
This team’s results also showed that C. racemosa does not for coronary heart disease, Cimicifuga racemosa was tested to
possess any antiestrogenic nor estrogenic properties. Instead, see if it could aid in bone mineral retention. Over one hundred
the results of their experiment indicated that the mechanism women were assigned to three different groups and subjected
responsible for the decrease in hot flashes may actually to different exercise routines involving high intensity
involve the 5-HT7 serotonin receptor pathway, which is resistance and high impact workouts with low intensity
involved in thermoregulation, through possible serotonin programs interspersed. Overall the study showed a positive
receptor ligands (Burdette et al 2003). correlation between exercise and dcreased risk of coronary
heart disease, but the addition of black cohosh showed no
In 2008, Powell et al performed in vitro experiments to
added benefits when paired with this exercise (Bebenek et al
uncover more about this possible mechanism of action by
2010). Phase III double-blind and randomized trials were
testing for receptor binding activity and cyclic AMP
performed between 2003 and 2004 in which the experimental
production. They found that, like many serotonin selective
group of postmenopausal women who had either completed
reuptake inhibitors (SSRIs), Nω-methylserotonin may be the
or were undergoing breast cancer treatment. Given a single
compound responsible for relieving hot flashes by working
capsule of 20 mg black cohosh, the women were to report
through the serotonin transporter (SERT) by binding to the 5-
their incidence of hot flashes in the form of a diary. The results
HT7 serotonin receptor and blocking serotonin re-uptake
of this study showed a mean decrease of 20% in hot flashes in
(Powell et al 2008). In an experiment to determine possible
comparison to the placebo-controlled group (Pojak et al
hepatotoxicity, 300mg/kg of dry root extract of C. racemosa
postmenopausal women who continued use of C. racemosa for
twelve months (Nasr and Nafeh 2009).
Contraindications
Though Cimicifuga racemosa is seen as relatively safe, there
was an instance of forty-two possible cases of hepatotoxic
effects being reported and investigated by the European
Medicines Agency (Mazzanti 2008). A follow-up was
conducted on four of the patients with the highest possibility
of C. racemosa related hepatotoxicity. The results of this
follow-up indicated no causality between the liver disease
present in the patients and the continued usage of
supplements from this plant (Teschke and Schwarzenboek
2009). Gastrointestinal upset and rash have also been
reported. A possible association between C. racemosa extract
performed in ethanol and hepatic mitochondrial toxicity (in
vivo and in vitro) has been indicated, but this possible
relationship is thought to be clinically irrelevant unless the
patient taking supplements has underlying risk factors for
liver disease (Lude et al 2007).

Since the method of action is still unknown, marketed
products that advertise Cimicifuga racemosa content typically
consist of the powdered dried root or powdered root extract
of this plant with no uniform composition across product
Figure 3. Marker compounds used for Cimicifuga lines. No single compound is recognized as a tell-tale sign of
racemosa. purity in the commercial black cohosh products, and as the
supplements fall under the DSHEA act of 1994, they are not
2006). In a 2009 longitudinal clinical trial, no evidence was subject to quality assurance standards. Of the products that
found to support hepatotoxic effects acting on have made attempts at quality control, many limit still their
focus on triterpene glycoside content. However, with this
limited basis of standardization, the large number of unknown References Cited
and undocumented compounds being ignored in the process Bebenek, M., Kemmler, W., von Stengel, S., Engelke, K., & Kalender,
may be lacking and nowhere near the original content levels of W. A. (2010). Effect of exercise and Cimicifuga racemosa (CR
the plant, itself (Zhou et al 2008). Though the search for the BNO 1055) on bone mineral density, 10-year coronary heart
active compound of C. racemosa continues, steps are being disease risk, and menopausal complaints: the randomized
taken to bring about some sort of standardization of products controlled Training and Cimicifuga racemosa Erlangen
using 16-18 of the most common constituents of C. racemosa (TRACE) study. [Randomized Controlled Trial]. Menopause,
listed in Figure 3 (Li et al 2002). Despite the lack of certainty 17(4), 791-800. doi: 10.1097/gme.0b013e3181cc4a00
in quality, sales of C. racemosa amounting to $79 million were Burdette, J. E., Liu, J. G., Chen, S. N., Fabricant, D. S., Piersen, C. E.,
reported in 2003 (Pojak et al 2006). Barker, E. L., . . . Bolton, J. L. (2003). Black cohosh acts as a
mixed competitive ligand and partial agonist of the
With many of the active compounds in black cohosh
serotonin receptor. [Article]. Journal of Agricultural and
remaining a mystery, correct dosing for various ailments
Food Chemistry, 51(19), 5661-5670. doi: 10.1021/jf034264r
remain tricky as well. Experiments conducted by Powell et al
in 2008, however, suggest that a 120 mg daily dose of C. Compton, J. A., Culham, A., & Jury, S. L. (1998). Reclassification of
racemosa could contain a therapeutic amount of Nω- Actaea to Include Cimicifuga and Souliea (Ranunculaceae):
methylserotonin (3.7µg), sufficient enough to battle hot Phylogeny Inferred from Morphology, nrDNA ITS, and
cpDNA trnL-F Sequence Variation. Taxon, 47(3), 593-634.
flashes and increase serotonin in postmenopausal women
(Powell et al 2008). Gori, L., & Firenzuoli, F. (2007). Is black cohosh a hepatotoxic
medicinal herb? [Letter]. Forsch Komplementmed, 14(2),
109-110. doi: 10.1159/0000101352
Discussion Li, W. K., Chen, S. N., Fabricant, D., Angerhofer, C. K., Fong, H. H. S.,
Though the scientific information on black cohosh is steadily Farnsworth, N. R., & Fitzloff, J. F. (2002). High-performance
liquid chromatographic analysis of Black Cohosh (Cimicifuga
developing, the long history that it has maintained as a helpful
racemosa) constituents with in-line evaporative light
aid in women’s health as well as other illnesses is sure to be a
scattering and photodiode array detection. [Article].
guide in future discoveries for the uses of this plant. Much Analytica Chimica Acta, 471(1), 61-75. doi: 10.1016/s0003-
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Cinnamomum verum J. Presl, Lauraceae
Leah Demakovsky
Introduction
The recognizably spicy flavor of ethnic foods is often
attributed to Cinnamomum verum, one of the major spices of
the ancient world and one that is still commonly used today.
There are several synonyms; Cinnamomum zeylancium,
Camphora mauritiana, and Laurus cinnamomum are all
recognized scientific names (Tropicos.org). In English the
most common colloquial name for Cinnamomum verum is
cinnamon, although it is also referred to as true cinnamon or
Ceylon cinnamon, where the latter describes cinnamon grown
specifically in Sri Lanka (Ravindra 2009). Cinnamon is a
member of the Lauraceae family, or the laurel family
(Tropicos.org). It has been used both in culinary practices and
medicinally for centuries due to its cinnamaldehyde-
containing volatile essential oils. It is a perennial tree that was
first recorded by Redgrove in the 1200’s (Ravindran, 2004).
Cinnamon is invasive in many areas of the world, but because
owning a cinnamon tree is a source of pride in places like the
Union of the Comoros, many people are happy to have it grow
(Vos, 2004). The spice is derived from the inner bark of the
tree, and the oils are distilled from both the leaves and bark
(Parthasarathy, 2008).
Figure 1. The Cinnamomum verum tree.

Botanical Description Source: (Yake, 2009)
The Cinnamomum verum plant, shown in Figure 1, is an are the source of the traditional ground spice. It is 0.2 -0.8mm
evergreen tree with green, oval shaped leaves, purple berry thick and is darker on the inside of the bark than on outside.
fruit and flowers, which are usually found in clusters The leaves have a leathery texture and grow in an opposite
(Parthasarathy, 2008). The bark is made up of quills, which pattern on the stem. They are typically 3.8-7.5 cm long and
in other areas of the tropics, and can survive in areas that are
more greatly affect by human disturbances (Vos, 2004). It has
been especially invasive in the Combani in Mayotte and on the
Mohéli mountains, as wells as some humid forests (Vos, 2004).
In Sri Lanka, locals have developed subclasses of the Ceylon
cinnamon based on specific plant properties. Pani kurundu
describes sweet, pani miris kurundu describes sweet and hot,
rasa kurundu describes tasty, suwanda kurundu describes
fragrant, and tita kurundu describes bitter cinnamon.
Although they are all scientifically classified as the same
Cinnamomum verum, differences in the soil and environment
of Sri Lanka gives the cinnamon that is grown there a unique
flavor (Ravindra 2009). Currently, cinnamon imports are
primarily from Sri Lanka, but the plant is also grown in Africa,
Figure 2. The buds and flower of Cinnamomum verum.
India, Indonesia, the Seychelles, South America and the West
Source: (Ambepitiyage, 2009)
Indies (Cepae, 1999).
7.5-20 cm wide and have more shine on the top than

underneath the leaf. The flowers are silky in texture and Traditional Uses
yellow in color, as seen in Figure 2. The perianths can grow Medicinal Uses
up to 5-6 mm and are longer than the inner tube of the flower,
which only grow to about 2.5 mm in length. Even smaller are Cinnamomum verum has been used extensively as a traditional
the fruit, which are only 1.3-1.7 cm in length and contain a medicine throughout the world. It was used as an anti-
single seed inside. They are both enclosed in an 8 mm purple diuretic, a digestive aid, and as a treatment for eye infections,
bell shaped perianth (Cepae, 1999). menstrual symptoms, inflammation of the kidney and
intestines, stomachaches, and as a topical for stings and bites
When ground, cinnamon is reddish brown in color. Cinnamon throughout Asia and Europe (Ravindran, 2004). The extracts
sticks are somewhat lighter than the ground plant, and are of cinnamon have been used in India for the treatment of
derived from peelings of the inner bark, which curl when diabetes (Subash, 2007). It was a common part of Traditional
dried This utilization of the cinnamon plant is the common Chinese Medicine, with uses in treating fever and diarrhea
form seen in culinary arts (Cepae, 1999). (Heinrich, 2004). Sho-seiryu-to, or Xian Qing Long Tang, is a
Cinnamon is indigenous to Sri Lanka and parts of India but mixture of several plant species including cinnamon bark that
was introduced to Seychelles and Madagascar by the Dutch was used in the treatment of perennial allergic rhinitis,
and British (Ravindra, 2009). However, the plant is invasive asthma, and other upper respiratory infections. Sairei, another
concoction used for the treatment of these illnesses, also vanillin (Parthasarathy, 2008). It is an integral part of Indian
contained cinnamon bark (Preedy, 2008). curry and other traditional ethnic foods. Due to its antioxidant
Cinamomum verum had a wide use in Ayyurvedic medicine. In properties, cinnamon was a common food preservative before
“The Indian Materia Medica” it is referenced as a treatment for refrigeration was available (Parthasarathy, 2008).
flatulence and stomachic and was used as an antispasmodic,
stimulant, astringent, antiseptic and antimicrobial. Each
Other Traditional Uses
specific grouping of cinnamon has a different use; the names
of the characteristics of cinnamon are similar to the Ceylon Cinnamomum verum was extensively used as a fragrance by
groupings. Tikarasm increases appetite and produces dry the ancient Egyptians in their embalming rituals (Heinrich,
mouth, ushnaveeryam raises body temperature, increases 2004). Cinnamon oils were commonly found in the perfumes
circulation, increases appetite and increases digestion and worn by Egyptian men, and was also added to oils used as
laghu increases digestion. Each class was used in the light to prevent harmful or bad smelling vapors. The spice
treatment of a variety of ailments including anorexia, cardiac was so highly prized by the Egyptians that Nero, the Emperor
diseases, bowel dysfunctions, and helminthic infections of Egypt in 66AD, was said to have burned a year’s supply of
(Thampuran, 2003). cinnamon at his wife’s funeral as a demonstration of his grief
and sorrow (Ravindran, 2004).
Cinnamomum verum is also used in “folk” medicine for
impotenence, frigidity, dysponea, eye inflammation, Cinnamomum verum is mentioned several times in the bible
leucorrhoea, vaginitis, rheumatism, neuralgia, wounds and and is one of the plants used in the holy anointing oil. It is also
toothaches, although there are no studies to show that it is described in Rev. xviii. 13, “cinnamon, and odours, and
effective for any of these ailments (Ravindran, 2004). ointments, and frankincense” (Grindon, 1883), giving light to
some of the uses of cinnamon during the time period.
Culinary Uses
Traditional Importance
Cinnamomum verum has been used as a spice in cooking for
centuries. The oils extracted from the bark and leaves are used Cinnamomum verum has been traded extensively for
to flavor numerous foods, drinks, sauces, baked goods, and centuries; there are records of its trade history during the
tobacco products (Flavours and Fragrances of Plant Origin, Roman era. It was passed to the Arabs who tried to keep its
2012). In Latin America, as well as many other places in the original location a secret from other traders, causing
world, the quills are boiled in water and are drunk as a tea. In European explorers to search for the plant during the 1400s
the United States it is used as a flavoring in the home as well (Ravindra, 2009). Herodotus, the "father of history", described
as in the food industry (Ravindra, 2009). Cinnamon is the cinnamon dilemma, and stated that the Arabs did not
commonly used in soaps, toothpastes, dentifrices and liquor know of its origins. The secrecy caused it to be one of the first
flavoring, and is also used in the synthetic production of plants which oriental traders searched extensively (Grindon,
1883). When it was found in Sri Lanka, the country was
eventually taken over by the Portuguese, Dutch and British
who propagated cinnamon cultivation (Ravindra, 2009).

While Cinnamomum verum has over one hundred chemical
components, cinnamaldehyde is the chemical responsible for
the strong smell and distinct flavor. Cinnamaldehyde, shown Figure 3. The chemical structure of cinnamaldehyde, the
in Figure 3 alongside eugenol, is an alkaloid with an aromatic primary constituent of Cinnamomum Verum and Eugenol,
ring that acts as a strong antioxidant by inhibiting amino acid one of the main chemical components of cinnamon oils.
decarboxlyase activity (Gupta et. al., 2008). Eugenol is a Source: (Cepae, 1999).
phenylpropene that is found in cinnamon leaves, giving them a
less appealing odor than the bark which contains much higher A recent study used matrix-assisted laser
concentrations of cinnamaldehyde (Flavours and Fragrances desorption/ionization tandem time-of-flight mass
of Plant Origin, 2012). spectrometry to determine the proanthocyanidins in
The bark contains 6,000-30,000 parts per million of cinnamon in order to better understand the chemical
cinnamaldehyde (Duke, 1996), which is its primary components, which yield cinnamon’s medicinal properties. It
constituent. Mucilage is another constituent in high amounts; was found that the proanthocyanidins contain (epi)catechin,
there are 20,000-37,000 parts per million found in the bark (epi)catechingallate, (epi)gallocatechin, and (epi)afzelechin
(Duke, 1996). Volatile components are found in every part of (Mateos-Martin, 2012).
the plant and consist of monoterpenes, sesquiterpenes and The chemical components of Cinnamomum verum (Table 1)
phenylpropenes (Parthasarathy, 2008). More specifically, can aid with the identification of the plant when compared to
these volatile oils include B-caryophyllene, linalool, safrole, other species of Cinnamomum. Cinnamomum verum contains
cinnamic aldehyde, cinnamyl acetate, cinnamyl alcohol and less than 2% foreign organic matter, less than 6% ash, with
benzly benzoate (Ravindran, 2004). The primary constituents less than 4% of this ash being insoluble in acidic solutions.
of the extracted volatile oils are cinnamaldehyde and eugenol, There also must be less than 6% sulfated ash due to
which make up 65-80 % and 10% of the oil, respectively government regulations on the treatment of plant products
(Cepae, 1999). with sulfides. Lastly, Cinnamomum verum extracts have a 14-
In the United States, the Fragrance Materials Association 16% solubility rate in 90% alcohol solutions (Cepae, 1999).
(FMA) monograph uses percent eugenol solubility in Other species of Cinnamomum have different percentages of
potassium hydroxide to regulate the standard of cinnamon; it these components, which may affect their different chemical
must be 80-88% soluble (FMA, 1992). properties.
Chemical Constituent in Chemical Constituent Chemical Constituent
Bark Amount in Bark Amount in Bark Amount
1,8 Cineole 165- 800ppm Fiber 270,000 ppm Trans-Linalol-Oxide 5-20 ppm
2-Vinylphenol 3-12 ppm Furfural 3-12 ppm Zinc 11.4-20 ppm
3-Phenyl-Propyl-Acetate 13-52 ppm Gamma- Terpinene 3-12 ppm
Chemical Constituents
Acetoeugenol 16-64 ppm Geraniol 6-24 ppm in Leaf Amount
Alpha-Pinene 20-236 ppm Humulene 20- 124 ppm Chromium 14.4 ppm
Alpha-Terpineol 40-264 ppm Hydrocinnamaldehyde 40-160 ppm Cobalt 1.1ppm
Alpha-Ylangene 31-124 ppm Iodine 3 ppm Copper 10.9 ppm
Ascorbic-Acid 309 ppm Iron 60- 421 ppm Manganese 101.6 ppm
Barium 60 ppm Isoeugenol 2-8 ppm Nickel 4.2 ppm
Beta-Carotene 1-2 ppm Limonene 46- 184 ppm Zinc 34 ppm
Beta- Pinene 14-76 ppm Linalol 230- 956 ppm
Chemical Constituents
Borneol 2-8 ppm Manganese 66-140 ppm in Plant Amount
Bornyl-Acetate 10-20 ppm Mucilage 20,000- 37,000 ppm 2-Phenylacetaldehyde
Boron 7-15 ppm Myrcene 5-20 ppm Alpha-Terpinene 42-168 ppm
Bromine 10 ppm Niacin 8 ppm Benzaldehyde 26-104 ppm
Calcium 5,329-6,000 ppm Nickel 1.1 ppm Peperitone 7-28 ppm
Camphene 18-72 ppm P-Cymene 55-448 ppm
Caryophyllene 135-1,316 ppm Phellandrene 63-252 ppm
Chlorine 300 ppm Phenyl-Ethyl-Alcohol 41- 164 ppm
Chromium 2-10 ppm Phenylethyl-Acetate 7-28 ppm
Cinnamaldehyde 6,000-30,000 ppm Phosphorus 674- 1,100 ppm
Cinnamyl-Acetate 510- 2,040 ppm Potassium 5,525-6,000 ppm
Cinnamyl- Alcohol 26- 104 ppm Protein 35,000- 43,000 ppm
Cis-Ocimene 3-12 ppm Riboflavin 1 ppm
Cobalt 0.6ppm Rubidium 20 ppm
Copper 4.9-9 ppm Sabinene 2-8 ppm
Cumene 66-264 ppm Sodium 287 ppm
Cuminaldehyde 4-100 ppm Strontium 80 ppm
Delta-3-Carene 3-12 ppm Sulfur 1,900 ppm
Eo 40,000 ppm Terpinen-4-Ol 36-144 ppm
Eugenol 220-3,520 ppm Terpinolene 11-44 ppm
Farnesol 3-12 ppm Thiamin 1 ppm
Fat 14,000 ppm Titanium 40 ppm
Table 1. The most abundant chemical components of Cinnamomum verum bark, plant, and leaves. Source: (Mathew, 2006;
Parthasarathy, 2008)
verum, has been found to have antiallergenic, antiulcerogenic,
antipyretic, antimicrobial, anesthetic and antimutagenic
properties (Mathew, 2006). There are also numerous
antibiotic uses; the essential oils have been found to act as an
antibacterial in vitro against Bacillus subtilis, Escherichia coli,
Staphylococcus aureus and Pseudomonas aeruginosa
(Ravindran, 2004). The oil has also been found to act as an
antifungal in vitro against Aspergillus spp., Cladosporium
werneckii, Geotrichum candidum, Kloechekera apivulata,
Candida lipolytica and C. albicans (Ravindran, 2004).
Additionally, a study examining the effects of cinnamon oil and
extracts found both to increase the zone of inhibition of
several food born bacteria. Cinnamon had the greatest effect
against Bacillus cereus, as shown in Figure 4 (Gupta et al.,
2008).
With the increasing problem of antibiotic resistance causing a
need for new therapies, cinnamon has been studied for its
antibacterial effects on resistant species of bacteria. The
essential oils of cinnamon were found to decrease the minimal
inhibitory concentration of amikacin needed to kill resistance
species in the Acinetobacter genus (Guerra, 2011).
Many of the biological activities seen when utilizing cinnamon
have been attributed to cinnamaldehyde,
methoxycinnamaldehyde, and other compounds found in high
Figure 4. A study examining the antimicrobial activity of concentrations in the bark and oil (Ravindran, 2004).
Cinnamomum verum against common food borne bacteria Cinnemaldehyde’s phenolic compounds act as an electron
demonstrated cinnamon’s effectiveness across a broad donor and catalyzes the reaction of hydrogen peroxide to
range of bacteria. The essential oils were found to be water (Gupta et al., 2008). Other studies have attributed many
particularly effective against Bacillius cereus, as shown above. of the beneficial properties of cinnamon to the phenolic
Adapted from Gupta et al., 2008. proanthocynidins also found in the essential oil (Cabello,
2009). The cinnamic aldehyde found in the essential oil
Biological Activity contains phenloic proanthocyidins, which have been found to
inhibit growth of melanoma in vitro and in vivo (Cabello,
Cinnamaldehyde, the primary constituent in Cinnamomum
2009).
Cinnamaldehyde also acts as an antispasmodic and has been directly attributed to the components of the cinnamon rather
found to decrease histamine and barium induced smooth than the other ingredients added. This finding explains the
muscle contractions in guinea pig trachea and ileum (Reiter results that people have been using for centuries, and
1985). although it is not a human clinical trial, has indications for use
The methanolic extracts of cinnamon have been shown to in humans.
have antioxidant properties and act as a hydroxl radical A study conducted in India found that cinnamaldehyde
scavenger, act as a reducing agent, and have demonstrated reduces blood glucose levels in steptozotocin induced diabetic
metal ion chelating activity. The cinnamon extracts act as a rats and thus has hypoglycemic and hypolipidemic effects
transition metal stabilizer which prevents the perpetuation of (Subash, 2007). This study was important for diabetes
the formation of new free radicals in the body (Mathew, research because it identified cinnamaldehyde as the
2006). The phenolic compounds can act as electron donors to component of cinnamon that decreased plasma glucose levels,
catalyze the reaction of H2O2, a toxic substance, to H2O or acted as an antidiabetic.
(Mathew, 2006).
Although this study did not directly involve humans, the rat
model is a fairly accurate indicator. Studies similar in nature
Clinical Studies have been conducted with humans. However, these studies
often do not specify the type of species used, or more
Several species of Cinnamomum have been used as medicine commonly or use a mixture of more than one species. Over all,
throughout history. Cinnamon and its active ingredients are the lack of causal evidence indicates that more clinical studies
generally regarded as safe by the ‘Flavor and Extract are needed to determine the specific effects of C. verum in
Manufacturers’ Association (FEMA no. 2286, 2201) (Cabello, humans.
2009). Although many studies fail to distinguish which sub-
species within the Cinnamomum genus were used, there are
numerous studies indicating Cinnamomum verum can have Contraindications
health benefits. Similarly, there have been\many clinical
Although Cinnamomum verum has numerous health benefits,
studies involving the efficacy of using cinnamon as a
Italy and Germany blocked some importation of cinnamon
treatment for several diseases, especially type 2 diabetes and
from Sri Lanka due to high sulfur content. Cinnamon does not
metabolic syndrome. Unfortunately, there are no current
have a high sulfur content naturally, but is often fumigated
studies examining just C. verum in humans.
with sulfur dioxide during processing as a preservative which
Sairei, the traditional Chinese remedy containing cinnamon coats the cinnamon in a sulfur residue. The acceptable
bark used to treat upper respiratory infections has been found maximum amount of sulfur is now regulated under the Codex
to inhibit basophil growth and histamine content in vivo Alimentarius Commission (CAC). Until 2006 the CAC did not
(Preedy, 2008), however, there is some uncertainty regarding have a standard maximum residue limit, and the level
the species of Cinnamomum used and if the results can be acceptable in Sri Lanka was more than the level acceptable in
the European countries, leading to the block of importation in alternative medicine (CAM) therapy may be its most well
certain parts of Europe (Ravindra, 2009). Although there are known medicinal use. There are few drugs on the market
limits in place currently, it is not known how the sulfur involving cinnamon or the active ingredients in cinnamon in
fumigation affects the medicinal properties of the plant. the United States however clinical trials are investigating the
Few cases of fever of unknown origin, pregnancy, stomach indigenous use of cinnamon to treat diabetes as well as a
ulcers, and duodenal ulcers have been indirectly associated variety of other diseases (Ravindran, 2004), Currently, there is
with the use of cinnamon (Bisset, 1994; Ravindran, 2004). an herbal treatment for inflammation of the eye called
Reactions to cinnamon have occurred in individuals who have Ophthacare which contains 0.5% cinnamon. When tested in
allergies to active ingredients in cinnamon or Peru balsam rabbits, it was found to be effective (Thampuran, 2003). The
(Ravindran, 2004). The “Indian Materia Medica” states bark and oil are included in drug cocktails as a carminative or
cinnamon can cause irritation and can be poisonous in large flavoring in several countries including India, Britain, China,
quantities (Thampuran, 2003). When used in food as a flavor Australia, Belgium, Europe, France, Germany, Hungary, Japan,
the Netherlands, Portugal and Switzerland (Thampuran,
additive, the daily intake should not exceed 700 µg per kg of
2003).
body weight per the World Health Organization and Food and
Drug Administration guidelines (Thampuran, 2003). Several studies have identified cinnamon as a CAM therapy
Occasionally the cinnamaldehyde can cause skin or mucus throughout the world. One study in Australia surveyed
membrane irritation when used as a perfume, or in diabetics and found that one-fourth of individuals with
toothpastes. Oral lesions after chewing cinnamon gum are diabetes mellitus who used CAM therapy used cinnamon.
rare but have been reported in those with sensitivity to However their sample size was small providing the need for a
cinnamaldehyde or cinnamon (Thampuran, 2003). larger study to confirm results. There were no significant
correlations between gender, age, income and severity of
The use of cinnamon in children has not been extensively
diabetes and using cinnamon as a CAM treatment. (Manya,
studied. There are no studies indicating that C. verum is unsafe
2012). Although the study uses the scientific name C. verum in
for use during pregnancy, nursing, or with certain other drugs.
its report, the common name cinnamon was used on the
However, studies have indicated other species of
questionnaire, meaning there was no way to know exactly
Cinnamomum do have associated risks (Ravindran, 2004).
what species of cinnamon was used. There was also no
Since C. verum has unique chemical properties, it does not
question regarding the amount of cinnamon taken or the
mean that all Cinnamomum has these risks, although one
frequency. It is assumed that the powdered (ground) form of
study did find cinnamaldehyde to be teratogenic in chick
cinnamon was used as the supplement.
embryos (Keller 1999).
A larger study found that thirty percent of individuals in
Bahrain with diabetes mellitus who used CAM therapies used
Current Use in Allopathic and CAM Therapies cinnamon for the treatment of their diabetes (Khalaf, 2010).
The use of Cinnamomum verum as a complementary and This study also did not have a way to identify the species of
cinnamon used or the amount taken by the patients, but its
results were similar to studies previously done on several species of Cinnamomum. Even today, there are numerous
world populations including the United States. Another even studies that fail to properly ensure that the substance they are
larger study conducted in Israel found 10.8% of diabetics used using is C. verum and not a cheaper species labeled as such.
cinnamon as a CAM remedy, but most individuals were from Studies also fail to mention which species of Cinnamomum
refugee camps (Ali-Shtayeh, 2012). A study using a random they used and simply refer to the plant as “cinnamon” despite
sample is needed to confirm results. the numerous differences in chemical constituents.
The World Health Organization estimates the average daily Further, due to the many methods of extracting the oils of the
dose of cinnamon taken by those who use cinnamon for bark and leaves, there is a high chance that one sample of oil
medicinal purposes is about 2- 4 grams per day when used may not match another sample chemically. Though they will
ground, or 0.05-0.2 grams when the volatile oil is used still contain the same basic constituents, the varied
(Ravindran, 2004). concentrations of such can yield entirely different effects. Also,
Throughout Africa and other developing countries, the lack of since the plant is grown in regions of the world with
legal, safe and affordable abortion or birth control services differences in environment, the concentration of chemicals
lead to the development of systemic abortifacients. Boiled may also vary from region to region (Flavours and Fragrances
wine, raisins and cinnamon is drunk as an oral abortifacient, of Plant Origin, 2012). These differences are roadblocks in
but is not considered to be safe and the efficacy has not been research involving cinnamon, but one that can be overcome as
studied (Warriner, 2006). technology advances.
Currently, scientists are attempting to cultivate cinnamon
with increased concentrations of cinnamaldehyde and eugenol
Discussion in order to use cinnamon more widely in the treatment of
Cinnamomum verum has a vast variety of uses and the disease. The major problem with cinnamon is that it is widely
potential for even more applications. There is an immense available but 68% of patients in the Israeli diabetes study did
cultural value associated with the plant due to its significance not report using cinnamon to their doctor, although this is far
in earlier centuries and its importance in many ethnic foods too common in many CAM remedies (Ali-Shtayeh, 2012). This
around the globe. Originating in Sri Lanka, the plant has has the potential for unknown medical complications. More
become invasive in many areas as it can outcompete other research will be necessary before these plants can be utilized,
species in a variety of climates. Cinnamaldehyde, the primary but the future for cinnamon looks promising (Flavours and
chemical constituent in cinnamon, has shown great promise in Fragrances of Plant Origin, 2012). Until then, it will be grown
the treatment of diabetes and other chronic illnesses. There is, and used as the spice the world has come to love.
however, some controversy regarding the use of cinnamon. In
ancient writings the exact species of cinnamon was not always
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Coffea arabica L., Rubiaceae
Alison Yarp
Introduction
Coffea arabica L., known to most of the world as coffee, is a
member of the Rubiaceae family. It is also known as the
“coffee shrub of Arabia” (Weinberg & Bealer, 2001), café, and
multiple other regional names (I. A. Ross, 2005). C. arabica is
the oldest known cultivated species of coffee (Weinberg &
Bealer, 2001). Originally from the Ethiopian mountains, it is
now cultivated in the subtropics and high altitude tropics and
now grows naturally in many of these environments. There
are 25 to 100 species in the genus Coffea, but C. arabica is one
of the two main species currently being used in coffee
production – the other being C. canephora (Rieger, 2006).
However, C. arabica makes up about 75% of the worldwide
coffee consumption (Weinberg & Bealer, 2001). One of the
main derivatives, caffeine, is a potent stimulant, and is
responsible for most of the effects, which includes central
nervous system stimulation, as well as stimulation of other
body systems (Kraft & Hobbs, 2004). Figure 1. Coffea arabica. Source:
http://www.gutenberg.org/files/28500/28500-h/28500-h.htm
(Roecklein & Leung, 1987). C. arabica growth can be hindered
Coffea arabica is a small evergreen tree and can grow up to 30 above 77°F, and frosts can kill the leaves and fruits (Francis).
feet in the wild, but is generally maintained at 6 to 8 feet However, for a tropical plant, C. arabica is still resilient at
(Rieger, 2006) for easier harvesting (Weinberg & Bealer, lower temperatures (Weinberg & Bealer, 2001). The
2001). It is cultivated primarily in tropical and subtropical appropriate amount of rainfall is about forty to sixty inches
countries including Brazil, Colombia, Mexico, and Guatemala throughout the year (Weinberg & Bealer, 2001).
(Khan & Abourashed, 2010). They are considered an “upland”
species, so the ideal places for growth are at 5000 to 7000 feet For a picture of Coffea arabica, see Figure 1. C. arabica can
at the equator. In the subtropics, it grows well at sea level grow as a single shoot, but it will often branch off into multiple
stems towards the bottom (Francis). The bark of the tree is an twelve pounds of dried beans in a year (Weinberg & Bealer,
ash white (PDR for herbal medicines, 1998). The leaves are 2001).
dark green with an oval shape (Francis). They are about half a
Traditional Uses
foot long and 1 to 2 inches wide (PDR for herbal medicines,
1998). They grow in pairs opposite each other on the stems. Medicinal
The dorsal sides have a “smooth and shiny” appearance with Depending on the region, Coffea arabica has many uses. As
obvious veins (Francis) and resemble leather (PDR for herbal seen by Table 1, these uses range from inducing labor to
medicines, 1998). These leaves can live about 2 to 3 years. treating headaches (I. A. Ross, 2005). In Brazil, the seed is
The flowers on C. arabica are white and fragrant (Francis), decocted and taken orally to treat influenza. In Cuba, a hot
with 5 petals coming out of a slender tube shaped base water extract of the seed is taken orally as an aphrodisiac for
(Rieger, 2006). Up to 20 flowers will grow on an axil, and they males (I. A. Ross, 2005). Haitians have multiple uses of the
each contain two ovules, allowing for possibly two seeds to plant: grilled decoction of the fruit and leaf is taken orally for
form (Rieger, 2006). Flowers that open when it is dry and anemia, fruit is eaten for hepatitis and liver troubles, soaked
sunny generally produce more fruit than those that open on a fruit is applied externally for nervous shock, and the leaf is
wet day because of the increased pollination by wind and decocted and taken orally or applied externally for headache
insects (Weinberg & Bealer, 2001). C. arabica is self (I. A. Ross, 2005). In Mexico, the leaf is made into a poultice
pollinating and can even pollinate itself when the flowers are and applied externally for fever, and the hot water extract of a
closed (Rieger, 2006). However, it also benefits from cross roasted seed is taken to increase milk production in nursing
pollination by bees (Klein, Steffan-Dewenter, & Tscharntke, mothers. Nicaraguans also have many ways of using coffee.
2003). They use the leaf externally to treat headache and orally as a
hot water extract to help with stomach pain. They also use the
The fruit, also known as berries or drupes, of C. arabica is
decoction of the seed orally for fever and externally for cuts
elliptical and is flat when observed by cross section. They are
and hemorrhage (I. A. Ross, 2005). In Uganda, a decoction of
about 12 to 18 mm long and 12 to 15 mm wide. They are
the leaves is used to treat aerophagia and a cough (Lacroix et
green until they become ripe, at which point they are yellow
al., 2011). In Peru, a hot water extract of dried fruit is used
and dark red (PDR for herbal medicines, 1998). Because of the
orally for sleepiness and drunkenness, while the leaf is used to
color of the berries after they mature, farmers and processors
induce labor or as an antitussive in flu and lung sicknesses.
commonly refer them to as cherries. Under the skin is a sweet
The Thai use the hot water extract of the dried seed orally as a
and moist fleshy pulp, which is commonly eaten (Weinberg &
cardiotonic or neurotonic. Lastly, in the West Indies, the hot
Bealer, 2001). The fruits generally contain two seeds, or
water extract of the seed is used orally for asthma, and juice
beans, which are between 8 and 12 mm long. They have one
from the root is taken orally for scorpion stings (I. A. Ross,
rounded and flattened end and have a groove on one of the
2005).
sides (Francis). Depending on the individual characteristics
and the climate conditions, a single tree can yield from one to While not necessarily just used to treat ailments, coffee has
also been used by many cultures as a general stimulant, to
Country Plant Preparation Route Use increase alertness and improve productivity (Chevallier,
Part 1996). For example, the average daily consumption of a coffee
Brazil Seed Decoction Oral Influenza drinker in the United States is 3.1 cups (Bisht & Sisodia, 2010).
Cuba Seed Hot water Oral Aphrodisiac
extract (males)
Haiti Fruit Grilled Oral Anemia,
and leaf Decoction edema, Food
asthenia, rage
Haiti Fruit - Oral Hepatitis, liver
Coffee has been consumed as a beverage for about 1000 years
trouble (Chevallier, 1996), and it has become the most consumed
Haiti Fruit Soaked External Nervous shock functional food around the world (Bisht & Sisodia, 2010). In
Haiti Leaf Decoction Oral, Headache the United States, 68% of people over the age of 10 consume
External coffee, and in 1969, 2.8 billion pounds of coffee, which equals
Mexico Leaf Poultice External Fever
Mexico Seed Roasted Oral Increase milk
approximately 150 billion cups (Lewis & Elvin-Lewis, 2003).
Hot water production in The main importers of coffee are the United States, Germany,
extract nursing and France (Roecklein & Leung, 1987), while the main
mothers producers are Brazil and Columbia (Bisht & Sisodia, 2010).
Nicaragua Leaf - External Headache
Nicaragua Leaf Hot water Oral Stomach Pain C. arabica has become a competitive crop in Costa Rica and is
extract important to the nation’s livelihood. To maintain this, they
Nicaragua Seed Decoction Oral Fever have to produce enough of it in a reasonable amount of time.
Nicaragua Seed Decoction External Cuts,
Small farm owners did this traditionally, but today this is
Hemorrhage
Peru Fruit Dried Oral Sleepiness, moving towards large plantations (Weinberg & Bealer, 2001).
Hot water drunkenness Gourmet coffees are generally high quality varieties of C.
extract
Peru Leaf Infusion Oral Induce labor
arabica without the harsh or hard taste. They mainly come
Peru Leaf Hot water Oral Antitussive in from Latin America, except Brazil (Weinberg & Bealer, 2001).
extract flu and lung However, they can also come from Kenya, Tanzania, Ethiopia,
ailments Cameroon, and Yemen. Fine coffee used to come exclusively
Thailand Seed Dried Oral Cardiotonic, from Yemen and would be shipped globally through the port
Hot water neurotonic
extract
of Mocha. After World War I, the wells in Mocha dried up, so
West Indies Seed Hot water Oral Asthma the coffee cultivation there was almost completely abandoned.
extract Small amounts of coffee still come from Yemen through the
West Indies Root Juice Oral Scorpion sting port of Hodeida, but it is still referred to as Mocha, as this
Table 1: Traditional Medicinal Uses of Coffea arabica name is still engrained in people’s minds as the best coffee
Source: (I. A. Ross, 2005)
beans (Weinberg & Bealer, 2001). Regarding Brazil, most
coffees coming from this country are Coffea arabica, but they
are known to have a less refined flavor and aroma than the Chemical Constituents in Coffea arabica
milder forms (Weinberg & Bealer, 2001). Plant Cholestanol, Cholesterol, Choline, Citric
Cyanidin, P-coumaric Acid, Sinapic Acid, Citrostadienol, Caffeoyl-3-Quinic
Acid Acid, Caffetannic Acid, Cahweol,
Calcium, Campestanol, Campesterol,
Other Fruit Caprinic Acid, Carbohydrates, Carnaubic
Caffeic Acid, L-Asparagine, L-Aspartic Acid, Cellulose, Chlorogenic Acid,
Other uses have included various parts of the tree. The bark Acid, Oxalic Acid Cholestanol, Cholesterol, Choline, Citric
can be made into parchment, mulch, manure, and pulp, which Acid, CitrostadienolCoffeasterol,
is occasionally fed to cattle in India (Roecklein & Leung, 1987). Leaf Cycloeucalenol, Cysteine, Cystine,
Allantoic Acid, Allantoin, Beta- Daturic Acid, Dextrins,
Carotene, Caffeic Acid, Calcium, Dihydrolanasterol, Dihydrositosterol,
Carbohydrates, Fat, Fiber, Iron, Niacin, EO, Eugenol, Fat, Fiber, Fufuryl Alcohol,
Chemistry and Pharmacology Phosphorus, Protein, Riboflavin, Furfuraldehyde, Galactan,
Theobromine, Theophylline Galactomannan, Gamma-sitosterol,
A list of the chemical constituents of Coffea arabica can be Gamma-tocopherol,
seen in Table 2 (Duke). However, the more important ones Seed Glucogalactomannan, Glutamic Acid,
2,3,5-trimethylphenol, 2-ethylphenol, Guaiacol, Guanosine, Hemicellulose,
out of the list are the purine (or also known as xanthine) 2-methoxy-4-ethylphenol, Homocellulose, Hydrogen Sulfide,
alkaloids, theobromine, theophylline, caffeic and ferulic acid 24-methylene-cycloartenol, Hypoxanthine, Iron, Isochlorogenic
esters of quinic acids, no-diterpine glycoside esters, 24-methylenephenol, Acid, Isoeugenol, Kahweol, Lanosterol,
3,4-dicaffeoyl-quinic-acid, Lignoceric Acid, Linoleic Acid, Linolenic
trigonellines, and diterpenes (Kraft & Hobbs, 2004). Among 3,5-dicaffeoyl-quinic-acid, Acid, M-Cresol, Mannan, Mannose,
these, the notable ones are caffeine, chlorogenic acid, 4,5-dicaffeoyl-quinic-acid, 4- Methionine, Myristic Acid, N-
theobromine, and theophylline, especially for their medicinal ethylphenol, Nonacosane, Niacin, Nitrogen, O-Cresol,
4-methoxy-4-vinylphenol, 5- O-Xylenol, Obtusifoliol, Oleic Acid, P-
and physiological effects. Caffeine, a purine alkaloid, can be avenasterol, Cresol, P-Xylenol, Palmitic Acid, Pectin,
seen in Figure 2 and can range in concentration from 600 to 7-stigmasterol, Acetaldehyde, Pentosane, Pentosans, Phosphorus,
32000 parts per million (ppm) (Duke). In an even greater Adenine, Phytate, Phytosterols, Polyamines,
Alpha-tocopherol, Arabinogalactose, Protein, Putrescine, Raffinose,
concentration is chlorogenic acid, with a range of 50000 to Arabinose, Arachidic Acid, Ash, Rhamnose, Riboflavin, Saccharose,
80000 ppm (Duke). Because of the high concentration of Asparagine, Aspartic Acid, Salicylates, Scopoletin, Spermidine,
chlorogenic acid, estimates have been made that state that the Atractyligenin, Beta-sitosterol, Beta- Spermine, Squalene, Stachyose, Stearic
tocopherol, Cafesterol, Cafestol, Acid, Stigmasterol, Sugar, Tannic Acid,
intake of chlorogenic acid is many times higher for people who Caffeine, Caffeol, Tannin, Tetracosic Acid, Theobromine,
consume coffee on a regular basis, especially when compared Caffeoyl-3-Quinic Acid, Caffetannic Theophylline, Thiamin, Trigonelline,
to non coffee consumers (Bisht & Sisodia, 2010). Theobromine Acid, Cahweol, Calcium, Campestanol, Water, Xanthine, Xylan
Campesterol, Caprinic Acid,
and theophylline are present as well in 35 to 40 and 7 to 23 Carbohydrates, Carnaubic Acid,
milligrams per kilogram, respectively (Weinberg & Bealer, Cellulose, Chlorogenic Acid,
2001). Regarding how some of the other constituents affect C. Table 2. Chemical Constituents in Coffea arabica
arabica, 2-furfurylthiol, 4-vinylguaiacol, alkyl pyrazines, Source: (Duke)
furanones, acetaldehyde, propanol, methylpropanol,
average increase of 10 mmHg in systolic blood pressure (Kraft
& Hobbs, 2004).
Caffeine works by binding to adenosine receptors and
blocking phosphodiesterase (Wyk & Wink, 2004). As stated
previously, it can affect many parts of the human body. In the
cardiovascular system, it has a positive inotropic effect on the
heart and a positive chronotropic effect on the sinoatrial node,
which causes increased heart rate, contraction force, and a
greater cardiac output (Walter & Maheswari, 2006). It can also
cause vasoconstriction in the cerebral vasculature, which
decreases the blood flow and the oxygen tension of the brain
(Walter & Maheswari, 2006). For some patients, this could
Figure 2 Structure of Caffeine. Source: provide relief from headache pain (Walter & Maheswari,
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=16514 2006). In the gastrointestinal system, caffeine initiates the
secretion of pepsin and gastric acid from the parietal cells
2-methylbutanol, 3-methylbutanol have greatest impact on (Walter & Maheswari, 2006). In the renal system, caffeine
coffee flavor (Czerny, Mayer, & Grosch, 1999). Also, caffeine is causes an increase in renal blood flow and the glomerular
actually a defense mechanism for C. arabica. It has the filtration rate, while decreasing the reabsorption of sodium
capability of destroying harmful bacteria and fungi and and water by the proximal tubules. This can create mild
sterilizing certain dangerous insects. If it has inhabited an area diuresis (Walter & Maheswari, 2006). Caffeine also impedes
for a long period of time, it could possibly inhibit weed growth uterine contractions and transiently increases plasma glucose
as well (Weinberg & Bealer, 2001). with stimulation of glycogenolysis and lipolysis (Walter &
Maheswari, 2006).
Biological Activity Studies have shown that the methylxanthines in coffee can
help with respiratory issues. Theophylline, an example of a
Most of the biological activity in Coffea arabica stems from the
xanthine, is present in C. arabica at about 7 to 23 milligrams
presence of caffeine (Khan & Abourashed, 2010). It’s stimulant
per kilogram, and has been used as a prescription medication
properties are responsible for stimulating the central nervous for the treatment of asthma (Bisht & Sisodia, 2010).
system, respiratory system, skeletal muscles, and performing
cardiac stimulation, arterial dilation, smooth muscle
relaxation, and acting as a diuretic (Khan & Abourashed, In vitro & ex vivo
2010). Also, it has been observed that within 1 hour of having
250 mg of caffeine, non-coffee drinkers tend to have an One study performed on Coffea arabica was done both in vitro
and ex vivo and was looking at the antioxidant and protective
properties of green and roasted coffee. For the in vitro part of asthma, while tea consumption did not have a significant
the study, the model system was β-carotene-linoleic acid relationship to asthma prevalence (Schwartz & Weiss, 1992).
(Daglia, Papetti, Gregotti, Berte, & Gazzani, 2000). According
to the study, the green coffee had a higher antioxidant activity
than the roasted (Daglia et al., 2000). However, when looking Caffeine and Analgesics
at the protective activity against rat liver cell microsome lipid Over the last twenty years, thirty clinical studies with over
peroxidation, the roasted coffee performed better than the 10,000 patients have been performed, and the data from these
green coffee (Daglia et al., 2000). was studied to see if caffeine was useful as an analgesic
adjuvant. Most of the studies involved patients with
postpartum uterine cramping or episiotomy pain, but some
Clinical Studies
had patients with pain from a headache or oral surgery. The
Blood Pressure results showed that to get the same response from an
A clinical study observing the amount of coffee consumed and analgesic without caffeine, one would have to take about 40%
increase in blood pressure was performed on 522 subjects. more than one with caffeine (Laska et al., 1984). Based on this
The average amount of coffee consumed per day over a study, it was determined that a reasonable conclusion would
median period of 56 days. After linear regression analysis, a be to add 65 milligrams of caffeine to an analgesic tablet to
positive relationship between amount of coffee consumed and create a more effective analgesic. According to the study, the
systolic blood pressure appeared (Jee, He, Whelton, Suh, & analgesic with caffeine has the capabilities of being an
Klag, 1999). important option for therapy and management of a patient’s
pain (Laska et al., 1984).
Caffeine and Asthma

Caffeine Consumption and Spontaneous Abortion
The methylxanthines in coffee have the capability of
functioning as bronchodilators. This idea was tested by A population based study of early spontaneous abortion was
looking at data from the Second National Health and Nutrition performed with 562 Swedish women who had a spontaneous
Examination Survey (NHANES II), which was taken from a abortion, or miscarriage, between six and twelve weeks
sample representing the civilian United States population. The gestation and 953 Swedish women who did not have an
possibility of relationships between normal coffee and tea abortion. The goal of the study was to see if caffeine
intake to asthma and wheezing symptoms was determined. consumption could increase the risk of an early spontaneous
After comparison to non-coffee drinkers, the results showed abortion in non-smoking women carrying fetuses with normal
that people who consumed coffee regularly saw a 29% karyotypes. Among the non-smoking women, there were an
decrease in the odds of presenting with current asthma increased number of occurrences of spontaneous abortions in
symptoms. An inverse relationship appeared between the the women who consumed at least 100 milligrams of caffeine
cups of coffee consumed per day and the occurrence of per day than in women who ingested less than that. With the
smoking women, no association between caffeine ingestion workload. In the end, the conclusion was made of causation
and increased risk of spontaneous abortion was found. The between caffeine and catecholamines (Papadelis et al., 2003).
conclusion was made that consumption of a moderate to high
amount of caffeine correlated with an increased risk of
spontaneous abortion when the fetus had a normal or Coffee and Parkinson Disease
unknown karyotype (I. A. Ross, 2005). Affecting about 3% of the population over 65 years of age,
Parkinson disease is a large source of morbidity in the United
States, and this statistic is expected to grow doubly over the
Mental Workload and Caffeine
next 3o to 40 years. One study began looking at the possible
Many studies have been performed and shown that caffeine is association of coffee and caffeine consumption and the
associated with the excretion of catecholamines and their incidence of Parkinson disease. The subject population
metabolites. They have also shown that urinary levels of consisted of 8004 Japanese-American men between the ages
norepinephrine and epinephrine increase after the of 45 and 68 who were a part of the Honolulu Heart Program
consumption of caffeine. This was seen in the levels of from 1965 to 1968. The incidence of Parkinson disease,
adrenaline and noradrenaline, as well, along with a dose amount of coffee consumption, and total dietary caffeine
dependent effect of caffeine (Papadelis et al., 2003). The intake were measured. The coffee consumption was measured
possibilities of correlations between caffeine and cognitive at the time of enrollment and at a 6-year follow-up, while the
performance, blood pressure, and catecholamines were caffeine intake was observed at enrollment. The results
observed under resting conditions and with a mental showed the incidence of Parkinson disease significantly
workload. The research subjects took the test after consuming decreased with the increase of coffee and caffeine
one cup of coffee and then three cups of coffee. Blood pressure consumption. The conclusion of the study was that caffeine
was taken at the beginning and end of each step of the intake was related to the decline of risk of Parkinson disease
experiment, and the root mean square error was watched and not the other nutrients in coffee (G. W. Ross et al., 2000).
continuously. After the three stages - at rest, under mental
stress, after one dose of caffeine under stress, and after a
triple dose of caffeine under stress - catecholamines were Contraindications
collected and measured (Papadelis et al., 2003). The only When consumed in large doses, the caffeine in Coffea arabica
group that showed a statistically significant difference was the can be harmful. One gram or more can cause “headache,
smokers and coffee drinkers. The study saw an increase in the nausea, insomnia, restlessness, excitement, mild delirium,
urine adrenaline after consumption of one cup of coffee and a muscle tremors, tachycardia, and extrasystoles” (Khan &
significant increase of noradrenaline in the urine. After an Abourashed, 2010). These symptoms have also been observed
intake of three cups of coffee, both catecholamines in people who consume more than 1.5 grams of caffeine a day
significantly increased. They also increased with a mental for a long period of time or with 300 to 500 mg per day for
individuals with more sensitivity (Kraft & Hobbs, 2004).
Consumption of over six cups of coffee per day can lead to a Caffeine is also used by the United States Pharmacopeia in
negative fluid balance, due to the increased urine production several different pharmaceuticals. These include “internal
caused by caffeine (Dorea & Costa, 2005). Also, for susceptible analgesics, cold and allergy products, weight control
groups like the elderly, drinking more than six cups of coffee is formulations (appetite depressants), and others” (Khan &
one of the factors related to short sleep (Dorea & Costa, 2005). Abourashed, 2010).
Some side effects coming from the chlorogenic acid In traditional Ayurvedic therapies, the unripen beans of C.
concentration in C. arabica are an increase in gastric acid, arabica are known to be used for headaches, while the ripened
gastric irritation, diarrhea, and a depressed appetite (Kraft & and roasted beans are used for diarrhea (Chevallier, 1996).
Hobbs, 2004). Two signs of poisoning are vomiting and
cramps in the abdomen (Kraft & Hobbs, 2004).
Discussion
Nursing mothers should not ingest caffeine because it can
cause the infant to have a sleeping disorder (PDR for herbal Coffea arabica has had many uses over the years, which range
medicines, 1998). Pregnant women should also avoid caffeine, from food to medicine. Because of it’s beneficial effects, it has
and if they consume it, they should not have more than 300 become the second largest commodity in the world after crude
mg per day (PDR for herbal medicines, 1998). oil (Meletis, 2006). This originally Ethiopian plant is now
cultivated in many places around the world, and exported to
The regular intake of caffeine can actually lead to “caffeinism,”
the others. Many people have become dependent on the
the psychic and physical dependency to caffeine. Withdrawal
effects that its main functional derivative, caffeine, gives them.
from this can present itself with headache and sleeping
While a lot of people use it for the stimulation of the central
disorders (PDR for herbal medicines, 1998).
nervous system, it also can affect the renal system,
gastrointestinal system, and musculoskeletal system. Before
Current Use in Allopathic and CAM Therapies being one of the top products in the world, it was used
traditionally by many cultures, and this has lead to it being
“Coffee charcoal” or Coffea carbo is created from carbonized, used in many different pharmaceuticals, including analgesics,
or roasted, seeds of Coffea arabica (Wyk & Wink, 2004). This cold remedies, stimulants, and diuretics. Unfortunately,
is generated through roasting the outer part, or exocarp, of caffeine does have its negative effects, including the possibility
green and dried fruit. After they become almost black, they are of addiction, but research is being done to see what else it
ground up. Coffea carbo is used for two main things: diarrhea affects. So far, this has included the possibility of helping
and inflammation in the mouth and pharynx (PDR for herbal asthma, pain, neurologic conditions, and more. Overall, C.
medicines, 1998). It is a powder that can be taken orally or arabica has provided the world with a stimulant that is used
applied topically. One dose of Coffea carbo is generally about 3 daily, not only for general stimulation but also medicinal
grams, and the daily dose is about 9 grams (for internal use) purposes.
(PDR for herbal medicines, 1998).
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(Rubiaceae). Am J Bot, 90(1), 153-157. doi: 90/1/153 Ross, I. A. (2005). Medicinal plants of the world: chemical
[pii]10.3732/ajb.90.1.153 constituents, traditional and modern medicinal uses (Vol. 3):
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Kraft, K., & Hobbs, C. (2004). Pocket Guide to Herbal Medicine. New
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Symptoms. Annals of Epidemiology, 2(5), 627-635.
Walter, T. M., & Maheswari, R. U. (2006). Therapeutic Uses of Coffea Wyk, B. E., & Wink, M. (2004). Medicinal Plants of the World.
arabica, Linn. Portland: Timber Press.
Weinberg, B. A., & Bealer, B. K. (2001). The world of caffeine : the
science and culture of the world's most popular drug. New
York: Routledge.
Cola nitida (Vent.) Schoot & Endl, Malvaceae
Ijeoma Okafor
Introduction
Cola nitida, also referred to as the Kola Nut, is a well-known
fruit in the Malvaceae (formerly in Sterculiaceae) family and
one of Africa’s most valuable plants. Originally given the name
Sterculia nitida by the French, it was later decided by the
Germans that it belonged in the Cola family. Depending on its
global location, it may also be referred to as gbanja kola, bitter
kola, bese, goro, bissy or biche, kolatier, or colatero. With over
sixteen different species in the Cola genus, the two most
common edible types are the C. nitida and C. acuminata. Both
C. nitida and C. acuminata are essential to African countries for
their usage and commercial value, but the more prevalent and
valuable of the two is the C. nitida. The kola nut coined the
phrase “the kola of the caravan trade”, as it is used for a
variety of functions (Lovejoy, 1980). Having been
transmigrated by the slave trade, the kola nut is quite versatile
and has been used as a mild stimulant, antidote for specific Figure 1. Cola nitida carpel and flowers: The kola nut can be
diseases, a hunger-suppressant, gift to royalty, a token of found inside the carpels, which are the seeds. Image source:
peace or war, and even as a dye for decorating cloth (Abaka, http://english.xtbg.cas.cn/rs/ma/201112/t20111206_79718.html
2005). Used in conjunction with herbal plants such as ma
huang and in well-known commodities like Coca-Cola soda,
the kola nut has become a major cash crop for its native Botanical Description
African countries. Although C. nitida has medicinal and Cola nitida is an understory, evergreen tree that produces the
recreational uses, the kola nut is commonly recognized as a kola nut fruit. The tree can reach up to 40-60 feet tall, 1.5
part of the stimulant substance group. Known for its meters in diameter, and is capable of producing light brown
astringent taste and high caffeine content, the kola nut carpels that can contain anywhere from one to fifteen seeds;
produces a mild stimulating and sustaining effect once allowing a single tree to produce well over a thousand nuts
consumed (Brooks, 1980). per year (Brooks, 1980). The carpels are accompanied by
flowers that are normally greenish-yellow or white with
Figure 3. Western African Tropics: The location for
indigenous C. nitida. Image source:
http://www.mnzoo.com/animals/animals_dwarfCroc.asp
C. nitida can be found in hot and humid climates located in

places such as Cote d’Ivoire, Ghana, Liberia, Nigeria, Sierra
Figure 2. Kola Nuts ranging in colors: The variety of color Leone, and the confluences of the Niger and Benue rivers.
between kola nuts can be found in every fruit. Image source: However, due to the frequent traveling by man and the rising
http://www.shamanaustralis.com/forum/index.php?showtopic=27 of trade routes, the kola nut can now be found in locations
47 such as the West and East Indies, Brazil, Jamaica, Mali,
Zimbabwe, Sudan, Ethiopia, Guinea, Somalia, Chad, Congo, and
purple tracing along the edges of the petal (Figure 1). The several other countries (Abaka, 2005). Low elevations, well-
kola nut, which is not a true nut but a seed from a follicular drained soil, and moderate rainfall are needed for the
fruit, is roughly the size of a Brazil nut or a chestnut ranging successful growth of C. nitida, which cannot withstand
approximately from 1 to 2 inches in size. The kola nut can also flooding (Abaka, 2005). Because most African countries
be found in a wide range of colors varying from a cream/white experience a dry season (December to March), it is important
when found fresh to a dark reddish brown when dried to grow C. nitida in areas where soil retains sufficient moisture
(Figure 2). The red kola nut is the likely choice for trade during this season. However, C. nitida has even been found in
because of its long-lasting qualities, while the white and pink altitudes over 300 meters high, where there is rich soil due to
kola nuts are generally more valued (Abaka, 2005). heavy rainfall (Lovejoy, 1980).
The genus Cola is mainly located in the African tropics. More Within six to seven years after planting, C. nitida is able to
specifically, C. nitida is primarily indigenous to the Western bear fruit that can be harvested seasonally between October
Africa regions (Figure 3). Originally a tropical rainforest tree, and February. After 5 days of fermentation, the ripe fruits are
harvested before the follicles are able to split open. The kola the elites gradually became available to the masses. Upon
nuts that are chosen for cultivation are left to fully mature and learning of its additional medicinal properties, the Islamic
ripen. C. nitida can then be spread by cuttings or aerial world further expanded the use and marketing of the kola nut.
layering. However, the most important pollinators for C. nitida Traditionally, traders venturing on long journeys would chew
are insects. One method used to obtain the maximum yield of the kola nut raw to reduce the effects of fatigue, hunger, and
kola nuts, is to cultivate it along with other crops. One crop, thirst, while maintaining alertness. In 1688, the historian Hans
Theobroma cacao can grow in the same climate conditions. Sloane examined the effects of kola nut samples taken from
Both species can actually be grown together, with C. nitida Jamaica. He discovered the kola nut could be used as a diuretic
acting as an intercrop by providing top shade for T. cacao. and was great for treating water retention caused by diseases
Both C. nitida and T. cacao are close relatives to one another. such as edema or dropsy (Mitchell, 2001). The kola was also
Both species are a part of the Sterculiaceae (now Malvaceae) known to provide cures for headaches and male sexual
family, which contain flowering plants and is also known as impotency (Lovejoy, 1980). It was believed that by
the cacao family. The moderate leaching and acidity of the submerging a minced kola nut in wine and taking it as a tonic
environment, in addition to 45-65 inches of rainfall, provides daily would help stimulate a man’s desire and sexuality
this climate with enough fertile soil to maintain the growth of (Brooks, 1980).
both the C. nitida and T. cacao (Abaka, 2005).
Ethnobotanical Uses
Traditional Uses
Even before the discovery of C. nitida’s medicinal uses, many
Traditional Medicinal Uses African tribes were aware of its stimulant properties and
For centuries no other African commodity has been held to integrated the masticatory process as a part of everyday life
such a high importance in West Africa than the kola nut. (Seeds, 2012). Now, many African societies see the kola nut as
Around the twelfth century, the Arabian doctor El-Ghafeky a high, valued commodity that is used in various ways in
first discovered the importance of C. nitida as a drug. He different cultures. In these societies, the social aspect
reported that the use of powdered kola nut had the ability to encompassing the kola nut holds great importance as well.
relieve colic and stomachaches, while possessing “warming The kola nut can be offered to friend the same way tobacco
properties” (Abaka, 2005). During the same century, the kola products are shared in Western societies, it can either be
nut was documented to help ease the pains of childbirth and chewed individually or in a group setting (Abaka, 2005). In
as a treatment for rheumatism and dyspnea. In the fifteenth certain Nigerian cultures, to be given a kola nut is a great
century, a report stating the existence of an African kola trade honor. There are special occasions and ceremonies that
was documented in Pacheco Pereira’s Esmeraldo de Situ Orbis encompass the use of or the giving of the kola nut. During
(Abaka, 2005). For Muslims, kola nut was, and still is, a high wedding ceremonies, the breaking and sharing of kola nuts is
demanding masticatory product because it is one of the only considered a vital component during the wedding reception.
stimulants Islam condones. What was once a commodity for The kola nut is also used as a way to accept or decline a
Figure 4. Caffeine. Image source:
Figure 5. Theobromine. Image source:
http://chemistry.about.com/od/factsstructures/a/theobromine-
http://chemistry.about.com/od/factsstructures/ig/Chemical-
chemistry.htm
Structures---T/Theobromine.htm
marriage proposal (returning a white kola means yes while a

the kola nut can also be combined with the coca leaves and
red kola means no), or could even be used to pay off part of a
incorporated into tonic wines, brands of cocoa, and other
dowry. The color of the kola nut also plays a significant role in
beverages. In Nigeria, kola nut is simply a common snack
social and cultural communication. In many African societies,
favored among the elderly (Adebola, 2011).
a white kola nut symbolizes friendship and could be used as
ratifying treaties, while a red kola nut symbolized enmity and
challenge to warfare. During a christening, a red kola Other Uses
represents life and the white kola purity. Also, the breaking of
a kola nut is said to be a valued expression of hospitality. In The kola nut is said to have multifarious uses. C. nitida can act
Western societies the kola nut, due to its high caffeine content, as a water purifier in addition to dyeing clothing and as a
was a major ingredient in the production of the Coca-Cola candle. The bark is strong enough to be used for timber. It has
products. Invented by John Pemberton, the original Coca-Cola been used for making furniture, house and boat buildings,
drink was made by combing coca and kola extracts with the domestic utensils, musical instruments, and wooden games
hopes of concocting a remedy for headaches and hangovers and toys. The pod husk of the kola has been integrated into the
(Burdock, 2009). production of liquid soap, and the most recent and remarkable
advancement is that the kola pod husk has replaced up to 60%
of maize for poultry feed formulations (Lim, 2011).
Food Source
The seeds of the C. nitida can be pounded into a powder and Chemistry and Pharmacology
boiled in water to prepare as a tea. Due to the kola nut’s strong
bitter taste followed by a sweet aftertaste, it has also been The two active constituents present in C. nitida are the
used as a sweetener to get rid of bad tastes (Lovejoy, 1980). In alkaloids, caffeine and theobromine (Figures 4 & 5). Both
addition to being implemented in soft drinks like Coca-Cola, stimulate the central nervous system and the amounts of each
Stimulant Caffeine (%) Theobromine (%) of the whole tree have been reported to have significant
medicinal uses. The cotyledon can be used to help treat herpes
Kola 1.0 – 4.0 .02 - .09 while the bark can be used for dystocia. The twigs can be
taken and made into a chewing stick, which acts like a
Coffee .7 – 2.3 None toothbrush by being able to clean the teeth and gums. A tonic
can be prepared using the leaves, twigs, flowers, fruit follicles,
Tea 1.0 – 4.7 None and the bark to concoct a remedy for dysentery, coughs,
diarrhea, vomiting, and chest complaints. There have also
Cocoa .08 - .23 .8 – 2.3 been reports about the extracts from the stem bark of C. nitida.
It may have the potential to regulate natural fertility (Adebola,
Table 1. Caffeine and theobromine content in mild 2011).
stimulants.
Elastase Reduction Activity

constituent in a kola nut fluctuate from one kola to the next.
While caffeine has the stronger presence in a kola nut, Inflammatory diseases like asthma or cystic fibrosis are
theobromine has the greater responsibility in stimulating the characterized by excess uninhibited neutrophil elastase,
skeletal muscles. However, there are only traces of which contributes to tissue destruction. α1PI is one major
theobromine present in C. nitida, while caffeine can make up inhibitor of elastase, and its presence or deficiency can also
anywhere from one to four percent of the kola nut. In addition cause physiological disorders such as emphysema. A study
to the two alkaloids, a glucoside heart stimulant, kolatin, is shows that kola nut extract, depending on its concentration,
also present (Lovejoy, 1980). The combination of these three can protect α1PI from HOCL inactivation by suppressing the
constituents makes the kola nut a highly effective stimulant in MPO-H2O2 system. The suppression is caused the phenolic
relations to other stimulants (Table 1). It is estimated that C. content in the extract scavenging oxygen species like H2O2
nitida has as much caffeine as 100 grams of coffee and as (Daels, 2003).
much theobromine as 100 grams of tea (Brooks, 1980).
Because of this, one average sized kola nut is equivalent to
approximately three cups of American coffee, but these effects Aphrodisiac
can vary from person to person. Other chemicals found in C. During the eighteenth and twentieth century kola
nitida are strychnine, catechin, flavonoids, anthocyanins, consumption in the Hausaland was promoted by the belief
quinine, theine, and tannin (Abaka, 2005). that a society’s interest in sex and sexuality could be
heightened (Brooks, 1980). Another study was performed on
adult male rats. The study substituted drinking water with
Biological Activity three different kola beverages for three months. At the end of
Biological activity is not only present in the kola nut, but parts the study the kola intake increased both oestradiol and
testosterone levels, suggesting that there is an additional (Ajarem, 1990). A later study explained the locomotors
mechanism of action beyond the effects of caffeine (Schliep, activity due to the caffeine content while kolanin is
2012). responsible for stimulating the heart (Lim, 2011).
Antimicrobial Ocular Activity

An in vitro study examines four human pathogenic bacteria Thirty grams of C. nitida was tested on visually acute and
against C. nitida. The results show that the presence of healthy volunteers to determine ocular effects. Results
secondary metabolites partially enhances the showed no effect on the pupil diameter of visual acuity but
chemotaxonomic characterization of C. nitida. The presence of improvement in the near point of convergence by 43%. The
antimicrobial activity allows for the C. nitida extract to inhibit amplitude of accommodation was increased by 11% while
growth of certain bacteria and fungi. C. nitida showed existing heterophorias were ameliorated. The kola nut
inhibitory activity against Aspergillus niger and Candida extracts allows near work to done without stress. The extract
albicans (Sonibare, 2009). could also aid the elder by relieving somnolence and ocular
muscle imbalance (Lim, 2011).
Antioxidant
The high levels of phenolic compounds found in kola nuts Antibacterial Activity
allow the extract to exhibit antioxidant capacities. The IC50 The methanol extract that can be extracted from the root bark
values range from 1.70-2.83 in hypoxanthine/xanthine of C. nitida is shown to affect Mycobacterium bovis and strains
oxidase and 2.75-4.08 mg/ml in 2-deoyguanosine HPLC-based of Mycobacterium vaccae. The aqueous and alcoholic extracts
assays. Of the secondary metabolites found in kola nut also found in the bark were show to inhibit growth of
extracts, caffeine has the most antioxidant capacity proving to Staphylococcus aureus, Pseudomonas aeruginosa, ß-haemolytic
be an effective cancer chemopreventive metabolite (Sunday, streptococci, Escherichia coli, and Neisseria gonorrhoeae (Lim,
2007). 2011).
Cardiovascular and CNS Activity Clinical Studies

Kola nut is reported to enhance alertness, physical energy, In 1888-1889, several tests were performed to examine
elevate moods, increase tactile sensitivity, and suppress the whether the kola nut could be beneficial to soldiers in the
appetite. Various doses of kola nut extract were giving to male battlefield. Ten pounds of kola nut varying in size were
mice. The results showed that at medium doses locomotors supplied R.H. Firth to test for four properties of a kola nut:
activity increased while low doses showed no effect and high whether a person could undergo long periods of fasting and
doses resulted in a depressive effect of locomotors activity fatigue without exhaustion, adjuvant to sustain the body
during exertion without food, restore a person in the drunken for recuperation. Therefore, the action of chewing a kola nut in
state to practical sobriety, and as a remedial agent allowing addition to the absence of food is an artificial stimulant to the
those to recover form lengthened sicknesses. The first central nervous system (Abaka, 2005).
experiment tested two patients who had venereal disease.
A clinical study was performed to show the effects of kola nut
They were administered a hot infusion of powdered kola and
extract on the heart. The concentration of kola nut extract is
boiling water with their diet unchanged and urine examined
directly related to the rate of metabolism and rhythmic heart
twice a day. The results showed that the men’s weight, pulse
activity. At low doses, the kola nut extract caused the rate of
and respiratory capacities were unchanged, but their daily
the heartbeat and the force of contraction to increase. When
total excretion and urine increased in watery content. Those
person consumed higher doses of the extract it resulted in the
were the only physical results, however, both men stated that
spike of metabolic rates (increasing approximately 118.76%)
they had “less appetite and felt less want of food.” The second
(Chukwu, 2006).
test examined three soldiers performing physical activities
without having eaten in 60 hours, but could be administered
an infusion of 200 grams of kola powder, milk, and sugar Contraindications
during this timeframe. The experiment was also performed by
Firth himself, and the three subjects concluded that the sense The FDA and FEMA have labeled the kola nut extract GRAS for
of hunger and exhaustion was less prominent. The third case the usage of a flavoring ingredient. However, in 1996, the FDA
used 50 men to show that the kola nut could sustain the body reported that the kola-mahuang combination for
against fatigue and hunger. They were only allowed to chew hallucinogenic effects is a deadly pair, and this brought
the kola nut bit by bit for the next two days. Only 26 of the attention to issue that more experiments involving the kola
soldiers followed the rules properly and gave an accurate nut and kola nut combinations needs to be further explored.
account of the experience. The majority stated that for the first One study shows a linkage between the consumption of kola
16 hours they felt hungry and tired, but for the reminder of nut and malaria morbidity. The results revealed that eating
the time they did not show signs of hunger or tiredness. The the kola nut increases the expression of malaria symptoms by
last experiment tested the ingestion of kola nut on a drunken favoring parasite multiplication. C. nitida also contains
person. The kola nut taken as a hot infusion was said to hydrocyanic acid which, if consumed in high doses for a short
relieved the head of “the sense of heaviness peculiar to period of time, is known to cause harm to the nervous,
alcoholic excess of the previous night” (Abaka, 2005). respiratory and cardiovascular systems. Also, if exposed to
hydrocyanic acid for longer durations, irritation of the eyes,
Branching off of the study previously mentioned, Firth was appetite loss, headaches, dizziness, and damages to the
also able to determine the kola nut’s direct relationship to the nervous system and thyroid gland could be potential results
central nervous system. After the conclusion of the study (Alaribe, 2003). There are also side effects to taking in too
involving the twenty-five soldiers that had eaten in two days, much caffeine. Problems that could arise are nausea, insomnia,
the majority of the men were craving fat and butter, allowing headaches, and tachycardia. If caffeine is ingested in
Firth to conclude that the body resorted to using fat reserves significantly large doses then muscle tumor and tinnitus could
certain chocolates and wine. Due to its high pectin content,
there is possibility that kola nut can be included in jams or
jelly. The kola nut also contains high protein content that
could be a useful ingredient in making fertilizers. The nuts can
also be used in tinctures or made into teas. Powdered kola is
now available in capsule form; however, in comparison to
naturally chewing the kola nut, the strength and its
effectiveness is much lower since the caffeine content is not as
high (Figure 6) (Burdock, 2009).
Discussion
Figure 6. Herbal supplement of kola nut: The kola nuts are Despite its economic importance in Western and Central
crushed into a powder and encapsulated and can now be Africa, much still unknown about C. nitida. Having been
found in certain drugstores. Image source: exported to all parts of the world, C. nitida is centuries old and
http://www.swansonvitamins.com/SW1122/ItemDetail will most likely remain a vital resource in many cultures for
centuries to come. The kola nut was already accepted amongst
be potential results. Peptic ulcer patients are advised not to African societies when only the stimulant effects were known.
kola nut since caffeine, along with theobromine, are known to Now that there is a worldwide awareness of the kola nut’s
stimulate gastric acid secretion. However, caffeine is still medicinal and recreational uses, the plants significance has
considered a GRAS but is regulated by FDA for the use in cola only gotten greater. With uses ranging from social and
beverages, with .02% being the maximum concentration cultural interactions to fighting off fatigue to a component in
allowed. The FDA also regulates the use of caffeine, alone, as beverages, as we begin to learn more about C. nitida and its
an OTC stimulant drug. Even with these precautions there is diversifying effects, its demand in the world will become more
always the rare chance of a person becoming hypersensitivity prevalent. With that being said, the kola nut will continue to
to the active substances in C. nitida (Burdock, 2009). play a significant role as an important economic crop for
internal, regional, and foreign trade (Adebola, 2011).

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Commiphora molmol (Engl.) Engl. ex Tschirch, Burseraceae
Elizabeth Giffen
Introduction
Commiphora molmol (Engl.) Engl. ex Tschirch, Burseraceae,
also known as Commiphora myrrha var. molmol Engl. and
commonly as the myrrh tree, ("Tropicos.Org," 2011) is an arid
tree or shrub from Somalia and Ethiopia (Figure 1). Its main
utilization is as a gum, resin or essential oil (Nomicos, 2007)
and has been in perfumes and incenses since ancient times. It
has religious significance in Judeo-Christian traditions and is
often used ritually. Myrrh has also seen use as a wine
preservative and in embalming fluids in ancient Egypt (Groom
1981). In medicine, myrrh has been traditionally used from
northern Africa east through India to treat a huge range of
ailments, as an anti-inflammatory, analgesic, emmenagogue,
antibacterial, and for oral maladies (Groom, 1981, Walter H.
Lewis, 2003). The plant produces an oleogum resin that is 2-
8% essential oil (El-Shahat, et al., 2011) 23-40% resin, 40-
60% gum and 10-25% bitter principles (Su, et al., 2011). Some
active constituents of myrrh include the sesquiterpenes
furanodiene-6-one and methoxyfuranoguaia-9-ene-8-one,
which have antibacterial, antifungal and local anesthetic
activities, (Dolara, et al., 2000) and furanoeudesma-1,3-diene Figure 1. Myrrh. (Source: h t t p : / / w w w . p l a n t s a s m e d i c i n e
.com/~cleanen2/index.php?title=Commiphora_myrrha)
and curzarene, which have potent analgesic effects (Dolara, et
al., 1996). The furanosesquiterpenoids lindestrene and its
analogues make up 19% of the essential oil and are Botanical Description
responsible for the famous scent associated with myrrh The myrrh plant is a small, thick-stemmed tree or shrub with
(Jensen). Other important constituents are terpenoids, a succulent trunk and spine-like twigs. It grows in arid and
steroids, flavonoids, lignans, carbohydrates, and long chain alpine habitats in Djibouti, Ethiopia, Somalia, Kenya, Oman
aliphatic alcohol derivatives; these various metabolites give and Yemen (USDA). The leaves are small and sparse, generally
myrrh its manifold biological activities (Su, et al., 2011). single and grey-green, and quite variable in size and shape,
but usually oval-shaped and trifoliate (Nomicos, 2007). The is one of the oldest therapies on record (Michie and Cooper,
leaves become yellow in autumn before falling off 1991).
(Cactuspedia). The bark is silver, papery and peeling, with In a temple near Thebes, we see some of the first evidence of
green bark underneath. Myrrh tree fruits are tiny and brown,
the myrrh trade in frescoes detailing the voyage of a fleet of
with a smooth, oval shape (Nomicos, 2007). Puncturing the
Egyptians sent by Queen Hatshepsut to the land of Punt, from
stems or trunk produces a pale yellow, oily myrrh resin with a
which they brought back, among many items, quantities of
bitter taste but a warm, smoky scent, which turns reddish and incense (‘ntyw is believed to be myrrh, although there is some
dusty upon hardening (Michie and Cooper, 1991).
debate that it may be frankincense (Lucas and Harris, 1999))
Myrrh resin is harvested by making incisions roughly 2 inches and incense-bearing trees. Texts from centuries earlier
long into the bark of the tree. The sap hardens when exposed indicate the ritual use of incense, however, and still earlier
to air and forms into pearls which are easily harvested around texts detail previous expeditions to Punt, although no
two weeks after the incision is made, and new incisions, or indication of incense is made (Groom, 1981).
“taps” can be made over old ones after removing the resin; Medicinally, it has been said that the Greek soldiers would not
these usually only require an additional scratch. Tapping is
go into battle without myrrh to treat wounds (Hanus, et al.,
done at certain times of year and specific duration depending
2005). The Ebers Papyrus, which dates back to c. 1550 BC,
on the region (Dharmananda 2003).
details its use as both incense and medicinal remedy
(Chisholm, 1910). It is listed as being used in funerals,
Traditional Uses mummifications and cremations, but also in the treatment of
wounds and skin sores (Michie and Cooper, 1991).
Traditions involving myrrh are well known in Western and Mesopotamian texts in Assyrian cuneiform script dating from
Christian-dominated cultures primarily because of the legend the 10th to 6th century BC record myrrh being used
of the Magi bringing the Christ-child gifts of gold, frankincense medicinally, and Pliny, Theophrastus and Dioscorides have all
and myrrh to the nativity (Matthew 2.11). In fact, myrrh is a made mention of it in various ancient texts, including the
prominent plant throughout Biblical literature, being famous De Materia Medica (Groom, 1981).
mentioned frequently in the Song of Solomon. It was also the
De Materia Medica (c. 65 A.D.) in particular mentions myrrh
last gift offered to Jesus before the crucifixion (presumably as
several times as an ingredient in concoctions as an
an analgesic): “Then they offered him wine mixed with myrrh,
abortifacient, antiseptic ointment and a diuretic, and to treat
but he did not take it,” (Mark 15.23). Nicodemus is also said to
asthma, “female ailments,” dandruff, varicose veins,
have brought myrrh and aloes for the embalming of his body
sleeplessness, cleaning boils, glaucoma, purging ulcers, and
after his death (John 19.39). Jewish tradition utilized myrrh as
softening various somatic scleroses. Stacte, the substance
a main component of anointing oil for the priests, tabernacle,
ark and altar (Groom, 1981). Myrrh was once as valuable as made from myrrh gum resin, has an entry in De Materia
Medica, which describes it as a precious ointment with a very
gold and ivory, and its use as a plant-based traditional remedy
sweet smell and a great deal of strength in small doses. In the
main entry on Smyrna (myrrh), Dioscorides even explains a when foul,” and when there is difficulty with urination, as well
method of counterfeiting myrrh by soaking gum in myrrh- as to treat anal fissures, canker sores and kidney stones. As an
infused water. When one is buying it, he recommends myrrh example, to induce menstruation, the prescription is for
that is fragrant, brittle, light, and monochromatic, smooth and pounded garlic with myrrh and lily ointment. Celsus writes
small when broken, and sharply bitter in taste. It is constantly that it is also useful for treating eye and ear afflictions, tooth
referred to as ‘warming’ in nature, and is also drying, pain (although it should be applied on the shoulder), swollen
astringent, and retaining. As a salve it is used to soothe and tonsils, and ulcerations of the mouth (Celsus, 25).
open the closed vulva, as an emmenagogue, and to expedite
Myrrh is used in Ayurveda, although it does not come from
birth. In pill form, myrrh would be taken to help a chronic
Commiphora myrrha but Commiphora mukul (Hook ex Stocks)
cough or asthma, side and chest pains, loose bowels and Engl. (C. wightii (Arnott.) Bhanol.), and is called guggul or false
dysentery, kill worms, and to calm feverish chills. It was held
myrrh. Guggul has been used to adulterate myrrh, ("Efloras,"
under the tongue like a cough drop to treat atherosclerosis
2008) and has some similar properties to C. myrrha but also
and hoarseness, or chewed to treat bad breath. Myrrh could contains many very different active compounds, such as
also be used in a mouthwash with wine to strengthen teeth
guggulsterone (Hanus, et al., 2005).
and gums. It was used to heal broken ears, exposed bones,
armpit sores, pus and inflammation in the ears, impetigo, Myrrh is first seen in traditional Chinese medicine (TCM) in
alopecia, and smoothing rough skin (Dioscorides, 50-70). Kaibao Bencao, 973 CE, under the name mo yao. It is still in
use as an aid in promoting circulation, treating traumatic
Additionally, myrrh is mentioned in the anonymous Syriac injury, and as an anti-inflammatory (Dharmananda, 2003).
book of medicine and the works of Avicenna (Michie and Myrrh has neutral, bitter properties, usually dosed at 3-10
Cooper, 1991) and by Hippocrates in the 4th century BCE grams in decoction (Sionneau, 1997), and is almost always
(Nomicos, 2007). Theophrastus says that myrrh would be
used together with frankincense (Jiao, 2003). In TCM, myrrh is
added to wine to add astringency because of its bitter sometimes soaked in rice vinegar and then stir-fried or baked
character. Athenaeus says that Aristotle wrote that myrrh (Dharmananda, 2003).
could be boiled in water and the liquid could then be added to
wine to “diminish drunkenness” (Groom, 1981).
Celsus, who lived from 25 BC to 50 AD, wrote extensively Chemistry and Pharmacology
about its use to treat a huge variety of ailments: a form of The main constituents of the myrrh oleo-gum resin are 2-8%
malaria, dropsy, intestinal pain, as a poison antidote, to volatile oil (El-Shahat, et al., 2011) 23-40% resin, and 40-60%
agglutinate wounds, and heal burns, for colic, throat ulcers gum (Su, et al., 2011). The gum is water-soluble and contains
and to treat abscesses and scabies. He also lists it among the polysaccharides, proteoglycans and proteins, as well as the
erodents and caustics, includes it as part of ointments for compounds D-galactose, L-arabinose, and 4-methyl D-
liver, chest and side pain, tuberculosis infection of the lymph glucoronic acid. The volatile oil is made of steroids, sterols and
nodes in the neck, neuralgia, as a plaster for “broken heads,” terpenes (Hanus, et al., 2005) including the
treatment of inflammation in the uvula and “for the genitals
furanosesquiterpenoids lindestrene and its analogues, which
account for 19% of the essential oil’s character and its
aromatic properties (Jensen). Close to 20
furanosesquiterpenoids have been isolated from myrrh
essential oil (Su, et al., 2011), including furanodiene-6-one
(0.4%) and methoxyfuranoguaia-9-ene-8-one (0.1%), (Dolara,
et al., 2000) furanoeudesma-1,3-diene (15%), and curzerene
(40.1%) (Dolara, et al., 1996). The essential oil can be
extracted from the resin by steam distillation (Walsh, et al.,
2010). The resin contains isolinalyl acetate, 3-epi-lupenyl
acetate, lupeone, 3-epi-α-amirin, α-amirone, acetyl β-
eudesmol, and a sesquiterpene lactone (Hanus, et al., 2005).
Other metabolites of myrrh are terpenoids, flavonoids,
lignans, carbohydrates, and long chain aliphatic alcohol
derivatives (Su, et al., 2011). Marker standards for myrrh are Figure 2. Marker compounds used in myrrh (Su, et al.,
shown in Figure 2. 2011).
Biological Activity writhes (completely rescued by naxolone and morphine) and

again increased latency to temperature-dependent pain
In an anti-inflammatory test, both an ethanol and a petroleum
reaction. The authors conclude that this suggests an
ether extraction of Commiphora myrrha significantly inhibited
interaction with opioid mechanisms in the central nervous
formalin-induced paw swelling and acetic acid-induced
system (Dolara, et al., 1996).
writhing in mice. Because no attenuation in temperature-
dependent nociception was shown in this study, the authors
noted that this suggests that myrrh extracts with analgesic Clinical Studies
properties act on the peripheral and not central nociceptive
pathway. A survey done in Ezbet El-Bakly, Egypt, assessed the efficacy
of myrrh extract, Mirazid, in the treatment of fascioliasis, a
A hexane (nonpolar) extraction of myrrh for analgesic activity helminthic disease. Those with fascioliasis were given two
identified furanoeudesma-1,3-diene and curzarene as having capsules of Mirazid (600 mg) every day an hour prior to
analgesic activity when injected intracerebroventricularly in breakfast for six days. The cure rate was 88.2% and 94.1%
mice at 1.25 mg per kg. Both significantly increased latency to two and three months after treatment, respectively (Abo-
pain reaction (paw licking when placed on a hot plate). Madyan, et al., 2004). The same drug was assessed on a
Furanoeudesma-1,3-diene given 50 mg per kg orally was also population of schistosomal infections in the same region and
effective in reducing the number of acetic acid-induced found to have similarly miraculous results, with the same
remedies decreased both pain and swelling significantly more
than placebo (Xu, et al., 2009).
Myrrh ethanolic extract in combination with aloe, mastic and
olibanum (the ingredients of the historic Jerusalem Balsam,
wildly popular in the early 1700s) has been shown to be
strongly antiseptic. Figure 3 shows the in vitro effect of
Jerusalem Balsam on Staphlococcus aureus; disc 1 is treated
with 20 μl balsam, disc 2 with 20 μl ethanol, (used to make the
extraction) and disc 3 with 20 μl chlorhexidine 0.2%, (a
known antiseptic). Disc 1, similar to disc 3, has almost no
colonies on it; compare with the ethanol-treated disc 2
(Moussaieff, et al., 2005).
Figure 3. In vitro antimicrobial activity of myrrh
(Moussaieff, et al., 2005). Contraindications
regimen showing a cure rate of 97.4% and 96.2% two and Myrrh is approved by the US FDA as a safe, natural flavoring
three months afterward (Abo-Madyan, et al., 2004). substance (Abdul-Ghani, et al., 2009). However, it should not
Unfortunately, neither of these figures stands up to rigorous be used by pregnant women as it is an abortifacient and
repetition. Multiple experimental and clinical studies show emmenagogue (Brinker, 2001). People with sensitive skin
myrrh has no significant efficacy in reducing parasite loads should avoid topical applications containing myrrh, as it has
(Abdul-Ghani, et al., 2009). However, the anthelmintic mode of been known to cause contact dermatitis (Lee and Lam, 1993).
action of myrrh is still unknown. Some have postulated that Raw myrrh can be taken internally in very small quantities,
myrrh causes the worms to lose muscle mass, which makes but too much will upset the stomach, thus myrrh in the raw
them move into the liver where they are destroyed (Abdul- form is generally used externally (Dharmananda 2003). The
Ghani, et al., 2009). LD50 value of Mirazid solution, a myrrh extract, is 3,139mg/kg
in mice (Abdul-Ghani, et al., 2009) and the LD50 value of myrrh
An unrelated study in India examined the efficacy of an herbal
oil is 1650mg/kg in rats (MSDS, 2005).
toothpaste containing myrrh compared with conventional
toothpaste for the control of plaque and gingivitis. The
researchers found the herbal toothpaste to be just as effective Current Use in Allopathic and CAM Therapies
as conventional toothpaste, without any additional benefit
(George, et al., 2009). Additionally, a Chinese study examined The People’s Republic of China is currently the leading
the efficacy of a number of TCM herbs for the treatment of consumer of myrrh medicinal products in the world (Nomicos,
reflex sympathetic dystrophy (RSD). It found that traditional 2007). It does see use elsewhere, however; a cross-sectional
study looked at how diabetics in Jeddah, Saudi Arabia treat
foot disorders (open wound, chronic ulcer, skin cracks). extreme promise and equal measures of disappointment in
52.9% of respondents said they had used CAM products, clinical and experimental treatments of helminthic diseases
among which 37.4% said they used myrrh (Bakhotmah and like schistosomiasis. More thorough, strictly controlled
Alzahrani, 2010). Although there are a plethora of products evidence is needed to determine whether or not this product
containing myrrh on the market today, most of them are shows real results, but it certainly seems to have promise.
fragrance products. Tom’s of Maine produces a toothpaste
containing myrrh, which is marketed as a fluoride-free option
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Laboratory.
Croton lechleri Mϋll.-Arg., Euphorbiaceae
Latavia Carroll
Introduction antioxidant (Gupta, 2008). Some common names of this

Croton lechleri Mϋll.-Arg. is a member of the Euphorbiaceae species include: Sangre de grado, sangre de drago, sangre de
family, consisting of plants that are known for the dark resins dragon, dragon’s blood, drago, sangue de drago, and sangue de
they produce. Croton has red latex that is released from its agua. In Belize it is called kush-uh-che; in Mexico: shonashe;
bark when slashed (Figure 1). This species is mostly found inHonduras: pela nariz, and in Cameroon it is called ebine,
growing in Mexico, Venezuela, Ecuador, Peru, Colombia, enok, ndouon, or nouogui (Quattrocchi, 2000). There are more
Bolivia, and Brazil (Gupta, 2008; Jones, 2003). This species than 750 species within the genus, Croton, that are found all
has many different uses including treatment of diarrhea, over the world (Duke, page 411). The phytochemistry of
wound healing, treatment of tuberculosis, bone cancer, to dragon’s blood consists of alkaloids: sinoacutine, found in the
treat insect bites, stomach ulcers, and it is used to promote leaves, and taspine, found in the sap; as well as
healing after an abortion or used as a vaginal douche after proanthocyanidins, diterpenes, steroids, and lignans. All of
childbirth (Castner, page 46). It also has other therapeutic these different chemical constituents provide the synergy that
uses as an antimicrobial, antiviral, anti-inflammatory, and makes dragon’s blood bioactive.
Botanical description
As mentioned previously Croton lechleri grows in the Amazon
rainforest of Peru, Colombia, Bolivia, and Ecuador where the
climate is very wet and humid. This species is a tree that
grows at a fast rate of 10-15 meters in three years and is
usually found at elevations of 100-600 meters (Jones, 2003). It
can grow between 10-20 meters high and usually has a
diameter of 30 cm (Figure 2). C. lechleri is also known as a
pioneer species because it is usually one of the first plants to
appear in areas that have been cleared and along roadsides
(Ubillas et al., 1994). The dark green leaves of this tree are
heart-shaped and are characterized by a long narrow drip-tip
at the end of the leaves (Figure 3 & 4). The leaves tend to
Figure 1. Croton lechleri tree. (Taken by Ricarda Riina, 2009. grow in clusters towards the ends of the branches, and can
http://cms.herbalgram.org). range in size from 13-30 cm long by 15-30 cm wide. There are
Figure 3. A volunteer holding a bundle of C. lechleri leaves,
2008. (Source: http://cms.herbalgram.org).
Figure2. Croton lechleri Mϋll. Arg. (Source: http://www.rain-
tree.com/Plant-Images/sangre-pic.htm). “Perilous of the Eritrean Sea” about a tree that yielded drops
of cinnabar on the island of Discordia (Gupta, 2008). Spanish
three main veins that palmate from the leaf base, as well as 6- naturalist and explorer P. Bernabe Cobo observed and
8 obvious parallel secondary veins that diverge diagonally recorded that Croton lechleri was widely used throughout the
from the mid-vein. The larger veins and petiole are covered indigenous tribes of Mexico, Peru, and Ecuador in the 1600s.
with tiny bumps or hairs that rub off, and the smaller veins This information can be found in the Mateo’s: Biblioteca de
have a dotted appearance (Castner, page 46). The greenish- Autores Espanoles Series of 1956 in volumes 91 and 92
white flowers bloom on a tall slender upright stalks that can (Gupta, 2008).
be from 30-50cm long (Figure 4). The fruits of this tree are
brown, three-parted capsules (Figure 5). Sangre de grado is used in traditional Ecuadorian and
Peruvian medicine to treat diverse illnesses in adults, children,
and infants (Jones, 2003). Its internal ethnomedical uses were
Traditional uses for treatment of diarrhea, dysentery, cholera, coughs, flu, lung
problems, stomach ulcers, and hives. Hives were treated by
The name “dragon’s blood” dates back to the 1st century AD
when a Greek sailor wrote in a shipping manual called the
Figure 5. Fruits of C. lechleri. (Source: Photo by: Brian A. Smith,
2006. http://www.discoverlife.org/mp/20p?see=I_GEO374).
2003). The sap is also used to treat tuberculosis and bone

cancer, and is used externally to treat insect bites, stings, and
for wound healing (Jones, 2003). The sap is also used in the
healing of open sores in the mouth or on the body, as well as
for herpes infection. The Quijos Quichua of eastern Ecuador
soak a piece of cotton in the sap form dragon’s blood and
apply it to alleviate the pain of tooth extractions and cavities.
The traditional internal dosage of the sap in Ecuador and Peru
is generally 5–10 drops, once to twice per day for 5 days, but
often the treatment is repeated for as long as 3 weeks. The sap
is taken in water (cold or warm), milk, or alcohol (Jones,
2003). The yield of latex from C. lechleri is traditionally
dependent on the age of the tree. The sap is usually harvested
by slashing from a tree up to 6 years old with a diameter of
about 25 cm. Felling the tree and scoring the bark produces
about 5–6 L of sap, which is why is the preferred method for
Figure 4. Close-up picture of the flowers and leaves of C. industrial scale production (Ubillas et al., 1994).
lechleri. (Source: Photo taken by Leslie Taylor, 2000. http://www.rain-
tree.com/Plant-Images/sangre-pic.htm). C. lechleri is also used in African-American folk magic or
voodoo where the resin is used in mojo hands for money-
orally taking the sap in pineapple juice at a dosage of 20 drops drawing or love-drawing; it is used as an incense to cleanse
per 200 mL (Jones, 2003). In the upper Amazon, the sap is negative entities or influences. In neopagan witchcraft, it is
taken diluted in hot water to speed internal healing after an used to increase the potency of spells for protection, love,
abortion, and used as a vaginal douche after childbirth (Jones, banishing and sexuality (Gupta, 2008).
Alkaloids Ligans Proanthocya Steroids Diterpenes
nidins and
Flavonols
Sinoacutine 3’, 4-O- (+/-)- β-sitosterol- Bincatriol
Taspine dimethylcedr galloepicate- β-D- Crolechinol
Magnoflorine usin chin glucopyran- Crolechinic
Isoboldine (-)- oside acid
Norisobold- epicatechin β-sitosterol Hardwickiic
ine (+)- catechin acid
Glaucine Koberins A
thaliporphine and B
Table 1. Some of the chemical constituents found in
Croton lechleri.
Figure 6. Taspine. (Source: http://en.wikipedia.org/wiki).
Chemistry and Pharmacology respectively. And Korberins A and B at administered amounts

of 0.04 µg and 0.05 µg also showed activity against B. subtilis
A list of chemical constituents of C. lechleri were taken from (Chen et al., 1994).
the text of Jones, 2003 and typed into table format (Table 1).
Taspine, 3’, 4-O-dimethylcedrusin, and proanthocyanidins According to an in vitro study conducted by Chen et al., 1994,
make up about 90% of the weight of dried dragon’s blood (Cai taspine, a major chemical constituent in dragon’s blood
et al., 1991). These chemical compounds are also responsible (Figure 6), was determined to have potent cytotoxicity
for the wound healing properties of dragon’s blood. An in vivo against KB cells (human oral epidermoid carcinoma). Taspine
study on female Wistar rats was conducted by Pieters et al. was able to inhibit KB tumor cell growth by 50% at a
1995 to determine the wound healing activity of dragon’s concentration of 0.39 µg/mL (Itokwa et al., 1991). The
blood. The study concluded that the proanthocyanidins mechanism of action is not known, but it is believed to be the
stimulated contraction of wounds cut into the rats’ back and result of immunostimulation that cytotoxicity (Chen et al.,
formation of crust; 3’, 4-O-dimethylcedrusin stimulated 1994).
formation of new collagen, and regeneration of the epithelial
or top-skin layer (Pieters et al., 1995).
Biological Activity
Antimicrobial activity of chemical compounds 2,4,6-
In vitro studies
trimethoxyphenol and 1,3,5-trimethoxybenzene at amounts of
0.0003 µg showed high potent activity against the bacteria, Pereira et al. 2010 conducted an in vitro study on the effects of
Bacillus subtilis, which at this small amount was thirty times de grado on cutaneous neurogenic inflammation (CNI). The
more active than chloramphenicol and penicillin (Chen et al., procedure for how the plant extract was prepared was not
1994). Crolechinic acid was also active against B. subtilis and mentioned, but concentrations of 1%, 0.1%, 0.01%, and
E. coli at administered amounts of 0.2 µg and 1.0 µg, 0.001% were made. These different concentrations of extract
were applied to cell cultures made up of porcine or swine skin
cells and a co-culture of dorsal root ganglion neurons and Aminoanthracene in the presence of S9. And a moderate
keratinocytes, to examine sangre de grado’s ability to reduce protective activity was shown against mutagens Sodium Azide
substance release of cutaneous neurogenic inflammation. The and 2-Nitrofluorene. Therefore it was suggested that C. lechleri
results yielded that there was a dose-dependent decrease in sap interacts with the enzymes of the S9 mix, thereby
substance P release after ten minutes of incubation at inhibiting the transformation of 2-Aminoantracene into its
concentrations of 1% with an average of 32% and at 0.1% active forms (Rossi et al., 2003).
with an average of 26%. This suggests that sangre de grado
does inhibit cutaneous neurogenic inflammation. The second
part of the study looked at sangre de grado’s effect on In vivo studies
substance P release when induced by capsaicin. The results Froldi et al. 2009 conducted a study on the activity of sap from
yielded that after a one-hour incubation, substance P was C. lechleri on rat vascular and gastric smooth muscles. The sap
strongly inhibited and after a 72-hour incubation, substance P was collected in a traditional way by cutting it from a tree
was completely stopped. The study concluded “that sangre de growing in Napo river region of Ecuador. The voucher code
grado is a potent inhibitor of CNI through direct inhibition of No: sangre de grado 005 for the crude drug was sent to the
neuropeptide release by sensory afferent nerves,” but more Department of Pharmaceutical Sciences of Padua University.
studies need to be conducted to determine which compounds The study revealed “Croton lechleri increased contractile
in the plant were responsible for the activity (Pereira, 2010). tension in a concentration-dependent way for both the
An in vitro study of SP-303 showed antiviral activity against vascular and gastric smooth muscles of rats” (Froldi, 2009).
Herpes simplex viruses (HSV-1 and HSV-2), when applied The purpose of the study was to look at how the sap increased
topically to infected guinea pigs. The inhibition of the contractile tension by observing if regulation of certain
thymidine kinase mutants of the viruses by SP-303 is probably receptors and ion channels by pharmacological drugs could
done at the plasma membrane level where penetration and/ stimulate the activity of sangre de grado. The drugs used were
or absorption are interrupted during the early stage of viral atropine, a competitive muscarinic antagonist; prazosin, a
activity (Barnard et al., 1993; Ubillas et al., 1994). selective antagonist of x1-adrenergic receptors; ritanserin, a
5-HT2a selective antagonist. All of these drugs had no effect
An in vitro study conducted by Rossi et al., 2003 examined the
on the vasoconstriction of sangre de grado, so therefore were
mutagenic, antimutagenic, and antiproliferative potential
not responsible for its activity.
properties of sangre de drago. Sangre de drago was
determined to have antiproliferative effects on the human
myelogenous leukemia K562 cells. The mutagenic and Clinical Studies
antimutagenic activity of C. lechleri sap was evaluated by
means of the Ames/Salmonella test. There was no mutagenic Dragon’s blood has many different traditional uses that have
activity found on neither of the Salmonella typhimurium been shown to be beneficial through scientific studies
strains T98 and T100. On the other hand, the sap showed an conducted. But one particular illness that has been explored
inhibitory effect against the mutagenic activity of mutagen 2- more in the potential development of drugs is diarrhea.
Diarrhea is a big problem, especially in underdeveloped areas
where access to conventional medicines is limited. But
another important issue that Daniel DiCesare el al. 1998
explored was traveler’s diarrhea, particularly people that
traveled to Jamaica and Mexico. He and his colleagues
conducted a clinical trial in which 184 people from the United
States with diarrhea from traveling to Jamaica and Mexico
participated in a double-blind, placebo- controlled study of SP-
303 or Provir, a plant-derived from C. lechleri with
antisecretory properties. The purpose of the study was to
determine the effectiveness of three doses of SP-303 given to
patients four times a day for 2 days in treating and reducing Figure 7. Chemical structure of Crofelemer. (Source:
acute diarrhea. Provir is a large heterogeneous natural http://www.theannals.com/content/44/5/878.abstract).
polymer that breaks down in the presence of gastric or
stomach acid and the mechanism of action of this drug is cAMP-stimulated cystic fibrosis transmembrane regulator
inhibition of intestinal chloride channels. The study (CFTR) and calcium-stimulated (CaCC). The mechanism of
concluded that Provir shortened the duration of diarrhea by action of Crofelemer in net reduction of Cl- secretion is
21% and the optimal dosage was determined to be between probably the result of inhibition of one or more transporters
125-250mg given 4 times a day for 2 days. The drug was also involved in transcellular Cl- secretion such as basolateral
well tolerated with no side effects which are probably due to Na+/K+ pump, NKCC symporter, or K+ channels.
the fact that it is minimally absorbed by the body (DiCesare,
1998).
Another developed drug, Crofelemer, is currently in the Contraindications
clinical trial phase for treatment of secretory diarrheas Given the cytotoxicity of taspine, it is recommended that
associated with acute infections like cholera, chronic diarrhea sangre de drago saps containing a high content of the alkaloid
related to HIV/AIDS, and diarrhea-predominant irritable should not be used for wound-healing or for internal use
bowel syndrome. Crofelemer is a dark reddish-brown powder (Chen et al., 1994). The latex on the other hand is considered
that consists of proanthocyanidin oligomer extracts from the non-toxic and is well-tolerated in clinical studies. According to
latex of C. lechleri (Figure 7). According to Lukmanee et al. Ubillas et al., 1994, there are no report side effects in
2009, Crofelemer gets its antisecretory and antidiarrheal traditional medicine of taking the sap of dragon’s blood
properties by inhibition of two major apical membrane internally.
transport processes involved in intestinal fluid transport.
These two apical membrane Cl- channels are A study conducted by Bussmann et al., 2011 used a brine-
shrimp assay to test the toxicity of medicinal plants used in
traditional medicine in Northern Peru. The results concluded itching and pain caused by insect bites. The study involved
that Croton lechleri was not toxic when prepared traditionally ten workers from the Terminex Pest Control Company in New
as an aqueous extract for oral or topical use, but it was very Orleans, LA who applied the balm topically to insect bites of
toxic when an extract was prepared with ethanol. fire ants over a period of three months. The results showed
According to the scientific literature, C. lechleri is considered that the workers experienced relief less than two minutes
to be non-toxic and well tolerated, but there is no research after applying the balm. This result provided evidence that
concerning its effect on pregnant or lactating mothers. sangre de drago inhibits sensory nerve afferent activity, but
the mechanism is unknown (Miller et al., 2001).
Shaman pharmaceuticals was a company that based its
Current us in Allopathic and CAM therapies development of natural products from the knowledge of
Published in 2010, a survey was conducted by Kazhila and traditional healers. Shaman is the creator of Provir, which at
Marius on plants used to manage HIV/AIDS opportunistic first was identified as a potential treatment for respiratory
infections in Katima Mulilo, Caprivi region, Namibia. The syncytial virus, but after Shaman scientists witnessed use of C.
purpose of the article was to collect and record knowledge of lechleri for a cholera outbreak in Peru of 1993, its target was
plants traditional healers used to treat illnesses related to switched to diarrhea treatment. As mentioned previously,
HIV/AIDS. Croton lechleri was one of the 72 species used that Provir works by slowing down loss of water in secretory
was listed in Table 1 of article. The common name for C. diarrhea and allows the body to get rid of toxins and bacteria
lechleri was tassel berry, but the local name was mukena. at a gradual pace. Shaman is also the creator of Virend, a
Traditional healers use the bark of mukena to form a drink topical formulation of the polyphenol found in Provir, SP-303.
that treated diarrhea, lack of appetite, and anemia. The Unfortunately this drug died in Phase III trials for herpes and
procedure for how the drink was prepared was not mentioned Shaman did not have enough money to support its trials and
and neither was the mechanism of action. However, the had to file for bankruptcy. On August 18, 2005 Shaman
article did mention that most plants used to treat AIDS- pharmacuetical was no more, but it was later bought by Napo
related opportunistic infections contained flavonoids, which pharmaceuticals.
have anti-oxidant properties that inhibit free radical
production and tissue damage associated with the onset of
AIDS (Chinsembu, 2010). This survey is important because it Discussion
is the basis for identifying plants with anti-HIV active Croton lechleri is an amazing plant that as many different uses
compounds, which could led to the development and usage of in South America and the United States. Most of its uses such
new drugs in allopathic therapies. for wound healing, pain relief of insect bites, treatment of
A study conducted by Miller et al., 2001, examined the herpes, treatment of diarrhea, and other uses have been
potential soothing effect of a 1% sangre de drago balm demonstrated in lab settings, where these properties have
(Zangrado Bug Bite Balm, Rainforest phytocecuticals) on been shown to be effective. This plant has been important in
the past to traditional cultures and it has now become
important in more developed nations where the need for new Itokwa H, Ichihara Y, Mochizuki M, Enomori T, Morita H, Shirota O,
effective drugs is of constant need. As time goes on and more Inamatsu M, Takeya K. A cytotoxic substance from sangre
is learned about this plant and the compounds responsible for de drago. Chem Pharm Bull 1991;39:1041–1042.
its activity, there will be great advancements in treatments Jones K. Review of sangre de drago (Croton lechleri)—a South
and medicines available to humanity. American tree sap in the treatment of diarrhea,
inflammation, insect bites, viral infections, and wounds:
traditional uses to clinical research. Journal Alternative
References Cited Complement Medicine 2003; 9: 877-96.
Barnard DL, Smee DF, Huffman JH, Meyerson LR, Sid- well RW.
Antiherpesvirus activity and mode of action of SP-303, a Lopes MI, Saffi J, Echeverrigaray S, Henriques JA, Salvador M.
novel plant flavonoid. Chemotherapy 1993;39:203–211. Mutagenic and antioxidant activities of Croton lechleri sap in
biological systems. Journal of Ethnopharmacol 2004; 25:
Bussmann, R.W., G. Malca, A. Glenn, D. Sharon, B. Nilsen, B. Parris, D. 437-45.
Dubose, D. Ruiz, J. Saleda, M. Matinez, L. Carillo, K. Walker, A.
Kuhlman, and A. Townesmith. Toxicity of medicinal plants Quattrocchi, Umberto. "Croton L. Euphorbiaceae." CRC World
used in traditional medicine in Northern Peru. Journal of Dictionary of Plant Names. 2000. Print
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Cai,Y., F.J. Evans, M.F. Roberts, J.D. Phillipson, M.H. Zenk, Y.Y. Gleba. Dorange G, Lefeuvre L, Gougerot A, Misery L. Effects of
Polyphenolic compounds from Croton lechleri. sangre de drago in an in vitro model of cutaneous
Phytochemistry 1991; 30(6): 2033-2040. neurogenic inflammation. Exp Dermatol 2010; 19: 796-9.
Castner, L. James, Stephen L. Timme, and James A. Duke. A Field Pieters, L., T. De Bruyne, B. Van Poel, R. Vingerhoets, J. Tottte, D.
Guide to Medicinal and Useful Plants of the Upper Amazon. Vanden Berghe and A. Vlietinck. In vivo wound healing
Gainesville, Florida: Feline Press, 1998. activity of Dragon’s Blood(Croton spp.), a traditional South
American drug, and its constituents. Phytomedicine 1995; 2:
Chen ZP, Cai Y, Phillipson JD. Studies on the antitumor, anti- 17-22.
bacterial, and wound-healing properties of dragon’s blood.
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A, Paganetto G. Evaluation of the mutagenic, antimutagenic
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of plants used to manage HIV/AIDS opportunistic infections Arg.) latex. Phytomedicine 2003; 10(2-3):139-44.
in Katima Mulilo, Caprivi region, Namibia.” Journal of
Ethnobiology and Ethnomedicine 2010, 6:25. Rossi, Damiano; Guerrini Alessandra; Maietti Silvia; et al. Chemical
fingerprinting and bioactivity of Amazonian Ecuador Croton
Duke, Allen. Amazonian Ethnobotanical Dictionary. London: CRC lechleri Mull. Arg. (Euphorbiaceae) stem bark essential oil: A
Press, 1994. new functional food ingredient? Food Chemistry 2011;
Froldi G, Zagotto G, Filippini R, Montopoli M, Dorigo P, Caparrotta L. 126(3): 837-848.
Activity of sap from Croton lechlerli on rat vascular and Ubillas R, Jolad SD, Bruening RC, Kernan MR, King SR, Sesin DF,
gastric smooth muscles. Phytomedicine 2009;16: 768-75. Barrett M, Stoddart CA, Flaster T, Kuo J, Ay- ala F, Meza E,
Castañel M, McMeekin D, Rozhon E, Tempesta MS, Barnard Vaisberg AJ, Milla M, Planas MC, Cordova JL, de Agusti ER, Ferreyra
D, Huffman J, Smee D, Sidwell R, Soike K, Brazier A, Safrin S, R, Mustiga MC, Carlin L, Hammond GB. Taspine is the
Orlando R, Kenny PTM, Berova N, Nakanishi K. SP-303, an cicatrizant principle in Sangre de Grado extracted from
antiviral oligomeric proanthocyanidin from the latex of Croton lechleri. Planta Medicine 1989; 55(2):140-3.
Croton lechleri (sangre de drago). Phytomedicine 1994;
1:77–106.
Curcuma longa L., Zingiberaceae
Ashvi Mittal
Introduction
Plants have been used medicinally throughout history by
various regions, cultures, and societies in the world. One such
plant with deep historical roots is Curcuma longa, commonly
known as Turmeric (Figure 1). The plant belongs to the
Zingiberaceae family. The name ‘turmeric’ is derived from the
ancient Medieval Latin name terramerita. This transformed
into terre merite in French, meaning meritorious Earth (P.N.
Ravindran, 2007). This was the original name that powdered
turmeric was referred to in commercial practices. A few
modern common names associated with the plant today
include Haldi (Hindi), Saffron de India (French), acafrao de
india (Portuguese), Ukon or Gajyutsu (Japanese), kurkuma
(German), Daruhaldi (Arabic), Chiang husang (Chinese) Kha
min chan (Thai) and Ulgeum or Gangwhang (Korean)
(Aggarwal, Sundaram, Malani, & Ichikawa, 2007a; Jansen,
2005),(P.N. Ravindran, 2007).
Figure 1. Photograph of the rhizomes and powder of
C. longa is believed to have originated in South Asia, primarily Curcuma longa (Image source: http://www.natural-healing-with-
India. Researchers believe that turmeric was introduced to foods.com/turmeric.html)
India through ancient tribal groups during their migration
from present day China (P.N. Ravindran, 2007). It has been diseases, and bacterial infections (Goel, Kunnumakkara, &
used in Asian medicines since the second millennium BC. It is Aggarwal, 2008; Society, 2008) Moreover, some researchers
mainly used in South and East Asia as part of Traditional believe that turmeric has the potential to treat certain types of
Chinese Medicine and Ayurveda (Aggarwal et al., 2007a). cancers including breast, skin, and stomach cancers (Society,
Turmeric is significantly known for its anti- inflammatory 2008).
effects in treating muscle sprains, swelling, arthritis, and The majority of these diverse properties of the plant are due
rheumatism. It also provides protection against high to the main compound in turmeric known as curcumin. The
cholesterol levels, angina, irritable bowel syndrome, liver phytochemicals in curcumin are responsible for the yellow
color of the plant (Goel et al., 2008). The compound displays a
wide array of properties such as antifungal, antiviral, anti-
inflammatory, antioxidant, and anticancer activities. It is also
effective against health conditions such as diabetes and
arthritis (Pari L, 2008). In addition to acting as a medicine, C.
longa is used as a spice in culinary practices, herb in religious
rituals, and a coloring agent for dying clothes (Muhammed
Majeed, 1996).
Curcuma longa is well known to be a perennial herb which
grows about 3-5 feet high. The plant is cultivated primarily in
tropical areas of Asia, namely China and India (Stewart &
Figure 2. Illustrations of Curcuma longa in various forms
Costerton, 2001). Its pointed, oblong leaves are about two feet
long with a consistent green color surrounded by yellow- Turmeric as a botanical illustration (A) and as a full grown
tinted funnel shaped flowers (Stewart & Costerton, 2001). The plant with green leaves and tinted yellow flowers (B). The
plant has tuberous roots like bulbs that produce rhizomes tuberous roots of the plants produce rhizomes (C). These are
which are used medicinally. In its fresh condition, the roots further boiled, cleaned, and dried to produce a powdered form
emit a spicy and aromatic odor (Jansen, 2005). The rhizomes (D). (Image sources: http://www.philographikon.com/
are commonly transformed into a yellow powder by boiling, botanicalsregault.html- A; http://database.prota.org/dbtwwpd/
cleaning, and drying (Figure 2) (Stewart & Costerton, 2001). exec/dbtwpub.dll?ac=qbe_query&bu=http://database.prota.org/se
C. longa generally thrives in warm and moist environmental arch.htm&tn=protab~1&qb0=and&qf0=Species+Code&qi0=Curcum
habitats. It is usually grown in the tropical regions with about a+longa&rf=Webdisplay -B; http://www.marxfoods.com/Fresh-
Turmeric-Rhizomes -C; http://organicindia.mercola.com/herbal-
640-4200 mm of rainfall (P.N. Ravindran, 2007). The plant is
supplements/turmeric.aspx -D)
grown well in soil that is well drained, fertile, loamy, or
alluvial as it cannot tolerate alkaline soil conditions (P.N.
Ravindran, 2007). For the efficient growth of rhizomes, stony Turmeric is also prone to certain herbivorous invaders. One
and bumpy areas are not preferred. The optimum such feeder is Taphrina malucans which is responsible for a
temperature for the sprouting of rhizomes is 25 to 35o Celsius. disease called leaf spots on the plant (Jansen, 2005). The
The plant is capable of growing in shaded areas; however, an leaves of the contaminated plant are dried up by the rhizome
exposure to the sun can enhance its growth. The flowers cot, causing the rhizomes to turn brown. The best way to
blossom about five months after planting and approximately control this phenomenon is to burn infected plants, and
7-10 months after the rhizomes have matured, the yellow sometimes, it is recommended to sanitize the soil using a
coloration of leaves begins to appear (Jansen, 2005) fungicide(Jansen, 2005). Examples of fungicide used to treat
Figure 3. Udaspes folus, commonly known as the grass
demon, feeds on the leaves of Curcuma longa.
(Image Source: http://www.butterflycircle.com/checklist%20V2/Cl
/index.php/start-page/startpage/showbutterfly/283)
Figure 4. Movement of Curcuma longa.
Turmeric is believed to originate in Asia, primarily in India
the soil include mancozeb and metalaxyl. In several Asian and later spread to the West via the spice trade.
countries such as India, caterpillars such as Udaspes folus, (Image source: http://ancientstandard.com/2011/02/11/how-
commonly known as the grass demon, is the main insect that cooking-changed-the-face-of-the-earth-the-spice-trade/)
feeds on the plant (Figure 3). In several countries of Africa, a
sucking insect named Aspidiella harti nourishes on the plant’s
regarding his 1280 AD journey to China and India (Aggarwal
rhizomes (Jansen, 2005).
et al., 2007a). Turmeric was exposed to North America during
the British colonial rule over America (Figure 4). It was then
Traditional Uses that turmeric combined with a variety of other spices and
remained curry power in the West (Aggarwal et al., 2007a).
The history of Curcuma longa in Asian medicine dates back to Today, C. longa is primarily grown in South and East Asia and
the second millennium BC (R.A. Sharma, 2005). Turmeric was some home gardens in parts of Africa. It is used not only as
initially cited in the Atharvaveda wherein it was prescribed to medicine, but also as a beauty care agent, spice, religious herb,
cure jaundice (P.N. Ravindran, 2007). It was introduced in and a coloring agent (P.N. Ravindran, 2007). The spice is
China before the 7th century and to Africa in the 13th century. widely used as a culinary enhancement to enrich foods with
The spice was first brought to the West, essentially to Europe its vivid yellow color and flavor. In the West, it is also used in
by Arab Sailors (Aggarwal et al., 2007a). The plant was also mustard and to give color to milk products such as cheese
listed as a coloring agent in the writings of Marco Polo ("Turmeric ", 2011).
Medicinal with powdered ginger and mix in a hot glass of milk as a tonic
C. longa has been traditionally used to treat a wide variety of drink to stay healthy. It is also believed that applying turmeric
ailments across Asia and Africa such as skin, pulmonary, poultice is beneficial in the healing of lacerations of the birth
gastrointestinal diseases, aches, wounds, and liver disorders canal (Pandeya, 2005). In addition, neem leaves and turmeric
(Aggarwal, Sundaram, Malani, & Ichikawa, 2007b). India is powder was used an anti-septic to treat chickenpox and
considered to be the central hub of the cultivation and smallpox. Turmeric was applied to the body and a bath was
application of turmeric. The spice has been used as part of taken in boiling water with neem leaves. The ash of the
Ayurvedic medicine (Ayurveda) for more than 6000 years. It rhizomes was also believed to cure the eruptions caused by
was applied as a blood purifier, used internally as a tonic for the infection (P.N. Ravindran, 2007).
stomach infections, and employed externally for skin diseases. In many African countries such as Ethiopia and Madagascar,
About half to one gram of powder was taken for relieving turmeric is grown in many residential home gardens. The
dyspepsia and flatulence (Muhammed Majeed, 1996) . In rhizomes of turmeric are considered to be highly aromatic and
order to cure nasal mucus, the fumes of burning C. longa were contain antibacterial properties (R.A. Sharma, 2005). The
inhaled which led to a discharge of the mucus relieving locals commonly use the rhizomes as an ailment for
blockage. In addition, turmeric was often boiled with sugar bronchitis, cold and, asthma (Pari L, 2008). The juices formed
and milk as an ancient remedy for the common cold from rhizomes are believed to be an effective remedy for
(Muhammed Majeed, 1996). The fresh rhizomes were used to several skin and eye infections (Jansen, 2005).
make medicinal juices to heal skin infections, wounds, sprains,
and inflammations. The powder made from these rhizomes
was often mixed with olive oil to enhance and soften the skin. Rituals/Beliefs
In rural villages in the Northern part of India, it is common to Hindus believe turmeric to be sacred and auspicious. In a few
get eye diseases (Pandeya, 2005). This is due to a lack of tribal communities in the southern states of India such as
availability of health practitioners and antibiotic ointments to Tamil Nadu, a piece of turmeric is tied to a string which is
cure such diseases. In these cases, the native people use believed to be a sacred nuptial string (P.N. Ravindran, 2007).
turmeric which they refer to as haldi, as a means of treatment This practice is still prominent in many areas of South India
and prevention (Pandeya, 2005). In the villages it has become today. In addition, a piece of turmeric is tied on the hand along
a folklore that if people do not include turmeric in their daily with an amulet as a way to fight evil spirits (P.N. Ravindran,
diet then they will be infected with diseases which may kill 2007). The upper class societies use a natural yellow rhizome
them (Pandeya, 2005). Turmeric paste is applied to the in the form of a gold chain, whereas, the lower class and poor
infected regions surrounding the eye. Generally, one ounce of rely on turmeric alone.
turmeric is added to twenty ounces of water to form a Traditionally, C. longa was used to give yellow coloration to
mixture. This mixture is then used as a cooling eyewash to clothing during religious festivals. The villagers believed that
heal an infection known as ‘country sore eye.’ In addition, the yellow color was associated with Lord Krishna who only
after the neonatal period, women make a paste of turmeric
Culinary
Turmeric remains a primary ingredient in culinary practices
today. It is frequently used to give rice and Indian curry their
yellow hue (Figure 5). It is added as a relish in authentic
dishes and gives food its necessary spice and color ("Turmeric
", 2011). In the South East Asia region, the native people
prefer turmeric dry. In Thailand, fresh rhizomes are used to
embellish curry dishes and to make yellow curry paste
(Aggarwal et al., 2007a).
Coloring Agent
Figure 5. Indian yellow rice prepared with turmeric In India, turmeric was believed to be used as a coloring dye by
(Image Source: the British. They used the plant as a coloring agent for
http://www.lifesambrosia.com/category/recipes/cuisine/ind commercial purposes and monetary gain. In the city of
ian/) Calcutta, the dyers make a bright yellow hue called basanti
wore yellow attires. In addition, in many rural and urban rang by mixing it with lemon and the carbonate of sodas (P.N.
communities, turmeric is used during marriage preparations Ravindran, 2007). The plant was also used to make shades of
and ceremonies. Before marriage, turmeric and oil are applied green and indigo. First, the cloth was dyed with indigo and
on the bride and their groom by their relatives (P.N. then exposed to a mixture of turmeric. In addition, the Indian
Ravindran, 2007). In the state of Punjab in Northern India, the Calico printers mixed turmeric with alum and pomegranate to
elders of the community place rice and an areca nut between make a dye (P.N. Ravindran, 2007). The mixture was later
the joined hands of the couple. Their hands are tied with dyed used to color silk and wool to produce different shades such as
turmeric seven times. The couples’ parents pour turmeric browns and olives. Currently, C. longa is not applied as a
water from a leaf seven times over their hands to conclude the commercial coloring agent.
marriage ceremony. In West Africa, rhizomes of the plant are used as yellow
In East Asia, C. longa has been an essential component of coloring dyes for products such as cotton clothing, thread,
Traditional Chinese Medicine throughout history. In palm fibers, and tanned leather (Jansen, 2005). In Nigeria, a
Indonesia, the yellow color derived from the spice is used in paste is made from the rhizomes with water and rubbed into
cooking yellow rice called nasi kuning (Aggarwal et al., tanned leather hides. This is a technique which is used to color
2007a). The nasi kuning has religious significance and is leather. In Ethiopia, the cloth for coloring is placed into a
believed to be a sacred dish as it is sacrificed to the Gods boiling decoction of turmeric paste. This method is commonly
(Aggarwal et al., 2007a). used in many regions of Ethiopia to dye clothes (Aggarwal et
al., 2007a). In addition, in many Asian nations, turmeric is
used to form different color combinations of yellow in cotton
and silk clothing which is subsequently sold for household
earnings (Jansen, 2005).
In European nations, the ground rhizome of turmeric is
Figure 6. Chemical structure of curcumin (main
employed in the food industry as well as a coloring agent in
compound in C. longa) (Image source:
several processed foods. In addition, turmeric is considered a http://www.scielo.br/img/fbpe/mioc/v96n5/html/404001.html)
cheaper substitute for saffron as it is utilized in
pharmaceutical companies and textile industries (Jansen,
2005) . Some European countries use turmeric in dyeing wool to acetone (R.A. Sharma, 2005). When curcumin is taken
to make various shades of yellow and gold (Jansen, 2005). In orally, it is broken apart into curcumin glucuronide and
North America, the oils of C. longa have been labeled as curcumin sulfonate. However, upon systematical
Generally Recognized as Safe (GRAS)(Jansen, 2005) administration it is metabolized into tetrayhudrocurcumin,
hexahydrocurcumin, and hexahydrocurcuminol (Aggarwal et
al., 2007a). Curcumin acts by down regulating iNOS enzymes
Chemistry and Pharmacology and COX-2 and suppressing the NFKB pathway (Appleton,
Curcuma longa comprises of a wide range of compounds 2011). It also inhibits the scavenging free radicals and
(Table 1). The plant contains essential macronutrients such proliferation of inflammatory cytokines (Appleton, 2011).
as minerals (3.5%), fats (5.1%), protein (6.3%), moisture
(13.1), and carbohydrates (69.4%) (Ishita Chattopadhyay,
2004) . The leaves are rich in various types of acids such as o- Biological Activity
coumaric acid, protocatechuic acid, ayringic acid, and vanillic Antioxidant Effects
acid (Duke, 2012). The essential oils consist primarily of
monoterpenes and sesqueterpenes. The root of the plant Turmeric is known for its high antioxidant effects. This is due
contains bisabolene and boron. The rhizomes contain the to curcumin behaving as a scavenger of oxygen free radicals
largest variety of chemical constituents which include (Ishita Chattopadhyay, 2004). In various in vitro studies,
polyphenols, monoterpenes, flavonoids, curcuminoids, curcumin was found to inhibit the generation of reactive
carotenes, alkaloids, minerals, fiber, and water(Araújo & Leon, oxygen species by stimulating macrophages. These species
2001; Duke, 2012). The primary compound of C. longa found include ROS, H202, and nitrate radicals. In transgenic mice
in the rhizomes is curcumin (Figure 6). The compound is a with Alzheimer’s disease, curcumin can decrease the oxidized
polyphenol, responsible for the yellow color of turmeric and proteins in amyloid pathology. In addition, it can reduce lipid
comprises approximately 2-5 percent of the spice(Aggarwal et peroxidation in rat brain homogenates, liver microsomes, and
al., 2007a). The phytochemical has hydrophobic properties erythrocyte membranes (Ishita Chattopadhyay, 2004).
and is soluble in several substances ranging from oils, ethanol, Numerous studies have been conducted to examine
Plant Active Constituents
Part
Rhizomes 1-8 Cineole, 2-Hydroxy-Methyl-Anthrauinone, 4-Hydroxy-Cinnamoyl-Methane, Alpha-Atlantone, Alpha-Terpineol, Ar-Turmerone,
Arabinose,Ascrobic Acid, Ash, Azulene, Beta-Carotene, Beta-Sesquiphellandrene, Bis Methane, Bis-Desmethoxycurcumin, Borneol,
Caffeic-Acid, Carbohydrates, Chromium, Cinnamic-Acid, Cobalt, Copper, Cuminyl-Alcohol, Curcumin, Curlone, Curzerenone, Cyclo-
Isoprenemyrcene, D-Alpha-Phellandrene, D-Camphene, D-Camphor, D-Sabinene, Dehydroturmerone, Desmethoxycurcumin, Di-
Coumaroyl-Methane, Didesmethoxycurcumin, Diferuloyl-Methane, Dihydrocurcumin, Eo, Fat, Fiber, Fructose, Gamma-Atlantone,
Glucose, Guicacol, Iron, L-Alpha-Curcumene, L-Beta-Curcumene, Manganese, Monodesmethoxycurcumin, Niacin, Nickel, P-
coumaric acid, P-Cymene, P-Tolymethyl Carbinol, Phosphorous, Potassium, Resin, Riboflavin, Sodium, Thiamin, Turmerone,
Ukonan, Water, Zinc, Zingiberene
Leaf O-Coumaric Acid, Protocatechuic Acid, Syringic Acid, Vanillic Acid
Essential Alph-Pinene, Beta-Pinene, Caryophyllene, Curcumene, Curcumenol, Curdione, Curzerenone-C, Eugenol, Limonene, Linalol,
Oils Terpinene, Terpineol,
Plant 2-Bornanol
Roots Bisabolene, Boron,
Table 1. The chemical constituents of C. longa according to corresponding parts of the plant
(Source: Information obtained from Dr. Duke’s Phytochemical and Ethnobotanical Databases http://www.ars-grin.gov/cgi-
bin/duke/farmacy2.pl)
In addition, curcumin’s effects on endothelial heme
curcumin’s effect on lipid peroxidation (Araújo & Leon, 2001).
oxygenase-1 were examined in a vitro study using bovine
It was consistently found that curcumin remains an effective
aortic endothelial cells. As a result of a seemingly incessant
antioxidant and restrains lipid peroxidation in rat livers (Pulla
incubation of approximately eighteen hours with curcumin, an
Reddy & Lokesh 1994). This lipid peroxidation plays an
increase in the cellular inhibition to oxidative damage was
essential part in cardiovascular effects, inflammatory effects,
and cancer (Araújo & Leon, 2001). detected. (Thorne Research, 2002a).
Some extracts of Curcuma longa are fat and water soluble.
These extracts along with curcumin exhibit strong antioxidant Hepatoprotective Effects
activities, comparable to vitamins C and E. One particular
study of cardiac ischemia showed that a pretreatment with Several animal studies have been conducted to determine
curcumin reduced ischemic injury (Thorne Research, 2002a). turmeric’s hepatoprotective effects. This ability to prevent
liver damage is due to the anti-hepatotoxic compounds in the topically to counter inflammation and irritation related to skin
plant, which include carbon tetrachloride, galactosamine, allergies (Thorne Research, 2002a).
acetaminophen, and aspergillus aflatoxin (Thorne Research,
2002b). These compounds decrease the formation of
inflammatory cytokines (Thorne Research, 2002a). Anti-carcinogenic/ Anti-tumor Effects
In addition, an interesting study done on ducklings infected In vivo studies on rats and mice, have exhibited the ability of
with fungus Asperigillus parasiticus, showed that turmeric curcumin to inhibit carcinogenesis at three different stages:
extract reduced the production of fungal aflatoxin by ninety during tumor promotion, angiogenesis, and tumor growth
percent (Thorne Research, 2002a). Moreover, research (Thorne Research, 2002a). Studies examining colon and
suggests that curcumin may also be used to treat prostate cancer show that curcumin suppressed cell division
cholelithiasis, commonly known as gallstones. (Thorne and tumor growth (Thorne Research, 2002a). Several in vitro
Research, 2002a). studies using human cell lines have indicated that turmeric
has the capacity to restrain mutagenic and carcinogenic
presence in various types of cells. This anti-carcinogenic effect
Anti-inflammatory Effects of the plant is because of its antioxidant effects and the ability
Curcumin acts by inhibiting the NF-kB activation and to help in hepatic detoxification of those carcinogens resulting
decreasing the TNF-a-induced expression of the gene in in reduced nitrosamine production(Thorne Research, 2002a).
endothelial cells (Ishita Chattopadhyay, 2004). The anti- A study was conducted by Huang et al. (1988) examining the
inflammatory effects of turmeric are stimulated by the down effects of ferulic acid, caffeic acid, chlorogenic acid, and
regulation of cyclooxygenase-2and inducible nitric oxide curcumin on tumor growth in mice. It was discovered that
synthetase through repressing the NF-kB pathway (Ishita curcumin was the most efficient in hindering the epidermal
Chattopadhyay, 2004). metabolism of arachidonic acid through the cyclooxygenase
and lipoxygenase passages (Araújo & Leon, 2001).
The volatile oils of turmeric along with curcumin produce
anti-inflammatory effects. A study using rats with arthritis
was performed in which curcumin was given orally. This Antimicrobial/ Anti-bacterial Effects
caused a great reduction in the inflammatory swelling
compared to the controls (Thorne Research, 2002a). Another Essential oils of C. longa and its extracts are known to inhibit
study conducted on monkeys illustrated inhibition of the proliferation of many types of bacteria, parasites, and
neutrophil aggregation which is related to inflammation fungi (Thorne Research, 2002a). An in vivo study conducted
(Thorne Research, 2002a). In studies on mice with diabetes, on chicks that had caecal parasite Eimera showed that the
curcumin has found to enhance the wound healing and the diets which were enhanced with one percent turmeric caused
damage caused by H202 in human fibroblasts(Ishita a decrease in small intestinal lesion scores and enhanced
Chattopadhyay, 2004). Curcumin can also be administered weight gain (Thorne Research, 2002a). In addition, a study
performed on guinea pigs infected with pathogenic molds or
yeast showed that turmeric oil applied topically aided in the pharmacological interventions to repair the calcium 2+
reduction of pathogenic fungi, however the curcumin did not homeostasis in the cardiac muscle by improving the Ca 2+
have an effect on the yeast. The guinea pigs infected with fungi transport (Ishita Chattopadhyay, 2004).
showed signs of improvements in the lesions. A week after the
turmeric was applied to the animals, no lesions were detected
(Thorne Research, 2002a). Gastrointestinal Effects
In 1979, Murthy and Bhavani Shankar performed an in vitro Several compounds in turmeric serve as effective protective
study of turmeric fractions applied to intestinal bacteria. The agents of the gastrointestinal tract (Thorne Research, 2002a).
results showed the inhibition of Lactobacilli growth when the C. longa is demonstrated to restrain the presence of ulcers due
bacterium was exposed to turmeric (Araújo & Leon, 2001). to factors such as stress, alcohol, indo methacin, pyloric
When examining the alcoholic extract, there were signs of ligation, and reserprine (Thorne Research, 2002a). A study
inhibition but they were not as effective as the application of done on rats who suffered with these gastrointestinal
the whole fraction of turmeric (Araújo & Leon, 2001). problems were found to have increased gastric wall mucus
production when exposed to the plant (Thorne Research,
2002a).
Cardiovascular Effects
Turmeric is also known to have positive effects on our
Clinical Studies
cardiovascular system (Thorne Research, 2002a). These
effects include lowering of triglyceride levels, cholesterol, and There have been clinical studies performed which apply
reducing vulnerability of low density lipoprotein to lipid turmeric power in patients with respiratory ailments (Ammon
peroxidation (Thorne Research, 2002a). It also aids in & Wahl 1991). It was discovered that the patients felt relief of
inhibiting platelet accumulation (Thorne Research, 2002b). An symptoms such as cough, dyspea, and sputum production.
in vivo study performed on rabbits that were exposed to a low Other studies accounted improvement in eighteen patients
dose of turmeric extract showed a decrease in susceptibility of with rheumatoid arthritis upon administration of the drug
LDL to lipid peroxidation and reduced triglyceride levels. orally on a daily bases (Araújo & Leon, 2001)
When the rabbits were exposed to a higher level of turmeric Studies examining curcumin have occurred over the last fifty
extract, the result indicated no decrease in lipid peroxidation years. The compound is known for its anti-carcinogenic
of LDL, however there was a reduction in triglyceride and properties as it suppresses the growth of tumor cells
cholesterol levels. This occurred due to the decreased (Anushree Kumar, 2003). Human clinical trials performed
cholesterol uptake in the intestines and increase in exchange showed no-dose limiting toxicity when given at doses up to
of cholesterol to bile acids found inside the liver (Thorne ten grams per day (Anushree Kumar, 2003). These studies
Research, 2002a). In addition, curcumin protects the harm indicated that curcumin had the ability to prevent and treat
caused by myocardial infarction by reducing the level of various types of cancers such as breast and colon cancer
severity of pathological changes. It increases the chances of (Anushree Kumar, 2003).
Another study was performed testing curcumin in cancer team of scientists chose fifty patients with osteoarthritis in the
treatment at initial stages (Society, 2008). Fifteen patients knee in order to test a special formulation of turmeric known
with colorectal cancer were examined to observe their intake as Meriva ("Special Turmeric Extract Benefits Osteoarthritis
of curcumin safely. It was found that the patients could take Patients," 2010). After separating the individuals into two
3.6 grams of curcumin without any side effects (Society, groups, the first group was exposed to the standard medical
2008). Some curcumin and its compounds were detected in treatment by physicians, while the individuals in the second
the blood at this level of high dose. The lower doses may be group were treated with curcumin extract in addition to the
beneficial for the intestine and stomach (Society, 2008). typical medical therapy. After a ninety day period, the
Although, it does not absorb effectively in the body, curcumin individuals exposed to the extract had a 58 percent increase in
is able to absorb into the cancerous tissues of the colon. It was their overall health and functionality when compared to the
recommended from the study that a high dose of curcumin control group. Moreover, the Social and Emotional Index score
should be used when examining effects outside of the for the Meriva patients increased by 300 percent, followed by
intestine. Further research indicated that individuals were a 16 fold decline of inflammation levels ("Special Turmeric
able to ingest ten grams of curcumin per day for a few weeks Extract Benefits Osteoarthritis Patients," 2010). The most
without observing any side effects (Society, 2008). Currently, astonishing finding of the study was that patients treated with
researchers are focusing on combining curcumin with other the turmeric extract reduced their use of NSAIDs (Non-
compounds in order to increase the absorption rate in the Steroidal Anti-Inflammatory Drugs) by 63 percent when
body (Society, 2008). compared to the patients with the standard medical treatment
("Special Turmeric Extract Benefits Osteoarthritis Patients,"
An interesting study was conducted on women in Southern
2010).
India who use turmeric in order to prevent acne and reduce
growth of hair (Jasmine H Shaffrathul, 2007). Seventy three
individuals including female nurses, visitors, and workers of a Contraindications
hospital were surveyed concerning the period and reason for
their turmeric use. The individuals were inspected for signs of Turmeric is generally considered to be a low toxicity plant,
acne. Thirty five of the 75 subjects used turmeric daily, while especially when used as a spice in foods. However, there needs
the remaining did not apply turmeric. The results of the study to be more research conducted to examine the side effects of
indicated no statistical significance in the p value between the using turmeric as a herbal remedy. It is believed that ingesting
individuals with acne who utilized turmeric and ones who did large amounts of the spice orally can lead to stomach pains,
not employ the herb (Jasmine H Shaffrathul, 2007). In indigestions, and nausea. Long term exposure to the plant can
addition, the subjects who used turmeric did not indicate a further be a cause of stomach ulcers and skin rashes.
reduction in the growth of hair when compared to the Individuals who have allergic reactions to ginger products or
individuals who did not use turmeric. food colorings are likely be allergic to turmeric. Furthermore,
women who are pregnant or breastfeeding and individuals
A recent clinical study examined the use of a distinctive
extract of C. longa on patients with osteoarthritis. In Italy, a
Therefore, it is vital to inform our health care practitioners
about any herbal supplements we taking. According to the
National Center for Complementary and Alternative Medicine,
turmeric is a safe plant for most adults. However, long term
exposure or high doses of the spice can be a cause of
indigestion and diarrhea. Many studies in animals have shown
that intake of high doses may lead to liver illnesses. Moreover,
individuals who have gallbladder infections should avoid the
Figure 7. The different forms of turmeric which are use of turmeric as a dietary supplement (NCCAM, 2007).
marketed: Capsules (A), Tinctures (B), and ground
powder (C) (Images Sources: http://www.nutritionexpress.com
/natures+way/natures+way+turmeric+extract+500+mg+120+table Current Use in Allopathic and CAM therapies
ts.aspx -A; http://www.dinnervine.com/2012/01/turmeric-and- Curcuma longa persists as an essential part of Ayurveda and
tinctures-and-rhizomes-oh-my/ -B; http://www.masterfoods.com. Chinese Medicine today. Auyrvedic medicine remains one of
au/products/productdetail/tabid/83/productid/1574/turmeric-
the oldest medical systems worldwide. Ayurveda is
ground.aspx -C)
comprised in the subcategory of CAM: whole medical system
(NCCAM, 2005). This category includes practices that have
with bleeding disorders or a record of ulcers should avoid the evolved over time. Ayurvedic therapies consist of herbs,
use of turmeric (Society, 2008). massages, and specialized diets (NCCAM, 2005). Studies have
exhibited that practice involves using herbal therapies which
A study conducted in humans indicated that curcumin has the include curcuminoids. This is believed to aid in cardiovascular
ability to make changes in the metabolism of oxalate. diseases. In addition, botanicals such as ginger, turmeric, and
According to the results, the researchers cautioned individuals boswellia are used in NCCAM as a treatment for inflammatory
in using curcumin with conditions which can lead to kidney illnesses such as arthritis and asthma (NCCAM, 2005)
stones. In addition, people taking blood thinners should avoid Turmeric is also used to cure dental related issues
the use of turmeric as a spice because it can cause detrimental (Chaturvedi, 2009). The process for treatment can include
herbal drug interactions (Society, 2008). rinsing the mouth with turmeric water for relief, massaging
In various in vivo studies, it was found that turmeric can the paining tooth with ground turmeric to eliminate any
reduce the effectiveness of many anti-cancer drugs (Society, swelling, employing turmeric powder with weed seeds to
2008). This is due to the antioxidant supplements which can clean the gums, and applying turmeric paste (½ teaspoon salt,
intervene with the efficacy of cancer treatments such as ½ teaspoon mustard oil) to prevent gingivitis and
radiation therapy and chemotherapy. It is often advised that periodontitis (Chaturvedi, 2009).
people should not solely depend on turmeric to cure cancer as Currently, there are not any drugs derived from this plant.
overuse of the plant can have side effects (Society, 2008). However, the roots of turmeric are on the approved list of
Form of turmeric applied Dose recommendation for frequently combined with the products of turmeric as it has
adults the ability to enhance the anti-inflammatory effects of
Cut root 1.5-3 g per day curcumin ("Turmeric ", 2011). The supplements of turmeric
have not been studied extensively in children; therefore there
Dried, powdered root 1-3 g per day
are no known recommended doses for children. However,
Standardized powder 400-600 mg, 3 times per day there are suggestions of doses for adults (Table 2). Several
(curcumin) sellers who market supplements of turmeric today argue that
Fluid extract (1:1) 30-90 drops per day their products comprise of 95 percent curcumin compounds
(Figure 8) (Society, 2008).
Tincture (1:2) 15-30 drops, 4 times per day
Table 2. The amount of dose recommended for adults

Discussion
according to the form of turmeric used.
(Source: http://www.umm.edu/altmed/articles/turmeric- The extensive use of Curcuma longa throughout history in
000277.htm) Ayurvedic and Traditional Chinese Medicine is truly
remarkable. Its wide array of uses as a spice, herb, medicine,
dye, and various other applications enable the plant to cure
and prevent numerous ailments. Moreover, the use of C. longa
as a spice to give authentic foods its flavor and color remains
an essential component of culinary practices today. Turmeric
is beneficial for patients suffering from liver disorders, heart
disease, diabetes, inflammations, osteoarthritis, and many
other illnesses. Currently, turmeric is being studied to prevent
aging, Alzheimer’s disease, and most essentially cancer. There
are numerous studies examining the ability of curcumin, the
main compound in C. longa, in the treatment of cancer by
Figure 8. Turmeric supplement marketed as containing inhibiting the proliferation of tumor cells. Despite widespread
ninety five percent curcumin. (Image Source: research on the possible medicinal applications of turmeric,
http://www.turmeric-curcumin.com/) there have not been any studies examining drug development
herbs which are accessible as a spice in local grocery shops of the plant. Today, curcumin is accessible in its pure form
(Society, 2008). The average turmeric consumed commonly by comprising of various biological activities. In the future, this
Asians ranges from .5-1.5 g/day/person producing no toxic could enable researchers to develop new drugs from curcumin
symptoms or side effects (Ishita Chattopadhyay, 2004). C. by observing the pharmacological effects and mechanism of
longa is available in the form of a capsule, tincture, and ground action of the compound. Curcumin may be employed as a
powder (Figure 7). Extracts of pineapple called bromalein are
novel drug in the coming decades, which could prevent and http://database.prota.org/PROTAhtml/Curcuma%20longa_
treat a wide range of illnesses. En.htm
Jasmine H Shaffrathul, P. S. K., Reena Rai, CR Srinivas. (2007).
Turmeric: Role in hypertrichosis and acne Indian Journal of
References Dermatology, 52(2), 116.
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Curcumin: The Indian Solid Gold Healing Curcuminoids. New York City: NutriScience
The Molecular Targets and Therapeutic Uses of Curcumin in Health Publishers.
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(Eds.), (Vol. 595, pp. 1-75): Springer US. http://nccam.nih.gov/health/ayurveda/introduction.htm
Aggarwal, B. B., Sundaram, C., Malani, N., & Ichikawa, H. (2007b). NCCAM. (2007, July 2010). Turmeric, 2012, from
CURCUMIN: THE INDIAN SOLID GOLD http://nccam.nih.gov/health/turmeric/ataglance.htm
The Molecular Targets and Therapeutic Uses of Curcumin in Health P.N. Ravindran, K. N. B., K.Silvaram (2007). Turmeric: The Genus
and Disease. In B. B. Aggarwal, Y.-J. Surh & S. Shishodia Curcuma Taylor and Francis Group
(Eds.), (Vol. 595, pp. 1-75): Springer US. Pandeya, N. K. (2005). Old Wives' Tales: Modern Miracles-Turmeric
Anushree Kumar, B. A., Alok Bharti. (2003). Anticancer Potential of as Traditional Medicine in India. Trees For Life Journal, 1(3).
Curcumin: Preclinical and Clinical Studies. Anticancer Pari L, T. D., Eckel J. (2008). Role of Curcumin in Health and Disease.
Research 23, 263-398. Archives of physiology and biochemistry, 114(2), 127-149.
Appleton, J. (2011). Tumeric and Frankincense in Inflammation: An R.A. Sharma, A. J. G., W.P. Steward. (2005). Curcumin: The story so
Update. Natural Medicine Journal far European Journal of Cancer (41).
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Chaturvedi, T. (2009). Use of Turmeric in Dentistry: An Update cts/ComplementaryandAlternativeMedicine/HerbsVitamins
Indian Journal of Dental Research 20(1), 107-109. andMinerals/turmeric
Duke, J. (2012). Dr. Duke's Phytochemical and Ethnobotanical . Special Turmeric Extract Benefits Osteoarthritis Patients. (2010),
Databases. Chemicals in: Curcuma longa L.(Zingiberaceae), 2012, from
2012, from http://www.ars-grin.gov/cgi- http://cms.herbalgram.org/press/2010/TurmericBenefitsO
bin/duke/farmacy2.pl steoarthritis.html
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and Medicinal Applications. Current Science, 87(1). 000277.htm
Jansen, P. C. M. (2005). Curcuma longa L. PROTA Retrieved February
25, 2012
Digitalis purpurea L., Plantaginaceae
Ian McCullough
Introduction
Commonly referred to as purple foxglove, Digitalis purpurea is
a flowering plant in the Plantaginaceae family (USDA, 2012).
D. purpurea is native to North Africa, Europe, as well as central
and western Asia (Lin, Yang, Phua, Deng, & Lu, 2010). It was
first mentioned in a Welsh Pharmacopeia published in the
early 12th century AD, and was described as having blossoms
which resembled a glove by Fuchsius in his ‘De Historia
Stirpium Commentarii Insignes,’ published in 1542 (Rietbrock
& Woodcock, 1985; Withering, 1785). Although D. purpurea
A)
has been used medically for over 700 years, the medicinal
properties of D. purpurea were categorized by Withering in
1785 as a treatment for dropsy, which is now referred to as
cardiac insufficiency or congestive heart failure resulting in
edema (Whitfield, 1985; Withering, 1785). The medicinal
value of D. purpurea results from high concentrations of
potent cardiac glycosides it contains (Norn & Kruse, 2004).
Two of these cardiac glycosides, digoxin, and digitoxin, have
since become the most potent inotropic agents yet identified,
as well as some of the most wildly prescribed inotropic agents
in the world (Rietbrock & Woodcock, 1985).
B)
Figure 1. Habitat of Digitalis purpurea in western Europe
Botanical Description (A), and North America (B).
Source A:
Digitalis purpurea, also known as common foxglove or purple http://pbio209.pbworks.com/w/page/11342445/Snyder,%20K%20-
foxglove, is a flowering plant that is native to North Africa, %20Digitalis%20purpurea
Europe, as well as Asia (Lin et al., 2010). However, purple Source B:
foxglove was extensively imported to North America following http://plants.usda.gov/java/profile?symbol=DIPU&photoID=dipu_008_ah
the publication of Withering’s book in the late 1700’s, and it is p.tif
Withering describes purple foxglove (Figure 2) as a biennial
common to dry gravely soil and flowering from late spring to
early summer (Withering, 1785). It is a herbaceous plant with
dark green foliage as well as a conspicuous purple flowers
from which D. purpurea originally derived its name (USDA,
2012; Withering, 1785). The scientific name Digitalis purpurea
directly translated to ‘purple fingers’ and was given to purple
foxglove by Leonard Fuchs in 1542 (Rietbrock & Woodcock,
1985). These purple flowers grow in elongated clusters
around the stem of D. purpurea and resemble fingers of a
glove (Rietbrock & Woodcock, 1985). The plant tends to be
between one and two meters tall at maturity and produces
only foliage during its first growing season then typically
flowers, produces seed, and dies in the subsequent growing
season (Rietbrock & Woodcock, 1985; USDA, 2012; Withering,
1785).
Nearly all of the bioactive constituents derived from D.
purpurea can be classified as cardiac glycosides (Doherty,
1973; Doherty & Kane, 1975). Although quantities of these
glycosides can vary depending on growing conditions, the
concentration typically found in as few as one or two leaves is
nearly always toxic and potentially even lethal (Ramlakhan &
Fletcher, 2007). That said, its bitter taste is generally sufficient
to deter ingestion by herbivores (Rietbrock & Woodcock,
1985).
Figure 2. Digitalis purpurea (Purple foxglove). Traditional Uses

Source:
http://plants.usda.gov/java/largeImage?imageID=dipu_007_avp.tif Historical accounts indicate that Digitalis purpurea has been
used medically for over 700 years as part of traditional
English folk medicine for treating dropsy, and written records
now commonly found in the wild (Figure 1) throughout much of D. purpurea being prescribed medically date to as early as
of New England, the Mid-Atlantic States, the Pacific Northwest, 1250 AD by Welsh physicians (Norn & Kruse, 2004). However,
as well as Canada (Rietbrock & Woodcock, 1985; USDA, 2012). its medicinal use was inconsistent until the late 18th century
(Norn & Kruse, 2004). An English physician named William Chemistry & Pharmacology
Withering became interested in D. purpurea in 1775 when he
The active components found in Digitalis purpurea include a
observed a patients recovery from dropsy, now referred to as
number of cardiac glycosides, however, it is most widely
congestive heart failure, following her consumption of herbal
known for containing the cardiac glycoside digitoxin
tea for several months (Rietbrock & Woodcock, 1985;
(Rietbrock & Woodcock, 1985; Walter Lewis, 2003). The
Withering, 1785). Withering identified the active ingredient of
direct inotropic effects of the cardiac glycosides found in D.
this herbal tea as D. purpurea, and began conducting research
purpurea result from their inhibition of the activity of the
into its effectiveness (Breckenridge, 2006). By 1785 he had
sodium/potassium ATPase, also known as the sodium
treated 163 patients suffering from dropsy with D. purpurea
potassium exchanger, in the myocardium (Eric J. Eichhorn &
and published his findings in ‘An Account of the Foxglove and
Mihai Gheorghiade, 2002). The predominant method of
Some of its Medical Uses’ (Whitfield, 1985). Withering drew
expelling calcium from myocardial cell between contractions
upon the treatment outcomes of his own patients to
is the action of the membrane bound sodium potassium
objectively demonstrate the efficacy of using D. purpurea in
antiporter protein (Khatter, Agbanyo, Navaratnam, Nero, &
treating dropsy, the edematous bodily swelling that typically
Hoeschen, 1989). This protein uses the energy produced from
accompanied heart failure (Withering, 1785). Withering, as
moving sodium ions down their concentration gradient into
well as medical practitioners in subsequent decades employed
the cell from the extracellular environment to pump calcium
D. purpurea therapeutically by boiling its leaves into a herbal
ions out of the cell against their concentration gradient
tea (Rietbrock & Woodcock, 1985). This process of boiling
(Khatter et al., 1989). By inhibiting the active transport of
served to extract some of the more water soluble cardiac
sodium ions out of the cell, D. purpurea derived cardiac
glycosides into the aqueous solution, including gitaloxin,
glycosides bring the intracellular and extracellular sodium
which will be discussed later (Rietbrock & Woodcock, 1985).
concentrations closer to equilibrium (Khatter et al., 1989).
Purple foxglove was widely cultivated throughout England Because the sodium/calcium antiporter is powered by the
and subsequently in North America following its introduction movement of sodium down its concentration gradient into the
in the late 1700’s (Rietbrock & Woodcock, 1985; USDA, 2012). cell, the reduction the sodium gradient decreases the activity
Prior to identification of its medicinal properties Digitalis of the sodium/calcium antiporter and results in increased
purpurea was predominantly grown for its ornamental levels of intracellular calcium ions (Eric J. Eichhorn & Mihai
flowers (Foster, 2000). D. purpurea proliferated widely in the Gheorghiade, 2002). Increasing the concentration of
United States following the discovery of its therapeutic intracellular calcium ions directly results in more interaction
properties. However, now that homemade D. purpurea between the actin and myosin contractile proteins within the
preparations are no longer commonly made for the treatment cells of the myocardium (Hauptman & Kelly, 1999). The
of congestive heart failure D. purpurea is once again cultivated increase in interaction between actin and myosin contractile
for its aesthetically pleasing flowers (Foster, 2000). proteins increase the contractile force generated by each
cardiac myocyte (Doherty, 1973) . The increase in contractility
results in a stronger heart beat as well as an increased ejection
Figure 3. Mechanism of action of cardiac glycosides. Source http://e-learning.perubatan.org/index.php?topic=738.0
fraction (Eric J. Eichhorn & Mihai Gheorghiade, 2002). D. foxglove leaf preparations were efficacious in small, non-toxic
purpurea derived cardiac glycosides also exert an effect on the doses and that their action varied according to the plant’s
cardiac conduction system via inhibition of the sodium stage of bloom (Rietbrock & Woodcock, 1985; Withering,
potassium exchanger (Doherty & Kane, 1975), Figure 3. 1785).
Multiple factors can and do influence the concentration of
cardiac glycosides present in D. purpurea preparations such as Major D. purpurea derived cardiac glycosides
the time of the year when the leaves are gathered, the climate
and the soil conditions where the plant is cultivated (Goldman, Of the 38 cardiac glycosides found in D. purpurea, the two
2001; Rietbrock & Woodcock, 1985). Withering noted that which have, or are currently used therapeutically are
Figure 4. Chemical structure of Digitoxin Figure 6. Chemical Structure of Digoxin
Source: http://www.soci.org/News/Hort-newsletter-jun-10 Source http://www.soci.org/News/Hort-newsletter-jun-10
traditional foxglove teas were made by boiling D. purpurea

leaves in water, it is highly likely that gitaloxin was the cardiac
glycoside responsible for the diuretic effects observed by
Withering and other traditional practitioners of foxglove
therapy (Rietbrock & Woodcock, 1985). The most commonly
used cardiac glycosides employed pharmacologically today
are digoxin (Figure 6) and digitoxin (Beermann, 1974;
Doherty, 1973).
Dosing considerations
The cardiac glycosides derived from Digitalis purpurea have a
relatively narrow therapeutic window with therapeutic
Figure 5. Chemical structure of Gitaloxin dosages which can be as high as seventy percent of the dose
Source: required for toxicity (Walter Lewis, 2003). Moreover, the
http://www.chemicalbook.com/ProductChemicalPropertiesCB687 therapeutic dose varies widely from patient to patient.
7110_EN.htm Withering, like physicians today, had to tailor the dose of D.
purpurea preparations specifically for each patient
digitoxin (Figure 4), and gitaloxin (Figure 5) (Rietbrock & individually as a dose which would be sub therapeutic on one
Woodcock, 1985). Gitaloxin is the only cardiac glycoside that patient may result in toxicity in another patient (Doherty,
can be collected from the leaves of D. purpurea in appreciable 1973; Doherty & Kane, 1975).
quantities by boiling (Rietbrock & Woodcock, 1985). Since
Causes, presentation, & management of overdose Fletcher, 2007). If untreated, cardiac glycoside toxicity may
The majority of cases involving D. purpurea toxicity result result in death from ventricular fibrillation (Doherty, 1973;
from an unintentional overdose on pharmacological agents Walter Lewis, 2003).
derived from the plant (Antman, Wenger, Butler, Haber, & The three primary objectives when treating a patient suffering
Smith, 1990). However, cases of toxicity resulting from from D. purpurea toxicity are supporting the heart and
intentional overdoses as well as from unintentional exposures preventing the occurrence of arrhythmias, preventing further
to the plant occur occasionally as well (Church, Schamroth, absorption of cardiac glycosides from the gastrointestinal
Schwartz, & Marriott, 1962). Accidental toxicity can result tract, and reducing the concentration of serum glycosides as
from ingestion of water with D. purpurea growing in it or rapidly as possible (Antman et al., 1990). Various medications
nearby (Ramlakhan & Fletcher, 2007). Toxicity may also result are used to protect the heart from arrhythmias. Atropine can
from inhalation of smoke produced by burning D. purpurea be administered to counter the increased parasympathetic
(Ramlakhan & Fletcher, 2007). Toxicity resulting from tone caused by the D. purpurea derived glycosides, short
accidental ingestion by wild food gatherers who mistake D. acting beta blockers may be administered to suppress
purpurea for comfrey is one of the most common causes for tachycardias, and lidocaine may be administer in the case of
toxicity not related to allopathic treatment with cardiac persistent ventricular ectopy (Khatter et al., 1989; Ramlakhan
glycosides (Lin et al., 2010; Ramlakhan & Fletcher, 2007). & Fletcher, 2007). Synchronized cardioversion is indicated in
Symptoms of overdose from cardiac glycosides will vary from cases of symptomatic tachycardias which are unresponsive to
patient to patient, however, the most common indicators of pharmacological interventions (Bourel & Gouffault, 1962;
toxicity include fatigue, anorexia, nausea, loss of visual acuity, Ramlakhan & Fletcher, 2007). Symptomatic bradycardias
as well as cardiac rhythm abnormalities which can be either should be electrically paced if they are unresponsive to
tachycardic or bradycardic in nature (Doherty & Kane, 1975; pharmacological interventions (Ramlakhan & Fletcher, 2007).
Fisch & Knoebel, 1985; Ramlakhan & Fletcher, 2007). Activated charcoal is commonly administered orally to
Symptomatic bradycardias induced by D. purpurea typically prevent further absorption of glycosides from the
result from decreased conduction through the gastrointestinal tract (Rodensky & Wasserman, 1962). Most
Atrioventricular node, and symptomatic tachycardias result importantly, the concentration of circulating cardiac
from spontaneous depolarization of autorhythmic cells glycosides should be rapidly reduced via intravenous
located in the ventricles (Fisch, 1962; Rodensky & administration of anti-digoxin antibodies (Antman et al.,
Wasserman, 1962). First and second degree Atrioventricular 1990). Antibodies to digoxin were first created in 1967, but
blocks, as well as junctional rhythms also occur frequently were only later employed as standard therapy for digoxin
following D. purpurea toxicity (Doherty & Kane, 1975; Fisch, toxicity (Doherty, 1973; Ramlakhan & Fletcher, 2007). These
1962). However, the most reliable indicator of D. purpurea antibodies to digoxin are currently marketed under the brand
toxicity observed on an electrocardiogram prior to such name Digibind and have also been effective in cases of
symptomatic arrhythmias is depression of the ST segment digitoxin toxicity, although to lesser extent (Antman et al.,
with a concave upward slope (Figure 7) (Ramlakhan & 1990; Ramlakhan & Fletcher, 2007).
Figure 7. Electrocardiogram displaying the effects of D. purpurea toxicity. (a) depicts a normal ECG. Note the concave
upwardly sloping ST segment depression in (b). Source (Ramlakhan & Fletcher, 2007)
Biological Activity which results in decreased heart rate which allows more time
Withering and others describe the diuretic effect of Digitalis for the ventricles to fill between each beet (Eric J. Eichhorn &
Mihai Gheorghiade, 2002). Finally, the third direct effect of D.
purpurea extracts; however, this effect is the indirect result of
purpurea derived glycosides is a slowing of the electrical
three direct effects of the cardiac glycosides found in D.
impulses through the cardiac conduction system (Krantz &
purpurea on the heart (Beermann, 1974; Doherty, 1973;
Ling, 1960). Such effects on the cardiac conduction system are
Doherty & Kane, 1975). The first of these three direct effects is
confined to the atria, notably decreasing spontaneous
an increase in myocardial contractility (Doherty & Kane,
depolarization in the Sinoatrial node and intermodal tracts,
1975). The second is an increase in parasympathetic tone
and slowing conduction through the Atrioventricular node
(Eric J. Eichhorn & Mihai Gheorghiade, 2002; Ramlakhan & effect of digoxin verses alternative medicinal therapies for
Fletcher, 2007). Together these three effects increase congestive heart failure. Over several months D. purpurea
contractility as well as decreased heart rate is in an increase in derived cardiac glycosides were shown to reduce
ejection fraction which increases the volume of blood pumped hospitalization for congestive heart failure by twenty five
from the heart with each contraction (Doherty & Kane, 1975; percent (Gheorghiade & Pitt, 1997). Moreover, D. purpurea
Soffer, 1962). This increase in ejection fraction results in derived cardiac glycosides is the only currently marketed oral
increased systemic perfusion. Specifically, renal perfusion is inotropic agents which do not result in increased mortality
increased which enhancing the production and excretion of when administered to patients suffering from congestive heart
urine thereby eliminating excess fluid form the body (Doherty failure (Eric J. Eichhorn & Mihai Gheorghiade, 2002).
& Kane, 1975; Rietbrock & Woodcock, 1985).
Lastly, studies have indicated that concurrent use of
aldosterone antagonists with the D. purpurea derived cardiac
Clinical Studies glycoside digitoxin may reduce the occurrence of toxicity
associated with their use (Eric J. Eichhorn & Mihai
Empirical evidence for the clinical effectiveness of Digitalis Gheorghiade, 2002). Aldosterone is a compound secreted by
purpurea dates to the time of Withering, formal clinical trials the adrenal cortex in response to activation of the rennin-
of various D. purpurea preparations began at least as early as angiotensin-aldosterone-cascade which is not only up
1915 (Simson, 1962). Since then numerous studies of D. regulated in response to hypotension, but also in response to
purpurea have demonstrated the positive inotropic effect of its administration of digoxin (Eric J. Eichhorn & Mihai
cardiac glycosides on the myocardium (Cattell & Goodell, Gheorghiade, 2002). Because aldosterone has been observed
1937). These studies have been conducted in animals such as to alter serum concentrations of potassium and potentially
frogs, cats and dogs to determine the mechanisms of action for result in arrhythmias and potentiate the effects of digoxin
the various cardiac glycosides extracted from D. purpurea (van toxicity, concurrently blocking the secretion aldosterone may
Dyke & Li, 1935). Moreover, these animals were also to increase the safety of D. purpurea based glycosides used for
develop standardized concentrations for administration of the management of congestive heart failure (Eric J. Eichhorn &
digoxin and digitoxin which are two more recently identified Mihai Gheorghiade, 2002).
cardiac glycosides (Doherty, 1973; van Dyke & Li, 1935)
Following the development of agreed upon standard for
dosing were developed in the early to mid 1900’s, studies into Contraindications
the effectiveness of the various glycosides were conducted The two most commonly prescribe cardiac glycosides derived
(van Dyke & Li, 1935). In a 300 patient multicenter trial from Digitalis purpurea are digoxin and digitoxin. Digoxin is
digoxin reduced hospitalization for congestive heart failure as excreted from the body via the kidneys and extreme care
well as increasing left ventricular ejection fraction (Eric J. should be taken when administering the drug to patients in
Eichhorn & Mihai Gheorghiade, 2002). The Digitalis renal failure their lack of renal clearance can result in the
Investigation Group (DIG) trial was another example of the increase of serum cardiac glycoside concentration to toxic
levels (Hauptman & Kelly, 1999). However, digitoxin clearance commonly referred to as comfrey (Lin et al., 2010). Leaves of
is independent of renal function and is widely considered the S. offcinale resemble those of D. purpurea, and during times of
safer of the two cardiac glycosides for administration to the year when D. purpurea lacks its distinctive purple flowers
patients suffering from renal failure (Genazzani, 1977). misidentification of the two plants becomes possible (Lin et
There are no medications which are completely incompatible al., 2010).
with cardiac glycosides derived from Digitalis purpurea;
however, diuretics which act by altering serum electrolyte
Discussion
concentrations, specifically potassium concentrations, such as
furosemide, should be administered with care, as such The cardiac glycosides found within purple foxglove both
medications can significantly increase the likelihood of increase contractility and reduces heart rate (Michael
developing arrhythmias (Ramirez-Ortega et al., 2007). Heinrich, 2004). This increase in inotropy and reduction in
chronotropy result in a slower but stronger heart beat and can
increase cardiac output by as much as thirty percent (Walter
Current Use in Allopathic and CAM Therapies Lewis, 2003).
The most widely prescribed Digitalis purpurea extract As in the time of Withering, therapeutic administration of
prescribed today is digoxin however, digitoxin is also modern cardiac glycosides is often problematic for three
occasionally prescribed as both are cardiac glycosides isolated reasons. First, its therapeutic window is very narrow, with the
in the early 1900’s and both have relatively similar effects on dosage required to achieve a physiological effect often
the body (Rietbrock & Woodcock, 1985; Walter Lewis, 2003). approaching seventy percent of the dose necessary to produce
These cardiac glycosides have become the most widely toxicity (Breckenridge, 2006). In addition to this narrow
proscribed inotropic agents in the United States (Doherty, therapeutic window, cardiac glycosides extracted from D.
1973). In fact, the D. purpurea derived cardiac glycosides are purpurea have relatively long half-lives, 36 to 48 hours in the
employed so widely in modern medicine that the term case of digoxin, and approximately 10 days in the case of
‘digitalis’ is commonly used in place of ‘cardiac glycosides’ digitoxin (Doherty, de Soyza, Kane, Bissett, & Murphy, 1978).
(Hauptman & Kelly, 1999). Repetitive dosing over time can, and often does progressively
No herbal supplements derived from D. purpurea are increase serum cardiac glycoside concentration eventually
currently marketed however; it may still be grown and used resulting in toxicity (E. J. Eichhorn & M. Gheorghiade, 2002;
by some practitioner’s in England for the treatment of Pruitt, 1962). Finally, therapeutic doses of D. purpurea
congestive heart failure (Rietbrock & Woodcock, 1985). It is extracts vary widely from patient to patient (Pruitt, 1962). For
worth noting that correct identification of plant species is example, the dosage required to achieve a therapeutic effect in
essential for practitioners of CAM. As previously mentioned, one patient may be significantly greater than the dosage
several instances of severe toxicity have resulted from the required for toxicity in another (Breckenridge, 2006; Pruitt,
misidentification of D. purpurea as Symphytum offcinale, 1962). In fact, even the plasma concentrations of digoxin
required to achieve a therapeutic effect can vary widely
between individuals (Breckenridge, 2006; Ramlakhan & Beermann, B. (1974). Pharmacokinetics of digitalis glycosides.
Fletcher, 2007). Drugs, 7(6), 482-485.
Interestingly, approximately twenty percent of patients Bourel, M., & Gouffault, J. (1962). [On digitalis intoxication]. Sem Hop
receiving D. purpurea derived cardiac glycoside therapy today Ther Paris, 38, 415-416.
report experiencing adverse side effects, whereas the Breckenridge, A. (2006). William Withering's legacy--for the good of
therapeutic success rate observed by Withering in the late the patient. [Biography Historical Article Lectures]. Clin Med,
1700’s was slightly higher, with only eighteen percent of his 6(4), 393-397.
patients reporting side effects (Rietbrock & Woodcock, 1985) Cattell, M., & Goodell, H. (1937). On the Mechanism of the Action of
Moreover, Withering achieved this success rate while Digitalis Glucosides on Muscle. Science, 86(2222), 106-107.
administering these glycosides in the form of teas brewed doi: 10.1126/science.86.2222.106
from foxglove, as opposed to modern practitioners who Church, G., Schamroth, L., Schwartz, N. L., & Marriott, H. J. (1962).
administer digoxin or digitoxin which are highly standardized Deliberate digitalis intoxication. A comparison of the toxic
and regulated D. purpurea derived cardiac glycoside, effects of four glycoside preparations. Ann Intern Med, 57,
suggesting that herbal treatment administered by early 946-956.
practitioners such as Withering was no less successful, and no
Doherty, J. E. (1973). Digitalis glycosides. Pharmacokinetics and
more likely to result in toxicity than modern synthetically their clinical implications. [Review]. Ann Intern Med, 79(2),
derived D. purpurea therapy (Rietbrock & Woodcock, 1985). 229-238.
Despite the potential for toxicity, D. purpurea derived cardiac Doherty, J. E., de Soyza, N., Kane, J. J., Bissett, J. K., & Murphy, M. L.
glycosides have been a fixture in the treatment of congestive (1978). Clinical pharmacokinetics of digitalis glycosides.
heart failure for over two centuries (Rietbrock & Woodcock, [Review]. Prog Cardiovasc Dis, 21(2), 141-158.
1985). The use of D. purpurea derived cardiac glycosides will Doherty, J. E., & Kane, J. J. (1975). Clinical pharmacology of digitalis
likely continue long into the future as they are the most potent glycosides. [Research Support, U.S. Gov't, P.H.S. Review].
inotropic agents yet identified and no suitable replacements Annu Rev Med, 26, 159-171. doi:
have been identified (Rietbrock & Woodcock, 1985; Rodensky 10.1146/annurev.me.26.020175.001111
& Wasserman, 1962; Simson, 1962).
Eichhorn, E. J., & Gheorghiade, M. (2002). Digoxin. Progress in
Cardiovascular Diseases, 44(4), 251-266. doi:
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Diospyros virginiana L., Ebenaceae
Ruby M. Lam
Introduction
Diospyros virginiana is a dicotyledon from the Ebenaceae
family (Ebony). It may also appear as Diospyros mosieri S.F.
Blake. In GRIN Taxonomy (Germplasm Resources Information
Network from the USDA). D. virginiana has many common
names including American Persimmon , Common Persimmon,
Eastern Persimmon, Simmon, Possumwood, Sugar-plum, Date
Plum, White Ebony, and Florida Persimmon. The genus name,
Diospyros, is derived from the Greek words διός (Δios)
meaning “god” and pyros (πυρος ) meaning “wheat” or “grain”;
which both allude to the life-giving properties of the edible
fruit (Department of Agriculture, 1949). The origin of the
name Persimmon is from the Algonquian tribes (Northern
First Nations people) words for dried fruit—putchamin,
pasiminan, or pessamin, which roughly translates to “choke
fruit” (Curtis, Bausor, & Curtis, 1943). D. virginiana grows
primarily in Southeastern United States but can be found as
far north as Massachusetts and as far west as
Oklahoma(Sargent, Faxon, & Gill, 1933). It was a very
important source of food in the winter for the first settlers of Figure1. A map showing the distribution of D. virginiana
Jamestown and confederate soldiers during the American Civil in 2010. Note that distribution in California and Utah are
War. Besides providing consumable fruit, the plant also reflections of agricultural cultivations and not found in the
provides wood used for carving and bark used for color dying. wilderness. Source:
The First Nation’s people utilized its astringent properties for http://plants.usda.gov/java/profile?symbol=DIVI5
various medical ailments including thrush, diarrhea,
gonorrhea, dropsy, dysentery, and bacterial infections minor fruit because its cousin the Japanese persimmon (D.
(Briand, 2005).The bark , unripe and ripe fruit contain lignin, kaki) cousin is cultivated, larger, and imported as an exotic
tannic acid, sugar, malic acid and pectin(Jiaofen, 2005). In the fruit. Few Americans even know that that there are species of
United States today, D. virginiana is often considered as just a persimmon native to the Americas and consequently don’t
Figure 3. Close up of the square scale-like bark in the
trunk of the D. virginiana tree. Source:
http://forestry.sfasu.edu/faculty/jstovall/dendro/index.php/fact-
sheets/photographs/82-diospyros-virginiana-common-persimmon
Diospyros virginiana L. is one of two native North American
Persimmon species and averages about 52-65 feet tall (16-20
Figure 2. Mature D. virginiana tree. Source: meters). It grows predominantly in the Southeastern region
http://plants.usda.gov/java/profile?symbol=DIVI5&photoID=divi5_ of the United States (Figure 1) in light, sandy, well-drained
016_avp.tif soil and sometimes the deep, rich, bottomlands of river
valleys. It is a deciduous woody perennial that is widely
give the same attention to it as all the other “All American” scattered and often covered with shrubby growth in
foods such as the pumpkin, cornbread and turkey borrowed abandoned fields and on the side of roads (Sargent et al.,
from the First Nations People (Native Americans). The 1933). D.virginiana is a hardwood tree with a short, narrow
American Persimmon’s low profile existence may have caused trunk about 2-3 inches in diameter and grows to about tall
many of us to overlook its cultural significance. with broadly spreading branches (Figure 2). It has a small,
Figure 5: Unripe Fruit of Diospyros virginiana in the fall.
Source: http://davesgarden.com/guides/pf/showimage/34301/
order to bear fruit. Only female trees with solitary, flowers

consisting of small stamens, smooth ovaries with eight
mounted on four hair styles will become fruits(Curtis et al.,
1943).The flowers are white and bloom in the spring; female
trees produce yellow–green fruits in the fall (Figure 5);which
ripens into an uneven dirty orange early in the spring after
Figure 4. A close up of the glossy, dark green color ,ovate- periods of frost (Figure 6). The unripe fruit is extremely
oblong leaves which are rounded at the base and astringent because of the high tannic acid content. As the fruit
arranged in an alternative fashion along the branch. ripens, tannin levels decreases dramatically and the fruit
Source: softens, becoming increasingly sweeter. The inner bark is also
http://forestry.sfasu.edu/faculty/jstovall/dendro/index.php/fact- astringent and bitter (Zim, Martin, Barlowe, & Barlowe, 1956).
sheets/photographs/82-diospyros-virginiana-common-persimmon There are several variations in the species that is not officially
recognized by the USDA NRCS (United States Department of
dark, brown/black core and pale white wood with thick, dark, Agriculture Natural Resources Conservation Service). These
brown-gray square scale-like bark (Department of categorizations are based on the different phenotypical
Agriculture, 1949) (Figure 3). The roots are thick, fleshy and expressions and include D. pubescens (Pursh) Dipp., D.
is taproot in structure, reaching vertically downwards with platycarpa Sarg,D. mosieri(Small) Sarg and called Fuzzy
smaller lateral roots (Sargent et al., 1933). They have ovate- Persimmon, Oklahoma Persimmon and Florida Persimmon
oblong to oval leaves that are rounded at the base and have a respectively by pomologists (Fernald, 1950; Little Jr, 1983;
glossy, dark green color which are arranged in an alternative Vines, 1960)
fashion along the branches (Figure 4). D. virginiana is a
dioecious species and therefore requires cross-pollination in
Use: The main use of D. virginiana was sustenance. Native
Americans incorporated it into bread, gruel, soup, stews,
cornbread and pudding and preserved whole fruits by sun
drying on the trees. The harvesting was usually in the late fall
in preparation for the winter months. They also used dried
seeds to brew beers and the leaves to brew teas.(Briand,
2005)
Medicine: Persimmon was made into poultices to treat burns
given that the astringency tightens tissue, preventing burns
from oozing liquids. Traditional American herbalists also use
it to treat gastrointestinal bleeding. For the treatment of the
fungal infection, thrush or “Oo-hah-lah-go-huh-skee”,
Cherokee Physicians made a mouth rinse from the inner bark
and ashes, which were boiled and sweetened with
honey(Chevallier, Compton, & Herrick, 2004; Foreman &
Mahoney, 1975).
Figure 6: Ripe fruit and seeds in winter or early spring.
Source:
http://www.missouriplants.com/Whitealt/Diospyros_virginiana_pa
Western/ Current
ge.html
History: The earliest reports of the Persimmon were in the 16-
17th centuries by English and French explorers in the New
Traditional Uses
World, who thought it looked like the medlar (Mespilus
First Nations people (Native American) germanicus, Rosaceae)(Gravier, 1701). The first written
Folklore: In Native American folklore, the raccoon was a man description was made in A Brief and True Report of the New
who was told by the Great Spirit to go on a spiritual journey of Found Land of Virginia by Roanoke colonist Thomas Harriot
the mind. He was not to stop to eat or drink until the task was and John White in 1588. One of the first records of Persimmon
completed. Unfortunately he was not ready for such a journey consumption was made by Captain John Smith who aided in
and indulged on the fruits of persimmon trees in a grove along the settlement of Jamestown in Virginia in 1612. He wrote, "If
the way. The furious Great Spirit turned him into a raccoon it be not ripe it will drawe a mans mouth arwie with much
which is why the raccoon leaves footprints like a human, uses torment; but when it is ripe, it is as delicious as an Apricock."
his hands like a man, and always knows when the persimmons It was quickly recognized as a vital part of the Native
are ripe (Dorsey, 1905). The persimmon tree and the fruit also American’s survival diets and adapted into the settlers’ diets
appears in many other traditional stories, poems and songs. as well.
Use: During the Civil War, the Union soldiers blocked ports in woodturning projects, screws, mallets and textile shuttles. It is
the gulf, cutting off the Confederate soldiers from their food also popular among bow craftsmen for the creation of
supply. Thus, they relied on Persimmon seeds as a substitute traditional longbows (Chen, 1996; Kalm & Forster, 1972; Lim,
for coffee. The seeds were first boiled to remove the 2012; Shukla & Bhatnagar, 1988).The ashes from burning the
mucilaginous materials, roasted, grounded, and finally boiled wood are also very high in alkali and therefore allowed for
in water with dried sweet potato to create the drink(Dodge, very good extractions of lye, which is needed for soap making
1886). The seeds were also used to make buttons given that (Candler, 1949).
they are extremely strong and would not break when using
the battling stick method to beat the laundry. (Dodge, 1886;
Mathis, 1975; Porcher, 1863) Medicine
The fruit was used to make wine (Mehl-Madrona, 2003), In the 18th century, D. virginiana was widely used as a
brandy (Briand, 2005; Schery, 1954) white wine vinegar medicinal plant. The inner bark, branches, roots and fruits
(Porcher, 1863) and beer (Edgeworth, 1860).The fruit was were all harvested for medicinal use. The bark of the root was
also used to make syrup and molasses by boiling its pulp until noted to have more medicinal value compared to the young
the saccharine material fully dissolves, straining the twigs (Cook, 1869). The ripe persimmon fruit was reported to
coagulations of fruit, and boiling off the juice until the desired be an antiseptic and could be used in the same manner as
viscosity is achieved (Shuster, Vigna, Sinha, & Tontonoz, Jesuit’s bark, Cinchona (Cook, 1869)The fruit and bark were
2011). Colonial settlers used the fruits to thicken and sweeten also used as an astringent for treating external ulcers, uterine
puddings. Persimmons were highly valued because they were hemorrhaging, and various other diseases such as diarrhea,
easily accessible and thus could be turned into puddings dysentery, dropsy, diphtheria, syphilis, and thrush
without additional thickeners or sweeteners (Cutillas‐ (Rafinesque, 1828). To treat diarrhea, a tonic made of the bark
Iturralde, Zarra, & Lorences, 1993; Elias & Dykeman, 2009). of D. virginiana and rhubarb (or unripe persimmon syrup with
Today, the fruit is used to make traditional baked pudding , sugar with lozenges of green persimmon, red oak bark and
which has the consistency of custard and served during blackberry preserve and gumarabic was commonly
holidays like Thanksgiving and Christmas. In the state of consumed(Butel-Dumont, 1753). To treat bacterial infections
Indiana, it is considered to be a legendary local dish (LASS, in the respiratory tract such as diphtheria, a tonic made from
1974). the inner bark of the D. virginiana tree and alum was gargled
to washout the bacteria-infected areas of the throat(King &
The unripe fruit is also used to make ink by mashing the fruits Felter, 1909; Rafinesque, 1828). For the treatment of dropsy,
and boiling it in water over a slow fire with small pieces of the seeds were often infused into the tonic with Digitalis to
coppera(ferrous sulfate/green vitriol).This ink was called negate the side effect of diarrhea. To treat malaria, an infusion
Gordon’s Indelible Ink(Mason, 1871). Because the wood is of the bark was used to subdue the fever (Lindley, 1836;
very strong, hard, heavy, fine-grained, elastic, and resistant to Rafinesque, 1828).A decoction of Persimmon can also be used
wear, Persimmon wood was used to make gun stocks, golf to treat sexually transmitted diseases (STIs) such as
clubs, drum sticks, billiard cues, wooden flutes, eating utensils,
gonorrhea and syphilis. The decoction for gonorrhea was shown to reduce the risk of lung cancer (Holick et al., 2002;
made of sumac root, blackberry, and persimmon bark, boiled Sies & Stahl, 1995) Papain and Bromelaine are protease
in 12 gallons of water until reduced to ½ gallon, and drunk enzymes that are present in the fruits which can help keep the
until discharge symptoms were minimized. The decoction inflammatory response in the body down and speed up
used to treat syphilis was made from white sumac, apple root, healing processes(Maurer, 2001; Nayak, Pereira, & Maharaj,
devils shoestring and persimmon root bark boiled in 4 gallons 2007).
of water and drunken 1/8 pint, 3 times per day (Foreman & The fruit is very high in glucose which is a dietary
Mahoney, 1975) monosaccharide that can be easily digested and absorbed into
A tonic made by boiling persimmon inner bark with ashes and the blood system. Because these carbohydrates provide
infused with honey in “The Cherokee Physician” and “Indian energy for cells to function, the fruit is very important for
Guide to Health” a was improved upon by the western settlers, sustenance. Persimmon fruit is also a very good source of
who added Borax to the concoction to treat the fungal Thrush vitamins A and C, which are important for normal retinal
infections(Foreman & Mahoney, 1975). function and wound-healing and maintaining the integrity of
capillaries respectively. Copper is a co-factor for vital
enzymes like cytochrome c-oxidase which is also required
Chemistry and Pharmacology for the production of red blood cells(Bertinato & L'Abbé,
The main known chemical constituents isolated from D. 2004; Soetan, Olaiya, & Oyewole, 2010). The manganese is a
virginiana are tannins (catechin, gallocatechin, betulinic acid), cofactor for the enzyme superoxide dismutase which acts as a
glucose, proteins, vitamins A and C, calcium, potassium, powerful free radical scavenger (Martin et al., 1986; Van
phosperous, iron, copper, manganese, carotenoids, and dietary Remmen et al., 1999)
fiber. They also contain the enzymes papain and bromelaine
(Table 1). The astringent properties of the unripe fruit are
Biological Activity
often thought to be the result of the high tannin levels in the
flesh. Animal Studies
Secondary metabolites like the flavonoid catechin and The tannins in the Persimmon are carcinogenic and can
gallocatechin consists of benzene rings with many –OH groups produce cancer in otherwise healthy rats. The tannin fractions
which have a anti-oxidative, anti-infective, anti-inflammatory from Diospyros virginiana and Camellia sinensis were very
and anti-hemorrhagic properties(Rice-Evans, Miller, & active and produced tumors at the subcutaneous injection site
Paganga, 1997). Betulinic acid is often correlated with in 66% or more of the treated animals. (Kapadia et al., 1997)
antiretroviral, antimalarial, and anti-inflammatory In addition to the carcinogenic effects in rats, larval
properties(Tzakos et al., 2012). Persimmon also has beta- mosquitoes’ performance ie: survival rate decreased and days
carotene, lycopene, lutein, zea-xanthin and cryptoxanthin, until pupation was increased significantly when treated with
which are also very effective free radical scavengers, have the leaves of the Persimmon plant as opposed to oak, maple or
Chemical Compound Part of ppm = parts per million KAEMPFEROL Plant
plant tr = trace KILOCALORIES Fruit 1,270 - 3,567 /kg
(E)-2-HEXENAL Fruit
LANTHANUM Leaf 1.5 - 15 ppm
ALUMINUM Stem 4 - 378 ppm
Stem 0.7 - 16.2 ppm
ASCORBIC-ACID Fruit 660 - 1,855 ppm
LEAD Leaf 0.5 - 35 ppm
ASH Fruit 9,000 - 25,280 ppm
Stem 0.2 - 81 ppm
Leaf 50,000 ppm
MAGNESIUM Leaf 1,500 - 5,000 ppm
Stem 22,000 - 54,000 ppm
Stem 660 - 5,400 ppm
BARIUM Leaf 1 - 910 ppm
MANGANESE Leaf 25 - 1,500 ppm
DUKE Stem 3 - 1,080 ppm
Stem 22 - 1,080 ppm
BENZOTHIAZOLE Fruit
MOLBDENUM Leaf 1 ppm
BORNEOL Fruit
MOLYBDENUM Stem 1.08 ppm;
BORNYL-ACETATE Fruit
MYRICETIN Plant
BORON Leaf 4 - 50 ppm
NEODYMIUM Leaf 3.5 - 15 ppm
Stem 1 - 38 ppm
Stem 1.5 - 37.8 ppm
CALCIUM Fruit 270 - 758 ppm
NERYL-ACETATE Fruit:
Leaf 1,150 - 12,500 ppm
NICKEL Leaf 0.3 - 16 ppm
Stem 2,640 - 17,820 ppm
Stem 0.1 - 8 ppm
CARBOHYDRATES Fruit 335,000 - 941,000 ppm
PALMITIC-ACID Fruit
CHROMIUM Leaf 1 ppm
PHENYL- Fruit
Stem 2.7 ppm;
ACETALDEHYDE
COBALT Leaf 100 ppm; PHENYLETHYL- Fruit
Stem 54 ppm; ACETATE
COPPER Leaf 1 - 7.5 ppm PHOSPHORUS Fruit 260 - 730 ppm
Stem 0.2 - 108 ppm Leaf 450 - 1,500 ppm
DELPHINIDIN Plant Stem 132 - 2,592 ppm
FAT Fruit 4,000 - 11,230 ppm POTASSIUM Fruit 3,100 - 8,710 ppm
Seed 26,000 ppm; Leaf 7,500 - 16,000 ppm
FIBER Fruit 15,000 - 42,135 ppm Stem 1,716 - 16,200 ppm
GALLIUM Leaf 0.25 ppm; PROTEIN Fruit 8,000 - 22,470 ppm
IRON Fruit 25 - 70 ppm Seed 100,000 ppm
Leaf 15 - 500 ppm QUERCETIN Plant
Stem 3 - 1,620 ppm SODIUM Fruit 10 - 28 ppm
STRONTIUM Leaf 7 - 1,000 ppm USG 1997). In another study, Korean scientists found that
Stem 6.6 - 378 ppm persimmon leaf extracts administered to 180 in vivo sarcoma
TITANIUM Leaf 0.2 - 50 ppm cells was cytotoxic (Park, Moon, & Kim, 1996).
Stem 162 ppm Chemicals such as 7-methyljuglone (5-hydroxy-7-methyl-1,4-
VANADIUM Leaf 0.25 - 1.5 ppm naphthoquinone or diospyrin) (Figure 7) and 8-6’ dimer,
Stem 0.11 - 1.08 ppm Isodiospyrin were isolated from the wood of Diospyros
WATER Fruit 644,000 ppm; virginiana and proved to be an effective termiticide (Carter,
YTTERBIUM Leaf 0.1 - 1 ppm Garlo, & Stanley, 1978). 7-methyljuglone and its synthetic
Stem 0.04 - 0.38 ppm derivatives have also shown antibacterial activity against
YTTRIUM Stem 0.1 - 16.2 ppm Mycobacterium tuberculosis both intracellularly and
ZINC Leaf 5 - 25 ppm extracellularly in cell cultures (Mahapatra et al., 2007). While
Stem 9 - 162 ppm there is a high concentration of 7-methyljuglone isolates, the
ZIRCONIUM Leaf 1 - 3.5 ppm medicinally significant chemical activity was found but not
Stem 0.4 - 1.6 ppm
discovered when investigating D. virginiana; they were
actually discovered while studying the South American
Table 1. Chemical components of D. virginiana (adapted medical plant Euclea natalensis. Studies that isolated 7-
mostly from Duke1992A). Source: (DUKE1992A: Duke, James A. methyljuglone and combined Euclea natalensis isolated 7-
1992. Handbook of phytochemical constituents of GRAS herbs and
methyljuglone with the administration of anti tuberculosis
other economic plants. Boca Raton, FL. CRC Press)
drugs like Isoniazid and Rifampicin and reported a synergistic
effect which increased the drug’s ability to inhibit
elm trees. This indicates that either the persimmon leaves extracellular and intracellular activity of M. tuberculosis by 4-6
have poor nutritional value or that there are active folds. Further research beyond recording the Fractional
compounds inhibiting the maturation of the mosquito larvae. inhibitory concentration (FIC) indexes of 7-methyljuglone
(Kesavaraju, Afify, & Gaugler, 2009) with different Tuberculosis drugs may lead to development of
There is also evidence that the naphthoquinones isolated from new drugs that work against multidrug-resistant (MDR)
D. virginiana, juglone and analogs of juglone, are chemo- strains of Mycobacterium tuberculosis. D. virginiana’s high 7-
preventive agents. Chemo-preventative agents inhibit, delay, methyljuglone bioavailability may prove to be extremely
or reverse disease progression by antibacterial, antifungal, important and lucrative when the demand for these drugs
antiviral, insecticidal, anti-inflammatory, or antipyretic increase.(Bapela, Lall, Fourie, Franzblau, & Van Rensburg,
activity. In one study the naphthoquinones from D. virginiana 2006)
showed potent anti-tumor promoting activity in vitro on the Many of the chemical constituents of D. virginiana show
Epstein-Barr virus early antigen activation produced by the promising preliminary data for possible medicinal uses,
tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) however, much more research must be done starting with live
and in vivo on stage 2 mouse skin carcinomas (Kapadia et al.,
Unripe persimmons have a significant amount of shibuol (a
type of tannin) that, when mixed with the acidic environment
of the stomach, polymerize to form a gluey precursor to a
phytobezoar, a coagulum which entraps cellulose,
hemicellulose, and protein in the stomach. Tannic acid also
reacts with mucin, and decrease the cytoprotective
mechanisms of the gastric mucosa. Today, in the United States
of America, more than 85 percent of phytobezoars are caused
by eating unripe Persimmon. Thus epidemics of phytobezoars
occur most frequently in the Southeastern region of the
Figure 7. 7-Chemical structure of Methyl-5-hydroxy-1,4- country. Diospyrobezoars are a specific type of phytobezoar
naphthoquinone isolated from the wood of Diospyros residing in the stomach made of a dense, wood-like trapped
virginiana. Source: mass of fibrous plant material with a skin-like layer covering
http://www.pherobase.com/database/synthesis/synthesis-detail-
the surface. It presents symptoms such as a distended and
7-methyljuglone.php
tender stomach, dyspepsia (pain or discomfort in the area
between the belly-button and the sternum), bloating,
animal models. Until then, consumers should take advantage vomiting, weakness, weight loss , nausea, gastric outlet
of the nutritional value of the . obstruction, perforation, abdominal pain, and
bleeding(Sanders, 2004). One case in medical literature from
2004 documented a 51 year old patient who ate 2.2 pounds of
Clinical Studies unpeeled Persimmons everyday for 40 years came in with
There are currently no major clinical studies using this plant obstructed bowels which required retrograde double balloon
or its extracts but perhaps a survey that looks at the health enteroscopy (DBE) to find the bezoars blocking the distal
differences between people and animals that eat persimmons ileum. Several days after having the bezoars surgically
yearly and those who don’t could yield some interesting extracted, he was allowed to return home (Doo, Leung, & Lan,
epidemiological patterns. Perhaps a closer look at the 2009).
cultivation practices in each state can tell us more about how Generally the recommendations for preventing the formation
important this plant is to the ecological, social, cultural and of Phytobezoars is to peel the fruit before consumption, not to
physical health of America. consume more than several portions of the ripe fruit at one
time, and to consume even smaller portions of the unripe,
highly astringent fruits. The high potassium may also pose a
Contraindications risk if the consumer suffers from hypotension because it will
Excessive consumption of Persimmon fruits or consumption decrease the fluid content in the blood and lower the blood
of unripe fruits may cause several gastrontestinal problems. pressure even more. The high sugar content of the ripe fruit
could also pose a risk for those who suffer from diabetes and
cause an onset of hyperglycemia.
There are no known drug interactions and there are no know
allergy reports, but there are several warnings about the
preparation of the fruit passed down from traditional cooking
practices. For example, persimmon is not encouraged to be
paired with crab meat, goose, sweet potato, eggs, sauerkraut,
black dates or with persimmon vinegar because it could
encourage the formation of bezoars. The mechanisms of
interaction is not known or studied very well, but these rules
are generally followed by several different ethnic groups that
consume a substantial amount of the persimmons produced
around the world. The carcinogenic activity seen when
extracts were injected into small rodents does not apply to
orally consuming the fruit. It is generally regarded as safe to Figure 8: Example of an organic hand cream that is
eat. The hand cream featured earlier in this article is also commercially available and marketed as rejuvenating by
GRAS and is made with organically grown persimmons. tighten facial pores and removing wrinkles.
Larger grazing animals such as horses and cows should be Source: http://www.buynaturalskincare.com/persimmon-
kept away from persimmon trees in the late fall and winter cantaloupe-cream-p-1004.html
because they will gorge themselves with these sweet fruits
and promptly develop very large phytobezoars which often effects of a high sodium diet. The highly astringent properties
leads to bowel obstructions and infections that can kill the of unripe Persimmon fruits may help patients with diarrhea or
animal. sore throats. However, the abundance of pectin in the ripe
Persimmon can treat constipation and increase the absorption
of cholesterol from the intestines before it enters the
Current Uses in Allopathic and CAM Therapies bloodstream. Since choosing how ripe the fruit is before
Though there are no current FDA approved uses for consumption depends on the state of the consumer, this is a
Persimmon, consumption and topical application of plant complimentary diet based therapy. Currently, there are
extracts can be beneficial in treatment of minor ailments. The several hand creams that are commercially available that
fruit, which is low in sodium, has diuretic properties. claim to be rejuvenating. This rejuvenation is accomplished by
Furthermore, patients with gout, arthritis, or hypertension the tannins that tighten facial pores, allowing for a youthful
can benefit from the high potassium content of the Persimmon glow (Figure 8).
because potassium negates some of the water retentioning
Discussion is naturally fungi and insect resistant and should be preserved
Diospyros virginiana is a plant with many historical and as part of the American heritage.
cultural ties to the United States but has been severely
overlooked due to the importation of the larger fruited
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Echinacea purpurea (L.) Moench, Asteraceae
Charity Coleman
Introduction Photograph by Rhonda Stewart. http://www.fs.fed.us/wildflowers

/pollinators/butterflies.shtml)
Echinacea purpurea (L.) Moench is 1 of the 477 genera in the coneflower, snakeroot, Kansas snakeroot, broad-leaved purple
Asteraceae family and 1 of 9 species in the Echinacea genus coneflower, scurvy root, Indian head, comb flower, black
(USDA 2011). It is most commonly known as the purple susans, hedgehog and American coneflower (MDidea 2010).
coneflower. Other common names include eastern purple Echinacea is one of the most popular, top-selling, and most
studied herbal treatments in today’s society. Traditionally,
Echinacea has been used to prevent and/or treat colds, flu and
other upper respiratory infections. It is believed that
Echinacea is capable of stimulating the immune system in
order to help fight off infections. Also, Echinacea has been
used to treat wounds and skin problems such as acne and
boils, although these uses of Echinacea are less common
(NCCAM 2005-2010). Echinacea is generally sold as a
preparation derived from 3 of the 9 species including
Echinacea purpurea, Echinacea angustifolia, and Echinacea
pallida. The most commonly used preparation in the United
States is a liquid extract made from the root of Echinacea
purpurea (Kligler 2003). The active component of the plant
has not been identified; however, the main components
believed to be responsible for its immune-stimulating effects
are the high-molecular-weight polysaccharides: heteroxylan
and arabino-glactan (Kligler 2003).
Description
Figure 1. Photograph of Echinacea purpurea and a female Echinacea purpurea is an herb that is native to the eastern and
Pipevine Swallowtail butterfly (Battus philenor). (Source: mid-western regions of North American and the southern
regions of Canada. Although it does not grow naturally
anywhere else, it is cultivated worldwide because of its great Echinacea has been used for hundreds of years among Native
use as an herbal medicine. Its habitat is mainly that of rocky Americans, North Americans and Europeans. Archaeological
areas, open woods, thickets, prairies, and roadsides. It is a digs in the Lakota Sioux village sites uncovered evidence of
single stem, erect, perennial with an active growth period in Echinacea plants dating back to the 1600’s. The use of
the spring and summer. Its mature height is approximately 1.2 Echinacea as an herbal medicine was introduced to Europe in
feet but can reach heights of up to 4 feet (Upton 1997). The the late 1800’s by H.C.F. Meyer (MDidea 2010). It has been
flower is purple in color, with elliptical petals radiating from used in Europe extensively since the 1930s and is used by
the spiny seed head (cone), which is responsible for the millions of Europeans today as their primary therapy for
plant’s name (echinos: Greek word-root for “hedgehog”) colds, flus and other upper respiratory infections (URIs)
(Upton 1997). Foliage color is green and the fruit and seed (MDidea 2010). As in European use, Echinacea is commonly
color is black (FNA 2011). The seeds are produced in the cone used in the North America to treat/prevent colds, flus, upper
and are small, 4 sided achenes. The stems are rough and have respiratory infections, and also for general immune-boosting
small hairs along their entire length with alternate, simple and effects. It is also used, less commonly, for the treatment of
ovate leads coming from them. The roots occur in a mass of urinary tract infections, treatment of wounds, and skin
thin, beige-brown rootlets that are approximately 12 inches in conditions such as acne, boils, psoriasis, and eczema (MDidea
length. The taste of the stem has been described as a sweet but 2010). E. purpurea has also been used in Canada to treat
acrid flavor (Upton 1997). The growth rate is moderate, but abscesses in livestock (Lans, Turner, Khan, Brauer and
regrowth rate after harvesting is quite slow (FNA 2011). Boepple 2007). Studies have shown activity against bacterial
Preferential growth requires full sun with low tolerance to and viral infections and some of the chemical compounds
drought. The optimum pH is between 6.5 and 7.2 for growth. extracted from Echinacea have shown inhibitory effects
Echinacea does not compete well with other plants (USDA against certain forms of cancer (USDA 2011). Echinacea was
2011). When in bloom, the flowers of Echinacea purpurea introduced into the 1887 Materia Medica but was eventually
attract pollinators such as insets and butterflies. Also, song removed due to lack of efficacy from clinical studies (MDidea
birds such as Goldfinches are fond of the seeds during the fall. 2010 and Upton 1997).
Figure 1 is a photo of Echinacea purpurea along with one of its
pollinators, the female Pipevine Swallowtail butterfly. There
are no known pests of potential problems associated with E. Traditional Medicinal Uses by Native Americans
purpurea. However, because it is such a popular herbal Echinacea is said to have been the most commonly used
remedy, it is becoming increasingly rare in its natural habitat medicinal plant by Native American tribes, being used for
due to over harvesting. more illnesses than any other plant (Upton 1997). The most
common uses of Echinacea by Native Americans were to treat
toothaches, sore throats, coughs, infections, burns, venereal
Traditional Uses
diseases, and even snake bites and other venomous bites,
stings, and poisonings. The most common method for treating
coughs was to chew the root and swallow the juices (Moerman let saliva run down their throats in order to treat colds and
2011). Use of Echinacea extended through many tribes sore throats. The Cheyenne also made tea from the leaves of
including the Blackfoot, Cheyenne, Choctaw, Comanche, Crow, Echinacea to treat sore mouths and gums, toothaches due to
Dakota, Delaware, Kiowa, Lakota, Omaha, Pawnee, Ponca, large cavities, rheumatism, arthritis, mumps and measles. This
Sioux, and more (Upton 1997). Use has also been reported by same liquid was also applied to necks to relieve sore neck
the Montana and Winnebago tribes (Borchers, Keen, Stern and pain. Salves were also made by the Cheyenne to treat the same
Gershwin 2000). When using Echinacea to treat snakebites, ailments externally. Echinacea root was also mixed with
most of the tribes employed the same preparations and Mentzelia laevicaulis (blazing star) and boiled to make a tea
applications. The root was used internally by chewing the for treating smallpox (MDidea 2010 and Upton 1997). The
fresh root, and externally by making a fresh poultice and Choctaw tribe is reported to have used E. purpurea as a cough
applying it to the bite to draw out the poison (Upton 1997). medicine by chewing the root and swallowing saliva
Another common application throughout the tribes was to containing the juice. They also prepared a tincture which they
suck on the root to treat toothaches, sore throats, coughs, and used for coughs as well. The Choctaw also used E. purpurea as
infections. Other tribes applied juice, from the roots, to burns, a gastrointestinal aid to help with dyspepsia. They used the
wounds, ulcers and other skin conditions (MDidea 2010). same methods of preparation as with the cough medicine
(Moerman 2011). This information was also reported in the
American Journal of Clinical Nutrition (Borchers, Keen, Stern
Specific Traditional Medicinal Uses by Tribe and Gershwin 2000).
The Blackfoot chewed the root to reduce pains from
toothaches. The Sioux used freshly scraped root to make a
poultice to treat hydrophobia caused by bites of rabid animals. Non-medicinal Traditional Uses
The Dakotas also used freshly scraped root to treat Echinacea had traditions not only in medicinal uses, but
hydrophobia, snakebites, and wounds that had putrefied decorative, ceremonial and other uses as well. Echinacea, due
(MDidea 2010). The Delaware tribe used E. purpurea to treat to its beautiful flowers, is grown as a decorative flower in
venereal disease by combining the roots with staghorn sumac many gardens and can be found in many homes. Native
roots. For more advanced cases of venereal disease, they American tribes would use Echinacea in many religious
would use an infusion of roots. The Delaware also reported ceremonies to show supernatural abilities. They would use the
high effectiveness with the use of E. purpurea in the treatment numbing qualities of Echinacea by mashing the fresh root and
of gonorrhea (Moerman 2011). The Lakota tribe used rubbing the juice on their hands with tallow to enable them to
Echinacea as a painkiller for toothache, tonsillitis, handle fire painlessly. Also, others would chew the root to
stomachache, pain in the bowels, and also when they were numb the mouth in order to hold a hot coal in their mouths for
thirsty or perspiring by eating the roots and green fruits of the religious ceremonies as well as for medicinal practices (Upton
plant. The Omaha tribe used some parts of the plant for sore 1997). Winnebago medicine men would do this in order to
eyes. The Kiowa and Cheyenne chewed pieces of the root and create confidence in their ability to heal (MDidea 2010).
Children of the Pawnee tribe used Echinacea in a game in have also been known to use the spiny seed cone as a hair
which the stems were twirled around each other. Many tribes comb (Upton 1997).
Plant Part Active Constituents

Flower Cichoric-Acid (12,000-31,000 ppm), Cyanadin-3-O-(6-O-Malonyl-Beta-D-Glycopyranoside), Cyanadin-3-O-(Beta-D-Glycopyranoside), EO (600-6,000 ppm)
Fruit Alpha-Pinene, Beta-Farnesene, Beta-Pinene, Epishiobunol, Limonene, Myrcene
Leaf 2,3-O-Diferuloyltartaric-Acid, 2-O-Caffeoyl-3-O-Feruloyltartaric-Acid, 2-O-Caffeoyltartaric-Acid, 2-O-Feruloyltartaric-Acid, Apigenin, Ascorbic-Acid (2,140
ppm),
EO (100-6,000 ppm), Flavanoids (3,800-4,800 ppm), Isorhamnetin-3-Rutinoside,
Kaempferol, Kaempferol-3-0-Glucoside, Kaempferol-3-0-Rutinoside, Luteolin, Luteolin-7-Glucoside, Quercetagetin-7-Glucoside, Quercetin, Quercetin-3’-
Glucoside, Quercetin-3-0-Galactoside, Quercetin-3-0-Xyloside, Quercetin-3-Robinoside, Quercetin-3-Xylosylgalactoside, Rutin, Rutoside, Selenium, Silicate
(15,340 ppm), Silicon (301 ppm), Sodium (90 ppm)
Plant (+)-Tartaric –Acid, (E)-10-Hydroxy-4,10-Dimethyl-4,11-Dodecadien-2-One, 2-Methyltetradeca-5,12-Diene, 2-Methyltetradeca-6,12-Diene, 2-O-Caffeoyl-3-(5-
(Alpha-Carboxy-Beta-(3,4-Dihydroyphenyl…), 3,5-Dicaffeoyl-Quinic Acid, 4,5-O-Dicaffeoylquinic-Acid, Borneol, Bornyl-Acetate, Caffeic-Acid, Ferulic-Acid,
Isotussilagine, Vanillin
Root 6-O-Caffeoylechinacoside, Alkylamides (40-1,510 ppm), Aluminum (786-12,900 ppm),
Arabinogalactan, Ascorbic-Acid (843 ppm), Ash (80,000 ppm), Behenic-Acid-Ethyl-Ester, Beta-Carotene, Betaine, Calcium (3,290-7,760 ppm), Carbonate
(7,100 ppm), Caryophyllene (42 ppm), Caryophyllene-Epoxide (26 ppm), Chloride (760 ppm), Chromium (19 ppm), Cichoric-Acid (6,000-21,000 ppm),
Cichoric-Acid-Methyl-Ester (6,000-21,000 ppm), Cobalt (148 ppm), Cynarin, Deca-(2E,4E,6E)-Trienoic-Acid-Isobutylamide , Des-Rhamnosylverbascoside,
Dodeca-(2E,4E)-Dienoic-Acid-Isobutylamide, Dodeca-(2E,6Z,8E,10E)-Tetraenoic-Acid-Isobutylamide, Dodeca-2,4-Dien-1-yl-Isovalerate, Echinacein (10-100
ppm), Echinacin, Echinacoside (3,000-17,000 ppm), Echinolone, EO (50-40,000 ppm), Fat (13,000 ppm), Fiber (111,000 ppm), Germacrene-Alcohol,
Germacrene-D, Heptadeca-(8Z,11Z)-Diene-2-one, Heteroxylan (800 ppm), Humulene (8-12 ppm), Inulin (59,000-200,000 ppm), Iron (700-4,800 ppm),
Kilocalories (2,800/kg), L-Pentadecene (400 ppm), Magnesium (1,170-1,860 ppm), Manganese (101 ppm), Niacin, Palmitic-Acid, Penta-(1,8Z)-Diene (400
ppm), Pentadeca-(8Z)-en-11,13-diyn-2-one, Pentadeca-(8Z)-en-2-one (4,000 ppm), Pentadeca-(8Z,11Z)-diene-2-one, Pentadeca-(8Z,13Z)-diene-11-yn-2-one,
Pentadeca-8-en-2-one, Phosphorus (790 ppm), Polyacetylenes (20 ppm), Polysaccharides, Ponticaepoxide, Potassium (3,140-8,090 ppm), Protein (92,000 ,
ppm), Rhamnoarabinogalactan, Sulfate (2,450 ppm), Tetradeca-(8Z)-en-11,13-diyn-2-one, Thiamin (2.6 ppm), Tin (17 ppm), Trideca-1-en-3,5,7,9,10-Pentayne,
Tussilagine, Verbascoside, Water (749,000 ppm), Zinc (51 ppm)
Shoot 12-Hydroxyoctadeca-(9Z,11E,15Z)-Trienoic Acid,2-O-Caffeoyl-3-O-Cumaroyltartaric-acid, Beta-Sitosterol, Chlorogenic-Acid, Isochlorogenic-Acid, N-
Triacontanol, Sitosterol-3-Beta-O-Glucoside, Stigmasterol
Table 1. Chemical composition of Echinacea purpurea. (Source: Information obtained from Dr. Duke’s Phytochemical and
Ethnobotanical Databases. http://www.ars-grin.gov/cgi-bin/duke/farmacy2.pl )
Chemistry and Pharmacology documented and is categorized based on plant parts in Table
1. The main constituents thought to be responsible for the
Due to the heterogeneity of the products used in the majority
immune-stimulating effects are heteroxylan and
of studies of Echinacea, the main active component of
arabinoglactan (Kligler 2003). Other classes of compounds
Echinacea purpurea is not known. Most studies examine
considered to contribute to the activity of Echinacea are
combinations of Echinacea species and others study Echinacea
alkaloids, polysaccharides, and polypropenoids, in particular,
combined with other herbs (Kligler 2003). However, the
caffeic acid derivatives echinacoside and cichoric acid
chemical composition of E. purpurea has been well
(MDidea 2010). Echinacoside is present in the roots at
approximately 7,000-13,000 ppm and cichoric acid is present Professionals.http://www.mdidea.com/products/herbextract/echi
in the flower at levels of 12,000-31,000 ppm and in the root at nacea/data05.html )
levels of 6,000-21,000 ppm (Duke 2011). Also, inulin is found
at very high concentrations ranging from 59,000-200,000 ppm of the main chemical compounds found in E. purpurea.
in the roots. Figure 2 shows the chemical structures of some
Biological Activity
There have been many in vitro and in vivo studies done to
evaluate the efficacy and to try and determine the main active
components of Echinacea purpurea. Due to the vastness of
chemical constituents and the different compounds present in
different parts of the plants and in different species, the main
active ingredients are not known. Therefore, when sold,
Echinacea extracts are generally a mixture of E. angustifolia, E.
pallida, and E. purpurea as many herbalists believe that the
effects of Echinacea are due to a complex interaction among
the constituents (Fiebert and Kemper 1999).
Immunostimulant
One study incubated mouse serum with polysaccharides
(thought to be one of the main active components for
immune-stimulation) from Echinacea purpurea roots. They
found that this stimulated proliferation of bone marrow cells
and promoted phagocytosis by macrophages. Also, another
study in rats showed that, in isolated, perfused rat livers,
Echinacea extracts enhanced phagocytosis. A study performed
in immunosuppressed mice showed a reduction in renal
Candida load by 80% when the mice were injected with
Echinacea polysaccharides prior to infection with Candida
albicans. Bacterial counts in both the liver and spleen were
Figure 2. Chemical compounds found in Echinacea also reduced by 95% in mice treated with Echinacea prior to
purpurea. (Source: Mdidea Exportind Division Extract infection with a lethal dose of Listeria monocytogenes (Fiebert
and Kemper 1999). A study in undefined murine animals
(mice or related rodents) sought to define the effects of E. showed that extracts of Echinacea have phototoxic
purpurea root and leaf extracts in dendritic cells. These cells antimicrobial activity against fungi. Under near UV irradiation,
are responsible for the generation of innate and adaptive growth inhibition was shown against yeast strains of
immune responses. This study concluded that E. purpurea can Saccharomyces cerevisiae, Candida shehata, C. kefyr, C. albicans,
function as an immunostimulant, immunosuppressive, and/or C. steatulytica and C. tropicalis. These affects were contributed
an anti-inflammatory agent. The achieved affects are to the ketoalkenes and ketoalkynes found in roots of E.
determined by the portion of the plant used as well as the purpurea (Binns, Purgina, Bergeron, Smith, Ball, Baum and
method of extraction applied (Benson, Pokorny, Rhule, Arnason 2000).
Wenner, Kandhi, Cech and Shepherd 2010). Aly and Mohamed
performed a study to investigate the immunostimulant effects
of E. purpurea and garlic in Nile tilapia. They found that fish Complementary immune support
supplemented with E. purpurea and garlic showed an In an in vitro study, a cytotoxic response of macrophages
improvement in body weight gain, increased survival rates against tumor targets was seen with use of purified
and increased resistance against challenged infections (Aly polysaccharides from Echinacea purpurea. One study with
and Mohamed 2010). mice showed as increase in the number of white blood cells,
compared to controls, after receiving intravenous E. purpurea
polysaccharides prior to injection of cyclophosphamide. A
Antimicrobial: Antiviral
study in rats that received dietary supplements of E. purpurea
In a study of cultured mouse cells, treatment with aqueous showed enhanced mobilization of vitamin E mediated
extracts of Echinacea purpurea caused a 50-80% resistance to oxidation/reduction pathways. This suggests that there is a
infection of Influenza and Herpes viruses when treated four to protectant effect against radiation damage (Fiebert and
six hours prior to exposure. The resistance lasted for 24 hours Kemper 1999).
after exposure, but after 48 hours the cells were sensitive to
infection (Fiebert and Kemper 1999).
Mechanism of Action
Since the exact active components of Echinacea purpurea have
Antifungal
not been identified, the exact mechanism of action is not
An in vitro study of human granulocytes and monocytes known. However, the mechanisms are known for many of the
treated with Echinacea purpurea extracts showed enhanced constituents found in Echinacea. Several studies show that
mobility. Also, there was an increase in phagocytosis of Echinacea provides an increase in immunological activity by
Candida albicans by 30-45%. Also in vitro, inhibition of increasing levels of interferon and increasing phagocytosis,
Candida albicans growth was seen with use of purified cellular respiratory activity, and lymphocyte activation. This is
polysaccharides from E. purpurea (Fiebert and Kemper 1999). achieved through the release of tumor necrosis factor,
A study on light-mediated antifungal activity of E. purpurea interleukin-1, and interferon beta-2 (Kligler 2003). Echinacea
promotes T-cell activation, natural killer-cell activity, of a 10-20% risk reduction with treatment of Echinacea
lymphatic function and antibody binding. It also increases the products (Melchart, Walther, Linde, Brandmaier, and Lersch
reticulo-endothelial layer which increases antibodies by 1998). Another randomized controlled trial on the
increasing the production of alpha, beta, and gamma globulin effectiveness of E. purpurea in treatment of URIs found there
(Valentino and Yance 1999). Echinacea is thought in assist in was no difference in duration or severity of symptoms
wound healing, a cortisone-like activity, by inhibiting between patients treated with E. purpurea and those receiving
hyaluronidase enzyme that is associated with swelling and a placebo (Taylor, Weber, Standish, Quinn, Goesling, McGann,
inflammation (Valentino and Yance 1999). This activity is and Calabrese 2003).
accomplished by Echinacea’s ability to maintain the structure
On the other hand, a study by Brinkeborn, Shah and Degenring
and integrity of the collagen matrix in connective tissue
(1999) concluded that preparations from E. purpurea,
(MDidea 2010). Echinacea is most properly termed an
including Echinacea concentrate and Echinaforce, were low-
immunomodulator as it stimulates in the immune system in
risk, effective alternatives to standard symptomatic medicines
some conditions and suppresses it in others (MDidea 2010).
in the treatment of the common cold. Also, according to the
There has been much debate about the length of use of University of Maryland Medical Center, a study of 95 people
Echinacea and its long term effectiveness. Some sources say with early symptoms of the flu who drank tea made from
that it is only efficient for a seven to ten day period. However, Echinacea felt better sooner than those who drank a placebo
one source indicates that this is a misconception and that it tea. They also reported that a review of 14 clinical trials
came from the mistranslation of a few German graphs from an revealed a 58% reduction in the odds of developing a cold
oral double blind study with E. purpurea vs. a placebo (MDidea when using Echinacea (UMMC 2011).
2010).
Contraindications
Clinical Studies
According to the National Center for Complementary and
Many clinical studies have been performed to determine the Alternative Medicine, when taken by mouth, Echinacea does
efficacy of Echinacea in treating human conditions with many not generally cause side effects. Generally uncommon and
mixed results reported. A double-blind, placebo-controlled minor side effects include abdominal upset, nausea and
randomized trial by Melchart, Walther, Linde, Brandmaier and dizziness (Kligler 2003). Although rare, some people have
Lersch on the prevention of upper respiratory tract infections experienced allergic reactions such as rashes, increased
found that no prophylactic effects of Echinacea extracts could asthma, and anaphylaxis (NCCAM 2010). People more likely to
be shown. The placebo group showed 36.7% infection while experience allergic reactions to Echinacea include those who
the group treated with E. purpurea only showed 29.3% are allergic to related plants in the daisy family such as
infection, however these results were not conclusive enough ragweed, chrysanthemums, marigolds and daisies, as well as
to confirm efficacy. They did conclude however, based on their individuals with asthma (NCCAM 2010).
research and 2 other studies, that there could be speculation
There have been no significant herb-drug interactions their labels. Moreover, approximately 10% of them had no
reported with the use of Echinacea. Although, theoretically the Echinacea in them at all! Also, half of them were mislabeled as
immune-stimulating properties of Echinacea could possibly to which species of Echinacea they contained and the
interfere with immunosuppressive medications taken by standardized preparations did not match the label (UMMC
individuals with autoimmune disease, such an effect has not 2011).
been documented in humans or animals. Also, in vitro studies
The UMMC recommends the following dosages of Echinacea
of Echinacea have shown that there may be a mild inhibition
for general immune stimulating effects, during colds, flus, URIs
of the cytochrome P450 3A4 enzyme complex system which
or bladder infections: 1-2 grams of dried root or herb as a tea,
causes an increase in levels of drugs metabolized by the
2-3 mL of standardized tincture extract, 6-9 mL of expressed
system. Drugs affected are itraconazole (Sporanox),
juice (succus), 300 mg of standardized, powdered extract
fexofenadine (Allegra), and lovastatin (Mevacor). None of
containing 4% phenolics, tincture (1:5): 1-3 mL (20-90 drops)
these interactions have been reported in humans but caution
or stabilized fresh extract: 0.75 mL (15-23 drops). It is
should be taken when using Echinacea along with these
recommended to choose one of these dosages and take it 3
medications (Kligler 2003).
times a day for 7-10 days (UMMC 2011).
Current Use in Allopathic & CAM Therapies

Discussion
There are literally hundreds of products containing Echinacea
Echinacea purpurea has played an extremely important role in
species currently on the market (Echinacea 2011). The most
natural medicine for hundreds of years, dating back to the
common uses of Echinacea today are for the
1600s. It was the most widely used medicinal plant by the
treatment/prevention of colds, flus, upper respiratory tract
Native Americans in the past and is still one of the most widely
infections, and general enhancement of the immune system.
used herbal medicines today. The vastness of use of this plant
Echinacea is generally sold as a combination of E. angustifolia,
is extraordinary, ranging from treatment of the common cold
E. pallida, and E. purpurea and can be purchased as extracts,
to its tumor fighting properties and hundreds of preparations
tinctures, tablets, capsules, ointments, and in teas. It is also
containing Echinacea are already on the market. Although the
sold in capsule forms combined with other immune boosting
efficacy of Echinacea has not yet been truly confirmed, it is
herbs, vitamins, and minerals (UMMC 2011).
used by millions of people worldwide with personal opinions
When purchasing Echinacea products, do take caution to make of success. With its use traversing hundreds of years, there are
sure you are purchasing from a reputable, established obviously some benefits. I believe that this plant will continue
company that distributes through trustworthy and to be highly regarded as a beneficial herbal supplement and
knowledgeable establishments. According to the University of that future studies will find and confirm its efficacy.
Maryland Medical Center, a study performed by
ConsumerLab.com found that only 4 out of 11 brands of
Echinacea purchased for testing contained what was stated on References Cited
Aly, Salah Mesalhy, and M.F. Mohamed. 2010. Echinacea purpurea Kligler, Bejamin M.D., M.P.H. 2003. Echinacea. American Family
and Allium sativum as immunostimulants in fish culture Physician. 67(1):77-80.
using Nile tilapia (Oreochromis niloticus). Journal of Animal
Lans, Cheryl, Nancy Turner, Tonya Khan, Gerhard Brauer, and Willi
Physiology and Animal Nutrition. 94(5):31-39.
Boepple. 2007. Ethnoveterinary medicines used for
Benson, Jenna M., Amanda J. Pokoryn, Ava Rhule, Cynthia A. ruminants in British Columbia, Canada. Journal of
Wenner, Vamsikrishna Kandhi, Nadja B. Cech, and David M. Ethnobiology and Ethnomedicine. 3:11.
Shepherd. 2010. Echinacea purpurea extracts modulate
MDidea herbalists. 2010. What is Echinacea Purpurea? Good
murine dendritic cell fate and function. Food and Chemical
function and application of Polyphenols and Chicoric
Toxicology. 48(5):1170-1177.
acid from Echinacea Purpurea Extract? MDidea Exporting
Binns, Shannon E., Bibianna Purgina, Christophe Bergeron, Matthew Division Extract Professionals. http://www.mdidea.
L. Smith, Lauren Ball, Bernard R. Baum, and John T. Arnason. com/products/herbextract/echinacea/data05.html
2000. Light- Mediated Antifungal Activity of Echinacea
Melchart, Dieter, Ellen Walther, Klaus Linde, Roland Zbrandmaier,
Extracts. Planta Med. 66(3):241-244.
and Christian Lersch. 1998. Echinacea Root Extracts for
Brinkeborn, R.M., Dhavan V. Shah, and Friedrich H. Degenring. 1999. the Prevention of Upper Respiratory Tract Infections: A
Echinaforce and other Echinacea fresh plant preparations in Double-blind, Placebo-Controlled Randomized Trial.
the treatment of the common cold: a randomized, Archives of Family Medicine. 7(6):541-545.
placebo controlled, double-blind clinical trial.
Moerman, Dan. Native American Ethnobotany. A Database of Foods,
Phytomedicine. 6(1):1-6.
Drugs, Dyes and Fibers of Native American Peoples,
Borchers, Andrea T., Carl L. Keen, Judy S. Stern, and M. Eric Derived from Plants. Accessed July 2011.
Gershwin. 2000. Inflammation and Native American http://herb.umd.umich.edu/
medicine: the role of botanicals. American Journal of Clinical
National Institutes of Health. National Center for Complementary
Nutrition. 72(2):339-347.
and Alternative Medicine. Herbs at a Glance. Echinacea.
Duke, James A. Dr. Duke’s Phytochemical and Ethnobotanical July 2005 – July 2010.
Database. Accessed July 2011. http://www.ars-grin.gov/cgi- http://nccam.nih.gov/health/echinacea/ataglance.htm
Taylor, James A., Wendy Weber, Leanna Standish, Hal Quinn, Jenna
Echinacea. Products Containing Echinacea. Accessed July 2011. Goesling, Mary McGann, and Carlo Calabrese. 2003.
http://naturalmedicinesofnc.org/Echinacea/Echinacea- Efficacy and Safety of Echinacea in Treating Upper
products.html Respiratory Tract Infections in Children: A Randomized
Controlled Trial. The Journal of the American Medical
Fiebert, Sara Goldhaber, and Kathi J. Kemper M.D., M.P.H. 1999.
Association. 290(21):2824-2830.
Echinacea (E. angustifolia, E. pallida, and E. purpurea. The
Center for Holistic Pediatric Education and Research. University of Maryland Medical Center. Echinacea. Accessed July
2011. http://www.umm.edu/altmed/articles/echinacea-
FNA. Echinacea purpurea (Linnaeus) Moench. Flora of North
000239.htm
America. 21:88,91,92 Accessed July 2011.
Upton, Roy. 1997. Echinacea: A Keats good herb guide. Boulder, July 2011 http://plants.usda.gov/java/profile?symbol
Colo., ebook. Obtained from Ottenheimer library. =ECPU
U.S. Department of Agriculture. Natural Resources Conservation Valentino, Arlene and Donald R. Yance. 1999. Herbal Medicine,
Service. PLANTS Database. PLANTS profile. Echinacea Healing & Cancer: a comprehensive program for
purpurea (L.) Moench eastern purple coneflower. Accessed prevention and treatment. Los Angeles, Calif., ebook.
Obtained from Ottenheimer library.
Ephedra sinica Stapf., Ephedraceae
Samuel C. Turner
Introduction
Ephedraceae is a family of herbs that have been exploited for
their stimulating properties for nearly 5,000 years.
Ephedraceae contains only one genus, Ephedra. Ephedra is
composed of about 40 species. Ephedra sinica is the most
potent in the genus Ephedra. E. sinica, known originally as Ma
Huang, has had many epithets, including; Chinese Ephedra,
Ephedra, upitonia, ephedrine (referring to its active
ingredient), desert tea, desert herb (referring to its ecology),
whorehouse tea and any number of other names
(asiarecipe.com).
The Chinese have used E. sinica for thousands of years as a
treatment of asthma, hay fevers, sweating and the common
cold. Although Ephedra is one of the earliest recorded
medicines; its active ingredients, ephedrine and
pseudophedrine, have only been isolated in recent history
(1887) (Frank, 2009). Ephedrine is an alkaloid that stimulates
the central nervous system, constricts the blood vessels and
opens lungs. Since its isolation it has used as a treatment for
asthma, weight loss and athletic performance enhancer, as
well as an antihistamine and decongestant (Thomas, 2010).
Its abuses have led to increased scrutiny on its dosage, usage
and availability. Figure 1. Ephedra sinica. (Source: http://www.herbie sherbs
.com/pages/herbpictures/ephedra2386L.jpg)
Description
other, similar habitats in the Mediterranean, India, Persia and
Ephedra sinica is a small, shrub-like plant that grows to a South America. Ephedra is dioecious and a gymnosperm. Its
maximum of three feet and is prevalent eastern China and ideal habitat includes dry regions of sandy or rocky deserts.
Mongolia. Since its mass production, it has been planted in This habitat provides the well-drained soil needed for growth,
but may not be conducive to the copious amounts of water portions of the Ma Huang into eight ounces of water, and
needed to provide the best conditions (Yang, 2004). boiling for ten minutes. This produces a 15 - 30 mg serving of
Ephedra is a green, erect species, with a plethora of branches, Ephedrine (Crazyfortea.com, 2007). Presently, synthetic
each individual branch contains roughly two opposing scale- Ephedrine has been administered in several ways, most often
like leaves, or a 'whorl' of three (Figure 1). During as dietary pills, which range in concentrations of 10 - 80 mg
propagation, the dioecious (rarely, some are found to be (Herb Research Foundation, 1995).
monoecious) males produce egg-shaped seeds, which it stores. Ephedra’s traditional use has been limited to its physiological
During autumn or spring, the smooth, mature male gametes properties. Its physical properties as a shrub, do not lend it to
are seeded into the female's mature, fleshy bract. Up to three more artistic uses, such as clothing or dye. But, its stimulant
seeds are inserted per bract. Ephedra can also propagate properties have led to more creative uses. Much like coffee, it
through root division, but this is a rare occurrence (Yang, has been brewed to make a recreational tea. Made by
2004). Characteristics of E. sinica include; dark, reddish- Mormon settlers in the 1800’s to replace tea (considered
brown seeds; bitter taste when brewed into coffee; and no taboo by their religion), Mormon settlers brewed to the herb
particular smell (although decomposition can cause a to produce “Mormon tea” (Larsen, 2009). After the synthesis
distracting odor.) of ephedrine, use of E. sinica and its derivatives skyrocketed.
Along with its prescribed use, ephedrine become synonymous
with weight loss, athletic enhancement and substance abuse.
Traditional Uses In particular, weight loss products contained considerably
Although Ephedra sinica has been used for many thousands of higher doses than traditional use. These can be dangerous
years, its history can be viewed as bleak. Its first use was concentrations and prompted criticism over Ephedra’s
noted around 3,000 B.C., where it was considered somewhat potential harm. Its abuse as an over-the-counter medication
of a miracle drug. Physicians would prescribe Ephedra, or has resulted in several deaths, especially in teenagers
more commonly known at the time as, Ma Huang, to treat a (Nertheim, 2003).
number of conditions, including; the common cold, asthma,
arthritis, hay fever, hypotension and other conditions.
Ma Huang was listed in the first chapter of a classical Chinese
herbalism text, written by Sheng Nong in the first century A.D. The chemical composition of E. sinica includes: Ephedrine
Its many manipulations have allowed for a broad range of alkaloids 0.481-2.47% (l-ephedrine, d-pseudoephedrine,l-
treatments. Although, E. sinica is limited to Asia, other norephedrine, d-norpseudoephedrine, lmethylephedrine, d-
Ephedra species have been used in the Middle East for asthma methylpseudoephedrine), 2,3,5,6-tetramethyl-pyrazine 2,3,4-
and other similar conditions (Frank, 2009). trimethyl-5-phenyloxazolidine-benzylmethylamine,
ephedroxane, essential oil 0.25% (l-α-terpineol) (Chen, 2004).
Traditionally, Ma Huang has been prepared and administered Although the amount of constituents is rather abundant, the
as a tea, by adding two grams of the most concentrated active ingredients comprise only a relatively small amount.
Figure 3. Structure of pseudoephedrine. (Source:
http://isomer design.com /Cdsa/C/dl375.png)
Figure 2. The structure of ephedrine. (Source:

increase in the enzyme kinase. This acts like a amino-acid
http://www.thekanjifoundrypress.com/sketch%20files/e%20GIF/
ephedrine.gif)
based hormone and stimulates cyclic AMP levels, which
increases lipid metabolism (Edward, 2009).
The active components of E. sinica are alkaloids. Of the total This mechanism (Figure 4) contains potential for medical
makeup, alkaloids compose about .5 - 2.5% of the entire miracles and recreational exploitation. The ability to
chemical composition. Of this .5 - 2.5%, ephedrine and manipulate the sympathetic nervous system allows for the
pseudophedrine account for up to 90% (Haller, 2010). systematic utilization of its benefits, such as increased
Ephedrine (Figure 2) and pseudophedrine (Figure 3) work metabolism. Conversely, this provides an amped or excited
by increasing the amount of epinephrine and norepinephrine, state popular among athletes. This explains the controversy
which are sympathetic nervous system neurotransmitters. As and numerous conflicting studies over its potentially harmful
well, ephedrine stimulates receptors found in the central effects.
nervous system and circulatory system (Edward, 2009).
Clinical Studies
Biological Activity In one study, the researchers investigated 37 cases of
Ephedrine, the most abundant and potent alkaloid in Ephedra cardiovascular disease that were directly related to the use of
sinica, works by increasing the amount of norepinephrine Ma Huang. The results indicated that Ma Huang was
reuptake. This is accomplished by increasing the amount of temporarily related to stroke and death, even if there was no
norepinephrine released from its terminal storage vesicles, underlying medical problems and dosage requirements were
into the synaptic cleft. More neurotransmitters allow for more followed (Samenuk, 2002). Another study was conducted
activated terminal receptors. In turn, these receptors initiate over its effects as a dietary supplement. This study reported
a cascade of enzymatic reactions. Receptor stimulation that its benefit/ detriment ratio that was well within
increases production of adenylate cyclase, which prompts an acceptable limits. Stating that after an eight week trial,
patients that used an E. sinica/caffeine combination lost over
E. sinica. The results can be construed to fit your needs, but
the overall consensus tends to be positive, if used under
appropriate conditions.
Contraindications
The dangers associated with this plant stem from its stimulant
activity. Patients should avoid E. sinica if they have a history
of cardiovascular disease, angina, hypertension, thyroid
disease, enlarged prostate, Insulin resistant diabetes, anxiety,
history of substance abuse and other similar conditions.
Adverse reactions can consist of nervousness, anxiety,
insomnia, anorexia, hypertension, tachycardia, arrhythmias.
Prolonged use can lead to addiction, eating disorders and its
use has been linked to psychoses, strokes, heart attacks and
abrupt deaths (Thomas, 2010).
Furthermore, care should be taken to avoid potentially
harmful drug interactions. Combination of Ephedra with
other stimulants can magnify the aforementioned adverse
reactions. As well, Beta blockers and monoamine oxidase
(MAO) inhibitors in conjunction with Ephedra can lead to
lethal hypertension. Phenothiazines can counter the effects of
Ephedra, causing an unsafe drop in blood pressure, known as
hypotension. Theophylline can increase the risk of CNS and GI
problems. Other examples of drug interactions that should be
watch for, include; oxytocin, antidepressants, digoxin,
Figure 4. Catabolism of ephedrine in the body. guanadrel, guanethidine, mecamylamine, methyldop, thyroid
therapies, diabetes medications, dexamethasone, diruetics,
ACE inhibitors, ergot alkaloids, anethetic drugs, Morphine,
two pounds (lbs) more, per month, than the placebo-control gout medications and St. John’s Wort. In short, any patient
group. However, the study also found that there was a debating on using this medication regularly should seek a
definite increase in gastrointestinal and psychiatric physician’s advice (Thomas, 2010).
symptoms, as well as an increased number of heart palpations
(Pittler, 2004). There is a plethora of conflicting research over
Current use in Allopathic and CAM therapies herbalremediesinfo.com/ephedra-medicinal-uses.html
(accessed 23 July, 2010).
Ephedra is a hybrid of sorts, graying the lines between
Allopathic and CAM therapies. Because of its properties of a Chen, John K.. "Ma Huang (Ephedra Herba)." January 1, 2004.
bronchodilator, it is used to treat asthma, bronchitis, nasal http://www.aompress
.com/book_herbology/pdfs/MaHuang.pdf (accessed July 22,
congestion, the common cold and sinusitis. These are both
2010).
traditional practices and common allopathic uses (although,
there are several more westernized medicines commonly used Crazyfortea.com, "Ma Huang Herb - Herbal Tea." January 1, 2007.
to treat these as well) (Thomas, 2010). Its effects as a http://www.crazyfortea.com /mahuangherb.html (accessed
stimulus have been used to treat hypotension, weight July 23, 2010).
management and more notably among the alternative side, it Edward, F.. "Forlean vs Ephedrine." May 26,
has been used to treat attention deficient disorder in children 2009.http://www.slimirex.com/forslean- vs-
(Myatt, 1990). ephedrine.html (accessed July 22, 2009).
Frank, Cara O. "Ephedra: A Historical Perspective." January 1,
2009.http://www.chinaherbco.com
Discussion /index.php?page=ephedra (accessed August 22, 2009).
Ephedra sinica is a unique and powerful medicine, that has Haller, Christine A.. "Pharmacology of ephedra alkaloids. Clinical
transcended generations and its use today is no less Pharmacology & Therapeutics 71 (2002), 421-432.
significant than its use 5,000 years ago. The ability of a single Herb Research Foundation, "Herbal Stimulants." April 20, 1995.
medicine to treat an array of conditions is unparalleled. http://www.herbs.org/ greenpapers/stimulant.html
Through its sympathetic-stimulating mechanism, E. sinica has
been able to treat conditions from hypotension to the common Larsen, Wes. "Mormon Tea." January 1,
2009.http://www.gcrg.org/bqr/7-3/mormon-
cold. This dynamic herb has had no humble beginning,
tea.htm (accessed August 22, 2010).
earning a rare spot among the world’s earliest medicines.
Thus, Ma huang remains ageless and will only become more Myatt, Dana. "ADD/ADHD in Children." January 1,
relevant in the next 5,000 years. 1990.http://www.drmyattswellnessclub.com/ADDlecture.h
tm
Nertheim, Jon. "Jolt of Reality." April 7th, 2003.
References Cited http://sportsillustrated.cnn.com/vault/article/magazine/M
AG1028517/2/index
Asiarecipe.com, "Ephedra: Chinese Ma Huang." January 1, 2010.
http://asiarecipe.com /herblist3.html (accessed 22 Pittler, Max. "Dietary supplements for body-weight reduction: a
August 2010). systematic review The American Journal of Clinical Nutrition
4. 79 (2004), 529.
Thomas, Peter. "Ephedra, or Ma Huang - Medicinal Uses,
Interactions,." January 2010.http://www.
Samenuk, David. "Adverse Cardiovascular Events Temporally herbalremediesinfo.com/ephedra-medicinal-uses.html
Associated With Ma Haung. Mayo Clinic Preceedings 77. 1 (accessed 23 July, 2010).
(2002), 12-16.
Yang, Yong. "Morphology and affinities of an Early Cretaceous
Thomas, Peter. "Ephedra, or Ma Huang - Medicinal Uses, Ephedra (Ephedraceae) from China.” American Journal of
Interactions,." January 2010.http://www. Botany 92 (2004), 231-241.
Ficus insipida Willd., Moraceae
Jennifer C. Howell
Introduction
Ficus insipida Willd. also known by its other scientific names,
Ficus glabrata H.B.K. and Ficus anthelmintica Martius and
common names such as wild fig, ojé, posen, higueron, and
glabrate fig belongs to the Moraceae family, also known as the
fig family (Smithsonian; Tropicos; University of Hawaii;
Hansson et al., 2005; de Armorin et al., 1999). It is a large
buttressed tree that produces relatively small fruits (figs) and
grows in the tropical regions of Central and South America,
including the Amazon basin (Smithsonian; Tropicos). The
latex of this tree has been copiously used throughout
Amazonian villages, particularly in Peru, where it is applied
traditionally as a vermifuge in both children and adults. The
latex is used to treat helminthiasis, anemia, diarrhea,
malnutrition, immune deficiency, and other such effects
resulting from these physiological compromises (Quave 2000; Figure 1. Ficus insipida tree (Smithsonian).
de Amorin et al., 1999; Jernigan 2011; Phillips 1990).
Very few studies have specifically investigated the biological Botanical Description
activity of latex derived from F. insipida. Of the studies Ficus insipida can be found in forest areas in places such as
conducted, the efficacy as an anthelmintic as well as the Mexico, Central America (mainly in Panama, Costa Rica, and
toxicity of the latex was proven, both at low and high doses Peru), South America (stretching as far as Brazil), and in the
(de Amorin et al., 1999; Hansson et al., 2005). The active Amazonian regions (Tropicos). This plant is a free-growing,
constituent found to digest and get rid of the parasites, non-flowering tree reaching approximately 40 m tall with a
causing helminthiasis, was ficin. Ficin is a class of papain-like grayish-tinted smooth bark and large buttressed roots
cysteine proteases (Gonzalez-Rabade et al., 2011). The use of protruding from the ground (Figure 1). Additionally, a milky
this tree’s latex is still in practice today as an alternative to latex sap can be found in the tree, which gives the tree one of
allopathic medicine and/or as the primary source of treatment its defining characteristics. The leaves of the tree are
(Hansson et al., 1986; Natural Remedies Haven Ltd.). characterized by their long stretched oval shape, ranging from
10-40 cm long and 5-16 cm wide depending on the maturity of
Figure 3. Ficus insipida fruit (Smithsonian).
(by untrained eyes) with species Ficus crassiuscula Warb. One

of the main tell tale signs that these species are not F. insipida
Figure 2. Ficus insipida leaves (Smithsonian).
is that F. insipida only proliferates at elevations below 500 m
the leaf; the veins occur in 15-30 pairs angled slightly up and whereas the other species occur at elevations above 1,000 m.
out from the center and base (Figure 2). The fig, F. insipda’s Also, F. insipida has a different pollinator from the other two
fruit, at maturity displays a yellowish-green color with lighter species (Smithsonian). Each Ficus species has a species-
yellowish-green spots. These figs only reach about 5-15 cm specific wasp that contributes to the pollination process. One
long when fully matured (Figure 3). In order for the tree to of the known pollinators of F. insipida is the agaonid wasp.
grow, the seedlings require a sufficient amount of light, These wasps, like many of the other fig wasps, use the
meaning many of these trees are found in “younger” or newly syconium, a fleshy hollow enclosure inside the surface of the
formed areas of forests (Smithsonian). The sustainability of fig fruit, as a mating receptacle. When these wasps retreat
these trees includes guidelines that only allow for a particular from the fruit, seeds are carried along and dropped along the
tree to be tapped after the tree has reached at least seven wasps’ path, thus spreading the seeds of the fig tree and
years of maturity, leaving a gap of twelve months between prolonging the existence of F. Insipida (Smith and Bronstein,
each tapping, and not allowing a cut of more than 1 cm in the 1996). While studying F. insipida at the Le Selva Biological
tree to ensure tree viability (Phillips 1990). Station in Costa Rica, bats and fish were also found to be
pollinators of the tree (Banack et al., 2002).
Because of its similarity to other species in Costa Rica and
Panama, this particular species of fig tree has been confused
Traditional Uses Among the peoples of the Peruvian Amazon that speak Iquito,
The latex from this species has been used traditionally as an the approach to healing involves not only dietary restrictions
anthelmintic in Central and South America (de Amorin et al., and limiting physical activity but also the use of plants
1999). Based on current knowledge sought out by Hansson et associated with specific plant spirits, to avoid exacerbating
al. (2005), indigenous populations living in the upper Napo illnesses. According to a study conducted by Jernigan (2011),
River region of Peru that have used or currently use Ficus the Iquito speaking people believe that diarrhea comes from
insipida to treat parasitic-related illnesses, mainly in children, temperature, dirty water, and bad food, parasites result from
did/do not relate the parasites to the illnesses (ex. anemia and walking barefoot and eating bad, and anemia comes from
diarrhea). Rather, they felt that since one was born with such having bad blood, lack of blood, and bad hygiene. Spirits
parasites, they were merely treating the symptoms, such as associated with certain plants are integral into the type of diet
diarrhea, respiratory complications, and pale complexion, and and illness treated. Unlike the peoples living in the Napo River
not the eradication of the parasites. Another reason for the region, this group believes F. insipida has a plant spirit that
disconnection between the parasites and illness is due to the helps in treating only parasites. F. insipida remedies are
fact that the transmission of these parasites to the child is accompanied by strict diet guidelines because it is believed, by
accomplished via non-boiled or unsanitized drinking water the Iquito, to be a “jealous” spirit. Another group that uses the
and/or via the soil. latex mixture are the Ese-Eja Indians, who tap the tree for
latex in the early morning when it is most viscous and
Preparation of the remedy involves collecting the latex in a jar distribute dosages according to the season (Phillips 1990).
the day before treatment, to ensure freshness. The latex is
then mixed with the juice of oranges, cocona, or sugar cane
and given orally in small doses (spoonfuls). The latex is Chemistry and Pharmacology
sometimes mixed with sugarcane brandy to prevent
In a recent study, the chemical constituents of Ficus insipida
decomposition and fungal growth, in order to prolong storage
were measured from the reserves at La Selva Biological
(Hansson et al., 2005). This is done in the early morning,
Reserve in Costa Rica via the leaves collected from the tree.
before sunrise. Accompanying the latex mixture is a period of
The leaves were dried and subsequently doused in 70%
fasting in which only sanitized water is drunk throughout the
acetone to extract constituents. All constituents found can be
day. At night a light meal of plantains and manioc is commonly
seen in Table 1 (Ardon and Pringle, 2009).
eaten; foods such as peppers, salt, and meat are avoided
several days before and after the use of this remedy. To treat The active constituent that gives this tree its anthelminitc
anemia, diarrhea, and abdominal distension, this remedy is properties is the proteolytic enzyme ficin, also known as ficain
taken for 2 consecutive days once every 4 months, to avoid (de Amorin et al., 1999). Ficin is a general term for the
overdose. The remedy is considered successful when visible cysteine proteases, in the papain family, found within the Ficus
symptoms have disappeared (Quave 2000). genus (Azarkan et al., 2011). Ficin contains 2 L-cysteine thiol
groups; these thiol groups act as catalytic sites (Malthouse and
Brocklehurst, 1976). It is at these sites that
Known Constituents % Mass Clinical Studies
Condensed Tannins 0.5
A clinical study consisting of 181 persons from three
Total Phenolics 11.8
Amazonian villages sought to determine the safe and effective
Hydrolysable Tannins 2.7
dosage of latex taken systemically. The persons involved held
Lignins 8.3
a 92% prevalence of helminthiasis: Ascaris 68%, Strongyloides
Cellulose 19.1
42%, Trichuris 41%, Ancylostoma/Necator 26%, and Taenia
Hemicelluloses 14.7
1%. Biological activity was measured using a milk coagulation
Table 1. Known constituents of Ficus insipida expressed as
test. Pharmacological efficacy was determined using live
a percent mass of the plant.
Ascaris, in vitro, in which concentrations of latex (in
physiological saline solution) as low as 0.05% was sufficient
ficin is able to digest the parasitic invaders without harming for the suppression and digestion of Ascaris (Hansson et al.,
the human host. Peak activity of ficin was found to be at pH 7.0 1986).
and found to be related to the solvents added, such as sucrose,
The anthelminitc activity of Ficus insipida was studied
trehalose, and xylitol (Devaraj et al., 2008). Cysteine proteases
retrospectively over a 12-year period by Hansson et al. (2005)
are used by the plant in insect resistance, protein degradation,
in Pucallpa, Peru. This area was of great interest due to the 39
maturation, to regulate the folding of proteins, and in some
reported cases, involving mostly children, of F. insipida-related
cases involved in proteolysis. They also are involved in the
symptoms due to toxicity. Of the 39 cases, the majority were
assembly of storage proteins for seed utilization. For insect
due to overdoses (small>1.5 cm3/kg, large>4 cm3/kg). One
resistance, it was found that the hydrolytic enzymes are
fatality occurred among the hospitalized patients, while two
involved in the inhibition of larvae growth (Gonzalez-Rabade
fatalities were reported to have occurred outside the confines
et al., 2011).
of the hospital. In severe cases of toxicity cerebral edema was
reported, for which the treatment was mannitol.
Biological Activity Additionally, in less severe overdoses adults were reported as
In a study conducted by de Amorin et al. (1999), mice infected having primarily cardiovascular and respiratory
with helminthes (Syphacia obelvata, Aspiculuris tetraptera, complications and children were reported as having more
and Vampirolepis nana) and treated with F. insipida-derived musculoskeletal complications, while both adults and children
latex at 3 ml/kg/day for 3 consecutive days showed significant were reported as having gastrointestinal issues. The
elimination of A. tetraptera and V. nana but not S. obvelata. treatment for the less severe cases involved various kinds of
During necropsy of the animals they found hemorrhagic drugs including antacids, pyridoxine, atropine, and
effects in the mucosa of the gastrointestinal tract. When a high dexamethasone, depending on the symptoms present.
dose of 10 ml/kg/day was applied for 3 consecutive days, the
authors found a lethality of 60%, thus, demonstrating the
toxicity of this latex at both high and low doses.
Contraindications
It has been reported in both adults and children that
gastrointestinal complications, cerebral edema, and death
have occurred. However, only large overdoses (>4 cm3/kg)
have been reported to cause the cerebral edema and fatalities
(Hansson et al., 2005).

There are no current uses of Ficus insipida latex in allopathic
medicine; however, it is still used in today among Amazonian
villagers and among those who live near those areas where F. Figure 4. The 25 ml bottle of F. insipida
insipida flourishes. In Peru, bottles of latex mixtures are sold latex marketed by Natural Remedies
by independent vendors in many of the main markets. Haven Ltd. (Source: http://www.weight-
Although the sale of the latex mixtures is still lucrative, it is care.com/herb_Ojelatex.htm)
not as prominent as it once was, due to the accessibility to
allopathic medicine. According to the vendors, the
one liter of water, and to drink this mixture every other day
recommended dose is approximately 2 cm3/kg, which can be
until the problems subside (Natural Remedies Haven Ltd.).
taken over the course of three days, and should be taken in the
early morning on an empty stomach, following a conservative
diet for the rest of the day. This regimen should be applied Discussion
once or twice a year, as needed (Hansson et al., 2005). This
slightly contradicts the recommended dose found to be safe The latex derived from Ficus insipida Willd. has been used
through clinical trials: 1 cm3 of latex mixture/kg for 3 days traditionally for generations among the peoples of the
every 3 months (Hansson et al., 1986). Amazonian region for the treatment of helminthiasis and its
resulting symptoms. Because of this tree’s distinct
Natural Remedies Haven Ltd. currently markets, online, F. characteristics and the vast exposure Amazonians have
insipida latex as an alternative supplement, in the form of ojé experienced with this tree, it is not confused with other
latex sold in 25 ml bottles, to current pharmaceuticals (Figure species from the Ficus genus. The traditional preparation of
4). The ojé latex is mixed with either water or fermented with the latex is still in practice today. The maximum biological
sugar. The company markets this to treat worms, bacteria, activity is achieved when the latex is mixed with sugar
anemia, and rheumatic inflammations. As for the dosage, they (sucrose), which reflects its traditional preparation. This latex
recommend mixing one tablespoon of the latex mixture with mixture is sold locally in markets and internationally (on a
very small scale) via the internet. Quality of the latex being
sold, at least among the local markets, is of little concern of five fully active ficin (iso)forms from Ficus carica latex.”
because of the abundance of the tree and the knowledge the Phytochemistry 72(14-15):1718-31.
vendors carry about the preparation and use of the latex. The de Amorin A, Borba HR, Carauta JP, Lopes D, Kaplan MA. (1999)
toxicity experienced from those taking F. insipida mixtures is “Anthelmintic activity of the latex of Ficus species”. J
not due to taking the improper latex from other Ficus species, Ethnopharmacol 64(3):255-8.
but rather taking an overdose of the F. insipida latex. Devaraj K, Ramesh K, Prakash V. (2008) Purification,
Furthermore, the use of this latex has yet to become a characterization, and solvent-induced thermal stabilization
dominant remedy globally due to the limited availability of the of ficin from Ficus carica.” J. Agric. Food Chem.
tree worldwide and to the ability to access either allopathic or 56(23):11417-11423.
safer, alternative CAM therapies. Another reason these latex González-Rábade N, Badillo-Corona JA, Aranda-Barradas JS, Oliver-
or pharmacologically-derived latex remedies are not found in Salvador Mdel C. (2011) “Production of plant proteases in
allopathic medicine is that the associated risks and possible vivo and in vitro — A review.” Biotechnol Adv. 29(6):983-96.
side effects far outweigh the benefits that come with the use of Hansson A, Veliz G, N’aquira C, Amr’en M, Ar’evalo G. (1986)
the latex compared allopathic remedies, which are often much “Preclinical and clinical studies with latex from Ficus
safer and more readily available. Additionally, the active glabrata HBK, a traditional intestinal anthelminitc in the
component, ficin, is currently not isolated from this tree, for Amazonian area.” Journal of Ethnopharmacology 17:105-
reasons unknown, even though ficin has been found to be 138.
involved in several diseases and cell signaling pathways. Hansson A, Zelada J, Noriega H. (2005) “Reevaluation of risks with
However, because of the relatively easy access to this the use of Ficus insipida latex as a traditional anthelmintic
particular species and the growing importance of the cysteine remedy in the Amazon.” Journal of Ethnopharmacology
proteases found within this plant, future pharmaceuticals will 98(3):251-257.
probably include some form the these cysteine proteases, Jernigan K. (2011) “Dietary restrictions in healing among speakers
whether it be synthetically derived forms or pure forms. of Iquito, an endangered language of the Peruvian Amazon.”
Journal of Ethnobiology and Ethnomedicine 7:20.
References Cited Malthouse P, Brocklehurst K. (1976) “Preparation of fully active

ficin from Ficus glabrata by covalent chromatography and
Ardon M, Pringle C. (2009) Does leaf chemistry differentially affect characterization of its active centre 2,2’-dipyridyl disulfide
breakdown in tropical vs temperate streams? Importance of as a reactivity probe.” Biochem J.159:221-234.
standardized analytical techniques to measure leaf
chemistry.” J. N. Am. Benthol. Soc. 28(2):440-453. Natural Remedies Haven Ltd. “Ojé / Doctor ojé – Latex.” Acessed
October 2011. <http://www.weight-care.com/herb
Azarkan M, Matagne A, Wattiez R, Bolle L, Vandenameele J, Baeyens- _Ojelatex.htm>
Volant D. (2011) “Selective and reversible thiol-pegylation,
an effective approach for purification and characterization
Phillips, Oliver. (1990) “Ficus insipida (Moraceae): Ethnobotany and Smithsonian Tropical Research Institute.Bocas del Toro: Species
Ecology of an Amazonian Anthelmintic.” Economic Botany Database. “Ficus insipida Willd.” Accessed October 2011.
44(4):534-536. <http://biogeodb.stri.si.edu/bocas_database/search/specie
s/2047>
Quave C. (2000) “Plants and Pills: Health consequences of western
medicine in the Peruvian amazon.” Emory University 1-11. Tropicos.org. Missouri Botanical Garden. Last Modified October 21,
2011. <http://www.tropicos.org/Name/21300606>
Sandra Anne Banack, Michael H. Horn and Anna Gawlicka. (2002)
“Disperser- vs. Establishment-Limited Distribution of a University of Hawaii. “Ficus insipida.” Accessed October 2011.
Riparian Fig Tree (Ficus insipida) in a Costa Rican Tropical <http://www.botany.hawaii.edu/herbarium/digitallib/colle
Rain Forest.” Biotropica 34(2):232-243. ctions/hlaplants/pdfs/Mor_Ficus_insipida_w.pdf>
Smith CM and Bronstein JL. (1996) “Site variation in reproductive
synchrony in three neotropical figs.” Journal of
Biogeography 23:477-486.
Ginkgo biloba L., Ginkgoaceae
Benjamin Kramer-Roach
Introduction
Ginkgo biloba L. (Figure 1) is the sole surviving member of the
Ginkgoaceae family, a family of “living fossils” that has its
roots in the Mesozoic era (Taylor, 1993). In more recent times
G. biloba is thought to only grow natively in a certain region of
Southeast but it is now common to find them in many
countries throughout the world. Botanist Engelbert Kaempfer
introduced the ginkgo tree to Europe in 1690 and gave it the
name “duck foot tree” due to the signature shape of its leaves
(Bilia, 2002). The name “ginkgo” is derived from the Chinese
word for silver apricot, and this name was given to the tree
because of the size and coloring of the fruit (Mahadevan,
2008). Other common names of G. biloba include silver
apricot, yajiao (duck foot), gong sun shu (grandfather tree),
maidenhair tree, temple tree, noyer du Japon, Kew tree, and
Ginkgobaum (Hori, 1997). The leaves and nuts of this tree
have been used in traditional Chinese medicine (TCM) for
millennia to treat a variety of ailments involving the brain,
heart, and lungs. In modern medicine gingko extract is
primarily known for cognitive enhancement and treatment of
cardiovascular problems, but the standardized extract (EGb
761) has shown promise as a cancer-preventative as well. As
with every plant-based medicine, it is challenging to attribute
the medicinal effects of G. biloba to a single chemical or Figure 1. Ginkgo biloba tree.
pathway because of the synergistic tendencies of the Source: David Stang,Tropicos.org
chemicals. Ginkgo leaves have been shown to contain terpene
lactones, biflavones, and flavonoid glycosides, which act on a insect invasions, which has led to its proliferation in cities and
variety of pathway and receptors (Spinella, 2001). These gardens and has made it extremely popular in global markets
chemicals provide it with ample resistance to infections and for its perceived cerebral enhancing properties. In addition, it
is annually a top-selling herbal supplement sold around the
world for its effects in boosting memory (van Dongen, 2000).
Approximately 180 million years ago, the Ginkgoaceae family
extended to nearly every continent, from sub-polar regions
like Canada to the tropics. Ginkgo biloba, though, the last
remaining species, is now thought to only grow in the wild in
the Zhejiang Province in China, specifically on the Tian Mu
Mountain (Shen, 2005). However, mystery still shrouds the Figure 2. Leaves and fruit of Ginkgo biloba.
origins of this population, and there is debate over whether Source: W. H. Hodge from Tropicos.org
the trees are truly wild or are merely semi-wild descendants
of trees cultivated in Buddhist temples (Del Tredici, 1992).
ornamental areas like cities and gardens to avoid the
Ginkgo trees grows best in cool, wet climates and in deep soil odoriferous fruit.
with good water retention, but in recent decades it has been
The leaves of Ginkgo biloba are flat and fan-shaped and exhibit
able to adapt to a variety of habitats around the world due to
two lobes divided by a cleft of varying sizes, a trait to which G.
their high resistance to disease, insects, and air pollution
biloba owes its name (Figure 2). Sprouting in clusters of 4 - 8
(Andrews, 1947). Ginkgo trees are dioecious, meaning that
from the short roots, the leaves emerge light green in the
each tree produces either all male or all female flowers. The
spring and fade through dark green to a golden color in late
trees themselves can grow to be around 100 feet (30 meters)
autumn. The veins on the leaves are unique from other shade
high and have been known to live thousands of years. They do
trees in that rather than having a mesh-like structure, ginkgo
not start producing seeds for up to 25 years, but can remain
leaves have a branching venous pattern that protrudes from
fertile for as long as they live (Taylor, 1993). Flowers appear
the stem and branches continuously to fill out the leaf
in spring from stubby appendages on the branches, called
(Andrews, 1947).
short roots, in small clusters as catkins. The plum-sized fruit
ripens throughout the fall to a golden color and covers the
seed in a plump outer covering and a woody shell. Traditional Uses
Fertilization occurs via motile, multi-flagellated sperm from
the pollen (Dallimore, 1948). Due to the butyric acid content Ethnomedicinal uses
of the fruit, when the ripe fruit falls and splits open during Ginkgo biloba has a long history of use in traditional Chinese
autumn, it emits a powerful odor, akin to rancid butter, medicine (TCM) with a host of uses. The seeds or nuts,
despite the edible nut inside (Andrews, 1947). Male trees, removed from the outer fruit, were used to treat certain
which do not bear fruit, tend to be more common in pulmonary disorders, like asthma, bronchitis, cough, and
enuresis, in addition to bladder inflammation, kidney
ailments, and leucorrhea (Mahadevan, 2008; Bilia, 2002;
Smith and Luo, 2004). The seeds have been used extensively
in TCM for millennia. In contrast, leaves of G. biloba were only
used marginally in the past and were first recorded to have
medicinal properties in a book by Lan Mao, published in 1436
C.E., when they were recorded to have effects on treating skin
disorders such as head sores. A little later, in 1505, C.E Liu
Wan-Tai wrote about the first internal use of ginkgo leaves,
which was for the treatment of diarrhoea (Bilia, 2002). The
leaves, though, have grown to be seen as being beneficial to Figure 3. Ginkgo biloba seeds and nuts.
the heart, brain, and lungs (Mahadevan, 2008; Bilia, 2002). Source: Oregon State University, 1999-2012.
Cultural uses
Uses in cuisine
Taoist beliefs incorporate the balances of yin and yang and are
The seeds, often called Pak-Ko (meaning white fruit), are a often represented by certain plants and animals. Ginkgo is
popular snack and considered a delicacy in many East-Asian used to exemplify this concept, with one temple serving a dish
countries, including Japan, Korea, and China. They can be called ginkgo chicken, with ginkgo representing yin and
cooked into sweet desserts, like the dish Cheng Tengm, or rooster symbolizing yang. It is believed that when eaten as a
roasted and eaten as an appetizer (Porterfield, 1951; Goh, whole, the dish replenishes vitality (Shermann, 1985).
2002). Ginkgo seeds, shown in Figure 3, are in season during
winter months after the fruit has matured (Goh, 2002). The Due to its beauty and hardiness against disease, insects, and
extraction of the seed begins by harvesting the plum-sized air pollution, G. biloba has been a popular ornamental tree for
fruits from the tree and allowing them to ferment in water for thousands of years (Briskin, 2000). It appears in Buddhist
several days. (This process causes a highly unpleasant temples in both China and Japan, but its popularity has grown
aroma.) If the fruit itself is eaten, it has a bitter taste and is and can now be found in many countries all across the world,
therefore typically fermented or cooked (Mahadevan, 2008). particularly in urban centers (Bilia, 2002). The unique
Once soaked in water, the flesh of the fruit can be easily elegance of the leaf has also led to its incorporation in various
removed from the edible seed within. The seeds must be forms of art and sculpture.
roasted or cooked because raw seeds are toxic and
consumption of them often results in serious food poisoning
(Bilia, 2002). Traditional Chinese foods like chawan-mushi, a Chemistry and Pharmacology
custard-like dish, and nabe-ryori incorporate ginkgo nuts as a Ginkgo biloba has a multitude of phytochemicals, including
main ingredient (Bilia, 2002). terpene trilactones, flavanol glycosides, biflavones,
Class Major Constituents Approximate
% in EGb 761
Flavanol glycosides Quercetin, kaempferol and 24
isorhamnetin
Carboxylic acids Phenolic and non-phenolc 13

acids
Proanthocyanidins - 7
Terpene Sesquiterpene trilactones 6
trilactones (bilobalide)
Ginkgolides A, B, C, J, and M
Alkylphenols Ginkgolic acids, ginkgols and 5 - 10 ppm
bilobols
Figure 4. Structure of bilobalide. Source: Biflavones Bilobetin, ginkgetin, 0
http://www.pipitech.com/newproduct/bilobalide/bilobalideLS.htm isoginkgetin and sciadopitysin
Polyprenols - 0
- B6 4-O-methylpyridoxine 0
proanthocyanidins, alkylphenols, polyprenols, and 4-O-
methylpyridoxine (van Beek, 2002). The unique, primary Table 1. Chemical constituents of G. biloba. (Information
constituents found in Ginkgo biloba are terpene lactones, derived from van Beek, 2002)
biflavones, and flavonoid glycosides. The terpene trilactones
include bilobalide (technically a sesquiterpene trilactone), concentration in the fall than in the spring, and therefore the
shown in Figure 4, and five types of ginkgolides (A, B, C, J, and leaves must be analyzed during the multi-step extraction
M), which are twenty-carbon terpenes manufactured in the process for chemical levels and presence of heavy metals
roots and leaves of the tree (Mahadevan, 2008; Smith, 2004; before being made into the extract (Mahadevan, 2008; Chan,
Spinella, 2001). The flavonol glycosides include compounds 2007). The creation of this extract involves many procedures,
such as quercetin, rutin, kaempferol, and isorhamnetin (van some of which are undisclosed, and condenses leaves to
Beek, 2002; Mahadevan, 2008). Other chemicals such as extract in the ratio of 50 to 1. This concentration also removes
Isoginkgetin, ginkgetin, bilobetin and sciadopitysin are all unwanted components like biflavones, catechins, and
biflavones (van Beek, 2002). polyprenols, which can have negative health effects (Chan,
2007; van Beek, 2002). Consuming ginkgo leaves, as in a tea
A standardized extract was developed by German and French for example, instead of extract has minimal health effects
pharmaceutical companies called EGb 761, which is the main because of the extremely low concentration of active chemical
extract used in experiments. The chemicals are extracted compounds (Chan, 2007). The standardized Ginkgo biloba
through either a water-ethanol or water-acetone process from extract contains approximately 6% terpene lactones, 24%
green leaves harvested and dried in the summer (Mahadevan, flavonoid glycosides and less than 5 ppm Ginkgolic acid (Van
2008; Bilia, 2002). The chemical constituency of the leaves Beek, 2009; Goh, 2002). The chemical constituents of G. biloba
varies depending on the season, with greater flavanoid
are listed in Table 1 with their associated concentrations in improve memory function and spatial learning in young and
the extract. old rats as well as short-term memory in mice (Perry, 2011).
Proanthocyanidins, also found in wine, are partly responsible By acting on the hippocampus in animals, which is involved
for the antioxidant properties of the extract and contribute to with the creation of new memories, EGb 761 was shown to
ginkgo extract’s medicinal effects (van Beek, 2002). B6 4-O- boost memory retention and acquisition in other vivo studies
methylpyridoxine, a chemical found in primarily in the seeds, as well (Smith and Luo, 2004). EGb 761 was found to be
is toxic to humans and is removed in the creation of the beneficially involved with the following processes in rats: free
extract (van Beek, 2002). radical scavenging, age-related brain losses, ischaemic
neuronal death, hippocampal function, hippocampal uptake of
high-affinity choline, regulation of hippocampal glucocorticoid
Biological Activity receptors, plasticity of neurons, and stress-related cognitive
In Vivo deficits (Smith and Luo, 2004).
Numerous studies have been conducted to test the benefits of Smith and Luo (2004) found that Caenorhabditis elegans, a
standardized Ginkgo biloba extract (EGb 761), particularly for nematode, demonstrated increased resistance to both thermal
its memory enhancement capabilities and its efficacy in and oxidative stress when fed EGb 761. Similarly, rats treated
protecting against neurodegeneration. with moderate amounts of ginkgo extract through their
drinking water showed reduced oxidative damage to
A study by Winter (1997) tested the memory effects of EGb mitochondrial DNA in the liver and brain (Chan, 2007). This
761 extract on rats. The rats were first acclimated to a multi- emphasizes the importance of antioxidants as a component of
armed maze and the number of false starts made by the rats ginkgo extract (Smith and Luo, 2004).
was recorded. The research found that rats that had been
orally administered EGb 761 via consumption of sweetened, To highlight another pathway that ginkgo extract effects, mice
condensed milk showed improved memory, as judged by fed EGb 761 for four weeks in one study showed a dramatic
fewer false starts. Moreover, rats that consumed EGb 761 up-regulation in ten genes that have neuroprotective roles
lived significantly longer than those that had not (Winter, (Smith and Luo, 2004). Other studies along the same theme
1997). A study by Anna Walesiuk et al. (2005) found that rats point towards the capability of ginkgo extract to regulate
subject to either stress or drug-induced memory loss regained transcription of certain genes pertaining to adaptive response
memory function with the addition of EGb 761 into their diet of organisms thereby increasing tolerance to oxidative stress
In an experiment by Yohitake (2010), aged rats improved (Smith and Luo, 2004). The stress-reducing activities of
their spatial cognition after doses of Ginkgo biloba extract ginkgo extract suggest effects on receptors in the
were administered. In addition, the extract was effective dopaminergic system (Yohitake, 2010).
against Alzheimer’s and Parkinson’s disease in animals tested Rats fed EGb 761, one study showed, had substantially
(Yohitake, 2010). Extracts have also been shown to decreased levels of stress, which researchers attributed to the
effects of the ginkgolides on the expression of the peripheral
benzodiazepine receptor in the adrenal cortex (Smith, 2004; Both the proanthrocyanidins and flavonol glycosides have
DeFeudis, 2000). This reduction helps to control levels of antioxidant properties, such as free-radical scavenging, which
circulating glucocorticoids, which has extensive favorable can reduce oxidative stress (Chan, 2007). This is also
consequences such as decreased immunosuppression, responsible for some of the relaxation of blood vessels, and
neurotoxicity, and neuroendangerment (Amri et al., 1996). thus the increased blood-flow, effects of the extract (Kleijnen
Certain flavanols, like kaempferol, have been tested for cancer and Knipschild, 2002).
prevention and some studies have found a positive effect on An altered version of EGb 761, called IPS200, was
colon and prostate cancers (DeFeudis et al., 2003). Monte et administered to human breast cells in an in vivo study
al. (2004) found that in mice, EGb 761 inhibited lymphocyte- conducted by DeFeudis et al. (2003). The study found that the
induced angiogenesis, a process essential to cancer growth. altered version had regulatory effects on a number of genes
Similarly, DeFeudis et al. (2003) found that mice given ginkgo involved with cell proliferation and apoptosis, suggesting anti-
extract showed decreased expression of peripheral cancer properties.
benzodiazepine receptor (PBR) and therefore suppressed
proliferation of breast cancer cells. Feng, et al. (2009) found
that the flavanoids in ginkgo extract exhibited anticancer Clinical Studies
properties. When the extract was administered to mice with There have been many clinical trials of Ginkgo biloba leaf
leukemia, many of the treated mice showed signs of tumor extract, particularly EGb 761, for its cognitive enhancing
suppression and reduction after a week and a half of abilities on both mentally impaired and healthy people, the
treatment (Feng, 2009). treatment of other conditions involving cardiovascular
deficiencies and neurodegenerative disorders, its antioxidant
and anxiolytic effects, and its efficacy in treating
In Vitro
antidepressant-induced sexual dysfunction. Many of these
The neuroprotective qualities of EGb 761 are derived from its found ginkgo extract to have an overall beneficial effect.
reaction with many cellular pathways simultaneously and
There is a wealth of studies demonstrating the beneficial
synergistically (Smith and Luo, 2004). In vitro EGb 761 was
characteristics of EGb 761 on a number of ailments, but there
observed to have multiple methods of action for its
are also many studies that found no substantial evidence
neuroprotective characteristics such as up-regulating certain
supporting the use of EGb 761 for treating many of them. One
proteins and maintaining membrane potential in
study highlighted this schism in the literature by first positing
mitochondria. (Smith and Luo, 2004). Likewise EGb 761 has
that while they found mild cognitive improvement in patients
been shown to improve cardiac conditions by altering ion
treated with ginkgo extract, the trials with overwhelming
concentrations across membranes, thus altering action
success might have been due to other factors, and then in the
potentials that results in vasorelaxation and vasodilation in
same study, admitting that G. biloba is one of the plants most
aortic smooth muscles (Satoh, 2004).
effective against dementia and other cognitive ailments like
premenstrual tension and tinnitus (Perry, 2010). The few The reduction in Aβ also leads to decreased apoptosis of
studies showing no effect are lost among the flood of studies neurons: a counter to the cause of many neurodegenerative
detailing the successes of ginkgo extract. In a series of clinical diseases (Mahadevan, 2008; Smith, 2004). Le Bars, et al.
trials conducted by a research team, extract of G. biloba was (1997) also found in a double-blind, placebo-controlled
found to be effective against a variety of conditions such as experiment that EGb 761 improved cognitive functioning in
“early-stage Alzheimer’s disease, vascular dementia, elderly patients with dementia or Alzheimer’s disease.
peripheral claudication, vertigo, heart disease, eye diseases, Kleijnen and Knipschild (1992) found that when ginkgo
chronic cerebral insufficiency, accidents involving brain extract (120-160 mg daily for a period of more than four
trauma, dementia, and tinnitus of vascular origin” (Cxavusxog˘ weeks) was given to forty patients with cerebral
lu, 2011; Napryeyenko, 2007). insufficiencies, most experienced beneficial outcomes. The
In two trials testing the effects of ginkgo extract on healthy cerebral insufficiencies encompassed a range of symptoms
volunteers aged 18-40 and 22-59, at the dosage of 120 from tiredness to confusion.
mg/day for thirty days and fourteen days respectively, both The alkaloids in the extract were found to be powerful
found that exposure to extract from the leaves increased the antagonists of platelet-activating factors (PAF) in several
working memory of volunteers, but did not effect long-term studies. Since PAF are inflammatory autacoids and are
memory (Hartley, 2003). Numerous other studies echo important to the pathologies of inflammatory conditions like
similar results in finding that healthy volunteers who had ischemia, asthma, CNS disorders, and shock, ginkgolides are a
ginkgo extract of a comparable dosage showed an improved valuable natural defense against these diseases (Braquet and
working memory, particularly in older subjects, while not Hosford, 1991). Along the same lines, ginkgolides reduce
exhibiting any changes in other types of memory like reaction aggregation, increase blood circulation, and can be used to
time, attention, or word recall (Hartley, 2003). From this increase blood flow to the brain after an ischemic incident
information it can be deduced that certain sections of the (Smith and Luo, 2004). The sesquiterpene trilactone
brain, most likely the frontal lobe (responsible for working bilobalide has shown promise in reducing volume of cortical
memory), and certain age groups (primarily the elderly) are infarct following a stroke or cerebral ischemia by amplifying
most affected by G. biloba extract (Hartley, 2003). flow of glucose and oxygen to the brain (Smith and Luo, 2004).
Most studies agree that Ginkgo biloba is effective in the There have also been several studies that found there was
treatment of Alzheimer’s disease and mental deterioration. statistically significant data to support the use of EGb 761 to
This effectiveness can be attributed to several characteristics increase standards of living and mental well being in terms of
of chemicals found in the leaves. The extract inhibits the decreased depression, anger, and fatigue (Cieza A et al.;
creation of the protein Aβ from its precursor β-amyloid, which Kennedy, 2007). Ginkgo extract was also found to be
is an essential step in Alzheimers disease pathogenesis. anxiolytic in humans and to reduce depression (Smith, 2004;
Aggregation of this proteolytic fragment exacerbates and DeFeudis, 2000; Evans, 2009).
promotes early onset and autosomal dominant versions of
Alzheimer’s disease, which can be suppressed by EGb 761.
The antioxidant properties in EGb 761 have also been found to taking high doses of G. biloba extract or consuming large
be useful in treating sexual dysfunction. The antioxidants amounts of the seeds (Spinella, 2001). In Germany, where
have the effect of protecting nitric oxide from degradation, much of the supply of EGb 761 is manufactured, companies
which in turn activates the enzyme guanylate cyclase. This are required to include on the label symptoms such as
effect leads to producing smooth muscle relaxation in the “headaches, dizziness, palpitations, gastrointestinal
penis, thus allowing an inflow of blood much like Viagra disturbances and allergic skin reactions” that can result from
(Chan, 2007). This explains the results of a similar study, in overdoses (Chan, 2007). Though these side effects must be
which ginkgo extract was found to be highly effective in included on the labels, a study by Kleijnen and
increasing sexual potency and minimizing the effects of Knipschild (1992) showed that there were no negative side
antidepressant-induced sexual dysfunction (Cohen, 1998). effects to taking EGb 761 over a period of three months (Chan,
2007).
Contraindications If the seeds are consumed raw they can produce symptoms of
food poisoning and gastrointestinal problems due to the
Ginkgo biloba leaf extract has been shown to have vasodilatory presence of the toxic 4-O-methylpyridoxine (van Beek, 2002).
properties, which has given rise to worries about possible
interactions with drugs that have anti-platelet forming or
blood-thinning effects. One study even found an increased Current Use in Allopathic and CAM Therapies
risk of hemorrhage when ginkgo extract was used in
Ginkgo biloba extract is one of the most popular drugs and
combination with more potent anticoagulants and blood
herbal supplements in Europe and the rest of the world, and it
thinners due to its effects on the platelet-activating factor
is part of a billion-dollar industry, primarily for its perceived
(Perry, 2010). However, similar to the debate over whether
value in increasing cognitive function (van Dongen, 2000). In
ginkgo extract has cerebral enhancing properties, there are
2008 in the U.S., Ginkgo biloba, as a dietary supplement and
conflicting studies involving the negative side effects of ginkgo
prescription drug, was the top-selling herbal medicinal
extract consumption. Specifically, one study focused on
product with a retail value of over $150 million, even
testing case studies that suggested negative synergistic
outselling popular herbal supplements such as echinacea,
reactions between G. biloba extract and drugs such as
garlic, and ginseng (Smith and Luo, 2004). It is sold under a
warfarin, aspirin, and ibuprofen (Izzo, 2009). Despite past
variety of trade names in America including “Ginkgobene,
claims that patients suffered from spontaneous hyphaemas or
Ginkgold, Ginkoba, Vasan” and many others (Spinella 2001).
intracerebral haemmorrhages due to drug reactions with
Popular prescription and over-the-counter ginkgo-based
ginkgo extract, this study found that there was no evidence for
drugs in Germany and France include brands like “Tebonin,
links between ginkgo extract and changes in blood coagulation
Kaveri, rökan, and Tanakan” (van Dongen, 2000).
parameters (Izzo, 2009).
As a dietary supplement ginkgo extract is typically taken by
On the other hand, there have been several instances of
people looking to increase mental alertness, memory, and
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Glycyrrhiza glabra L., Fabaceae
Elsa Lake
Introduction
Glycyrrhiza glabra L. belongs to the Fabaceae family. The
extract obtained from the roots is called licorice, and this is
the part of the plant that people use in foods and medicine.
The scientific name of the plant comes from the Greek word
glukurrhiza, which means “sweet root” (Edwards, 2000, p.
119). Common names for G. glabra include European licorice,
Spanish juice licorice root, liquorice, sweet wood, sweet
licorice, lacrisse (German), reglisse (French), and regolizia
(Italian) (Sena, 2010, p. 256; Lakshmi, 2011). The plant is
native to the lands around the Mediterranean, and it is alleged
that in the 1560’s it was brought to Britain by Dominican
monks (Edwards, 2000, p. 119). There are two closely related
species which originate in different parts of the world: G.
uralensis, which is known as Chinese licorice, and G. lepidota,
known as American licorice (Sena, 2010, 256). The main
active constituent of all three species of licorice is
Glycyrrhizin, which has a sweet taste (Li et al, 2011). For this
reason, licorice is commonly used to mask bitter tastes in
medicinal preparations (“Glycyrrhiza glabra”, 2005). The plant
has also been used as a mild laxative, anti‐arthritic,
antiinflammatory, anti‐biotic, anti‐viral, anti‐ulcer, memory
stimulant (being an MAOinhibitor), anti‐tussive, aphrodisiac,
anti‐mycotic, estrogenic, antioxidant, anti‐caries agent, anti‐
neoplastic, anti‐cholinergic, anti‐diuretic, and hypolipidemic
agent (Lakshmi, 2011). The many different chemicals in Figure 1. Drawing of Glycyrrhiza glabra. (Source: Koehler’s
licorice continue to be studied for these and more medicinal Medicinal-Plants
http://upload.wikimedia.org/wikipedia/commons/a/a4/Glycyrrhiz
properties.
a_glabra_-_K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-
207.jpg)
Glycyrrhiza glabra is a halophytic perennial shrub that grows
to a height of four or five feet (Figure 1) (Li et al, 2011;
“Glycyrrhiza glabra”, 2005). Every year, new stems are
produced, which are sturdy, erect, rough at the top, and
branched either from the base or from further up. The foliage
leaves are 10 to 20 cm long, alternate, and odd pinnate. The
leaflets are in three to eight pairs, and the stipules are very
small and drooping (Lakshmi et al, 2011). The plant has pale,
white to purplish flowers that resemble lilacs (Sena, 2010,
256). The axillary inflorescences resemble spikes, are 10-15
cm long, and are upright. Each flower is 1 to 1.5 cm long and
short-pedicled. The petals are narrow. The carina petals are
not fused, or beaked, but are pointed. The calyx is short,
shaped like a bell, and glandular-haired. The tips of the calyx Figure 2. A Comparison of Fruits of G. uralensis (left), the
are pointed lanceolate and are longer than the tube. The fruit Intermediate Plant (middle), and G. glabra (right) from
is a pod which is 1.5 to 2.5 cm long and 4 to 6 mm wide. It is Kazakhstan. (Source: Hayashi et al, 2003)
flat with thick sutures, erect and splayed, glabrous, somewhat
reticulate-pitted, and usually has three to five brown, reniform
(kidney-shaped) seeds (Lakshmi et al, 2011). medicinal use, is soft, fibrous, and has a bright yellow interior
G. glabra and G. uralensis look very similar in many respects, (Loftin, 1953; “Glycyrrhiza glabra”, 2005).
but they can be distinguished in that G. glabra has straight In symbiosis with rhizobia, Glycyrrhiza spp. fix nitrogen from
pods and linear-oblong shaped leaves, while G. uralensis has the atmosphere. G. glabra provides nutrients and shelter to
falcated pods and ovate shaped leaves (Figure 2) (Hayashi et rhizobia (Li et al, 2011).
al, 2003). There have also been plants documented in
Kazakhstan that have fruit and leaves with an appearance in G. glabra thrives best in fertile, sandy or clay soil near a river
between that of the two species; these plants are thought to be or stream or under cultivation where it can be irrigated
hybrids (Hayashi et al, 2003). (Lakshmi et al, 2011). It tends to grow on the riverbanks and
in the flooded fields of Mediterranean countries, which are
There is an extensive root system that is subdivided into three subtropical (Loftin, 1953; “Glycyrrhiza glabra”, 2005). G.
to five subsidiary roots that are 1.25 m in length. The main glabra can currently be found in Spain, Italy, Turkey, the
taproot is 15 cm long. There are also several horizontal woody Caucasus, Central Asia and the western part of China (Hayashi
stolons that can reach eight meters (Lakshmi et al, 2011). The et al, 2003).
main taproot, which is harvested every third or fourth year for
Traditional Uses dropsy, ulcerous sores of the mouth and genitals, and bladder
Preparation of Licorice Extract and kidney ailments (Sena, 2010, p. 260).
Dried roots of Glycyrrhiza glabra are collected in autumn, and During the Middle Ages, the knowledge of licorice was kept
the powdered and finely cut roots are used to prepare dry and alive in southern European monasteries (Loftin, 1953). It was
fluid extracts (Barceloux, 2008, p. 538). A simple aqueous used at that time to treat hypotension (Barceloux, 2008, p.
extract is prepared by boiling the root and then allowing most 537).
of the water to evaporate (Sena, 2010, p. 256). From this Licorice also plays a large part in traditional Chinese
extract commercial forms of licorice can be made. The three medicine; the Shen Nong Ben Cao Jing contains references to it
main ones are licorice powder, licorice paste and ammoniated (Barceloux, 2008, p. 537). The Chinese make frequent use of
glycyrrhizin crystals. the species G. uralensis, but this species does share major
active constituents with G. glabra (Kondo, 2007).
Ethnomedical Uses
Stores of G. glabra roots were found in the tombs of Egyptian Usage in Food, Beverages, and Tobacco
pharaohs such as the 3000-year-old tomb of King Licorice candies consist of three main ingredients: licorice
Tutankhamen (Loftin, 1953). These roots were placed there extract, sugar, and a binder (Sena, 2010, p. 258). The licorice
for the pharaohs to make a sweet beverage called mai sus in extract is in the form of a spray dried powder or ‘block juice’.
the afterlife. This ceremonial drink, still used today in modern The powder has a mild licorice aroma and bitter-sweet taste
Egypt, is used to honor the pharaohs (Sena, 2010, 259-60). (Edwards, 2000, p. 119). Contrary to common beliefs, licorice
The Greek botanist Theophrastus, who lived in the fourth powder is actually a light brown color. Artificial black coloring
century BC, stated that licorice could be used to quench thirst is frequently “added to licorice candy just to humor the
and treat asthma, dry cough, and other respiratory diseases consumers' preconceptions of what licorice should look like”
(Barceloux, 2008, p. 537). He also said it could be used to heal (Loftin, 1953). Block juice is a solid block resembling coal and
wounds when mixed with honey. The armies of Alexander has an overpowering licorice flavor and bitter-sweet taste
the Great and later the Roman armies carried licorice root (Edwards, 2000, p. 119). Not all candies labeled “licorice”
with them to quench soldiers’ thirst during long marches actually contain licorice extract; “red licorice” is actually made
(Sena, 2010, p. 260). In the first century BC, the Roman with cherry, strawberry, or raspberry flavorings, and many
naturalist Pliny the Elder wrote in his work Naturalis Historia “black licorice” candies are actually flavored with anise seed
about the usage of licorice for reducing hunger and thirst and oil, synthetic anisole, or anethole (Sena, 2010, p. 259).
for treating asthma and sterility in women (Sena, 2010, p. 260; Licorice is used to flavor and sweeten soft drinks, herbal teas
Barceloux, 2008, p. 537). He also wrote that licorice could be and various liqueurs, among other beverages. For example,
used in lozenges to clear the throat and as a remedy for glycyrrhizin crystals are used as a sweetening and foaming
Root Plant below the critical level. The plant decreased the soil and water
18-ALPHA-GLYCYRRHETINIC-ACID GLYCYRRHIZIC-ACID salinity and increased the productivity of wheat and cotton
18-BETA-GLYCYRRHETINIC-ACID crops (Li et al, 2011).
ASPARAGINE Leaf After licorice is extracted from the roots of the G. glabra, the
GLABRIDIN LICOFLAVANONE root fiber itself has a variety of uses. It can be boiled with
GLYCYRRHETINIC-ACID NICOTINIC-ACID caustic soda to make a stabilizer used in fire-fighting foam,
GLYCYRRHIZIN and it can be used to make a very effective insulation board.
GLYCYRRHETINIC-ACID- Rhizome Essential Pulp made from the leftover roots can be used to make a
MONOGLUCURONIDE Oil superior boxboard. The leftover roots can also be fortified
ISOLIQUIRITIGENIN ALPHA-TERPINEOL with chemicals and composted for about a month, and the
LIGNIN BENZALDEHYDE resulting fibers can be used as groundwork on which to grow
O-ACETYL-SALICYLIC-ACID OCTANOIC-ACID mushrooms (Loftin, 1953).
SUGAR PAEONOL
Shoot Rhizome
GLABRANIN GLABRIDIN Some major chemical constituents in Glycyrrhiza glabra are
PINOCEMBRIN listed in Table 1 (Duke, 2012). Glycyrrhizin, also called
URALENIC-ACID glycyrrhizic acid, is the main compound in G. glabra root
extract (Figure 3). It is a triterpenoid saponin glycoside, and
URALOZIDE-ACID
licorice root contains around 2-15 % triterpenoid saponins
Table 1. Non-ubiquitous chemicals in G. glabra that have a
(Sena, 2010, p. 256). Glycyrrhizin, when isolated as the pure
concentration over 1,000 ppm. (Source: Duke 2012).
compound, is an odorless, crystalline solid that is partially
soluble in cold water and very soluble in both hot water and
agent for beverages like root beer and birch beer” (Loftin, alcohol (Sena, 2010, p. 258). Glycyrrhizin tastes much sweeter
1953). than sucrose; Sena (2010, p. 258) reports that it is 30-50 times
sweeter, while Barceloux (2008, p. 539) reports that it is
In Italy and Spain, the root of G. glabra is chewed for use as a around 100-200 times sweeter. The sweet flavor is recognized
mouth freshener. Licorice is also a conditioning and flavoring more slowly and lasts longer than sucrose (Sena, 2010, p.
agent in many tobacco products (Sena, 2010, p. 259). 258).
Glycyrrhizin is found in G. glabra, G. uralensis, and G. inflate.
Miscellaneous Uses Other compounds common to all three species include
liquiritin, liquiritin apioside, isoliquiritin, isoliquiritin
G. glabra was cultivated in Uzbekistan for a period of four apioside, and liquiritigenin (Kondo, 2007). Glabridin, a
years in water-logged saline soils to keep the water table
Biological Activity
Antiviral activity
Glycyrrhizin and glycyrrhizic acid have been shown to inhibit
growth and cytopathology of numerous RNA and DNA viruses.
In vitro research with a human hepatoma cell line has shown
that glycyrrhizin completely suppresses the expression of the
hepatitis A virus’ antigen. Glycyrrhizin was proved to be 10
times more potent at reducing the infectivity of the virus. It
was also more cell-selective by five-fold, meaning that it was
less cytotoxic to the hepatoma cells. Glycyrrhizin has been
shown to irreversibly inactivate the Herpes simplex virus, and
it has been shown to inhibit viral replication and the
infectivity of HIV, herpes zoster, Varicella zoster, and CMV
(“Glycyrrhiza glabra”, 2005).
Figure 3. The Chemical Structure of Glycyrrhizin. (Source:

http://riodb01.ibase.aist.go.jp/sdbs/cgi-bin/direct_frame_top.cgi). Steroid-like anti-inflammatory activity
This activity is due to the inhibition of phospholipase A2
activity. In vitro research has also shown that glycyrrhizic acid
polyphenic flavonoid, is a major compound specific to the
inhibits cyclooxygenase activity and prostaglandin formation,
species G. glabra (Hayashi et al, 2003). When licorice is used
as well as indirectly inhibiting platelet aggregation
for medicinal purposes, the species does need to be taken into
(“Glycyrrhiza glabra”, 2005).
consideration because of the difference in constituents. Kondo
(2007) advises that “in the assessment of the six kinds of main
constituent contents, G. glabra and G. inflate can be used Antioxidant and hepatoprotective properties
equally as medicine, but G. uralensis might be not able to use
similarly with G. glabra or G. inflate.” Glycyrrhizin and glabridin inhibit the generation of reactive
oxygen species by neutrophils at the site of an inflammation.
Percentages of constituents also vary depending on the In vitro studies have demonstrated that the licorice
geographic location of the plant. Rutin was the major flavonol isoflavones hispaglabridin A and B inhibit Fe3+-induced
glycoside found in the leaves in Kazakhstan, but isoquercitrin mitochondrial lipid peroxidation in rat liver cells (“Glycyrrhiza
was the major leaf flavonoid glycoside in specimens collected glabra”, 2005).
in Turkey, Italy, and Spain (Hayashi et al, 2003).
Anticarcinogenic properties Memory enhancement
Research has found that glycyrrhizin and other licorice Maze and passive avoidance testing in mice indicate that
components inhibit abnormal cell proliferation, tumor aqueous extracts of licorice may have memory-enhancing
formation, and growth in breast, liver, and skin cancers properties by reversing chemically-induced amnesia.
(“Glycyrrhiza glabra”, 2005). The licochalcones have been
found to have radical scavenging properties, which may be
due to the regulation of (per)oxidizing enzymes. Clinical Studies
Herpes simplex virus
Antibacterial activity In one case report, a two-percent topical glycyrrhizic acid
cream (carbenoxolone sodium) was applied six times daily to
Nand, Drabu, and Gupta (2011) found that methanolic extracts
12 patients with acute oral herpetic infections, and the result
of licorice have broad-spectrum antibacterial activity. An in
was that pain and dysphagia were resolved within 24-48
vitro study showed that licorice flavonoids show activity
hours of the beginning of treatment. Ulceration and
against clarithromycin and amoxicilin-resistant strains of
lymphadenopathy gradually healed within 24-72 hours
Helicobacter pylori. Deglycyrrhizinated licorice (DGL)
(Lakshmi et al, 2011).
preparations may be effective against H. pylori infection since
the flavonoids seem to be what is behind the antimicrobial Stronger Neo Minophagen C (SNMC) is comprised of 0.2 %
property (“Glycyrrhiza glabra”, 2005). Licorice root extract glycyrrhizin, 0.1% cysteine, and 2.0% glycine (Coon & Ernst,
also showed significant antibacterial activity against the gram 2004). Oral and IV preparations of SNMC were given to infants
positive Bacillus subtili and Stapphylococcus aureus and the with CMV (Cytomegalovirus, a genus of herpes virus). Liver
gram negative Escherichia coli and Pseudomonas aeruginosa dysfunction and weight gain improved in nearly all cases as
(Lakshmi et al, 2011). compared to groups without treatment (Lakshmi et al, 2011).
Antifungal activity HIV

The compounds licochalcone A and glabridin are effective A clinical study consisted of three HIV patients with
antifungal agents (Messier & Grenier, 2011). G. glabra extracts hemophilia who were administered glycyrrhizin by IV at 400-
with 80% methanol (oil-based extract of licorice; OEL) were 1600 mg on six occasions over a one month period. The HIV
effective against filamentous fungi and some thermo-resistant p24 antigen, which was detected in all patients at the
bacilli. It also lessened contamination in beginning of treatment, had either decreased significantly or
polyethyleneterephthalate bottled tea based beverages, become negative by the end of one month. P24 antigen levels
indicating potential application in the prevention of beverage immediately elevated when the glycyrrhizin dose was tapered
and food spoilage due to microorganisms (Lakshmi et al, off (Glycyrrhiza glabra”, 2005).
2011).
Ulcers Weight Loss
In a double-blind study, 70 patients with endoscopically Fifteen normal-weight subjects (seven males, eight females,
confirmed gastric or duodenal ulcers were given either 300 ages 22-26) were given 3.5 mg of a commercial licorice
mg of carbenoxolone sodium or a placebo daily for seven days, preparation every day for two months. Plasma rennin activity
then 150 mg daily for the next 3-5 weeks. In the experimental and aldosterone were suppressed and there was a decrease in
group, there was an increase in pH of the stomach antrum body fat mass, but there were no changes in body mass index.
from 1.1 to 6.0 and a reduction in basal and histamine-induced The results indicate that licorice and its components may be
gastric acid secretion at pH 3 and 5. 70 percent of ulcers in the able to reduce body fat by inhibiting 11-R-hydroxysteroid
experimental group healed within 3-5 weeks, while 36 dehydrogenase in fat cells (“Glycyrrhiza glabra”, 2005).
percent of ulcers in the placebo group healed within that time
frame (Glycyrrhiza glabra”, 2005).
Contraindications
In one study on aphthous ulcers, twenty patients used a DGL
mouthwash four times a day, and in fifteen there was 50-75 Side Effects and Toxicity
percent clinical improvement after just one day, and after In the United States, the US Food and Drug Administration
three days, the canker sores completely healed. A double-blind (FDA) regulated licorice as a food supplement. As a flavoring
trial was completed where 24 patients with recurrent agent in food products, the FDA regards licorice as GRAS
aphthous ulcers were randomly allocated to consume either (generally recognized as safe) (Barceloux, 2008, p. 538). When
oral licorice mouthwash or a placebo three times a day after taken in higher concentrations as a supplement, however, a
meals for four weeks. The mouthwash consisted of 2 g common side effect of licorice consumption is a condition
glycyrrhizin (carbenoxolone sodium) in 30 mL of warm water. known as pseudoaldosteronism. Glycyrrhizin’s structure is
The use of the mouthwash significantly reduced the average very similar to the hormones secreted by the adrenal cortex,
number of ulcers per day, pain sores, and the development of so glycyrrhizin is capable of potentiating aldosterone action
new ulcers compared to the placebo (Glycyrrhiza glabra”, while binding to mineralocorticoid receptors in the kidneys.
2005). This can cause high blood pressure, hypokalemia (potassium
Clinical trials using DGL formulations, however, do not all loss), high blood pressure, and sodium retention, which
show clear evidence of effectiveness in treatment of ulcers. In results in edema (“Glycyrrhiza glabra”, 2005).
a placebo-controlled, randomized clinical trial of 96 patients The high concentration of glycyrrhizin in the root of G. glabra
with gastric ulcers, the group given DGL showed no is also evidenced to be toxic when chronically ingested in
differences in healing than the placebo group over a period of moderate to excessive amounts. An example of an “excessive”
4 weeks (Barceloux, 2008, p. 538). amount would be the ingestion of two to four licorice twists
daily for a month, which can increase glycyrrhizin levels to
over 400 ng/mL. Symptoms are usually related to
abnormalities in cortisol metabolism and include edema,
weight loss, weakness, hypertension, confusion, and 2008, p. 538). Licorice extract is also available as the above
hypokalemia. The toxic effects of high levels of glycyrrhizin in mentioned deglycyrrhizinated licorice (DGL) for treatment of
the body usually fade away by themselves once the ulcers (“Glycyrrhiza glabra”, 2005). Glycyrrhizin has been
consumption of licorice is halted (McLawhon, 2010, p. 438) removed from these extracts, and thus the metabolic side
effects caused by glycyrrhizin do not appear to occur with use.
DGL comes in tablet form and in studies on peptic ulcer
Drug Interactions treatment, DGL was used in dosages ranging from 760- 2,280
There are reported licorice-drug interactions with mg daily (Sena, 2010, p. 259; Glycyrrhiza glabra”, 2005). DGL
hydrocortisone, prednisolone, and oral contraceptives (Sena, formulations use a different mechanism than many other
2010, p. 268). Use of diuretics and licorice simultaneously may medications for ulcers. Others act by suppressing gastric acid
cause hypokalemia in patients with essential benign release, but DGL formulations increase mucous production
hypertension. When licorice is used in conjunction with and blood supply to the damaged stomach mucosa, which aids
digoxin, there is an increased likelihood of cardiac in mucosal healing (“Glycyrrhiza glabra”, 2005).
arrhythmias, especially in people with ischemic heart disease Several preparations specific to other countries include
(“Glycyrrhiza glabra”, 2005). constituents from G. glabra. Stronger Neo Minophagen C
(SNMC), mentioned above, has been used by the Japanese for
over 40 years in the treatment of Hepatitis C (Kumada, 2002).
Current Use in Allopathic and CAM Therapies It is an intravenous drug containing glycyrrhizin, glycine, and
Powdered preparations of licorice root usually contain 4-9 L-cysteine (Miyake et al., 2002). Ankaferd Blood Stopper
percent glycyrrhizin, and oral doses of 1-4 g per day divided (Figure 4) is used in Turkey for the management of external
into three to four doses have been used. Licorice extract is also hemorrhage and dental surgery bleedings. It is a standardized
available in liquid form, which contains 10-20 percent mixture of G. glabra, Thymus vulgaris, Vitis vinifera, Alpinia
glycyrrhizin, and oral doses of 2 – 4 mL per day are used officinarum and Urtica dioica (Goker et al., 2008).
(Sena, 2010, p. 259). Individuals vary widely in how much Licorice is also used in hand, skin, and body lotions, and as an
licorice is safe to consume, but at daily oral intake, the 1-10 ingredient in anti-aging creams (Sena, 2010, p. 259).
mg of glycyrrhizin (1-5 g of licorice, which contains 2% Glycyrrhizin crystals are also used to mask disagreeable
glycyrrhizin) is an estimated safe dose for most healthy adults. flavors and as a base for many drugs (Loftin, 1953)
In studies of DGL for peptic ulcers, the dosages ranged from
760 to 2,280 mg daily (“Glycyrrhiza glabra”, 2005).
The German Commission E approved daily doses of 200 – 600
mg glycyrrhizic acid for the treatment of peptic ulcers.
However, treatment is limited to five weeks, and patients with
cardiovascular or renal disease are discouraged from using
licorice unless closely supervised by a physician (Barceloux,
human health. One must keep in mind, however, that just like
many other medicinal plants, licorice is a flavoring in small
amounts, a medicine in average amounts, and in large
amounts, it can be a deadly poison.
References Cited
Actor, J. K. (2010). Herbal Medicines with Immunomodulatory
Effects Herbal Supplements (pp. 73-124): John Wiley & Sons,
Inc.
Barceloux, D. G. (2008). Licorice (Glycyrrhiza Species) Medical
Toxicology of Natural Substances (pp. 537-544): John Wiley
& Sons, Inc.
Coon, J. T., & Ernst, E. (2004). Complementary and alternative
therapies in the treatment of chronic hepatitis C: a
Figure 4. Ankaferd Blood Stopper (Source:
systematic review. J Hepatol, 40(3), 491-500. doi:
http://www.pakimarket.com/wp-
10.1016/j.jhep.2003.11.014
content/uploads/classipress/ankaferd-blood-stopp-
592027747.jpg). Duke, J. A. (2012). Dr. Duke’s Phytochemical and Ethnobotanical
Database. Retrieved from http://www.ars-grin.gov/cgi-
Discussion Edwards, W. P., & Royal Society of Chemistry (Great Britain).
Glycyrrhiza glabra has been used, documented, and (2000). The science of sugar confectionery. Cambridge: Royal
recommended by a variety of prominent figures throughout Society of Chemistry.
history for many different ailments such as ulcers, bacterial Goker, H., Haznedaroglu, I. C., Ercetin, S., Kirazli, S., Akman, U.,
and viral infections, and inflammation. Constituents of the Ozturk, Y., & Firat, H. C. (2008). Haemostatic Actions of the
plant, especially glycrrhizin, have been and continue to be Folkloric Medicinal Plant Extract Ankaferd Blood Stopper.
extensively studied for medicinal properties. However, The Journal of International Medical Research, 36(1), 163-
conclusive evidence regarding the effectiveness of standard 170.
licorice preparations for many conditions still has not been Glycyrrhiza glabra. (2005). Alternative Medicine Review, 10(3), 230-
established. The extent to which licorice has been used in 237.
traditional medicine, however, does suggest strong medicinal Hayashi, H., Hattori, S., Inoue, K., Sarsenbaev, K., Ito, M., & Honda, G.
properties, and more research will likely lead to development (2003). Field survey of Glycyrrhiza plants in Central Asia
of powerful new drugs in the future. Overall, G. glabra has (1). Characterization of G. uralensis, G. glabra and the
very useful components that will certainly continue to benefit
putative intermediate collected in Kazakhstan. [Research Messier, C., & Grenier, D. (2011). Effect of licorice compounds
Support, Non-U.S. Gov't]. Biol Pharm Bull, 26(6), 867-871. licochalcone A, glabridin and glycyrrhizic acid on growth
and virulence properties of Candida albicans. Mycoses, 54(6),
Kondo, K., Shiba, M., Nakamura, R., Morota, T., & Shoyama, Y. (2007).
e801-e806. doi: 10.1111/j.1439-0507.2011.02028.x
Constituent properties of licorices derived from Glycyrrhiza
uralensis, G. glabra, or G. inflata identified by genetic Miyake, K., Tango, T., Ota, Y., Mitamura, K., Yoshiba, M., Kako, M., . . .
information. Biol Pharm Bull, 30(7), 1271-1277. Suzuki, H. (2002). Efficacy of Stronger Neo-Minophagen C
compared between two doses administered three times a
Kumada, H. (2002). Long-term treatment of chronic hepatitis C with
week on patients with chronic viral hepatitis. J Gastroenterol
glycyrrhizin [stronger neo-minophagen C (SNMC)] for
Hepatol, 17(11), 1198-1204. doi: 10.1046/j.1440-
preventing liver cirrhosis and hepatocellular carcinoma.
1746.2002.02876.x
Oncology, 62 Suppl 1, 94-100.
Nand, P., Drabu, S., & Gupta, R. K. (2012). IN VITRO ANTIBACTERIAL
Li, L., Sinkko, H., Montonen, L., Wei, G., Lindstrom, K., & Rasanen, L.
AND ANTIOXIDANT POTENTIAL OF MEDICINAL PLANTS
A. (2012). Biogeography of symbiotic and other endophytic
USED IN THE TREATMENT OF ACNE. [Article]. International
bacteria isolated from medicinal Glycyrrhiza species in
Journal of Pharmacy & Pharmaceutical Sciences, 4(1), 185-
China. [Research Support, Non-U.S. Gov't]. FEMS Microbiol
190.
Ecol, 79(1), 46-68. doi: 10.1111/j.1574-6941.2011.01198.x
Sena, S. F. (2010). Licorice and Laboratory Tests Herbal Supplements
Loftin, H. (1953). King Tut's Black Treasure. The Science News-
(pp. 255-272): John Wiley & Sons, Inc.
Letter, 64(6), 90-91.
T, L., & R.V, G. (2011). GLYCYRRHIZA GLABRA LINN COMMONLY
McLawhon, R. W. (2010). Role of the Clinical Laboratory in
KNOWN AS LICORICE: A THERAPEUTIC REVIEW.
Detecting Plant Poisoning Herbal Supplements (pp. 425-
International Journal of Pharmacy & Pharmaceutical
442): John Wiley & Sons, Inc.
Sciences, 3(4), 20-25.
Hamamelis virginiana L. Hamamelidaceae
Sarah Howard
Introduction
Hamamelis virginiana L. is of the Hamamelidaceae family and
the Hamamelidales order. Most commonly known as
American witch hazel, H. virginiana is also known as spotted
alder, snapping hazel, tobacco wood, pistachio, and winter
bloom (Erichsen-Brown, 1979). Found in the Eastern region
of the United States of America, the leaves, bark, and twigs
have been used to treat a wide variety of illnesses, including
skin irritation, burns, insect bites, sore throats, colds, fevers,
etc. Its uses were first recorded by Native Americans who
used the plant in a wide variety of medical treatments. H.
virginiana is most commonly used today for its astringent
qualities in cosmetics and relief from skin inflammation or
irritation. Its main active chemical constituents are
hamamelitannins and proanthocyanidins, which have been Figure 1. Hamamelis Tree
well established for their astringent properties. Notice how the tree is developed from several small trunks
clumped and rooted together, opening up into a leafy, bushy
canopy. Source: http://www.bestplants.org
Growing up to six meters tall, Hamamelis virginiana is a shape of the leaf varies but is most frequently obovate or
deciduous shrub, often with several trunks growing together subcordate with crenated edges and can be up to 6 cm broad
in one cluster (Figure 1), with an average trunk diameter of and 2 cm long. The top side of the leaf is dark green while the
0.3 meters. Often, several smaller trunks grow together in bottom side is a pale green. The entire leaf is glabrous with the
clusters, forming what appears to be a single tree. The bark of exception of pubescent veins. Flowers are found in small,
the trunk is light brown and slightly scaled. The thin twigs are axillary clusters with four bright yellow, linear petals (Figure
orange-brown to red-brown in color and transition from 2) (Mohlenbrock & Thomson, 2009). The delicate flowers
pubescent 1 to glabrous 2 over the course of their lifetime. The bloom after the foliage drops in October or November and
have a light, spicy fragrance (Brand, 2001).
1Pubescent: with hair 2 Glabrous: smooth surface, no hair present
Figure 2. Petals of Hamamelis virginiana
Each flower has four bright yellow thin petals radiating from
the center. Each stem has multiple flowers. Source:
http://www.ausable.org
H. virginiana is bisexual but remains dependent on insect

pollination, most frequently flies of genus Bradysia and small
bees (Anderson & Hill, 2002). The capsular fruits are orange-
brown, pubescent, and obovoid in character. Within each Figure 3. Opened H. virginiana capsules
capsule is two hard, elongated black seeds up to 5 mm long As visible by the far left capsule, each capsule has two pods,
(Mohlenbrock & Thomson, 2009). The fruits mature in late which each contains one black seed. Upon opening, the seeds
August and remain on the plant until the capsule dries and are expelled from the plant. Source: USDA-NRCS PLANTS
erupts, expelling the seeds (Figure 3). The freshly expelled Database
seeds travel an average distance of 3.45 meters. The only
species of genus Hamamelis to blossom in the fall (most flower
from late winter to early summer), it is suspected that H. soil. H. virginiana grows in the eastern half of North America
virginiana evolved the early blossom to avoid competition for (Figure 4).
pollination with H. vernalis (Anderson & Hill, 2002). The H. virginiana is largely unaffected by pests but may host the
preferred habitat for H. virginiana is a moist forest with rich saddled prominent caterpillar and the witch hazel leaf gall
aphid (Gilman & Watson, 1993). The saddled prominent is a
Figure 5. Saddled prominent caterpillars
Source: US Department of Agriculture, Forest Service
Figure 4. Distribution across North America green galls 3 up to ½ inch long to form on upper leaves. The
The green shading indicates the presence of Hamamelis galls cause no permanent damage to the plant and the aphids
virginiana in at least one area of the region. Based on the map, are usually controlled by natural predators (Gilman & Watson,
H. virginiana is primarily located in the eastern half of North 1993).
America. Source: USDA-NRCS PLANTS Database
Traditional Uses
yellow-green to brown caterpillar named for the red marking
Native American tribes, including the Cherokee, Chippewa,
on its back resembling a saddle (Figure 5). Though saddled
Iroquois, Monhegan, Menomini, Potawatomi, Mahican, and
prominent caterpillars will occasionally feed on H. virginiana,
Mohawk Indians, used Hamamelis virginiana extensively, but
they prefer American beech, sugar maple, yellow birch, and
primarily for medicinal use (Spruce & Thrasher, 2008).
paper birch (Rush & Allen, 1987). The primary pest of H.
virginiana is the witch hazel leaf gall aphid, which can cause
3Gall: abnormal growth formed on plants and trees in response to

presence of insect activity.
Magical Properties Poultice
The most common name of the plant, witch hazel, was initially Native Americans, particularly Cherokee and Monhegan
assigned to H. virginiana due to the many magical qualities the tribes, used H. virginiana to treat a wide variety of topical
plant was believed to possess. Menomini and Monhegan conditions including cuts, bruises, insect bites, burns, varicose
Indians both used forked branches of witch hazel as a diviner veins, tumors, and hemorrhoids, etc. (Hamel & Chiltoskey,
of water and buried treasure, specifically silver and gold 2002; Tantaquidgeon, 1972). In one account, a visitor to a
(Smith, 1970; Tantaquidgeon, 1972). Forked branches are tribe of Mohawk Indians described the healing of a man who
held in each hand and the location of the water or treasure is had reached almost total blindness due to blunt force trauma
indicated by where the point of the fork drops to the ground. to his head (treating a large bruise). Ultimately, he was healed
The Menomini also used the dried, blackened seeds of the by a warm stream of water that had soaked the bark of H.
“pisewa’xtîk” or “pisä’-kiwûs” to test the potential recovery of virginiana was poured over the location of injury. Of course,
an ill individual in a traditional medical ceremony known as the preparation of the plant depends on the specific use. When
“mê’gîsê” (Densmore, 1932; Smith, 1970). Other noted non- treating a small cut or insect bite, the leaves are often ground
medicinal uses of H. virginiana by Native American tribes are or chewed and applied topically as a paste (Hamel &
the use of its twigs and branches to fashion brooms, brushes, Chiltoskey, 2002). In treatment of varicose veins, a condition
and even bows (Tantaquidgeon, 1972). The hard wood, of enlarged and painful veins, a white cotton cloth is soaked in
weighted at approximately 43 pounds per foot would be a the extract and applied to the site. Tumors are dressed with a
sturdy option for the creation of such products (Erichsen- combination of H. virginiana and flax seed. Painful, inflamed
Brown, 1979). eyes are treated with a poultice of inner bark rind from the
plant.
Muscle Relaxer
Known to the Forest Potawatomi tribe as “bwaote’ît” or Anti-hemorrhagic
“paga’nîmîg,” H. virginiana twigs were placed in water with Due to the astringent properties of the plant, anti-hemorrhagic
hot rocks to create a steaming bath said to bathe sore muscles properties of H. virginiana have been used extensively by
(Smith, 1933). Similarly, the Menomini tribe steeped twigs to Native Americans to treat everything from heavy menstrual
cure lame backs, adapted as a known use by neighboring bleeding, ulcers, bleeding in the mouth and throat, dysentery,
Stockbridge Indians. There were also reports of a sudorific and any internal bleeding. The dried powdered capsules of the
bath prepared with seven different herbs, including the twigs flower can also stop bleeding of small cuts (Erichsen-Brown,
of H. virginiana. Also in the Menomini tribe, a decoction of the 1979). These inflictions are most commonly treated with a
plant applied topically to the legs was believed to be useful decoction of the witch hazel, which is taken in the form of tea,
during games to keep the athletes “limbered up” (Smith, 3-4 times per day. Alternatively, if experiencing bloody
1970). discharge, the extract, prepared by simmering one ounce of
bark or leaves in one pint of water for ten minutes, is injected
directly into the rectum after each bloody discharge. The The notable astringent qualities of H. virginiana are
Iroquois also had an interesting pattern of using a decoction of attributable to the tannins present in the leaves and bark.
the leaves and twigs to regulate blood in the kidneys. Tannins are polymeric phenolic compounds, meaning they
consist of repeating phenolic groups. The astringent qualities
of tannins are a result of the fact that they cause proteins to
Upper Throat and Lungs complex, which ultimately decreases the permeability, and
Iroquois used a decoction specifically from young twigs as a therefore the secretions, of the dermis (Brown & Dattner,
respiratory aid for chest colds as asthma (Herrick, 1997). 1998). The leaves boast 9.6% tannins including oligomeric
Cherokee tribes also used teas from the leaves and twigs of H. proanthocyanidins and gallotannins, which are composed of
virginiana to treat a wide variety of ailments including colds, glucose and gallic acid. The tannin content corresponds to
sore throats, general pain, tuberculosis, and fevers (Hamel & nearly 39% of the leaf’s dry matter. Hamamelitannin, the
Chiltoskey, 2002; Moerman, 2010). The taste of the raw plant object of many scientific studies, is largely found in the bark,
is described as initially bitter, noticeably astringent, and which consists of 6–9% tannins.
ultimately leaves a sweet after taste. The volatile oil, known to have anti-inflammatory effects, is
present anywhere from 0.1-0.5% in the bark and 0.01%-0.5%
in the leaves. The oil consists of 40% aliphatic alcohols, 15%
Chemistry and Pharmacology aliphatic esters, 25% generic carbonyls (groups with a double
Many of the chemical constituents of Hamamelis virginiana bonded carbon and oxygen), and up to 0.2% safrole.
have been identified by both structure and function. Given Specifically the ketones and esters of the volatile oil reduce
that they serve notably different purposes to the plant, the inflammation.
leaves and bark of H. virginiana also vary in the chemical Flavonoids are another form of a phenolic structure and are
constituents they possess. The most well established thus hydroxylated (containing an alcohol or –OH group) but
constituents of the plant are its tannins, flavonoids, and they also include a carbonyl group. There is a wide range of
volatile oil. flavonoids active in H. virginiana including kaempferol,
The over-arching group of phenolic compounds is vital to the quercetin, quercitrin, and isoquercitrin in the leaves. Other
function of the plant in treating various illnesses. A phenolic catechins, a subgroup of flavonoids, are found in the bark:
compound is a benzene ring with at least one alcohol group ellagitannin, gallocatechin, epicatechingallate, and
attached. An analysis of an extract of H. virginiana leaves epigallocatechingallate(Zeylstra, 1998). Finally, the bark also
resulted in the identification of 27 different phenolic includes procyanidins and proanthocyanidins, yet another
constituents. It was found using a high-performance liquid subgroup of flavonoids, which have been identified for their
chromatography diode-array detection that gallotannins with efficacy in tumor treatment.
6-11 galloyl units constitute the majority of phenolics
(Duckstein & Stintzing, 2011).
Other constituents include gallic acid, caffeic acid, resin, and Flavonol - Leaf and
fat. See Table 1 for a table of the above chemical constituents Proanthocyanidins bark
Oligomeric cyanidin
and their structures. and delphinidin
Biological Activity
There have been numerous in vivo and in vitro studies
conducted regarding the efficiency of extracts of H. virginiana
in treatment of tumors, dermatitis, and aging. Though general
functions of the main constituents have been assigned, the
research outlined below extends the knowledge of specific Source: WHO Monographs
treatments and uses. Flavonoids Leaf
Kaempferol
Chemical name Location Chemical structures Quercetin
and Quercitrin
Percentag Isoquercitrin
es
Tannins – Leaf, 9.6%
Gallotannins and (39% of
Shown: kaempferol
hamamelitannins dry matter)
Aliphatic alcohol Leaf, 40%
Bark, 6-9%
(volatile oil)
Aliphatic esters Leaf, 15%
(volatile oil)
Carbonyl substances Leaf, 25%
Source: American Society for
(volatile oil)
Pharmacology and Experimental
Safrole 0.2%
Therapeutics
Phenol - Catechin Leaf and
(+)-catechin, bark
(+)-gallocatechin, Table 1. Chemical Constituents of Hamamelis virginiana
(-)-
and their structures Source: Hamamelis virginiana, British
epicatechingallate
(-)- Journal of Phytotherapy
epigallocatechingall
ate
Tumor Treatment
One study in 2012 indicated that hamamelitannins and
pentagalloylculcose with proanthocyanidin from the bark of H.
virginiana were successful in inducing apoptosis, necrosis, and effects were due to the scavenging of the mutagen by the plant
the prevention of DNA replication in the S-phase specifically in constituents (Dauer, Hensel, Lhoste, Knasmuller, & Mersch-
colon cancer growth. While hamamelitannin had no harmful Sundermann, 2003).
effects on the processes of normal colon cells,
pentagalloylglucose inhibited both cancer and normal cell
growth (Sanchez-Tena et al., 2012). Erythema 4 Treatment
In another in vitro study using human cells, hamamelitannins In two in vivo studies by Hughes-Formella et al, H. virginiana
inhibited the apoptosis and endothelial cell death caused by extracts were tested for their ability to treat erythema. In
the tumor necrosis factor-α (TNF). TNF was investigated not 1998, 30 volunteers were exposed to ultraviolet B
only for its effect on endothelial cell death but also its (shortwave) rays to induce erythema and then treated with
adhesion to monocytes, which are the white blood cells one of three ointments – pH5 aftersun lotion with 10%
involved in immune system responses. Treatment of cells hamamelis distillate, pH5 aftersun lotion without hamamelis
with TNF led to DNA fragmentation while treatment with distillate, and a former pH5 lotion of different composition.
concentrations of hamamelitannin, the major tannin found in Erythema was suppressed by 27% at 48 hours after exposure
H. virginiana, inhibits the apoptosis and fragmentation caused compared to about 15% suppression of the other lotions. Not
by TNF. This is consistent with the observation that the only did the hamamelis extract reduce the erythema more
hamamelitannins in the prior study did not cause damage to effectively than the other lotions, but it also was demonstrated
the non-cancerous cells. There was still a TNF-induced to have anti-inflammatory action at just 10% potency
increase in the number of receptors on the surface of target (Hughes-Formella et al., 1998).
cells indicating that there are different pathways in the In 2002, 40 volunteers were exposed to three different UV
expression of cell adhesion molecules and endothelial cell doses and given one of three different lotions. The lotions
death (Habtemariam, 2002). contained 10% hamamelis distillates in three different
vehicles: dimethindene maleate 0.1% gel, hydrocortisone 1%
cream, or hydrocortisone 0.25% lotion. Anti-inflammatory
Anti-Cancer
effects were observed for each lotion in the 48 hours after
An in vivo study with human derived hepatoma (liver cancer) exposure. Though the discrepancy between the lotions was
cells demonstrated that H. virginiana extracts are not only minimal, it was noted that the hydrocortisone formulations
tumor suppressors but can also inhibit the reproduction of the were most effective in treating erythema (Hughes-Formella,
cancerous cells and also reduce the DNA damage the cells Filbry, Gassmueller, & Rippke, 2002).
cause. The study tested three main chemical constituents of H. The effect of hydrocortisone was also investigated in a study
virginiana: hamamelitannin and two proanthocyanidins. The regarding the anti-inflammatory properties of hamamelis
effects of proanthocyanidin became evident at a minimum distillate. Twenty-four healthy subjects were exposed to
dose of 2 μg/mL and were significantly stronger than the
catechins and hamamelitannin. Further tests revealed that the 4 Erythema: superficial redness of skin
PC cream by four times did not improve activity of the
treatment. Regardless, anti-inflammatory properties were
confirmed (Korting, Schafer-Korting, Hart, Laux, & Schmid,
1993).
Anti-oxidative Properties
In addition to anti-inflammatory and anti-tumor properties, H.
virginiana extracts were also found to have strong antioxidant
properties. An in vitro study by Masaki et al. in 1995 found
that hamamelitannin has superoxide-anion scavenging
activity. Furthermore, hamamelitannin is more effective than
gallic acid in preventing cell damage by superoxide anions,
another constituent of H. virginiana extracts. The minimum
concentration of efficacy for hamamelitannin, 50 μM, was half
of that of the necessary concentration of gallic acid, which was
100 μM (Figure 6). Thus, pre-treatment of fibroblasts, cells
Figure 6. Graph of Cell Survival After Treatment of that synthesizes the extracellular matrix and collagen, with H.
Hamamelitannin and Gallic Acid virginiana extracts increases their survival rate (Masaki,
Treatment with increasingly higher doses of hamamelitannin Atsumi, & Sakurai, 1995).
increases the survival rate of cells under attack by superoxide
anion radicals. Gallic acid does not have a significant impact
General Anti-inflammatory Properties
on the survival but increases slightly at a dose of 200 μM.
Source: Biological and Pharmaceutical Bulletin, 1995 In an in vivo study of human keratinocytes 5 by Deters et al,
polysaccharides and proanthocyanidins were tested for their
impact on keratinocyte proliferation and differentiation.
While the polysaccharides did not impact the keratinocytes,
ultraviolet irradiation and cellophane tape to induce erythema the proanthocyanidins increased the proliferation of cells.
and subsequently treated with hydrocortisone cream, Proanthocyanidins were also shown to reduce transepidermal
hamamelis phosphatidylcholine cream, hamamelis cream water loss and erythema formation. This study confirmed the
(without PC), or chamomile cream. The results demonstrated efficacy of chemical constituents found in the bark of H.
that inflammation was reduced when treated with hamamelis
PC cream but that the hydrocortisone treatment was more 5Keratinocyte: epidermal cell producing keratin, a fibrous protein with
effective. Furthermore, an increase in dosage of the hamamelis important structural properties.
virginiana. Furthermore, it established that not only does an
extract of the plant reduce erythema, but also specifically the Reference: vehicle Reference: hydrocortisone
Age: 32 (13) years Age: 32 (10) years
proanthocyanidins cause these effects (Deters, Dauer, Schnetz,
Weight: 64 (12) kg Sex: Weight: 67 (14) kg Sex: 9 m,
Fartasch, & Hensel, 2001). 3 m, 33 f 27 f
In an in vivo study with rats, the anti-inflammatory properties Parameter Hamamelis Vehicle Hamamelis Hydrocortisone
Itching 2.0 2.0 2.1 2.1
of H. virginiana, Polygonum bistorta, and Guaiacum officinale
Baseline
were used to treat arthritis. H. virginiana and G. officinale were Itching 1 1.5 1.6 1.5 1.3
only active during chronic phases of swelling while P. bistorta week
was inhibited both phases of the arthritis (Duwiejua, Zeitlin, Itching 2 1.4 1.4 1.2 0.8
Waterman, & Gray, 1994). weeks
Erythema 1.9 1.9 1.7 1.8
Baseline
Erythema 1.6 1.6 1.5 1.3
Anti-viral 1 week
In an in vivo study with the Herpes simplex virus type 1, an Erythema 1.4 1.2 1.4 1.0
extract of H. virginiana bark was shown to have significant 2 weeks
anti-viral activity. The same extract was also shown to have Table 2. Effect of Hamamelis ointment on atopic eczema
anti-oxidative properties that led to the inhibition of human The table below displays that over the course of two weeks,
leukocytes (Erdelmeier et al., 1996). the hamamelis ointment reduced both itching and erythema.
However, the hydrocortisone was more effective, dropping
itching at erythema by 1.3 and 0.8, respectively compared to
Clinical Studies 0.9 and 0.3. Source: European Journal of Clinical
Pharmacology (17)
Wolff and Kieser conducted one of the first clinical studies
with hamamelis ointment on children. There is little data
regarding potential effects on children or pregnant women; more effective than the dexpanthenol (p < 0.001). Specifically,
thus, its use is often not recommended. In the study, 309 there were clear advantages in infants with diaper dermatitis
children from the age of 27 days to 11 years with minor skin and in 1 – 5 year olds with skin inflammation (Wolff & Kieser,
injuries, diaper dermatitis, or a localized inflammation of skin 2007).
were prescribed either hamamelis ointment or dexpanthenol. Despite the evident anti-inflammatory and protective
Dexpanthenol is a well-established option to heal topical properties of H. virginiana extracts, a study pertaining to
wounds by stimulating epithelization and granulation. It has atopic eczema found that hamamelis cream was not more
also been proven useful in the reduction of itching and the effective than the results obtained from base preparation
treatment of diaper dermatitis. Although the two ointments (Table 2). Although no significant benefits were observed, it
are very similar in composition and the results were was still noted that the hamamelis cream was very well
ultimately similar, hamamelis treatment was significantly
tolerated and can be considered for higher doses than other Current Use in Allopathic and CAM Therapies
treatments. Given that this was a clinical study, the treatment
Today, the astringent properties of Hamamelis virginiana,
course was adhered to for 14 days. Patients made note that
largely attributable to the tannins present in the extract, are
the treatment was considerably slower to take effect than the
used to tighten pores after washing or shaving. Thus, the
glucocorticoids they were used to (Korting et al., 1995).
extract is frequently used in commercial shaving creams and
To date, there are no prominent clinical trials regarding the toners. The extract of witch hazel is also often commonly
effectiveness of H. virginiana extracts in treatment of bruises, found in mouthwashes.
hemorrhoids, hemostasis, or of use as an antioxidant.
H. virginiana, sold commercially as Witch Hazel, is found in
numerous natural products but has not yet been used in the
Contraindications development of a new pharmaceutical drug. Thus, all forms of
witch hazel are sold over the counter. Stand-alone witch hazel
Hamamelis virginiana is generally recognized as safe for products include distilled witch hazel, which is available in
topical application. In fact, in an in vivo study with mice and pharmacies and grocery stores and is advertised as an “All
rats, oral doses of 10-20 mg showed no adverse effects. Natural Astringent for Face and Body.” The CVS brand
Furthermore, daily oral doses of 100 mg per kg body weight contains 86% witch hazel and 14% alcohol. The alcohol is
also showed no toxic effects. However, regular ingestion, added to prolong the product’s shelf life and prevent the loss
particularly by pregnant women, is not recommended due to of efficacy. This product can be used for homemade toners
the high tannin content of the plant. Hypersensitivity or (used cosmetically to tighten facial pores) or to remove make-
allergies to the active substances may lead to allergic contact up. H. virginiana leaves are also sold in capsules, marketed to
dermatitis, or severe irritation of the skin (Zeylstra, 1998). support health circulation and veins with a daily dosage of 1-2
There are no known drug interactions with H. virginiana but capsules, three times per day.
patients should use caution and inform their doctors if they
use the product regularly. Witch hazel has been incorporated into elective medicine in
America since the 1850s in the form of Pond’s Extract, used by
Individuals with allergies to the Asteraceae or Compasitae many Homeopathic and Allopathic doctors as a cure-all for
family should exercise caution when using products of H. any skin complaint, ranging from burns to bites to “female
virginiana. In an in vitro study of patients with the allergy, they complaints”. Theron Pond took an interest in the plant that
were exposed to chamomile-containing preparations, arnica- many Native Americans believed to have magical properties.
based preparations, avocado oil, and H. virginiana. Though He formed a partnership with the Indian Medicine Man he had
neither avocado nor witch hazel is in the Asteraceae family, been learning form and began to sell the product. A small
they were consistently detected as sensitizers and may cause production at first, it eventually expanded from the “Golden
an allergic reaction (Paulsen, Chistensen, & Andersen, 2008). Treasure” to Pond’s Extract, which is still sold today in a
variety of creams with small amounts of witch hazel included
(Lloyd & Lloyd, 1935).
Arnica Plus, sold by Peaceful Mountain, Inc, as an unapproved hamamelitannins such as gallotannins, proanthocyanins, and
homeopathic product, is marketed for relief from sore muscles catechins. Currently, there is a great deal of research that can
(similarly to how the Potowatomi and Menominee Indians be done to further our knowledge of medicinal uses of H.
used the extract). The product is sold with a labeled warning virginiana. For example, Native Americans used the plant in
that the FDA is “not aware of scientific evidence to support the form of tea, paste, and distillate. Given the wide
homeopathy as effective.” Interestingly, Hamamelis virginiana availability of Hamamelis virginiana in the United States,
root bark and stem bark is listed as an active ingredient at 6X further research is a logical investment given that it is highly
and 12X dilutions and witch hazel bark is listed as an inactive coveted and has been repeatedly documented by indigenous
ingredient. The product is recommended for topical use, to be cultures.
applied daily over the affected area (NLM, 2013).
Due to its astringent properties, witch hazel is found in
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Chapel Hill, NC: University of North Carolina Press in
Humulus lupulus L., Cannabaceae
David Kyle Choe
Introduction mostly on their geographic localities. H. lupulus, is the

Humulus lupulus L, most commonly known as hops, is not only common hop found widely in the northern hemisphere in
a major ingredient in the production of the alcoholic beverage,
beer but also for its practical and traditional medical uses. It
was first used to brew beer in England in the 1500s where it
was immediately characterized as a “‘wicked weed’ that would
‘endanger the people’” (Chevallier, 102). H. lupulus is
commonly found in Europe and Asia where it grows on the
sides of roads (Chevallier, 102). Brewing the strobiles or the
female flowers (Figure 1), of the bines is the most common
preparation of hops, however, there have also been other uses
such as aromatherapy. The bitterness of hops is a distinct
mark of not only its famous taste but also its chemical
constituents that are essential to its medicinal uses. H. lupulus
is comprised mainly of bitter compounds, flavonoids, tannins,
and other constituents. The bitter compounds including
lupulin, lipulon, and valerianic acid, also a sedative, are
digestive stimulants (Chevallier, 102). There have been many
recent studies undertaken in which the antibiotic and
antiseptic qualities of H. lupulus have been tested, with
varying results.
The only other member and perhaps an equally well-known
member of the cannabaceae family is Cannabis sativa, more
commonly known as marijuana, a popular recreational drug. Figure 1. Picture of a H. lupulus strobile (Chevallier, A. (1996).
Within the genus Humulus, there are other species based The encyclopedia of medicinal plants. New York, NY: DK
Publishing.)
areas such as Europe and North America. H. japonicus is found
throughout China and Japan and is not found elsewhere. H.
yunnanensis is found mostly in Asia, however very little is
known about this particular species because there are very
few observable specimen and no cultivated plants (Neve, 1).
H. lupulus is a dioecious species, meaning that this species has
distinct male and female reproductive bodies, most visible in
their difference in physical morphology (Neve, 2). H. lupulus is
a climbing plant yet it does not use tendrils to bind to climbing
surfaces, however, its bines or stems climb up anything on
which they are able to entwine (Figure 2). The bines round up
in a clockwise direction and use hooked hairs, to ascend their
climbing surface. (Neve, 2). The leaves of the plant are most
commonly found in pairs, but there have been instances in
which three-leaf arrangements have also been found (Neve,
2). The flowers of the plant differ by the sex of the plant. Its
loose panicles, or a cluster of flowers with a grouping of five
sepals and five anthers, characterizes the male plant. The
anthers have a small cavity in which the valuable resins are
located. It is in these small cavities that the pollen is produced
in large quantities. Hops are majorly pollinated by the wind
(Neve, 2). The female flowers are found in similar clusters of
flowers as the male but differ in that they are found on a Figure 2. Breakdown of H. lupulus
central nave (Neve, 2). Each section of the flower has two (http://www.pfaf.org/user/Plant.aspx?LatinName=H.+lupulus)
bracts; these are the leaves, which surround the small flower
of the female plant. The flower houses the ovary together with male flower. The resins, which are produced by the lupulin
two stigmas (Neve, 2). As these clusters of flowers grow and glands, are most active in the seeded hops wherein which one
age, the bracts become larger and eventually form the third of the total resins are produced (Neve, 2).
strobiles. The strobiles are the cones containing the main
Also previously mentioned, these plants are perennial where
commercial product of the plant (Neve, 2). Pollinated plants
the supra terram part of the plant or the aboveground part,
are easily distinguished from the non-pollinated plants
dies each winter but the roots are able to survive (Neve, 5).
because of the differences in coloration.
A variety of geographical conditions leads to key differences in
Although aforementioned resin is found in both the male and
the morphology of the plant. Noteworthy examples include the
female flowers it is comes in much smaller quantities in the
H. japonicus and the H. yunnanensis. The H. japonicus has been manufacture industry, which is similar to the value of hemp in
identified as an annual species. Similar to H. lupulus, it is a terms of fabric-making (Zanoli, 385). The plant also contains
dioecious but the cones look very different morphologically. H. active ingredients found in perfumes and for skin creams and
japonicus does not have many lupulin glands and are lotions (Zanoli, 385).
consequently not commonly used to brew beer with. H.
yunnanensis is mostly found in the higher altitudes of China,
particularly the Yunnan Province (from which the name is Traditional Medicinal Uses
derived). There is little known about this species, as alluded to Famously, H. lupulus has been used to treat a wide range of
previously, yet there is limited evidence suggesting that it may maladies. Its volatile oil is mildly sedative, so hops alleviate
have been the origins of the commercially bred variety (Nave, insomnia and anxiety (Zanoli, 385). H. lupulus remits
9-10). excitability and restlessness, attributed to tension headaches.
It aids appetite and digestion. Additionally, it also relieves
tooth pain as well as ear pain and neuralgia (Zanoli, 385).
Traditional Uses
Hops also allegedly works as a “diuretic, antispasmodic, and
In Europe, where H. lupulus has been used since the mid-ninth anaphrodisiac” agent (Zanoli, 385).
century, the plant was traditionally harvested from the wild. It
In Native American tribes it has been used similarly as a
was favored mostly as a substitute for the more widely
sedative, to treat rheumatoid arthritis, as a pain reliever and
consumed beer additive, Myrica gale. It was not until the
as an urination aid (Zanoli, 385). The Native Americans also
eighteenth century when H. lupulus became more popular
utilized H. lupulus as a pneumonia treatment. They would heat
than Myrica gale because of its preservative advantage
up hops and use it as a poultice. Decocted hops were used for
(Zanoli, 384). The beer brewing industry currently utilizes
intestinal pain and fevers as well (Zanoli, 385).
98% of all hops worldwide, which is drastically different from
its original use as a preservative (Zanoli, 384). The H. lupulus has also been known in Indian Ayurvedic medicine
antimicrobial activity of hops that is currently under as a treatment for restlessness caused by tension, headache
investigation was identified early on, but only later were hops and indigestion (Zanoli, 385). It is also found in traditional
used for their distinct flavor. Medicinal values of H. lupulus Chinese medicine (TCM) where it used similarly to treat
were noted by the renowned ancient healer, Pliny the Elder. “insomnia, restlessness, dyspepsia, and lack of appetite”
He first used the plant’s younger shoots as an edible vegetable, (Zanoli, 385). The Chinese have also used alcoholic forms of
common among the Romans (Zanoli, 384). The leaves and the hops to successfully treat conditions such as leprosy,
heads of the flowers give brown dye extracts. The flowers pulmonary tuberculosis, acute bacterial dysentery, silicosis
were also used as food-additives that would give unique and asbestosis” (Zanoli, 385). Hops have been used in treating
flavorings to “cereals, spices, sauces, tobacco and alcoholic skin conditions such as crual ulcers and other skin injuries. It
beverages other than beer” (Zanoli, 385). The fabric- has been applied to areas where muscle spasms and nerve
generating stems played an important role in the paper
pain occur. They were also used aromatically for the skin, for
breathing aid, restlessness and other conditions (Zanoli, 385).

Though H. lupulus is filled with many different and potentially
useful chemical constituents, its main chemical compounds
are terpenes, bitter acids and chalcones. Flavonol glycosides
and catechins are also present in abundance. In fact, dozens of
terpenoic compounds were found in the volatile oils making
up around 0.3-1.0% of its chemical composition. These
terpenoid compounds included B-caryophyllen, farnesene,
and humulene, and myrcene. The bitter acids, mainly α-acids
and β-acids, constitute the bulk of the chemical composition of
the plants with 5-20% of the strobile weight (Zanoli, 385),
Figure 3. These bitter acids exist in hops in various and Figure 3. Molecular structure of an alpha acid.
complex forms and concentrations, serving different purposes
for the well being of the plant. The α-acids are composed of
mainly humulone (35-70% of total α-acids), cohumulone (20- In terms of extraction itself, the hop cones must be dried by
65% of all α-acids), adhumulone (10-15% of all α-acids). The artificial heat, wherein the water inside the cones must be
β-acids mostly consist of lupulone (30-55% of all β-acids), significantly reduced (to 8-10% water). The method of
colupulone and adlupulone (Zanoli, 386). Between these two extraction has changed from water and ethanol to more
acids are the α-acids that are responsible for the high-quality advanced methods utilizing steam and carbon disulfide.
hops used for the brewing of beer. These α-acids are not only
crucial for the flavor of the beer, but they are also essential for
the foam stability and for the antibacterial activity exhibited Biological Activity
by hops-based beverages (Zanoli, 385). There are also crucial Sedative properties
prenylflavonoids in the plant. The most important is chalcone
The mildly sedative activity of hops was first observed when
xanthohumol, which can be converted to isoxanthohumol in
hop-pickers were reported to suffer from sleepiness and
the presence of heat, therefore, making it the main flavonoid
fatigue, which was surmised due to unconscious digestion
in beer (Zanoli, 386). The presence of these bitter acids and
during harvesting (Zanoli, 387). Germany was among the first
XH differ based on geography, species and sex of the flower.
countries to approve hops as an acceptable treatment for
Male plants have been shown to have similar levels of XH and
“mood disturbances, such as restlessness and anxiety and
bitter acids as young flowering cones (Zanoli, 386).
sleep disturbances”, however it was not closely studied until
pentobarbital effects coupled with the antidepressant activity
found after the administration of the drug.
Antimicrobial and antibacterial properties

Perhaps one of the most interesting and potentially beneficial
studies done on H. lupulus is that of its effect on the
Mycobacterium tuberculosis. This study, done by Serkani et al,
examined the possibility of in the treatment of M. tuberculosis,
which currently affects one third of the world’s population.
Thirty-seven M. tuberculosis strands from varying regions of
Figure 4. Biomedical properties of hops. (Source: Iran were tested using the proportion method. Hops extracts
http://pubs.acs.org/doi/full/10.1021/np800740m) were also tested on a wide array of bacteria including Bacillus
subtilis, E. coli, Pseudomonas aeruginosa, and Staphylococcus
aureus. The tests showed that there were statistically
more recently (Zanoli, 388). Numerous studies on its sedative
significant inhibitory effects against M. tuberculosis strains,
properties yielded mixed results. In the first in vivo study done
with the female plants having the strongest effects. This result
by Hansel and Wagener in 1967, the researchers treated the
is interesting in comparison to its lack of effects against other
mice with three different types of hop extracts prepared from
bacteria such as E. coli and Pseudomonas aeruginosa. The
two different solvents: ethanol and methylisobutyl-ketone;
efficacy of H. lupulus was close to that of the drug rifampin
however, they did not find any conclusive results indicating
(Serkani et al, 235-242).
any muscle-relaxant effects (Zanoli 388). In another study
where the neuropharmacological effects of hops were tested, Another study evaluated the effectiveness of the chemical
hop extracts were injected into mice in order to evaluate the constituents in hops against acne vulgaris and different
hypothermic, analgesic and anticonvulsant activities, in which bacteria associated with the proliferation of acne (Yamaguchi
positive results were found that they did indeed serve as et al, 369). They targeted this disease because it is one of the
hypothermics, analgesics and anticonvulsants (Zanoli, 388). most prevalent skin diseases, affecting both children and
adolescents. Acne vulgaris is caused mainly at the onset of
A particularly significant study done by Zanoli focused on the
puberty with secondary infections occurring because of
use of hops with a CO2 extract and “single fractions containing
various bacteria present on the skin. Yamaguchi conducted
α-acids and β-acids”. This CO2 extract displayed remarkable
the research by comparing the effectiveness of the hops’ main
“pentobarbital” sleep-enhancing effect. However, the test
chemical constituents to well-known antimicrobials. The
showed a striking result in which the hops extract produced
efficacy was measured by the minimum inhibitory
an antidepressant-like effect. They further studied and
concentration (MIC) and the minimum bactericidal
concluded that the α-acids were producing these
concentrations (MBC), where the MIC stands for the “lowest
concentration that resulted in no visible growth after two days Clinical Studies
for P. acnes or 1 day for the others” and the MBC being defined
In another study, tests were done on human subjects where
as the “lowest concentration at which the microorganisms
subjects were treated with 250mg/day of hops extract for five
failed to grow in each medium” (Yamaguchi et al, 371). They
days to treat epilepsy. In this test researchers found that there
found that the lowest MIC values, which indicate the most
was indeed a significant decrease in the spontaneous motor
potent of the chemical constituents, were the naturally
activity. However, this decrease was related to the type of
derived lupulones. The researchers have claimed that there
solvent used to extract the .
has not been such a strong inhibitory ability of any natural
product from an edible plant. This research has significant A major and novel study done by Heyerick et al was the first
implications on the future of skincare products made from “prospective, randomized, double-blind, placebo-controlled
these naturally derived matter. study on the use of a standardized hop extract to alleviate
menopausal discomforts” (Heyerick et al, 164). The
introduction of the hops-based dietary supplement began to
Estrogenic activity pique interest in its medicinal potential specifically its
Rich evidence shows that H. lupulus demonstrates significant estrogenic potential. It was found that it was the closest plant
estrogenic activity, first identified when female hops pickers compound to the 17β-estradiol, which is naturally found in the
experienced menstrual abnormalities (Milligan et al, 4912). female body (Heyerick et al, 164). This study focused on the
Hop baths were used in Germany to treat certain daily intake of a hops based dietary supplements, which are
gynecological disorders and have also been used to reduce hot supposed to have beneficial effects on the experience of
flushes in menopausal women (Milligan et al, 4912). It is uncomfortable menopausal conditions. This study stands out
currently being used in commercial products and being in that it was done using three groups, a control receiving a
marketed and breast enlargement products. The chemical placebo, and two active groups receiving 100 and 250 μg of 8-
compound that is highlighted in this study is 8- PN, respectively (Heyerick et al, 164). The study was done
prenylnaringenin, which has been widely accepted as a using a qualitative measure of the Kupperman index used to
powerful phytoestrogen. In fact, 8-prenylnaringenin, has been measure the level of discomfort caused by menopausal side
shown to have the one of the greatest phytoestrogenic effects. The results showed that there was a significant
activities among all the plant estrogens (Milligan et al, 4912). reduction of menopausal discomfort after six weeks of use.
This study concludes that the endocrine activity of hops is However, there was neither a dose-response nor a change in
because of the chemical compound 8-prenylnaringenin. discomfort after the twelve-week period. This study is
Because of this recognition of its potency as a phytoestrogen, significant in that is one of the only clinical trials done using
concerns have been raised as to possible threats and dangers hop extracts that definitively show the efficacy of the 8-PN for
in over-exposure to this chemical, but also suggest potential treatment of a disorder (Heyerick et al, 173). Because of the
benefits in menopausal therapy. thorough nature of the study, it might be said that there is
greater potential for this drug to be developed for future use
for menopausal symptoms.
In another study done by Wei-Jen Chen and Jen-Kun Lin, they Perhaps one of the most important chemical compounds that
found that the major constituents of hops, namely β-acids are derived from H. lupulus is xanthohumol (XN), which was
presented strong inhibitory effects on specific leukemia cells. mentioned in the study above. In a review done by Clarissa
This shows that bitter acids in hops may be a potential source Gerhauser, she goes through the effects of XN on bacteria,
of future cancer therapies. viruses, fungi and malaria. One study by Bhattacharya et al
Focusing on the strong barbiturate properties of hops, this that Gerhauser reviews is that of the efficacy of XN verses a
study by Zanoli et al (2005), showed interesting and major compound found in a popular mouthwash, thymol
promising results concerning sleep-enhancing and (Gerhauser, 829). This study showed that XN stopped the
antidepressant activities of H. lupulus. The researchers found growth of S. mutans significantly more than the most potent
that the age old practice of using hops as a sleeping aid to be version of the common additive. Another study that she
supported by the dose-dependent responses to hops. In reviews is by Buckwold et al, in which hop chemical
addition to this finding, the researchers observed there to be a constituents were tested against a line of different DNA and
reduction of immobility after use of the drug that they RNA viruses. This study was particularly exciting because of
connected to anti-depressant effects by comparing the results XN’s inhibitory effects against bovine viral diarrhea virus,
to that of synthesized antidepressants. cytomegalovirus, herpes simplex 1 and herpes simplex 2.
However, the most potent example of the utility of XN was
found in its effectiveness against HIV-1. In this study by Wang
Current Use in Allopathic and CAM Therapies et al, it was found that XN “was able to inhibit HIV-1 induced
CPE” which essentially suggests that XN inhibits key
As mentioned previously one of the most widely studied uses replication activity of the HIV-1 virus. This study has larger
of H. lupulus is found in its antimicrobial properties. This implications on the potential for the XN compound for future
study done by Natarajan et al, reviews the efficacy of derived research and development (Gerhauser, 830). XN’s antifungal
compounds lupulone and xanthohumol in their antibiotic properties were also reviewed in this article. The study done
qualities. The researchers then proceeded to create an by Mizobuchi and Sato tested the constituents XN, naringenin,
antibiotic cream in which the active ingredients were added 6-prenylnaringenin, 8-prenylnaringenin and IXN against the
into the mix. They tested the antibacterial mixes on bacterial human fungi Trichophyton mentagrophytes, Trichophyton
lawns and measured the size of the inhibitory zone in the dish. rubrum, Candida albicans, Fusarium oxysporum and Mucor
They found that that the greatest coaction found was between rouxianus. The results showed that XN and 6-prenylnaringenin
the hop constituents and the sulfa or polymyxin drug that was were the most effective in fighting off the fungi. However, it is
dropped into the dish. These researchers support other also significant to point out that IXN was more potent when it
studies’ method of action that suggests the mechanism of was subject to methylation. The last and perhaps one of the
action being that hop constituents cause a change in the more exciting developments is XN’s activity against malaria.
permeability of the membrane. The study concludes that the Infamously known as the disease that was failed to be
use of hop constituents might be expanded to include co- eradicated, malaria continues to take a major toll on this earth,
action with existing anti-bacterials (Natarajan et al, 194-201). combatted with an outdated and resisted drug, choloroquine.
However, using XN, researchers such as Herath et al and alternatives, and H. lupulus seems like a great place to start.
Frolich et al have been able to support the findings that XN has Plants like H. lupulus serve as an impetus of hope and a well of
antiplasmodial effects that inhibited the activities of the potential for future cures and vaccinations, and ultimately a
malaria strains (Gerhauser, 830). healthier world.
Discussion References Cited

It seems to be the case that H. lupulus has played a larger role Chen, W., & Lin, J. (2004). Mechanisms of Cancer Chemoprevention
in history of the earth than one might initially think. As a key by Hop Bitter Acids (Beer Aroma) through Induction of
ingredient to the fine beverage that beer is, H. lupulus has Apoptosis Mediated by Fas and Caspase Cascades. Journal
affected and will continue to affect such a large number of of Agricultural and Food Chemistry, 52(1), 55-64. doi:
10.1021/jf034737u
people across every culture and every geography. Many of its
traditional uses: as a sedative, antimicrobial and antibacterial, Chevallier, A. (1996). The encyclopedia of medicinal plants. New
seem to be shaping the ways in which the drug is being York, NY: DK Publishing.
studied today. The very fact that H. lupulus was first used as a Gerhauser, C. (2005). Broad-spectrum antiinfective potential of
preservative in beer is a clear indication to scientists that xanthohumol from hop (H. lupulus L.) in comparison with
there exists potential in this plant for future study. It was activities of other hop constituents and xanthohumol
discovered that this plant has the potential not only to flavor metabolites. Molecular Nutrition and Food Research, 49(9),
alcoholic drinks but also to preserve them. Though alcohol 827-831.
often has a deeply negative connotation, it seems as if the key Heyerick, A., Vervarcke, S., Depypere, H., Bracke, M., & De
chemical constituents within hops, and therefore in beer, have Keukeleire, D. (2006). A first prospective, randomized,
unique and vital roles to play in the future of botanical double-blind, placebo-controlled study on the use of a
medicine. standardized hop extract to alleviate menopausal
discomforts. Maturitas, 54(2), 164-175.
Although they have been studied for many years now,
compounds such as XN and 8-PN are only just being studied Hougee, S., Faber, J., Sanders, A., Berg, W. B., Garssen, J., Smit, H. F., &
in-depth and their powerful medicinal properties only barely Hoijer, M. A. (2006). Selective Inhibition of COX-2 by a
beginning to be understood. To think that the future of Standardized COExtract ofand its Activity in a Mouse Model
of Zymosan-Induced Arthritis. Planta Medica, 72(3), 228-
malarial drugs, HIV drugs, cancer drugs, and estrogenic drugs
233. doi: 10.1055/s-2005-916212
might be found in H. lupulus is an incredible idea to grasp.
Though it may not seem a researcher’s first choice of subject, Milligan, S., Kalita, J., Pocock, V., Van de Kauter, V., Stevens, J.,
hops is an ideal plant to invest more research into because of Deinzer, M., De Keukeleire, D. (2000). The endocrine
its availability and relatively low variety within its genus. And activities of 8-prenylnaringenin and related hope (H.
lupulus L.) flavonoids. Journal of Clinical Endocrinology
in our current medical world, wrought with drug-resistant
and Metabolism, 85(12), 4912-4915.
strands it seems imperative that we begin to look for
Natarajan, P., Katta, S., Andrei, I., Ambati, B. R., Leonida, M., & Haas, Van Cleemput, M., Cattoor, K., De Bosscher, K., Haegeman, G., De
G. (2008). Positive antibacterial co-action between hop (H. Keukeleire, D., & Heyerick, A. (2009). Hop ()-Derived Bitter
lupulus) constituents and selected antibiotics. Acids as Multipotent Bioactive Compounds. Journal of
Phytomedicine, 15, 194-201. Natural Products, 72(6), 1220-1230. doi:
10.1021/np800740m
Zanoli, P., Rivasi, M., Zavatti, M., Brusiani, F., & Baraldi, M. (2005).
New insight in the neuropharmacological activity of Yamaguchi, N., Satoh- Yamaguhi, K., & Ono, M. (2009). In vitro
Humulus lupulus L. Journal of Ethnopharmacology, 102(1), evaluation of antibacterial, anticollagenase, and antioxidant
102-106. doi: 10.1016/j.jep.2005.05.040 activities of hop components (H. lupulus) addressing acne
vulgaris. Phytomedicine, 16, 369-376.
Serkani, J. E., Ishfahani, B. N., Safaei, H. G., Kermanshahi, R. K., &
Asghari, G. (2012). Evaluation of the effect of H. lupulus Neve, R. (1991). Hops. Chapman and Hall.
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Zanoli, P., & Zavatti, M. (2008). Pharmacognostic and
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Ethnopharmacology, 116, 383-396.
Hypericum perforatum L., Hypericaceae
Yinan Yang
Introduction
The genus of Hypericum contains about 370 species; within
this large group, Hypericum perforatum or St. John’s wort is
known to be a highly variable tetraploid that propagates
asexually. Hypericum is derived from its Greek name,
hyperikon, meaning above (hyper) and image (eikon) (Radun
2007). The common name, St. John’s wort, is named after
John the Baptist in Christian tradition. The herb H. perforatum
is usually harvested on June 23rd, the eve of the festival that
celebrates St. John the Baptist, and it was used to ward off evil
spirits, purify the surroundings and promote the harvest.
Wort also comes from the Anglo-Saxon origin meaning
medicine (Kim et al. 1999).
The use of H. perforatum can be traced back to ancient times
and is currently widely cultivated around certain continents of
the world like Asia and Europe. It is traditionally used as an
herbal tea and antiseptic or as a topical medicine for burns
and wounds but recently most commonly for its
antidepressant activities. St. John’s wort can also be used for
treating skin irritation, asthma, inflammation and ulcers.
Although the main components of St. John’s wort extract are
hyperforin, hypericin and pseudohypericin, the 2 latter ones
are not yet linked with mechanisms for reducing depression.
Other compounds in St. John’s wort include tannins,
flavonoids, proanthocyanidins and xanthones. St. John’s wort
is one of the top 15 best selling herbs in the world (Radun
2007). H. perforatum is a perennial herb but is also invasive; it
was first introduced to the US in 1700s for ornamental
Figure 1. Illustration of Hypericum perforatum.
purposes but has been overtaken some the native species (De
Smet et al. 1996). In terms of medicine, St. John’s wort is one H. perforatum is an invasive species that is capable of self-
of the top 15 best selling herbs in the world (Radun 2007). pollination and therefore, does not depend on pollination by
insects. In many instances, H. perforatum is introduced to a
new habitat along with an alien insect species that feeds on it.
Description Alien insect species are more likely to feed on the plant they
Until recently, the origin of St. John’s wort was thought to be in are familiar with than those that are not and H. perforatum is
Africa that later spread to Asia, Australia and America. an example of an invasive weed species that has been
However, recent evidence tells us that it actually originated in biologically controlled by specialist insect herbivores (De
the Mediterranean in Europe and later grew all over Europe, Smet et al. 1996).
except in the coldest of places (Radun 2007). Today, St. John’s
wort can be located in most parts of Europe, North America,
Australia and Asia, in the temperate climates and also in the Traditional Uses
tropics. St. John’s wort grows in the shrub habit and also in Uses of St. John’s wort have been thought to exist from
tree-like habit in the tropics. Its habitat also includes the prehistory. St. John’s wort is documented to be used mostly as
prairie, woodland, forest and rangeland (Radun 2007). While medicine as other uses such decoration and food has not been
St. John’s wort doesn’t have very strict conditions for growth, found. Uses of St. John’s wort as a medicine have had a long
its growth is optimally in the full sunlight with plenty of history whether as a topical medicine or an oral medicine.
moisture. Lean or gravel soil is also a good condition to grow The uses of St. John’s wort are many and are described as
in as it reduces growths of other plants (Radun 2007). follow, however, in current times, St. John’s wort is mainly
St. John’s wort grows upright and ranges from 30-100cm in used as an antidepressant. For example, in historical Britain,
height (Radun 2007). Its stems have 2 distinct ridges and doctors used St. John’s wort as a tranquilizer and to ward off
branches off in bundles at the upper part of the plant (Figure evil spirits (Radun 2007). In Herzegovina (Southern region of
1). The leaves of St. John’s wort are narrow and oval, ranging Bosnia), the documented use of St. John’s wort has been traced
from 1.5-3cm in length and 1.5-5mm in width; they also have back to the 13th century (Radun 2007). The perforation of the
leaves of St. John’s wort was thought to be useful in covering
perforated holes spread throughout the leaves that produces
deep wounds as it had antimicrobial properties (De Smet and
essential oil (Radun 2007). In the summer, St. John’s wort
Nolen 1996). Many notable Greek figures such as Hippocrates,
produces bundles of small yellow flowers with black dots;
Dioscorides, Theophrastus and Galen have been documented
they are very abundant, often produced in clusters of 25-100
in using St. John’s wort for treating menstrual problems,
per stem. The fruits of St. John’s wort look like capsules that
neurological disorders, treating wounds and as a diuretic. The
store around 50 seeds per plant. Each plant produces up to
Greeks also used it to ward off evil spirits in religious rituals
34,000 seeds per season and the seeds are around 5mm in
and valued the plant greatly; this practice was carried on in
length and black in color (Radun 2007).
Britain until recently (Zobayed, Murch, Rupasinghe and
Saxena 2003). Paracelsus is also documented to use St. John’s
Figure 2. Structure of hyperforin (Source: biologie.uni-
hamburg.de).
wort for treating wounds in the 1500s (Radun 2007).

Traditionally among the ordinary citizens, St. John’s wort has Figure 3. Structure of hypericin (Source: biopsychiatry.
been used in Europe for treating anxiety, depression, wounds, com).
inflammation and burns (Radun 2007). St. Johns wort is also
used as herbal tea and it is widespread in many countries such hypericin and pseudo-hypericin), vitamin C and A and
as Turkey, Bosnia, Pakistan, Britain, Germany and China as xanthoes (10ppm) (Radun 2007).
well as by Native Americans. The tea is used to treat ulcers,
The most notable compounds are hyperforin (Figure 2),
asthma, and bronchitis. An oil extract can also be used for
hypericins (Figure 3) and pseudohypericin (Figure 4).
skin irritation and bruises (Radun 2007). St. John’s wort has
Capsules of St. John’s wort have a standard dose around
also be used as liquid extracts, powdered herbs and tinctures,
300mg (0.3% hypericin) standardized around hypericin and
and is applied orally or topically in historical Europe (De Smet
pseudohypericin (Kopleman, Augsburger, NguyenPho, Zito
et al. 1996). Many of these methods to using St. John’s wort is
and Muller 2001). Hyperforin is a compound that is naturally
still being used today like oral capsules.
present in humans, and this is the compound responsible for
inducing metabolism of St. John’s wort. Among some popular
Chemistry and Pharmacology brands that are sold in stores, the content of hyperforin
ranged from 0.01-1.89%. Normally 1-6% of hyperforin is
Many kinds of chemicals are naturally found in St. John’s wort: required in treating mild depression (De Los Reyes and Koda
they are tannins and proanthocyanidins (catechin, 2002). The content of hypericin and pseudohypericin in
epicatechin, leucocyanidin) (6.5-15%), flavonoids (hypero- commonly sold drugs can be highly variable and in a study by
side, rutin, quercitrin, isoquercitrin, quercetin and De Los Reyes and Koda (2002), these compounds ranged from
kaempferol) (2-5%), biflavonoids, phloroglucinol derivatives 0.03-1.29% in weight: this is approximately 56.6-130% of
(including 4% hyperiforin), phenolic acids, volatiles oil (up to what all of the labels claimed to have in the amount of
1%), higher alkanes, sterols, naphthadian-thrones (including hypericin and pseudohypericin (0.15, 0.2 or 0.3%).
glutamate. It is hypothesized that another mechanism using
sodium ion channels is responsible for the mechanism. So far,
hypericin is the only compound known to be a preclinical
antidepressant with a completely new mechanism (Lewis and
Elvin-Lewis 2003).
Clinical Studies
Figure 4. Structure of psuedohypericin (Source: In clinical studies, extract of St. John’s wort has proven to be
chemicalbook.com). significantly more effective than placebo in treating mild to
moderate depression. The efficacy is not significantly
Biological Activity different as that of tricyclic antidepressants, but it seems that
St. John’s wort causes fewer side effects than those other
Flavonoids (rutin, hyperoside, isoquercitrin, quercitrin and antidepressants. These conclusions are based on a meta-
quercetin) are thought to be responsible for the analysis of 23 randomized trials with over 1700 patients
antidepressant activity of St. John’s wort as well as some (Lewis and Elvin-Lewis 2003). Several clinical trials have
antioxidant activities (which are thought to increase the been used in testing St. John’s wort: one study compared the
amount of extraction by preventing degradation of other efficacy of 800mg of St. John’s wort with 20mg of Prozac, and
chemicals). The napthodianthrones (hypericin and found that these had equal efficacy.
pseudohypericin) are used as standards in pharmacy, and was
until recently also thought to contribute to antidepressant Other recent clinical studies and meta-analysis have found
activity (Lewis and Elvin-Lewis 2003). that the use of St. John’s wort is twice as less likely in causing
side effects as the tricyclic antidepressants. There were also
St. John’s wort is an inhibitor of the reuptake of serotonin at less drop outs observed in using St. John’s wort than tricyclic
the presynaptic axons and it also seem to alter antidepressants in those trials: both of these are importnat
neurotransmitters at the postsynaptic axons. Norepinephrine factors for the patients since many treatments are abandoned
is also inhibited during reuptake but to a lesser extent. In due to onset of side effects causing patients to drop out (Kim,
vitro studies revealed that the ß-adrenoceptor is down- Streltzer and Goebert 1999).
regulated in a dose-dependent manner in similar fashion to
other anti-depressants, however, the activity could not be Many of the clinical trials, however, have design problems
traced back to hypericin nor hyperforin and therefore, the with methods and sample sizes so a definitive conclusion that
identity of this active chemical is still currently unknown. Still St. John’s wort is effective cannot be drawn (Kim, Streltzer and
in other studies like by Muller et al. (2001) it was found that Goebert 1999). For example, some of these studies used only
St. John’s wort extract was able to inhibit not only serotonin subjective standards or older diagnostic criteria to measure
and norepinepherine, but also dopamine, GABA and L- the presence of depression (Kim, Streltzer and Goebert 1999).
Certain studies also lack certain information that are critical to reactions and fatigue, but all of these complaints combined
the study like the patient’s history of depression, family constituted less than 2% of all clinical uses. On the other
history of depression, and the duration of depression which all hand, St. John’s wort is poisonous to livestock especially in the
cause the studies to lack strong support and structured tropical regions or Southern regions of the US due to
diagnosis (Kim, Streltzer and Goebert 1999). photosensitization of the chemicals (Lewis and Elvin-Lewis
Another questionable point in many of the clinical studies 2003).
involving St. John’s wort and depression is that many of these Another point to consider is the amount of variation in the
trials last only 4-6 weeks often with no follow up and so do active ingredients found in different brands of St. John’s wort
not address any long term effect of St. John’s wort. Currently that are sold. As mentioned before, hypericin and
there haven’t been any study involved in using St. John’s wort pseudohypericin are used to measure the standard dose, but
over the long-term efficacy, side effects, relapse…etc. for research done by Liu et al. found that there were significant
depression and other ailments. variations in other compounds within the different products
Finally, many of these clinical trials and diagnosis were done that are sold (De Los Reyes and Koda 2002). Since hyperforin
by generalized primary care physicians instead of specialized is considered to be the main ingredient in treating depression,
psychiatrics. This raises the question of the accuracy in and that it is not standardized (since it is difficult to
treating and diagnosing patients as primary physician have standardize), different brands of St. John’s wort may cause
been known to mistreat and misdiagnose depression 50% of different degrees of effectiveness.
time (Kim, Streltzer and Goebert 1999), and so this further Research has not yet shown that the effect of St. John’s wort is
weakens the conclusions gotten by these clinical studies (Kim, linked to hypericin and having variable amounts of other
Streltzer and Goebert 1999). ingredients may cause deleterious effects, especially when
combined with other drugs. It is still currently generally
unknown that combination with any other drug may lead to
Contraindications dangerous effects and more research is needed.
So far, St. John’s wort has had no indication of any significant
severe adverse effect that has been observed (Jobst, McIntyre,
St. George and Whitelegg 2000). St. John’s wort is currently Current Use in Allopathic & CAM Therapies
used in clinical setting in Germany and has so far produced no Currently, the only nation in the world that allows its doctors
record of any severe implications, overdose or toxicity (De to prescribe St. John’s wort as anti-depressant is Germany. In
Smet and Nolen 1996). St. John’s wort is currently used in fact, in 1994, German doctors prescribed 66 million doses of
Germany for mild to moderate depression, anxiety, medicine containing hypericum each day (De Smet and Nolen
psychogenic disturbances and nervousness (De Smet and 1996). There are currently 20 times more St. John’s wort
Nolen 1996). Some common mild side effects have been prescriptions in Germany than Prozac that are used to treat
reported which include gastrointestinal problems, allergic depression (Kim, Streltzer and Goebert 1999). The German
healthcare system favors individualized and subjective widespread use across the world that dates back to ancient
standards for evaluating depression as opposed to a more times. Although allopathic medicine continues to grow, the
objective system, and this may be another reason why they reality is that a large portion of the population in the world
use St. John’s wort in mainstream medicine (Kim, Streltzer and depends on traditional methods like medicinal plants to
Goebert 1999). support their well being and cure diseases. This is especially
Despite these promising data, the use of St. John’s wort toward true for rural areas around the world where there is no access
major depression, especially long-term trials, lack sufficient to allopathic medicine. Plants like St. John’s wort are also used
number of study and therefore, is not proven to be yet to for food, flavoring, liquors, perfumes, cleaning products and
effective in treating them. Furthermore, relapse of depression essential oil.
and late side effects haven’t been adequately studied (De Smet Many clinical trials have obtained significant result for St.
and Nolen 1996). In order for the extracts to be used for John’s wort versus placebo, however, lack of an organized and
major depression, further research is needed and it must also standardized procedure and diagnosis for clinical trials
meet the same regulations that govern other antidepressants. confounds the promising results obtained: further studies are
The extracts of St. John’s wort also need 2 to 4 weeks to affect seriously needed in long-term trials that objectively assess the
the mood. follow up of patients to definitely conclude that St. John’s wort
There are currently many herbal supplements in the US and is effective in treating depression.
can often be seen sold in bottles over the counter as oral The use of St. John’s wort is not recommended as a stand-
capsules. In the US, they are simply marked as capsules alone treatment for depression and any use should be
containing St. John’s wort branded under certain names like consulted by a doctor. The fact that St. John’s wort produces
Nature’s Way, Sundown and Now Foods. The standard dose of fewer side effects than conventional anti-depressants opens a
hypericin and pseudohypericin in these capsules are around door for doctors to consider using it for patients that have side
300mg. effects with conventional antidepressants (Kim, Streltzer and
The use of St. John’s wort is also growing in North America Goebert 1999). However, this can only be said for mild to
and it has also been used in aromatherapy and is currently moderate depression, and major depression and other severe
under investigation for using it against HIV. The traditional psychiatric disorders require more attention.
uses of St. John’s wort for curing wounds, bruises, ulcers and It is interesting to note that St. John’s wort is widely
inflammation still remain (Radun 2007). prescribed in Germany by doctors even though the effects of
St. John’s wort are not totally conclusive. As mentioned
before, this is probably due to the more subjective treatments
Discussion practices utilized.
St. John’s wort is a commonly known herb that almost One point that needs to be researched is whether hypericin
everyone in North America has heard of its existence. The and pseudohypericin have any effect against treating
popularity of this well known herb can be partly due to its depression through an alternative mechanism yet to be
discovered. The difficulty in storing hyperforin (the main
ingredient acting against depression) prevents it from being Kim, Hannah, Streltzer, Jon, and Deborah Goebert. 1999. St. John’s
used as the standard in conventional drugs. There is also the wort for depression: A meta-analysis of well-defined clinical
possibility that some other compounds may be responsible. trials. The Journal of Nervous and Mental Disease. 187; 532-
538.
The traditional use of St. John’s wort around Europe for
treating wounds and inflammation still exists today after Kopleman, Susan, Augsburger, Larry, NguyenPho, Agnes, Zito,
thousands of years. Due to its multitude of uses, Hypericum William, S., and Fran Muller. 2001. Selected physical and
perforatum will probably never cease to be used by people chemical properties of commercial Hypericum perforatum
around the world, at least not in the foreseeable future. extracts relevant for formulated product quality and
performance. AAPS PharmSci, 3; 26.
Lewis, Walter, and Memory Elvin-Lewis. 2003. Medical botany:
References Cited Plants affecting human health. New Jersey: John Wiley &
Sons, Inc.
De Los Reyes, Gerlie, and Robert Koda. 2002 Determining
hyperforin and hypericin content in eight brands of St. Radun, Marina. 2007. Conservation and utilization of St. John’s wort
John’s wort. Am J Health-Syst Pharm. 59; 545-7. (Hypericum perforatum L.) in Herzegovina. Master theses 47:
1-37.
De Smet, Peter, and Willem Nolen. 1996. St. John’s wort as an
antidepressant. British Medical Journal. 313: 241. Zobayed, S., Murch, S. J., Rupasinghe, H.P.V. and P.K. Saxena. 2003. In
vitro production and chemical characterization of St. Johns
Jobst, Kim, McIntyre, Michael, St. George, David, and Midge
wort (Hypericum perforatum L. cv ‘New Stem’). Plant
Whitelegg. 2000. Safety of St. John’s wort (Hypericum
Science, 166; 333-340.
perforatum). The Lancet. 355; 575.
Ilex paraguariensis A. St.-Hil., Aquifoliaceae
Avery Berlin
Introduction
Ilex paraguariensis A. St.-Hil is a member of Aquifoliaceae or
the holly family (Tropicos 2012). Classified by Auguste
Francois César Prouvencal de Saint-Hilare, its common names
include “té del Paraguay” in Paraguay, “erva mate” and
“chimarrão” in Brazil, and “maté” in Uruguay and Argentina
(Figure 1). These refer to its hot tea form. But when it is
prepared as a cold beverage, it is called “tereré” (Cordoba et
al. 2011). However, it is also universally known throughout
most of the world as yerba maté. Yerba comes from the word
‘herb’ in the Quichua language, and maté is the name of the
gourd from which it is traditionally consumed (Stern 2000).
Grown naturally as well as cultivated throughout South
America, this plant has remained an integral part of the
culture of Argentina, Brazil, Paraguay, and Uruguay since the
time of the Guaraní Indians, who employed this tea as a form
of social ritual (Joyce 1934). Now, it is universally consumed
throughout South America as well as around the world within
everything from candy to beer to soft drinks to creams and
even energy drinks (Andrade et al. 2012). However, the most
common method of consumption of I. paraguariensis is in the
form of tea (Figure 2) also known as “maté cebado” (Conforti Figure 1. Ilex paraguariensis plant (leaves, flowers, and
et al. 2012). berries).
Recently, I. paraguariensis has become available in the form of Source: http://www.nhm.ac.uk/nature-online/species-of-the-
day/biodiversity/economic-impact/ilex-paraguariensis/index.html
supplements and pills. Mainly consumed as a tonic and a
stimulant, it is used in the treatment of cardiovascular,
hepatic, digestive, and inflammatory disorders. People purine alkaloids, phenolic compounds, saponins, tannins, and
commonly ingest yerba maté for its elevated caffeine content flavonoids provide I. paraguariensis with anti-oxidant, anti-
to combat fatigue and to promote weight loss. Important viral as well as anti-inflammatory effects, which in turn give
Aquifoliaceae, otherwise known as the holly family, yerba
maté expresses “monopodial and rhythmic” proliferation,
occurring in biannual growth spurts in the spring and autumn
seasons (Giberti 1998; Rakocevic et al. 2011). It can even live
up to one hundred years. The pollination that it undergoes is
entomophilous or via insects such as bees and flies; birds then
scatter the seeds within the fruit of I. paraguariensis (Gauer &
Cavalli-Molina 1999).
The characteristics of this perennial, dioecious plant depend
on how it is grown—whether it is grown naturally or
cultivated. Naturally, wild yerba maté resides in the South
American forests as an understory evergreen tree, preferring
the sandy and clay soils present on the banks of local
waterways. Here, this small to medium sized tree grows
upwards of eighteen meters tall. It is, however, cultivated
Figure 2. Traditional yerba maté tea contained in a gourd throughout South America as a part of their agroforestry
with a ‘bombilla’. Source: http://guayaki.com/product/61/Pre- programs, seeking to combine the benefits of both agriculture
Columbian-Gourd-Gift-Pack.html and forestry in order to produce a flourishing crop population
(Giberti 1998).
this plant much of its medicinal properties (Bastos et al. In addition to agroforestry, yerba maté farmers cultivate this
2007). plant as the sole crop on plantations due to the increasing
demand for the leaves of this plant (Rakocevic et al. 2011).
Compared to the wild versions, cultivated I. paraguariensis
Botanical Description remains smaller, about two to three meters total in height
Native to South America, Ilex paraguariensis mainly occupies (Shua & Prada 2003). By comparing the picture of cultivated
the subtropical region of the continent (Rakocevic et al. 2011). yerba maté in Figure 3 to the wild version of the plant in
While this shrub tree grows in Bolivia, Colombia, and Ecuador, Figure 4, the height differences remain quite noticeable.
it flourishes specifically in northeastern Argentina, southern There are also distinct leaf differences in addition to the
Brazil, eastern Paraguay, as well as throughout Uruguay asymmetry in stature between the wild and cultivated yerba
(Service, U. N. R. C.; Gorzalczany et al. 2001). I. paraguariensis maté. The leaves of I. paraguariensis, which are the part of the
prefers the full, direct sunlight and extreme humid conditions plant most commonly used, average twenty centimeters in
of this subtropical region, enjoying temperatures averaging size in the wild (Giberti 1998; Stern 2000; Shua & Prada
around 21 degrees Celsius (Giberti 1998). As a member of 2003). The cultivated leaves are much smaller, only about five
Figure 3. Ilex paraguariensis cultivated through
monoculture on plantations.
Source: http://www.nhm.ac.uk/nature-online/species-of-the-
day/biodiversity/economic-impact/ilex-
paraguariensis/biology/index.html
centimeters. (Shua & Prada 2003). The tea from cultivated

leaves also tastes less bitter (Rakocevic et al. 2008).
Despite how they are grown, the leaves are eye-shaped with
tooth-like edges. These shiny, deep green colored leaves have
a leathery, fleshy quality. The leaves are attached via deep red
petioles. Figure 1 displays the specific leaf, fruit and flower Figure 4. Wild Ilex paraguariensis grown in the forests of
structures. The tree’s flat and somewhat smooth bark South America.
alternates in color between brown, gray, and green. The white Source: http://www.nativayerbamate.com/12.jpg
colored flowers of I. paraguariensis give rise to spherical
shaped fruits—magenta tinted berries—in the autumn increasing demand. This abuse directly influenced the I.
months (Giberti 1998). paraguariensis population, causing a significant decrease in
Due to I. paraguariensis’ significant and ever present role in numbers. Even through cultivation, specifically the use of
South American society as well as their economy, the plant plantations to grow this crop, the population continues to
population has suffered. No longer can the naturally grown deteriorate until a balance is created between supply and
tree stripped of its leaves produce enough supply for its demand (Giberti 1998).
Traditional Uses who were missionaries to the Guaraní then proceeded to
Since ancient times, Ilex paraguariensis has been richly cultivate the plant for the first time on plantations. The
steeped in South American culture. Recently, this plant’s Guaraní Indians also chewed the leaves to extract the caffeine
cultural role remains severely intertwined with its economical (Butler 1900).
importance. However, for hundreds of years, I. paraguariensis In addition, this tea was used historically for its medicinal
has continued to occupy an integral part of South American properties, which have provided relief from a wide variety of
society. Not only did the ancient South Americans recognize ailments for hundreds of years. These include, but are not
the important medicinal implications held by this plant, but limited to, digestive disorders, inflammatory processes,
they also utilized this tea within social settings. Dating back weakness of the body and mind, cardiovascular problems, as
hundreds of years, the Guaraní Indians, dwelling in the well as joint issues (Andrade et al. 2012). The plant is mainly
regions of Brazil and Paraguay, consumed this plant known to ingested via tonics. However, cataplasms, moist compresses
them as ‘caamini’ or ‘caaguazú’ (Gorzalczany et al. 2001; Joyce with pulverized plant parts, were also placed on inflamed and
1934). Its tea was deemed a social and ritual drink, one that ulcerated skin lesions in order to soothe as well as treat. The
promoted “trust and communion” between people and plant was first documented in South America for its remedial
facilitated meaningful conversations. It was also involved in effects within Examen de los Simples Medicinales in 1617
relaxation rituals (Gorzalczany et al. 2001). (Joyce 1934). Due to these yerba maté botanical remedies,
Legend has is that yerba maté was given to the Guaraní studies have resulted in order to not only isolate the active
Indians by the Goddess of the Moon. Yasí, the moon goddess, compounds, but also to potentially find treatments or cures
and her sister Araí, the cloud goddess, left Heaven one night to for specific illnesses.
travel to Earth. Unable to defend themselves against a jaguar
attack, they were rescued by an elderly Guaraní Indian who
shot the jaguar with a bow and arrow and saved the
goddesses lives. Out of thanks, the Goddess of the Moon gave The active constituents within Ilex paraguariensis are
this Guaraní yerba maté, along with directions on its responsible for not only increased plant survival, but also the
preparation. This drink was then shared with the rest of the plant’s medicinal properties. Amongst the plant’s most
Guaraní tribe (Shua & Prada 2003). prominent constituents are alkaloids, phenols, flavonoids,
saponins, tannins, as well as a host of vitamins and minerals
The traditional method of drinking the yerba maté tea can be
(Bastos et al. 2007). Table 1 lists these major constituents
seen in Figure 2. The leaves are gathered, dried over the fire,
within I. paraguariensis.
pulverized, and then steeped in water to produce a brewed
tea. The gourd that the tea is commonly contained in is known The three most active alkaloids, specifically purine alkaloids,
as a maté, and a metal ‘bombilla’ strains the dried leaf within yerba maté are caffeine (1,3,7-trimethylxanthine),
particles as it is being consumed (Conforti et al. 2012). theobromine (3,7-dimethylxanthine), and theophylline (1,3-
Amazed at the tea’s caffeinated effects, the Spanish Jesuits dimethylxanthine). Figure 5 shows the structural differences
Compound Class of Compound
Caffeine Purine alkaloid
Theobromine Purine alkaloid
Theophylline Purine alkaloid
Caffeic acid Phenol

Ferulic acid Phenol
Sinapic acid Phenol
p-coumaric acid Phenol
5-O-caffeoylquinic acid Phenol
caffeoylshikimic acid Phenol
dicaffeoylshikimic acid Phenol
caffeoyl glucose Phenol
Matesaponin Saponin
Ursolic acid Saponin
Oleanolic acid Saponin
Quercetin Flavonoid
Rutin Flavonoid
Figure 5. The chemical structures of the major alkaloid
A Vitamin constituents within Ilex paraguariensis, which are
B complex Vitamin
caffeine, theophylline, and theobromine (the three most
C Vitamin
E Vitamin prevalent xanthines).
Table 1: Major Constituents within Ilex paraguariensis A. Source: http://www.benbest.com/health/xanthines.gif
St.-Hil.
Source: Bastos et al. 2007 may be due to the time of year as well as the location that the
plant is growing. The winter and autumn months result in a
between these three types of xanthines. While some scientists decreased concentration of caffeine. “Light intensity and
still debate the presence of theophylline within the plant, temperature, stress conditions, presence of predators, kind
caffeine and theobromine are present in high doses, with and frequency of trimming” may also influence the amounts
caffeine being the highest. This provides the plant with a present. Also, studies differ on whether or not the
means of preventing predation as well as fighting off concentrations of these purine alkaloids are elevated post-
competing plants in its surrounding area. The differences in drying of the leaves (Bastos et al. 2007).
the caffeine concentrations among plants of I. paraguariensis
In addition to alkaloids, phenolic compounds are present A, B complex, C, and E are present; however, their amounts are
within the leaves of I. paraguariensis, making up roughly thirty highly influenced by how the tea is produced as well as where
percent of the plant constituents (Matsumoto et al. 2009). it is grown (Bracesco et al. 2011).
These mainly occur in the form of esters as chlorogenic acids
or CGAs and include caffeic (3,4-dihydroxicinnamic), ferulic
(3-methoxy, 4-hydroxy), sinapic (3,5-dimethoxy, 4-hydroxy) Biological Activity
and p-coumaric (4-hydroxy) acids. Amongst these acids, the Over the past few decades, many researchers have studied the
characteristic chlorogenic acid within yerba maté is 5-O- effects and mechanisms of action of Ilex paraguariensis in
caffeoylquinic acid or 5-CQA. Other extracts of the dried leaves hopes of gaining new and more in depth medical insight.
revealed caffeoylshikimic acid and dicaffeoylshikimic acid. Because this plant has been used for years in medical
Caffeoyl glucose remains another present polyphenol within treatments, researchers are determined to uncover the
the plant. The anti-oxidant properties owe themselves mainly medicinal basis of yerba maté. In order to do so, biological
to the phenolic compounds present in yerba maté. However, assays are performed in vitro as well as in vivo in reference to
there is debate over the methodology responsible for the anti- a variety of different health issues and diseases.
oxidant properties. This oxidation prevention occurs either
due to the donation of excess electrons to “free radical
scavengers” or the “chelating [action] of transition metal ions” Herpes
(Bastos et al. 2007).
Due to the rapid increase in drug resistance, researchers are
Similarly, saponins are prevalent throughout the I. desperately searching for new modes of action in the
paraguariensis plant. The majority of these glycosides are treatment of infections due to the herpes simplex virus.
triterpenoid, but there are “monodesmosidic and Because certain constituents of the plant have anti-viral
bidesmosidic saponins found in the aerial parts of the plants” effects, yerba maté was examined for its potential anti-herpes
(Bastos et al. 2007). In 1989, research of yerba maté yielded properties. Extracts from I. paraguariensis were tested against
the “isolation and elucidation of a new saponin” known as HSV-1, KOS strain, and HSV-2. Through the laboratory study,
matesaponin, a “three sugar residue bidesmoside” (Bastos et all plant samples used were positive for anti-herpes effects.
al. 2007). Since then, research observed matesaponin 1 Furthermore, it showed “reduced HSV-1 and HSV-2 infectivity
through 5 within the plant. Ursolic acid and its isomer to concentrations ranging from one to three times below their
oleanolic acid are minor saponins occupying the leaves of the original infectivity concentration value.” This information may
plant. In all, 29 different saponins have been identified within propose microbicidal properties, which may “inactivate the
I. paraguariensis (Bastos et al. 2007). herpes virus and interfere with virion envelope structures or
The rest of the important constituents are flavonoids and mask viral structures necessary for absorption or entry into
tannins, as well as some vitamins. Quercetin and rutin are two host cells.” The studied fraction decreased the spread of the
common flavonoids present in yerba maté. The tannin content virus into adjacent cells and the number of virions transferred
is partly responsible for the bitter nature of the tea. Vitamins to unaffected cells. The saponins found in yerba maté were
specifically believed to be responsible for its anti-herpes intestinal propulsion via peristalsis, mice were fed charcoal
effects (Lückemeyer et al. 2011). and killed approximately twenty minutes later. The distance
that the charcoal traveled down the small intestine was
measured. A considerable increase of bile flow resulted from
Weight Loss the 250 milligram per kilogram dose. I. paraguariensis failed
I. paraguariensis has long been associated with weight to show any effects on peristalsis. However, it does increase
reduction. Therefore, studies were performed to assess the the output of bile from the liver, thereby restating the
accuracy behind this association. One particular in vivo study hepatoprotective effects (Gorzalczany et al. 2001).
sought to examine the effects of yerba maté on mice obesity.
These mice were fed high fat diets and then were randomly
assigned either water or yerba maté extracts. The results Clinical Studies
proved that the extracts in fact led to a considerable reduction Bone Mineral Density
in body mass of those mice, which consumed the extract. The
Ilex paraguariensis has been involved in a multitude of clinical
evaluation of the mice showed a minimization in “serum levels
studies to further test the notions of health benefits associated
of cholesterol, triglycerides, LDL cholesterol, and glucose.” In
with this plant. One such study sought to investigate bone
addition, the expression of many genes and proteins that were
mineral density associated with osteoporosis in
increased due to the high fat diet experienced a reduction.
postmenopausal women. This study examined 146 women
Chlorogenic acid, a phenolic compound, is believed to be
who drank an average of one liter per day of yerba maté tea
associated with the metabolism of glucose via the enzymatic
and 146 women who never ingested the tea as the control
activity of glucose-6-phosphatase. It also plays a role in the
group. Bone mineral density or BMD was measured for each
prevention of cardiovascular disease by the anti-oxidation of
woman’s lumbar spinal region and hip joint via a dual-energy
cholesterol. The purine alkaloids and saponins potentially
X-ray absorptiometry. Women who regularly consumed yerba
work with the phenolic compounds to produce these effects
maté tea showed considerably higher bone mineral density in
visible in the mice (Arcari et al. 2009).
both of the regions. This amounted to an increase of 9.7% for
the lumbar spine and 6.2% for the femoral neck of the hip
Bile Flow joint. Therefore, I. paraguariensis shows protective activity
against osteoporosis in postmenopausal women (Conforti et
Because I. paraguariensis was historically utilized to treat al. 2012).
digestive and hepatic disorders, this in vivo study examines
the effects of yerba maté on bile flow and peristalsis of the
digestive tract. While under anesthesia, the rats underwent Diabetes
surgery to measure their bile output in order to calculate bile
Another clinical study set to investigate the correlation
flow. They then received either saline or I. paraguariensis
between I. paraguariensis and diabetes, specifically patients
extract intravenously or intraduodenally. To measure the
who are type II diabetic and pre-diabetic. Because research
has proved that this plant decreases blood sugar in some However, this particular study found that the increased risk
animals as well as decreases cholesterol levels in humans, this was greater for those who drank the tea either cold or warm
study wanted to test the notion that yerba maté may be of than those who drank it hot or very hot. This proposes that
benefit to these people. There were three treatment groups— yerba maté may in fact have carcinogenic effects especially in
yerba maté tea, dietary counseling, and yerba maté tea in the UADT (Szymańska et al. 2010).
conjunction with dietary counseling. 29 individuals with
diabetes mellitus and 29 pre-diabetic individuals were utilized
in this study. The yerba maté tea reduced “levels of fasting Contraindications
glucose, glycated hemoglobin, and low density lipoprotein Ilex paraguariensis ingested in any form is considered GRAS or
cholesterol.” The clinical study found that yerba maté generally recognized as safe. However, despite the fact that it
regulated blood sugar levels and decreased cholesterol in is described as nontoxic whether in the form of tea, pills,
these diabetic and pre-diabetic individuals. This may point to supplements, etc., there remain contraindications as well as
yerba maté containing preventative means against coronary positive associations with certain diseases and cancers. Due to
artery disease (Klein et al. 2011). these dangerous interactions, I. paraguariensis should
potentially be avoided by certain people whose health issues
may be exacerbated by the active constituents within the
UADT Cancers
plant.
Because the incidence of upper aerodigestive tract cancers is
An in vivo study with rats and rabbits tested toxicity levels
significantly greater in South America, a clinical study was
immediately following consumption as well as after continued
performed to test the hypothesis that the increased
intake for up to three months. Not only did the study show no
consumption of yerba maté may influence these rates. Upper
forms of toxicity for a single dosage, it was also found to be
aerodigestive tract cancers include cancers of the oral cavity,
safe for chronic consumption. Other studies have confirmed
oropharynx, hypopharynx, larynx, and esophagus. 1,168
that there is no toxicity associated with the liver, the kidneys,
individuals as well as 1,026 control individuals were involved
or the bladder. I. paraguariensis even shows a potential
in this clinical study. This study was indicative of a positive
protection again DNA strand damage in an ex vivo study. The
correlation between esophageal cancer and excessive
constituents prevented the DNA strands from damage due to
consumption of yerba maté tea. If an individual drank the tea
peroxide content, and they enhanced the mending of DNA
consistently for roughly twenty years, he/she was 3.5 times
within liver cells (Andrade et al. 2012).
more likely to acquire this type of cancer than someone who
had never drank the tea. For forty years of consumption, the Because I. paraguariensis contains caffeine and other
likelihood increases to five times. There has been controversy xanthines, people that consume any form of this plant should
regarding previous studies, which believe that this association avoid it if they have allergies to either compound. In addition,
is due to the temperature of the tea. A high temperature could women who are either pregnant or breastfeeding should
induce thermal damage to the head and neck regions. refrain from ingesting yerba maté. The caffeine within the
plant reduces fatigue and increases alertness; therefore, it including capsules, tablets, and pills. The majority of these
may cause problems with sleep if ingested around bedtime. It medicinal remedies remain in the form of supplements.
also should be avoided when taken in conjunction with Mainly, yerba maté is utilized as a stimulant to increase
sleeping medications due to drug interference. Yerba maté alertness and decrease fatigue (Gorzalczany et al. 2001).
also has diuretic effects and should not be consumed if These supplements on many occasions are used in
diuretic effects are to be avoided especially with urinary tract conjunction with guarana, kola nut, and green tea to enhance
obstruction. People suffering from cardiovascular diseases the effects (Bastos et al. 2007). 29 different dietary
such as hypertension and arrhythmia should avoid yerba supplements of yerba maté from the years 1963 to 2006
maté. Those who show signs of hyperthyroidism and gastric gained international patents with a significant influx in
and duodenal ulcers should refrain from consumption. In supplements after the turn of the century. These included but
addition, use with monoamine oxidase inhibitor drugs or were not limited to supplements to facilitate weight loss,
MAO-inhibitors should not occur. These drugs are used in the promote sexual arousal, enhance hair thickness, and decrease
treatment of depression. I. paraguariensis decreases the levels of cholesterol. Other uses for yerba maté aim to treat
sedative and anti-anxiety processes within these drugs and the underlying issues of “arthritis, headache, constipation,
therefore, exacerbate the side effects associated with rheumatism, hemorrhoids, obesity, fatigue, fluid retention,
sympathomimetic drugs (Products, C. o. H. M. 2010). hypertension, slow digestion, and hepatic disorders”
Unfortunately, there has been a positive correlation with head (Gorzalczany et al. 2001).
and neck cancers, especially oropharyngeal and esophageal
Albeit no prescription or over the counter drugs are either on
cancers (Szymańska et al. 2010). However, due to the anti-
the market or have been approved by the FDA, many studies
oxidant effects of yerba maté, some of the constituents have
are attempting to gather more information regarding I.
anti-carcinogenic effects. While people with specific health
paraguariensis in the hopes of isolating the mechanisms of
conditions should avoid I. paraguariensis, the plant remains
action for its active constituents. While studies have produced
GRAS and is established as nontoxic.
positive results concerning the treatment for
hypercholesterolemia as well as osteoporosis, more research
Current Use in Allopathic and CAM Therapies needs to be done in order for a FDA-approved drug. Until
more information is known, yerba maté will continue to be a
Today, Ilex paraguariensis still remains a leading medicinal commonly used supplement and CAM therapy.
plant. Based on the knowledge that native South American
Indians possessed of its curative properties, yerba maté
continues to be used to treat a multitude of ailments. Use of Discussion
this plant within traditional medical practices propagated its
Hundreds of years ago, the Guaraní Indians of South America
use in the current world of complementary and alternative
recognized the importance as well as the medicinal potential
medical therapies. This has instigated the creation,
of Ilex paraguariensis. Today, researchers are beginning to
production, and use of I. paraguariensis in many forms,
recognize this same thing. For the Guaraní, this highly
regarded tea remained an integral part of their culture, from supplements commonly purchased in the US: analysis of 53
social rituals to traditional medicinal practices. Over the years, products with caffeine-containing ingredients. Analytical
it has been associated with the treatment of a variety of and Bioanalytical Chemistry, 389(1), 231-239. doi:
different ailments. This yerba maté decoction treats 10.1007/s00216-007-1437-2
everything from weakness of the body and mind, digestive Arcari, D. P., Bartchewsky, W., dos Santos, T. W., Oliveira, K. A.,
disorders, inflammatory processes, cardiovascular problems, Funck, A., Pedrazzoli, J., . . . Ribeiro, M. L. (2009). Antiobesity
as well as joint issues. Effects of yerba mate Extract (Ilex paraguariensis) in High-
fat Diet-induced Obese Mice. Obesity, 17(12), 2127-2133.
Recently, researchers have gone further to investigate these
treatments, looking at the constituents of I. paraguariensis as Bastos, D. H. M., de Oliveira, D. M., Matsumoto, R. L. T., de Oliveira
Carvalho, P., & Ribeiro, M. L. (2007). Yerba maté:
well as their mechanisms of action. These constituents include
Pharmacological Properties, Research and Biotechnology
purine alkaloids, phenolic compounds, saponins, tannins, and
Medicinal and Aromatic Plant Science and Biotechnology:
flavonoids, providing anti-inflammatory, anti-viral, and anti- Global Science Books.
oxidant effects. Within in vitro and in vivo studies, I.
paraguaniensis showed anti-herpes activity, weight loss as Bracesco, N., Sanchez, A. G., Contreras, V., Menini, T., & Gugliucci, A.
well as a reduction in LDL cholesterol and an increase in bile (2011). Recent advances on Ilex paraguariensis research:
Minireview. Journal of Ethnopharmacology, 136(3), 378-384.
flow. In regards to clinical studies, while it increased BMD and
doi: 10.1016/j.jep.2010.06.032
lowered LDL in diabetic patients, it did show a carcinogenic
effect. Knowing which problems yerba maté has been known Butler, W. M. (1900). Yerba Maté Tea: The History of Its Early
to treat through traditional medicine, researchers may be able Discovery in Paraguay, Its Preparation in that Country and in
to learn more about I. paraguariensis and its potential for the Brazil, and Its Introduction into the United States.
Philadelphia: The Yerba Maté Tea Co.
future. However, to be able to utilize this plant for generations
to come, we must protect it from environmental abuse and Conforti, A. S., Gallo, M. E., & Saraví, F. D. (2012). Yerba Mate (Ilex
overharvesting. paraguariensis) consumption is associated with higher bone
mineral density in postmenopausal women. Bone, 50(1), 9-
13. doi: 10.1016/j.bone.2011.08.029
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Lavandula angustifolia Mill., Lamiaceae
Cimma Sefat
Introduction
Lavandula angustifolia, also known as true lavender, is a
member of the Lamiaceae family (Figure 1). It is commonly
known as English lavender or xun yi cao in Chinese
("Lavandula angustifolia Mill. ," 2012). L. angustifolia is the
most common species of lavender, and other species include L.
burnamii, L. dentate, L. dhofarensis, L. latifolia, and L. stoechas
(Basch et al., 2004). This plant is native to the western
Figure 1. Lavender field in Provence, France. (Source:
Mediterranean region, and its hybrid lavandin is widely http://gourmetcyclingtravel.com/wp-content/uploads/Lavender-
cultivated in Australia, Europe, and the United States. L. Field-800X2752.jpg).
angustifolia has been known for its cosmetic and medicinal
uses throughout history (Basch et al., 2004). Advertised as a
calming agent, L. angustifolia is said to ease restless minds. Its angustifolia originated in the Mediterranean basin and is
aromatic essential oils are highly prized and used for cultivated in Albania, Argentina, Australia, Bulgaria, China,
aromatherapy, candles, cooking, laundry detergent, massage France, Hungary, Italy, Moldova, Montenegro, the Netherlands,
oils, perfume, and soap (Basch et al., 2004). Being a member Russia, Serbia, Spain, the United Kingdom, and the United
of the Lamiaceae or mint family, lavender leaves also serve a States (Craig, 2006). L. angustifolia is capable of surviving in
culinary purpose and are commonly used in salads, stews, tea, temperatures as low as -15°C (Bourne, 2004). This plant
honey, jam, and jelly (Craig, 2006). prefers full sun and can also survive in a wide range of soils
but these soils must be well drained since the plant cannot
tolerate sitting in very wet soils (Fowler, 2004). L. angustifolia
Botanical Description flourishes on hard pruning, and if pruned every year, it can
survive for approximately 20 years (Bourne, 2004). Lavender
Lavender is an evergreen subshrub plan that grows
is a popular and reliable drought-tolerant perennial for
approximately two to three feet tall and produces small,
gardens and hedges, requires little fertilizer, and is bothered
slender blue-violet flower spikes on the stalks and narrow
by few pests (Anonymous, 2011).
silver green foliage. This detail can be noted in Figure 2. The
angustifolia species is a stockier plant with fuller flowers The hybrid lavandin is much more widely cultivated and
unlike other the lavender species ("Lavender," 2007). Native exceeds L. angustifolia in essential oil production; however,
to low mountains and altitudes of 1,970-3,940 feet, L. the finest oil used in cosmetics, perfume, and aromatherapy
of casting. The bodies would be wrapped in these linens and
dried in the sun until the casts hardened (Craig, 2006).
Lavender is known as a “healing agent” in India and Tibet, and
can also be used medicinally to treat insanity and psychoses in
Tibetan Buddhism (Basch et al., 2004). It has been reported
that in fourteenth century France, Charles VI’s court used
cushions stuffed with lavender which provided not only a
pleasant aroma but also helped repel insects (Craig, 2006).
During the twelfth century in Grasse, located in southeast
France, lavender oil was the main component of commercial
perfumes. Many thought the scent of lavender surpassed all
other scents due to its delicate and unique aroma (Craig,
2006). In Iranian folk medicine, lavender leaves are used to
treat various inflammatory diseases (Hajhashemi, Ghannadi, &
Sharif, 2003). Infusions of the plant have been used as a
carminative, diuretic, anti-epileptic, anti-rheumatic, and pain
Figure 2. Close up of L. angustifolia (Source: reliever especially for headache and migraine pain.
http://scienceray.com/biology/lavender-a-fragrant-plant-of-the- Associated with cleanliness, lavender maintains great
family-lamiaceae/). popularity as fresh or dried flowers, potpourri, gifts, crafts,
and more (Anonymous, 2011).
come from L. angustifolia (Bourne, 2004). Since lavender has
been cultivated for so long, most lavender found in gardens
are hybrids and identification can be difficult (Craig, 2006). Chemistry and Pharmacology
Dried lavender flowers contain less than 13 ml/kg of essential Lavender is known for its rich content of volatile oils, and for
oil that is obtained by steam distillation from the flowering centuries it has been used for both fragrance and medicine.
parts (Basch et al., 2004). Aromatherapy is thought to be effective due to the effect of
odor and the physiological effect of inhaling volatile
compounds like the oil of L. angustifolia. Lavender is
Traditional Uses composed of several hundred constituents which include
Lavender is derived from the Latin word lavare, which means flavonoids, cineole, coumarins, triterpenes, tannins, limonene,
to wash. The Grecians, Persians, and Romans used lavender camphor, linalyl acetate (Figure 3), perillyl alcohol, and
flowers as a perfume in the baths and for laundry (Craig, linalool (Figure 4) (Basch et al., 2004). The highest
2006). As a part of mummification, ancient Egyptians soaked concentration of naturally occurring compounds in lavender
wrapping linen in lavender oil containing asphalt as a method oil include linalool, linalyl acetate, 1,8-cineole, beta-ocimene,
Figure 3. Linalyl acetate (Source: Figure 4. Linalool (Source:
http://www.rdchemicals.com/chemicals.php?mode=details&mol_id http://www.rdchemicals.com/chemicals.php?mode=details&mol_id
=8000). =7998).
terpinen-4-ol, and camphor (Oliff, 2003). Linalool and linalyl

acetate are rapidly drawn into the skin when massaged and
believed to cause central nervous system depression. Linalyl
acetate has narcotic actions while linalool acts as a sedative
(Basch et al., 2004). Due to the calming actions of these
constituents, they may be the origin of the use of lavender
pillows to induce sleep (Oliff, 2003). Lavender leaves yield a
pale-yellowish essential oil with a fresh and pleasant odor
(Hajhashemi et al., 2003). Twenty-one components were
characterized which represent 99.1% of the total oil
components detected, listed in Table 1.
Biological Activity
In Vitro
Oil of L. angustifolia is active against several bacterial and
fungal species, and it has been suggested that lavender oil may
be useful in treating bacterial infections resistant of antibiotics
(Lodhia, Bhatt, & Thaker, 2009). In a study by Hui et al., L. Table 1. List of essential oils in L. angustifolia (Source:
angustifolia oil was studied for antimicrobial activity for Hajhashemi et al., 2003).
temperature (22 °C). The mites were exposed to a series of
doses. To verify that linalool was the only effective
constituent responsible for acaricidal activity, an artificial
mixture of 27% linalool (the percentage found in the essential
oil) and 73% saline (1mL/plate) with 2% vaseline oil
Table 2. Anti-bacterial activities of lavender essential oil
(1mL/plate) was tested the same way. The controls used
(Source: Lu Hui, 2010).
were plates containing just the physiological saline and plates
containing solely vaseline oil. Motionless mites were
potential treatment for rhinitis patients. It was found to be observed with a stereoscopic microscope after a 24-hour
active against all tested strains of bacteria seen in Table 2. period, and then transferred to a fresh petri dish and observed
The oil’s activity is dependent on concentration. At 51 mg/ml, again for another 24 hours. The mites were stimulated with a
none of the tested bacteria survived. The study believes that needle, and any lack of reaction or continued immobility
the L. angustifolia’s essential oil is capable of disrupting the indicated death. However, further studies on the toxicity and
cell membrane, and the cell looses chemiosmotic control (Lu mode of action and in vivo activity are necessary to confirm
Hui, 2010). Antimicrobial activity of lavender oil may not be whether lavender essential oil and linalool can be used as an
related to the main constituents in the oil and there is little alternative acaricide.
known about the possible relationship. Many of the lavender
antimicrobial studies do not have standardization so directly
comparing studies is impossible (Oliff, 2003). In Vivo
Another study published in 2007 studies essential oils in There also was a study on anti-inflammatory and analgesic
plants like L. angustifolia as an acaricide, or a substance properties of leaf extracts and essential oil of L. angustifolia
poisonous to mites or ticks. There is a long tradition that published in 2003. The study evalulates the analgesic and
aromatic herbs such as lavender are used to repel insects. In anti-inflammatory activities of the hydroalcoholic extract,
folklore, essential oils are held in high regard because of their polyphenolic fraction and essential oil of plant leaves in mice
use as an insecticide and repellent. It is known that different and rats. The leaves of L. angustifolia were collected near
essential oil components render different species of insect Isfahan, Iran. The leaves were then air dried and powdered,
susceptible. The study performed by Perruci et. al has shown and the essential oil was isolated by hydro distillation. The
that when the mites Psoroptes cuniculi (mange mite of the hydroalcoholic extract was made by taking the powdered L.
rabbit) is exposed to linalool, the parasite looses mobility (5). angustifolia leaves (100 g) and macerating with EtOH-H2O
It is suggested that inhalation and direct contact to linalool (500 g) for 48 hours. The extract was shaken, filtered, and
causes lose of mobility. The experiment placed the mites (10- evaporated until dry. The polyphenolic fraction of the plant
15/sample) on a 6 cm petri dish covered with a filter. Then (100 g) was made in 2 steps. The fraction was extracted with
that petri dish is placed in a 9 cm petri dish containing the L. EtOH:H2O (9:1) then again with a 1:1 ration of the same
angustifolia oil. The experiement was done at room solution. The mixture was left for 12 hours. Then the two
extracts were combined and evaporated to 1/3 its original the polyphenolic fraction in high doses (such as 4000 mg/kg)
volume. The remaining aqueous solution was extracted with did not exhibit a considerable anti-inflammatory effect. At a
chloroform and evaporated until dry, which left semi-solid dose of 200 mg/kg, the essential oil showed a 48% inhibition
masses of both the hydroalcoholic extract and polyphenolic of carrageenan-induce paw edema (S. Perrucci, 1996).
fraction (yield 42.0% and 12.2%, respectively). Analgesic
A study by the Cline group investigates the anxiolytic effects of
activity was tested with two tests: a formalin test and an acetic
the compound linalool and the GABAA receptors in rats. Forty-
acid-induced writhing test. For the first test, mice were four rats were given a 1 mL total volume intraperitoneal
injected with 20 μl of 2.5% formalin (in 0.9% saline) in their injection of positive control, midazalom, linalool, or a linalool
right hind paw. The hydroalcoholic extract, polyphenolic and flumazenil mixture. Then, they were put on an elevated
fraction and essential oil were given orally prior to the maze and had their corticosterone levels measured. The data
formalin injection. suggests that linalool does not produce anxiolytic effects by
For the acetic acid-induced writhing test, 6 mice received regulating GABAA receptors but it may modulate motor
different oral doses of hydroalcoholic extract, polyphenolic movements in the rats. The rats were placed on an open arm
fraction, and essential oil one hour prior to the intraperitoneal of the elevated plus maze (EPM) for a 5-minute evaluation of
injection of 1% acetic acid (volume 10 ml/kg). Anti- behavioral response to anxiety. The EPM was networked with
inflammatory activity was evaluated by carrageenan-induced MotorMonitor software to track the number of times the rats
paw edema test in the rat. The rats were anaesthetized with would enter either type of arm (open or closed), time spent in
either and injected with 0.1 ml of 1% suspension of the arms, and basic motor movement. After the 5-minute test
carrageenan in isotonic saline. The left hind paw was injected on the EPM, the rats were humanely killed by guillotine and
with 0.1 ml saline as a control. The extract and essential oil their blood was collected for corticosterone and
mixture was diluted and administered 1 hour before the catecholamine (epinephrine and noepinephrine) analysis.
carrageenan injection. There was no significant analysis of the ratio of open arm time
versus total time in the EPM between the linalool and the
While the hydroalcoholic extract failed to produce any
flumazenil plus linalool group. There was significant
significant analgesic effects in the first phase, when given in
difference in the open arm, a measurement of behavioral
does of 400, 800, and 1600 mg/kg, paw licking time was
changes with anxiety, between the midazolam and the control
reduced 69, 72, and 93%, respectively. The polyphenolic
groups. As for fine motor movements, analysis showed a
fraction and essential oil suppressed paw licking in both
significant decrease in movement in both the midazolam
phases of formalin test. For the acetic-induced writhing test,
group and flumazenil plus linalool group compared to the
hydroalcoholic extract did not apply a significant decline of
control. The behavioral measurements comparing time spend
abdominal twitches, while the polyphenolic fractions (doses of
in different arms on the EPM does not suggest that linalool
400 and 800 mg/kg) and essential oil (100 and 200 mg/kg)
produces anxiolysis. There was no difference between the
significantly reduced writhing. The results were not dose-
mixture group therefore suggesting that linalool does not
dependent since the increased dose did not alter the response.
regulate the benzodiazepine receptor site. The results do not
For the carrageenan test, the neither the hydroalcoholic nor
support that linalool modulates the GABAA receptor. The administered for 3 weeks with a wash out period (2 weeks) in
neurohormonal data did not demonstrate a significant between treatments. Then, the other treatment was given.
difference amongst the groups. Motor movement exhibited Treatment A was L. angustifolia inhalation, and treatment B
that midazolam and the flumazenil and linalool combination was sunflower inhalation (placebo). Aroma diffusers were
significantly decreased both basic and fine motor movements. placed at each side of the participants’ bed during sleep at
The study is unsure how to interpret these results but it is night for 1 hour. No adverse effects were reported from
speculated that another neurotransmitter site is being either staff or patients during the study period. Caregivers
modulated. It is suggested that linalool modulates receptors noted a significant decrease in agitated behavior in patients
at the neuromuscular junction thus decreasing acetylcholine recieving Treatment A. Agitation scores decreased from 6.49
release and limiting motor activity. Although the data does to 5.63. Irritability decreased from 4.81 to 4.53. The
not support anxiolytic effects of linalool in rats, there is aromatherapy treatment was well tolerated and resulted in a
evidence to suggest linalool regulates the central nervous significant decrease in agitation of patients with dementia
system by producing unconsciousness and deterioration of (Wan-ki Lin, Wai-chi, Fung-leung Ng, & Chiu-wa Lam, 2007).
motor movements (Cline, Taylor, Flores, & Bracken, 2006).
Support of lavender as an anxiolytic is still weak but some
evidence does suggest an effect in the plant’s ability to relieve
Clinical Studies anxiety (Basch et al., 2004). In one study, nurses used
aromatherapy on 20 hospitalized children with HIV to relieve
The chemical composition and pharmacological study and them of physical pain. They used a variety of essential oils
evaluation of L. angustifolia have been the subject of several known for their “analgesic and nervine” properties including
studies for years. Most of these studies focus on extracts and L. angustifolia oil. Nurses noted that the children responded
essential oils of lavender. In pharmacological studies, the well to the essential oils, which helped reduce the need for
extracts and essential oils are believed to have CNS- analgesic drugs. Chronic chest pain, intermittent muscle
depressant, anti-convulsive, sedative, spasmolytic, local spasm, and peripheral neuropathy were alleviated almost
anesthetic, antioxidant, anti-bacterial, and mast cell completely. This is a descriptive study and no statistical data
degrandulation effects (Hajhashemi et al., 2003). was analyzed (Buckle, 1999, p. 44).
A cross-over randomized study conducted at nursing homes in Another study suggests that there is some scientific evidence
Hong Kong studied pharmacological intervention of L. regarding the use of lavender oil baths for relieving
angustifolia for agitated behaviors among people with postpartum perineal pain. The effect of lavender oil baths was
dementia. Seventy participants diagnosed with dementia with examined on 635 postpartum women in a randomized trial.
significant agitation were recruited, and participants taking The women were divided into three groups. One group added
psychotropic medication to control their aggression (51.4%) a natural lavender oil extract, the second group added
continued to take their medication. Participants were synthetic lavender oil, and the third group added a GRAS
assigned to group A or B but both groups received both substance. Neither the midwives nor the mothers know what
treatments. Either treatment A or treatment B was kind of oil was administered. Daily baths were routine for the
mother’s care after delivery, and each day the midwife added L. angustiofolia but nausea, vomiting, and anorexia were
six drops of the oil from which the mother’s name was placed reported after consuming large doses of lavender (>0.5
on the bottle. Thirty minutes after the bath, the mothers were g/day). Lavender has still not been proven safe for
asked to record the degree of discomfort experienced, and the consumption for pregnant women or children, and more
midwives assessed the mother’s perineum as part of the research is necessary to understand the medicinal action of
normal daily examination of the mother. Daily visits helped lavender (Basch et al., 2004). Those should avoid the plant if
reinforce the procedure for the mother, and assessment they allergies to members of the Lamiaceae family. People
continued until the 10th day. Mood scores were analyzed over with sensitivity to plants with volatile oils or sensitivity to
a 10-day period. The mean discomfort scores showed a strong smells are advised to avoid contact with L. angustifolia.
steady reduction. There was missing data from this study
possibly due to the fact that those whose pain improved were
more likely to stop recording the amount of discomfort Current Use in Allopathic and CAM Therapies
experienced. The women in the pure lavender oil group Throughout the United States and Europe, lavender oil has
showed the lowest mean discomfort scores after the first 5 been used in aromatherapy, balneotherapy (treatment of
days of childbirth. No side effects by the mothers or midwives disease by bath), and massage therapy. In Germany, lavender
were reported during the trial (Dale & Cornwell, 1994). tea is used to promote sleep and ease stomach illness and
nervous conditions. Lavender is used as an anti-depressant in
Ayurvedic medicine in India while Tibet includes the plant in
Contraindications
psychiatric treatment. Also, lavender oil is used externally to
There have been few reports of sensitization after topical use medicate burns, sunburn, wounds, insect bites, and muscle
of lavender. The lavender species is considered “likely safe” or pain (Craig, 2006).
GRAS (generally recognized as safe) for internal and external
Aromatherapy is acknowledged as complementary therapy for
use. Generally, lavender is well tolerated with mild side
“increased comfort, relief of pain, relaxation, improved coping,
effects. People with known allergy or hypersensitivity to
reduction or moderation of stress, and an increased sense of
lavender should exercise caution when using this plant.
well-being” (Buckle, 1998, p. 56). Because many essential oils
People with lavender allergy may experience mild local skin
like lavender have calming and soothing properties
reactions after topical use of lavender oil. Lavender is
aromatherapy has gained popularity in the general population
believed to the potential of heightening effects of barbiturates
and specifically among nurses who want to incorporate a
and other depressants to the central nervous system. It is said
holistic approach to their care (Buckle, 1998, p. 54). This kind
to exhibit narcotic like effects on both humans and animals. In
of aromatherapy is known as clinical aromatherapy. Unlike
theory, lavender may intensify the effects of other sedative or
recreational aromatherapy, clinical aromatherapy heavily
hypnotic agents. Since lavender contains varying amounts of
relies on understanding the different species of the plant, not
coumarins, it theoretically can increase the effect of
just their common name. For example, L. angustifolia is a
anticoagulant medications. There is no reported lethal dose of
relaxant, L. latifolia is a stimulant, and L. stoechas may exhibit
neurtoxic properties but is effective in treating pseudomonads chronic pain therefore utilizing L. angustifolia oil can be a
or gram-negative bacteria (Buckle, 1998, p. 59). holistic and cost-effective approach to pain management.
In nursing, aromatherapy often times is used with topical Lavender is an extremely diverse plant in terms of its uses
applications such as compresses, therapeutic baths, or gentle from cosmetic to culinary to medicinal. One cannot deny the
massage. For each method, 1 to 5 drops of essential oil is historical significance of L. angustifolia as well as its fantastic
diluted; essential oils are highly concentrated and should not and pleasant scent.
be directly applied to skin if undiluted. The essential oil can
be diluted in cold-pressed vegetable oil, cream, gel, or water.
References Cited
For baths, the essential oils should be diluted in a small
amount of milk before being added to the tub since these oils Anonymous. (2011). Lavender has long history, many uses,
are insoluble in water and will merely float on the surface of Redlands Daily Facts, p. n/a. Retrieved from
the water and provide uneven treatment (Buckle, 1998, p. 57). https://login.proxy.library.emory.edu/login?url=http://sea
rch.proquest.com/docview/884656681?accountid=10747
One example of clinical aromatherapy that utilizes lavender is
to mimic the effect of diazepam (valium). Diazepam reduces http://sfxhosted.exlibrisgroup.com/emu?url_ver=Z39.88-
the effect of external emotional stimuli by increasing 2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&genre=unk
inhibitory neurons in the amygdala, which governs emotional nown&sid=ProQ:ProQ%3Anewsstand&atitle=Lavender+has
response in the brain. L. angustifolia is thought to have a +long+history%2C+many+uses&title=Redlands+Daily+Fact
s&issn=1069-2819&date=2011-08-
similar effect and produce a sedative effect on patients
22&volume=1&issue=&spage=&au=Anonymous&isbn=&jtitl
(Buckle, 1998, p. 56). e=Redlands+Daily+Facts&btitle=
Basch, E., Foppa, I., Liebowitz, R., Nelson, J., Smith, M., Sollars, D., &
Discussion Ulbricht, C. (2004). Lavender (Lavandula angustifolia
Miller). [Article]. Journal of Herbal Pharmacotherapy, 4(2),
There is a lack of consistent data and reporting on the true 63-78. doi: 10.1300/J157v04n02_07
effects of lavender and its therapeutic importance (Oliff,
Bourne, V. (2004). Four colours blue Can you tell the true from the
2003). Although research is still needed, the potential
tufted, the velvet- leaved from the lavandins? Val Bourne
contribution lavender has on human health can be visits one of the country's foremost lavender nurseries to
noteworthy. Its use in clinical aromatherapy offers a more take a lesson in purple etiquette, The Daily Telegraph, pp.
sensitive, holistic care especially for critical care patients. 04-04. Retrieved from
Also, there can be future research opportunities to explore the https://login.proxy.library.emory.edu/login?url=http://sea
efficacy of linalool as a complement with anesthesia or the rch.proquest.com/docview/316992325?accountid=10747
interactions with anesthesia medication. Many of the studies, http://sfxhosted.exlibrisgroup.com/emu?url_ver=Z39.88-
especially concerning the research done by Buckle, show that 2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&genre=unk
L. angustifolia oil can help with pain management. According nown&sid=ProQ:ProQ%3Anewsstand&atitle=Four+colours
to Buckle, the United States spends over $70 million on +blue+Can+you+tell+the+true+from+the+tufted%2C+the+v
elvet- Lavandula angustifolia Mill. . (2012). Tropicos
+leaved+from+the+lavandins%3F+Val+Bourne+visits+one+ http://www.tropicos.org/Name/17600103
of+the+country%27s+foremost+lavender+nurseries+to+tak
Lavender. (2007). The Journal of the American Botanical Council,
e+a+lesson+in+purple+etiquette.&title=The+Daily+Telegra
0(73), 0.
ph&issn=&date=2004-07-
31&volume=1&issue=&spage=04&au=Bourne%2C+Val&isb Lodhia, M. H., Bhatt, K. R., & Thaker, V. S. (2009). Antibacterial
n=&jtitle=The+Daily+Telegraph&btitle= activity of essential oils from palmarosa, evening primrose,
lavender and tuberose. Indian J Pharm Sci, 71(2), 134-136.
Buckle, J. (1998). Clinical aromatherapy and touch: Complementary
doi: 10.4103/0250-474x.54278
therapies for nursing practice. Critical Care Nurse, 18(5), 54-
61. Lu Hui, L. H., Lu Huan, Li Xiao Lan, and Zhou Ai Guo. (2010).
Chemical composition of lavender essential oil and its
Buckle, J. (1999). Use of aromatherapy as a complementary
antioxidant activity and inhibition against rhinitis related
treatment for chronic pain. Alternative Therapies in Health
bacteria. [Research Paper]. African Jounal of Microbiology
and Medicine, 5(5), 42-51.
Researc, 4(4), 4.
Cline, M., Taylor, J., Flores, J., & Bracken, S. (2006). Investigation of
Oliff, H. (2003). Review of Lavender Oil Biological Activity. In M.
the anxiolytic effects of linalool, a lavender extract, in male
Blumenthal (Ed.), HerbClip (Vol. 16, pp. 2). Austin, TX:
Sprague-Dawley rats... State of the Science Oral and Poster
American Botanical Council.
Sessions: part 2. AANA Journal, 74(6), 456-456.
S. Perrucci, G. M., P.C. Cioni, G. Flamini, I. Morelli, F. Taccini. (1996).
Craig, W. J. (2006). Lavender. [Article]. Vibrant Life, 22(2), 20-21.
The Activity of Volatile Compounds from Lavandula
Dale, A., & Cornwell, S. (1994). The role of lavender oil in relieving angustifolia Against Psoroptes cuniculi. Phytotherapy
perineal discomfort following childbirth: a blind Research, 10, 3.
randomized clinical trial. Journal of Advanced Nursing, 19(1),
Wan-ki Lin, P., Wai-chi, C., Fung-leung Ng, B., & Chiu-wa Lam, L.
89-96. doi: 10.1111/j.1365-2648.1994.tb01056.x
(2007). Efficacy of aromatherapy (Lavandula angustifolia)
Fowler, A. (2004). Lavandula. Horticulture Week, 18-18. as an intervention for agitated behaviours in Chinese older
persons with dementia: a cross-over randomized trial.
Hajhashemi, V., Ghannadi, A., & Sharif, B. (2003). Anti-Inflammatory
[Article]. International Journal of Geriatric Psychiatry, 22(5),
and Analgesic Properties of the Leaf Extracts and Essential
405-410. doi: 10.1002/gps.1688
Oil of Lavandula angustifolia Mill. J Ethnopharmacol, 89(1),
67-71.
Linum usitatissimum L., Linaceae
Alexa Kahn
Introduction
Linum usitatissimum L., commonly referred to as Flax, is a
member of the Linaceae family. Another common name is
linseed (Linnaeus 1857). Flaxseeds are known to be rich in α-
linolenic acid and when used in the diet, it can be a therapy for
reducing serum cholesterol and triglyceride levels, and
ultimately used as a supplement to reduce platelet
aggregation. Some data on antiplatelet effects are
inconclusive, and more research needs to be conducted to
better define flax as a functional food in reducing diseases
such as cardiovascular disease. Secoisolariciresinol
diglucoside (SDG) is another main constituent of flax and is
the primary lignan found in the crop that is responsible for its
therapeutic benefits. Flaxseeds have been studied for their
benefits in treating conditions such as arteriosclerosis and
high cholesterol (Lewis and Elvin-Lewis 2003). Flax is
available in multiple forms such as, raw seeds, powder and oil.
All forms are beneficial for both industry as well as in the
human and animal diet and nutrition.
Figure 1. Linum usitatissimum (Flax capsules)
Source: http://en.wikipedia.org/wiki/Flax
Linum usitatissimum is among the oldest crop plant that is
The plant is short in height and has secondary branches and
cultivated for obtaining fiber and oil. In Linnaeus’ book
seed balls (Figure 1) (Jhala & Hall, 2010). Flax is a blue
“Species Plantarum” he gave the botanical name for flaxseed:
flowering crop that can produce small seeds that are flat,
Linum usitatissimum (Linnaeus 1857). There are currently 200
ranging in golden yellow to a reddish brown in color (Figure
species of flaxseed known. It has a shallow root system and is
2). In stores, flaxseeds sold in stores are normally available in
known to be an annual herbaceous plant. The shallow system
ground seed (powder-like), whole seeds, and also in an oil
allows the plant to better survive on sandy or rocky terrain.
form. The varieties of flax used for fiber come from plants with
Figure 3. Golden Flax
Figure 2. Linum usitatissimum (flower and seeds). Source: http://en.wikipedia.org/wiki/Flax
Source. http://www.colourbox.com/preview/2288281-427644-
flax-seeds-with-flower.jpg
longer stems, 80-120 cm tall, containing fewer branches and

seeds. The oil forms come from shorter plants approximately
60-80 cm tall, and has stems dense with branches. The flax
used to extract oil, also generally has a greater number of seed
capsules and larger seeds itself (Shahidi 2005). Due to the
versatility of flax, many universities and laboratories around
the United States are showing an increased interest in
studying the plant to solidify and learn more about its
medicinal properties.
The flaxseed is home to warm and cool climates, and has been Figure 4. Brown Flax
cultivated for many centuries across the world, primarily for Source: http://en.wikipedia.org/wiki/Flax
its stem fiber, seed and linen cloth. Another common name
used is linseed (Carter 1993). In India and the United
in color are generally aesthetic (Figures 3 and 4) (Shahidi
Kingdom, the crop is called linseed, whereas throughout the
United States and Canada the crop is termed flaxseed. In 2005) and not significant medicinally.
Canada, flax has a dark brown seed coat. In the United States, During a ten-year period, the total average yearly production
flaxseeds are available with yellow seed coats. The differences of flax was 2.52 million metric tons. This ranked higher than
Figure 6. Schematic diagram of flax uses (Jhala & Hall,
Figure 5. Graph of the major world producers of flaxseed 2010).
during a ten year period (Shahidi, 2005).
Canada, as a commercial oilseed crop sold in many “health
sunflower, yet slightly lower than the soybean. Canada is foods” stores as a dietary supplement (Carter 1993). Flax is
shown to be the highest growing region for flax (Figure 5). In grown in a wide range of countries and is known for its
the northern latitudes, higher production of oil from the seeds adaptability and product diversity (Jhala & Hall 2010)
is seen with high levels of polyunsaturated fatty acids
Flax has many uses (Figure 6) and has stemmed back to
contained in the oil. In the United States, North Dakota is the
ancient cultures in China, Greece, Egypt and India. In the flax
flaxseed production leader with over 95% of the region
growing region of the People’s Republic of China, many of the
growing with flax (Shahidi 2005).
villages used flaxseed oil for low temperature stir-frying in
many of their home cooked food dishes. (Carter 1993). In
Traditional Uses ancient Greek and Egyptian cultures, flax was utilized as a
natural laxative and food source by many of the villagers.
Flax has been used in food cooking throughout Europe and
Asia since 5000-8000 BCE. Specially, the fiber contained in the In India, flax was mainly grown for its oil, as a baking and
flax stem has been utilized for linen cloth (Bloedon & Szapary, cooking item. However, flax was additionally used as a fiber
2004). Originally, the stem fiber was brought to North source to make blankets, mattresses, linen clothes, and
America for its use in making linen and parchment paper. parchment paper (Vajpeyi, Abhishek, Shukla & Srivastava,
Over the past 100 years, flaxseed has been used throughout 2008). As a result, the fiber obtained from flax was a main
the Northern Great Plains region of the United States and contributor to the textile industry of India. In Egypt, the art of
Linum usitatissimum, the whole flaxseed
% Fat 41
% Protein 21
% Dietary Fiber 28
Table 1. The percentage components of one whole flaxseed Figure 7. alpha-Linolenic acid molecule
(Bloedon & Szapary, 2004). Source: http://en.wikipedia.org/wiki/Alpha-Linolenic_acid
woven flax fiber to linen became important for the making of polyunsaturated fatty acids, 18% monounsaturated fatty
clothes for the upper class figures, such as Pharaohs in their acids, and only 9% saturated fatty acids. This lends itself to be
society (Jhala & Hall 2010). Additionally, they used linseed oil considered a low-saturated fat food. The richest source of
as the main ingredient of the “finishing oil” for their woven omega-3 fatty acid comes from flaxseed oil, which comprises
and wooden furniture. The linseed oil is added to paints to approximately 55% of the total fatty acids (Bloedon &
create a more fluid and transparent liquid that can then be Szapary, 2004).
applied to hard surfaces, specifically wood. This leaves a nice, Flax is known for its higher fiber content, both an insoluble
shiny appearance before it is then sold in markets in their and a soluble source of fiber. They are rich in α-Linolenic acids
villages. (Figure 7) as well as phytoestrogens, or lignans. Lignans are
It was measured that Europe generally has taller flax phenolic compounds. The richest source lignans are,
compared to the United States, which can be a reason why seciosolariciresino diglucosides (SDG) (Figure 8) (Bloedon &
Europeans still use flax for linen cloth. The United States uses Szapary, 2004).
the fiber from flax less for linen and clothing since the Flaxseed is known to contain approximately 35-45% oil, 25%
discovery of cotton has been made (Carter 1993). While today protein with 10% moisture. The flaxseed has high constituents
flax is less used for its properties useful for parchment making of oil, but extracting this oil is difficult to do and often requires
or clothing for a community of people, we still do use flax as a double pressing to do so. Prior to crushing the seeds, clean
cooking item. Today many people add flax in the form of seeds ones are needed in order to ensure moisture levels of 9.5-
or even powder to their cooking to meet their daily fiber 10%. Ultimately, this will minimize the formation of fine
requirements. particles when the seeds are cracked and will then maximize
the removal of oil from them. Next, the moisturized seeds pass
through a set of corrugated and smooth rolls to be cracked
and then flaked. Consequently, the production of flax oil is
Linum usitatissimum, the whole flaxseed, is composed of 41% differentiated from that of Solin or Linola oil. In order for
fat, 21% protein, and 28% dietary fiber, along with other flaxseed to be consumed by humans, it is necessary for it to be
minerals and vitamins (Table 1). The oil in flaxseed on the cold-pressed. The process of cold-pressing entrails the
other hand, isunique in that it is concentration in 73% temperature of oil coming from extruder to not exceed 35 °C,
specifically, 7α-hydroxylase and acyl CoA cholesterol
transferase, which are both involved in cholesterol
metabolism. The lignans in flax have been shown to reduce
oxidative stress, and SDG, has been shown to act as an
antioxidant and further as an antagonist of platelet activating
factor (Lewis and Elvin-Lewis 2003).
Biological Activity
Figure 8. Seciosolariciresino diglucosides (SDG) Many studies have been conducted to assess the biological
Source: activity of flax. Both in vivo and in vitro studies have been
http://www.biopurify.com/admin/editor/UploadFile/2007101814 conducted to determine the mechanism of action of flaxseeds
1427125.gif to ultimately better understand the biological activity in
animals as well as humans
(Carter 1993) and the pressing is done under a blanket of
nitrogen in order to protect it from oxygen. Expellers can be
used to cool parts of the press that are in contact with the In vivo
seeds and the oil in hopes of controlling the temperature Animal studies have been conducted to question the capability
during the extensive processing technique (Vassel & Nesbitt of flaxseed products improving serum lipids. The rats fed 20%
1945). and 40% flaxseed for 90 days has substantially lower serum
Flax may be used as a protective agent against cardiovascular total cholesterol and LDL level than those rats that had a diet
disease through a number of different mechanisms of action. absent of flax. The results found that SDG found in flax
Flax is capable of reducing serum cholesterol, inflammatory reduced hypercholesterolemic atherosclerosis by 73%
marks, and platelet aggregations. Furthermore it acts as an suggesting the effect was associated with lower serum levels
antioxidant. The high soluble fiber content of flax allows for (Prasad 1997). Additionally, the antioxidant activity of
enhanced gastric emptying, which interferes with the bulk flaxseed lignans in rabbits was evaluated in vivo. Results
phase diffusion of fat, while also increasing the excretion of showed that a 7.5 g/kg regular flaxseed added to an
bile acids. The viscous fiber component of flax has been antioxidant free diet, along with the addition of 1%
associated with increase glucose tolerance (Bloedon & cholesterol, decreased atherosclerosis in the aorta by nearly
Szapary, 2004). 46% and lowered the number of inflammatory
polymorphonuclear leukocytes as compared to the same diet
Some evidence suggests that SDG is correlated with lower in the absence of flax. The study projects that dietary flaxseed
serum cholesterol levels. Lignans are potentially capable of supplementation could be used to minimized heart attacks
lowering serum cholesterol through the modeling of enzymes, and strokes (Prasad 1999).
Overall, purified SDG from flax seed have been evaluated in that were given the other two types of oil. The results suggests
mammary, colon, prostate, and thyroid cancers as well as that the increase in immunoresponsiveness in the linseed oil
diabetes, liver and heart disease in animal rat models. On the fed rabbits may be useful in fighting infections in the body
whole, results suggest beneficial effects of lignans. Some (Kelley, Nelson, Senator, Schmidt & Branch, 1988). Based on
caution should be taken in relation to the dose of lignan and the results of this study, researchers hope to investigate the
time of administration during reproductive stages in females effects of a linseed oil based diet in immunocompromised
(Westcott & Muir, 2003). Although the mechanism of action is humans as well as healthy individuals for comparison.
not completely understood, researchers suggest that it may
involve influence of hormonal or anti-oxidant activity.
Clinical Studies
Skin and hair conditions were studied in animals that
consumed flaxseed or flaxseed oil. In Capuchin monkeys, it In a North Dakota State University clinical study, the effects of
was reported that severe skin lesions were healed after flaxseed supplementation were examined in overweight
consumption of flaxseed. Although the scientists have not yet patients who had hypertension and a family history of
confirmed and documented the effects of flax in human skin diabetes. The study determined that flaxseed consumption
conditions, current research suggests possible improvements decreased insulin resistance, in other words, decreased
of a variety of skin disorders after assessing the glucose concentration in patients after use of flaxseed
improvements of psoriasis in humans who had sufficient supplementation. The bioactive component of flaxseed, lignan,
consumption of flaxseed (Sinclair, Fiennes, & Crawford, 1973). is responsible for do decreasing insulin resistance as well as
Additionally, a study with Swiss mice showed that α-linolenic inflammation (Rhee & Brunt 2011). Another study looked at
acid inhibited progression of skin cancer development the relationship between flax consumption and treatment of
(Ramesh & Das, 1993). diabetes. 6 patients were monitered as they fasted overnight,
and in the morning were randomly given a meal that consisted
of 50g carbohydrate bread that was either made from white
In vitro flour (control) or flax flour (experimental). The researchers
concluded that the blood glucose levels were 28% in those
The outcome of linseed oil fed to New Zealand white rabbits
subjects that were given the flax bread (Shahidi 2005).
were compared to the outcomes of a diet that consisted of soy
oil and safflower oil. An in vitro study looked at peripheral In Toronto, flaxseed was used as alternative to hormone
blood lymphocytes that were cultured with T-cells mitigens. replacement therapy, since it is rich in the phytoestrogen
The blood lymphocytes were noticeably higher in the group of precursor, secoisolaricriesinol diglucoside (SDG) and α-
rabbits that were fed linseed oil as compared to the group that linolenic acid. It was hypothesized that these factors may be
was given either soy or safflower oil. Lymphocytes are a type protective against vascular disease. The study analyzed 35
of white blood cell that is in the immune system of women with vascular disease ranging from ages 54 to 70.
vertebrates. The immune system of the rats that were fed These women were administered different strains of flax:
linseed oil appeared more responsive compared to the rabbits Flanders (high in α-Linolenic acid and low in lignan), AC
Linors (a mixture of intermediate levels of lignan and α- assignment to the 300mg SDG, 600mg SDG or the placebo
Linolenic acid) as well as Linola 989 (low α-Linolenic acid and group. Results showed that the dietary flaxseed lignan extract
high lignan). Results showed that all three types of flax (SDG) did decrease plasma cholesterol and glucose
lowered blood pressuring during mental stress. The Flax concentrations significantly in hypercholesterolaemic subjects
phytoestrogens ameliorate specific responses to stress, which (Zhang, Wang, Lui & Tian, 2007).
in turn can protect patients against atherosclerosis, thickening
of the arteries (Spence, Thornton, Muir & Westcott, 1973).
Contraindications
A two year study was done with subjects having multiple
cardiovascular risk factors, correlating the risk of ischemia There is minimal risk with the consumption of flaxseeds in
heart disease and nutritional diets. Two groups were humans. Food allergies to flax seem to be quite rare. Those
randomized, giving one group margarine righ in α-linolenic who question a possible allergy to Flaxseed should consult
acid while the other group obtained margarine that was rich their physician for permission of use prior to incorporating it
in linoleic acid. After the two year period, results suggest that into their daily diet. Those individuals with allergies to nuts
individuals who had a rich source of α-linolenic acid, showed a should be cautious. It’s also important to realize that flaxseed
higher total cholesterol to HDL cholesterol ratio than when is rich in α-linolenic acid, which is has been a major
the experiment first began. This improvement of cholesterol component of the Mediterranean diet for many years. In a 5-
levels decreased estimated ischemia heart disease year prevention trial, a high content α-linolenic acid
(Bemelmans, Broer, Feskens & Smit, 2002). Mediterranean proved to be more efficient than present day
diets in preventing coronary diagnosis and deaths
In another study in Toronto, seven eldery patients were give (Bemelmans, Broer, Feskens & Smit, 2002). Its wide use for
two flax muffins per day. The results of the study reported many years with no major side effects allows it to be viewed
increased bowel movements and frequency of bowel as safe.
movements per day (Cunnane, Ganguli, Liede, Hamadeh, Chen,
Wolever & Jenkins, 1993). This increase of bowel movements However, one concern lies in the consumption of uncooked
suggests the laxative properties of flax. flaxseed due to cyanogenic glycosides (HCN) content, which in
high quantities can be toxic to animals as well as humans. No
A clinical trial in China examined the SDG-rich flaxseed extract cases have been reported of acute or chronic cyanide toxicity
to determine the possible effects of SDG on total cholesterol, from flaxseed consumption. It is important to note that baking
HDL-cholesterol, LDL-cholesterol as well as glucose flaxseed is capable of removing any potential risks from HCN
concentrations in a group of 35 men and 20 women over the (Bloedon & Szapary, 2004). By cooking the raw flaxseeds (in
course of 8 weeks. In order to be eligible, subjects needed to baking products or hot cereals; some oatmeal’s contain
meet the requirements of LDL-cholesterol levels no lower flaxseed) this seems to eliminate the potentially toxic
than 1400 mg/l. Additionally, they could not be taking any cyanogenic glycosides (Cunnane et al, 1993). Furthermore,
drugs, herbal supplements, products containing flax, or any those who experience harmful side effects from cyanogenic
products used to lower cholesterol. Subjects were randomly glycosides generally have a poor quality diet as well. For the
most part, populations in North America have well-balanced health but also is known to be protective against cancer and
diets and receive proper nutrients that allow the body to cardiovascular disease (Carter, 1993).
eliminate the potentially harmful, HCN, which is found flax
Another fairly new and current use of flax is in the form of
(Shahidi, 2005).
flaxseed gum, or mucilage (Mazza, 1989). The gum is reported
to be extracted using hot and cold water. Then it can be mixed
Current Uses in Allopathic and CAM Therapies with ethanol, eventually dehydrated and then freeze-dried.
The acid hydrolysis of gum then produces polysaccharides. In
The flaxseed has only recently been introduced in North experimental study, it was found that flaxseed gum is a similar
America. Some known benefits of flaxseed in human and alternative to gum arabic, which is a mixture of complex
animal nutrition include, its high component of alpha linolenic polysaccharides, which is used as a food stabilizer. In fact, it
acid (also known as omega-3 fatty acid) content pertinent to was noted that flaxseed mucilage has great emulsifying
humans, its high percentage of insoluble and soluble dietary properties compared to gum arabic, enabling it to be more
fiber, and lastly, it has the highest content of plant “lignans”. efficient. It was estimated about 7-10 lbs of gum could be
Lignans are important because they are known for their anti- yielded from about 100 lbs of flaxseed. Today, the usefulness
carcinogenic properties (Shahidi, 2005). of flaxseed gum is in improving loaf volume of bread while
The use of flax in industry and food is continuing to grow and also keeping the quality fresh (Mazza, 1992).
develop. Around 200 new food and health care products were Today, the Food and Drug Administration and several
introduced and marketed in the United States in 2005 (Jhala & universities are conducting extensive research in feeding
Hall, 2010). Today, ground or whole flaxseed can be easily flaxseed to animals as well as humans to further discover
added to almost any baking recipe. Ground flax in a powder health benefits of flax. Although flaxseed and cold-pressed
form is often used in liquid foods such as yogurt and soup to linseed oil don’t already have the Generally Recognized as
hide the taste, whereas whole flaxseed can be used in bread, Sage status, there is a “no objection” status, that seems to be
pancakes, waffles to add a nutty flavor. Whole flaxseeds are a adequate while flax undergoes more testing in the laboratory
great food additive in recipes to add a crunch (Shahidi, 2005). (Carter,1993).
Many U.S. companies are manufacturing fiber bars for those
who don’t receive adequate amounts of daily fiber that contain
high quantities of flax. Additionally, there are few side effects Discussion
of flaxseed making it a more widely used product among many
Linum usitatissimum is a crop grown in various countries and
Americans.
climates for different purposes, and has been around for over
The National Cancer Institute is now considering flax a 6,000 years. Flax is known for its adaptability and diversity as
“designer” food. The term “designer” means the product a product traditionally, as well as in current allopathic and
consists of more than one ingredient that contributes to the CAM therapies. Its prime use today is in dietary supplements
overall beneficial qualities. Flax contains nutrients for good and cooking. North Dakota is currently the leading state for
flax production. With the high content of α-linolenic acid and Carter, J. F. (1993). Potential of flaxseed and flaxseed oil in baked
SDG in flax, both in vivo and in vitro studies as well as goods and other products in human nutrition. American
numerous clinical trials have examined its effects in Association of Cereal Chemists, 38(10), 753-759.
controlling diabetes, as a laxative, managing cardiovascular Cunnane, S. C., Ganguli, S., Menard, C., Liede, A. C., Hamadeh, M. J.,
disease as well as a tool to enhance the immune system. Some Chen, JY., Wolever., T. M., Jenkins, D. J. (1993). High α-
in vivo studies also looked at flax in monkeys and its effects on linolenic acid flaxseed (Linum usitatissimum): some
fur condition. From this research in monkeys, scientists nutritional prosperities in humans. British Journal of
predict that flax can be a source of improving skin conditions Nutrition, 69, 443-453.
such as psoriasis. Since the flax is available in the form of oil, Friel, James. (2004). Antioxidant status after consuming flax
the scientist suggests topical use of flaxseed oil can be products. Flax Council of Canda,
beneficial to numerous skin diseases in individuals. However, Jhala, A. J. & Hall, L. M. (2010). Flax (Linum usitatissimum L.):
more clinical trials are underway to confirm theses current uses and future applications. Australian Journal of
hypotheses. Basic and Applied Sciences, 4(9), 4304-4312. doi: 1991-8178
Many Americans are first becoming aware of flax and its Kelley, D. S., Nelson, G. L., Senator, C. M., Schmidt, P. C., & Branch, L.
health benefits. Flax is an easy food supplement to any current B. (1988). Effects of type of dietary fat on indices of immune
diet and has a high nutritional component with a great source status of rabbits. Journal of Nutrition, 118, 1376-1386. doi:
of fiber. The high fiber contents are not only beneficial for food 0022-3166/88
intake but also in the linen and parchment paper industry. Linnaeus, C., 1857. Species Plantarum. The Royal Society of London,
Although flax has been used for many years now, further London, UK, pp:300.
clinical studies can be done to better understand the
Lewis, Walter, and Memory Elvin-Lewis. 2003. Medical botany:
mechanism of action of flax itself as well its main components Plants affecting human health. New Jersey: John Wiley &
such as omega-3 fatty acids, α-Linolenic acid, and SDG. Sons, Inc.
Mazza, G., Biliaderis, C. G., & Oomah, B. D. (1992). Extraction and
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of an increased intake of α-linolenic acid and group Mazza, G., & Billiaderis, C. G. (1989). Functional properties of flax
nutritional education on cardiovascular risk factors: the seed mucilage. Journal of Food Science, 54, 1302.
Mediterranean alpha-linolenic enriched Groningen dietary Prasad, K. (1997). Dietary flax seed in prevention of
intervention (margarine) study. American Journal of Clinical hypercholesterolemic atherosclerosis. Elsevier Science
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risk. Nutrition Reviews, 62(1), 18-27. hypercholesterolemic atherosclerosis in rabbits by
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linolenic acid and lignans on response to mental stress.
Matricaria recutita L., Asteraceae
Carolyn Wiegert
Introduction
Matricaria recutita, most commonly known as German
chamomile, (synonymous with Matricaria chamomilla L.) is a
flowering plant of the daisy family, Asteraceae. It is also
known as Hungarian Chamomile, mayweed, sweet false
chamomile or wild chamomile (McKay & Blumberg, 2006).
With a history dating back to ancient foundation societies like
Rome, Egypt, and Greece German chamomile has been an
ever-present herb in world history. Prized for its essential oil
known as “blue oil” and flower heads, M. recutita appears in
traditional and modern cultures—both western and eastern—
as a common herbal medicine. Its main chemical constituents
are of the flavonoid and sesquiterpene families. Examples are
apigenin, chamazulene, and α-bisabolol. Although scientific
studies of the plant are all fairly recent—within the last two
decades—German chamomile possess great medicinal
potential.
Botanical Description Figure 4. Wild growth of Matricaria recutita; plant in its

Herbaceous Matricaria recutita is an indigenous plant of uncultivated form. Image source:
Southern and Eastern Europe (Guimaraes et al., 2013), but http://www.flickr.com/photos/hinkelstone/2811407254/.
additional countries across the world cultivate it. Cultivators
include India, Germany, France, Russia, Italy, South America,
and the United States. Hungary, who exports the flowers and the world. On the international market, traders refer to its
essential oil to other European countries, produces the largest essential oil as “blue oil” and with the rising popularity of CAM
quantity of the plant in the world. The plant flourishes in (Complementary and Alternative Medicine) and allopathic
nearly any soil type and propagates via seeds, making it a therapies, an increase in demand should be expected (Barnes,
versatile cultivar. M. recutita is the fifth most traded herb in Powell-Griner, McFann, & Nahin, 2004; Singh, Khanam, Misra,
& Srivastava, 2011). As shown in Figure 1, the plant
resembles other daisy species from the Asteraceae family with
similar petal shape and size. Singh et al. (2011) describes the
flowering annual plant as having spindle shaped-roots and an
erect stem that can grow to more than 80 cm high (Figure 2).
It produces golden yellow florets with small, white petals and
yellowish-brown fruit. Its odor is described as “sweet, grassy,
and lightly fruity” ("Matricaria chamomilla (German
chamomile)," 2008).
Traditional Uses
The most common traditional preparations of Matricaria
recutita are teas and tisanes, used by various cultures both in
ethnobotanical and ethnomedical contexts. Most of the alleged
health claims from traditional uses have little or no scientific
evidence to back them simply because all research on the
plant is fairly recent and few studies have been replicated. In
addition to teas, dried flower heads are also utilized for
multiple flavoring, aromatic, and dyeing uses (McKay &
Blumberg, 2006). Although German chamomile teas are
present in all areas of the globe, several particular populations
in Southern Italy, the Italian Archipelago, Mexico, Central
Serbia and Syria give the herb to a special cultural status.
Figure 2. Botanical illustration of Matricaria recutita;
notice the small white petals and yellow stamen. Image
Basilicata, Southern Italy source:
http://commons.wikimedia.org/wiki/File:Matricaria_recutita_Stur
The Albanian minority ethnic group known as the Arbëreshë m13045.jpg.
uses Matricaria recutita in two key ways. This small group
lives in the Basilicata province, also referred to as Lucania,
located in southern Italy. Today, this group utilizes western is used for its flowers, leaves, and other aerial parts. Most
medicine as their primary form of health care, but plant traditional knowledge of the plant has been preserved by the
remedies are still used to supplement western treatment. elderly women of this cultural group and therefore, these
Referred to as Kamohill in the Arbëreshë language, M. recutita women prescribe and administer most ethnomedical
treatments. Tea decoctions of the plant’s parts are used as fever, high pressure, conjunctivitis, flu, sore throat, and
digestives and sedatives. Parts of the plants are also used to diseases of the “evil eye” (Josabad Alonso-Castro et al., 2012).
treat the Arbëreshë wind illness known as mal vjnt. To treat
In addition, even after emigration, Mexican Americans also
mal vjnt, which appears as a skin rash on the body, the whole
rely on Manzanilla as a key home herbal remedy. Continuing
form of the plant is bundled with other gathered plants and
to prepare the plant as a decoction tea in the United States,
waved over the rash while simultaneously reciting a special
adult Mexican American women prepare the drink by adding
prayer. The herb bundle ceremony is repeated for 9 nights.
an unmeasured handful of dried flower heads to boiling water
Both of these uses are documented in the research of Pieroni,
and allowing them to steep for 5-10 minutes (Waldstein,
Quave, Nebel, and Heinrich (2002).
2006). Waldstein (2006) explains that the plant can be
purchased fresh in its whole form at many Mexican American
Tuscan Archipelago, Northern Italy grocery stores. In accordance with ancient medicinal humoral
theory, Manzanilla is administered as a “hot” therapy for
To a lesser extent, Matricaria recutita is also used as an herbal “cold” ailments such as menstrual cramps, stomachaches,
remedy on island of Elba. Elba is a member of a small chain of infant colic, sinus cleanses, and evening tonics or eyewashes
islands off the coast of northern Italy known as the Tuscan for anxiety. The “hot” humoral properties are believed to be
Archipelago. Locally referred to as Camomilla di Campo or purifying to the stomach by relieving bloating, pain and
Camomilla masseta, the plant is used in both its decoction and prompting burping, which is believed to be the release of
infusion form. Decoctions are used for external treatments anxiety by the body. After administering its curative
while infusions are ingested to treat internal ailments. The properties to the body, Manzanilla is believed to exit the body
island’s population uses the plant as an analgesic, anti- through urine (Waldstein, 2006). For Mexican Americans, M.
inflammatory, digestive, eye compress, and a topical recutita is just one of many herbal remedies used to
treatment for reddened skin (Uncini Manganelli & Tomei, supplement an adoption of conventional medicine.
1999).
Central Serbia
Mexico
In a survey ethnobotanical study of Kopaonik Mountain in
Commonly referred to as Manzanilla té in the country, Central Serbia, Matricaria recutita was found to be one of the
Matricaria recutita is the second most cited plant used in most consumed plants for medicinal and functional food
combinational herbal remedies by Mexicans. Utilized purposes (Jaric et al., 2007). Only collected and consumed in
primarily in its tea decoction form to treat conditions of its wild form, the plant is locally known as Kamilica. Jaric et al.
gastrointestinal distress, special Chamanes healers in rural (2007) explains that the mountain’s population of Serbians is
areas or a female relative in urban areas are often the main mostly elderly with livelihoods dependent on cattle herding or
prescribers. The plant is also prescribed for conditions of agriculture. Kamilica is referred to as a panacea (remedy for
all illnesses) by the local population and can be found in most
species depending on which dealer they are purchased from,
and are a key component to Middle Eastern Unani medicine.
The tea is served hot after meals in Damascus restaurants,
homes, and cafes and is thought to have digestive properties
(Carmona, Llorach, Obon, & Rivera, 2005). Syrian people
believe found that the plant contains medicinal properties for
the following body systems: digestive system, infectious
ailments, circulatory system, respiratory system, nervous
system, and skin ailments (Carmona et al., 2005).
Figure 3 Chemical structure of apigenin. Image source:
http://commons.wikimedia.org/wiki/File:Apigenin.svg.
homes on reserve. Locals scald the plant parts before storing Over 120 chemical constituents have been identified over the
them with the belief that this better preserves their active years in Matricaria recutita (McKay & Blumberg, 2006). The
ingredients. M. recutita, only used in tea form, is ingested and compounds of primary importance are mainly of the
applied externally for antiseptic, anti-inflammatory, and sesquiterpene and flavonoid families and their derivatives.
sedative purposes. Serbians ingest the tea as a stomach Many of these compounds are found within the plant’s
painkiller and a treatment for dyspepsia and constipation. The flowers’ essential oil, which is approximately 0.24 to 2.0
tea form is applied externally to treat skin wounds, burns, and percent of the flower ("Matricaria chamomilla (German
galls or as a vaginal douche. The steam of the tea is inhaled to chamomile)," 2008). The research of McKay and Blumberg
clear the sinuses of those suffering from sinusitis. Serbians (2006) shows that the flower heads contain the following
prefer phytotherapy uses like these to conventional medicine approximate percentages of phenolic compounds: 16.8
and very few members ever visit an actual doctor (Jaric et al., percent of the notable flavone glycoside apigenin (chemical
2007). structure shown in Figure 3), 9.9 percent of the flavonoid
quercetin, 6.5 percent of the flavonal patuletin, 1.9 percent of
the flavone Luteolin, both coumarins herniarin and
Syria umbelliferone, and ferulic and caffeic acid derivatives.
Important essential oil compounds are α-bisabolol, a
In Syria, Matricaria recutita exists as a functional food and sesquiterpene alcohol, and chamazulene, a sesquiterpene
post-meal digestive. It is a single herbal component of a multi- derivative. Other notable chemical constituents are tannins,
species herbal tea commonly known as Zahraa. Zahraa is sold choline (0.3 percent in plant) ("Matricaria chamomilla
from market stands and dispensaries across the country, but (German chamomile)," 2008), polysaccharides, and amino and
is particularly common in Damascus marketplaces. Bedouin fatty acids (McKay & Blumberg, 2006). It is important to note
herders and rural populations do much of the collection of M. that these concentrations decrease when the plant is prepared
recutita for sale. Zahraa tea mixtures can contain up to 14
in decoction or infusion form. Decoctions possess higher Rats were divided into six groups for the study: control,
concentrations of phenolic compounds relative to infusions normal (sham), M. recutita (German chamomile), mix group 1,
(Guimaraes et al., 2013). McKay and Blumberg (2006) states mix group 2, mix group 3, and a loperamide group for
that teas brewed of M. recutita only contain 10-15 percent of comparison. Loperamide is an opiod drug commonly used to
the plant’s original volatile oil content. treat diarrhea. For seven days, animal groups were
administered either saline (control and normal), 300
mg/(kg -150),of300
d) German cham
Biological Activity (Mix-300), or 450 (Mix-450) mg/(kg d) of a 5
Matricaria recutita has been studied for biological activity A. vera and German chamomile, or 10 mg/(kg d) of
with encouraging preliminary results. In various studies, M. loperamide. Whole leaves of A. vera and the flower heads of M.
recutita has shown antioxidant, anti-inflammatory, anti- recutita were used to produce aqueous extracts of German
tumor, antimicrobial, anti-platelet, anti-cancer, anti-genotoxic, chamomile and extracts of combined A. vera and German
and hypocholesterolemic activity. Much of the anti-cancer chamomile. After day 2, experimenters induced IBS in rats
potential of the plant is attributed to the chemical constituent using plastic tube retainers for forced restraint. After day 7,
apigenin. With more research, German chamomile has the gastric emptying and small bowel movement were measured
potential to benefit the heart, liver, gastrointestinal and via phenol red, colonic transit evaluation was measured via
central nervous systems of the body. Some examples of the fecal pellet count, and biochemical assays were used to
mechanisms of action of this plant and its chemical measure effects on inflammatory markers TNF-α, MPO, and
constituents are explained in more detail below. LPO via TBARS as well as the total protein of colon
homogenate content.
German chamomile exhibited significant treatment potential
Irritable Bowel Syndrome on its own by reducing gastric emptying and small bowel
Because inflammatory markers and oxidative stress have been transit, TNF-α, MPO, and increasing colonic antioxidant
linked to the expression of irritable bowel syndrome (IBS), capacity in comparison to the control group. However, the
Asadi-Shahmirzadi et al. (2012) conducted a study on male synergistic effect of combined A. vera and German chamomile
albino rats to test the combined effect of Matricaria recutita seemed to be more powerful as an anti-inflammatory and
and Aloe vera, and individual effect of M. recutita on the treatment for IBS overall. Results were not be dose dependent
diarrhea-predominant form of IBS. Both A. vera and M. (Asadi-Shahmirzadi et al., 2012). However, mix-150 did
recutita are known to possess inflammation-inhibiting demonstrate more potential than higher dose mixes, but not in
qualities. A. vera has been shown to inhibit inflammation a statistically significant manner. A combination of A. vera and
biomarkers TNF-α, IL-1 β and IL-6. Although not thoroughly M. recutita could be used to reduce diarrheal movements of
tested, M. recutita’s compounds chamazulene, α-bisabolol, and the bowels from IBS and the oxidative stress associated with
apigenin have been shown to possess anti-inflammatory it. On it’s own, M. recutita shows promise for reducing
properties (Asadi-Shahmirzadi et al., 2012). inflammatory biomarkers and small bowel transit, but more
research is necessary to determine its exact method of action. recutita’s coumarins, terpenes, and spiroethers, are thought to
be responsible for this method of action. Shikov et al. (2008)
concluded that German chamomile could be a viable
Heliobacter pylori Infections treatment option for suffers of H. pylori who are allergic or
Heliobacter pylori bacteria are one of the main causes of possess resistant strains to antibiotics.
general gastrointestinal distress and gastrointestinal
disorders and diseases. H. pylori infections have been linked to
the development of chronic gastritis, ulcer disease, gastric Allergic Reactions
neoplasms, and peptic ulcers. Combinational therapies of Mast cells, present in many tissues and organs of the body, are
antibiotics, proton pump inhibitors, bismuth subsalicylate, known to be important regulators of the body’s allergic
and H-2 blockers are the current conventional treatment for reaction response and histamine release. Chandrashekhar et
H. pylori. These treatments can be and are effective, however al. (2011) conducted an in vivo study in male albino rats to
they often produce unwanted side effects and are not effective examine the potential anti-allergic activity of Matricaria
against antibiotic resistant strains in patients (Shikov, recutita. Chandrashekhar et al. (2011) noted that German
Pozharitskaya, Makarov, & Kvetnaya, 2008). Shikov et al. Chamomile possesses significant tannin and flavonoid content
(2008) details an in vitro investigation of the potential that may help inhibit anaphylaxis, pruritus (itching of the
inhibitory effects of an olive oil Matricaria recutita extract on skin), and histamine release during allergic reactions.
H. pylori.
For the experiment, methanol extracts made from the dried
For the experiment, dried M. recutita flowers were used to flower heads of M. recutita in dosage quantities of 100, 200,
create an olive oil extract. A Heliobacter pylori strain, and 300 mg were administered to three experimental groups
Heliobacter pylori ATCC 43504, was inoculated into liquid of ten rats each. A separate group of ten rats was administered
media and cultured in a micro aerobic atmosphere. 10 mg of the mast-cell stabilizing drug disodium
Researchers obtained a single colony from the culture and cromoglycate. Control and normal groups of ten rats each
placed it on Colombia agar plates containing 10 percent were administered saline. To induce pruritus and anaphylaxis,
sheep’s blood. The H. pylori strain was tested both with the compound 48/80 in dosage quantities of 3 mg/kg and 8
German Chamomile extract and olive oil alone as a control mg/kg was administered to rats respectively in all groups
(Shikov et al., 2008). except normal. Scratching behavior and death from
German chamomile olive oil extract prevented the growth of anaphylactic shock was observed. Mast-cell stabilizing
H. pylori into full, opaque colonies. The colony treated with the potential, blood histamine release, and nitric oxide levels in
olive oil extract produced colonies smaller in size with rough the rats were also measured (Chandrashekhar et al., 2011).
edges. German chamomile seems to inhibit growth by M. recutita showed dose-dependent protection and inhibition
preventing the bacteria from producing urease, a substance from pruritus and anaphylaxis, with the 300 mg dose showing
necessary for the bacteria’s survival in the stomach. M. the greatest positive effect. M. recutita also dose-dependently
lowered histamine release in the blood and nitric oxide levels time intervals (every 12 hours) during the 14-day experiment
throughout the body. Nitric oxide is thought to increase free period depending on the rats’ test group designation. On days
radical production in the body by inducing inflammatory 1, 3, 5, 7, and 14 experimenters examined the tongues for
responses. Tannins and flavonoids have been shown to wound healing progress in five sacrificed rats from each
suppress histamine release and therefore, the experimenters group. Wounds were classified either “in repaired” or “no
hypothesize M. recutita’s tannin and apigenin and luteolin repaired” (Martins et al., 2009) based on a scale of grades 1 to
flavonoid content may be responsible for its anti-allergic 5. Grade 1 represented the greatest wound healing progress
activity. Further research is necessary to determine German and 5 the least.
chamomile’s exact method of action.
Study results revealed M. recutita to be non-toxic after
cytotoxicity tests. Surprisingly, M. recutita demonstrated the
Wound Healing least wound healing power out of all groups in vitro, but the
greatest power in vivo. Rats who were in the German
According to Martins et al. (2009), corticosteroids are the chamomile group had almost all their lacerations healed
most common form of therapy used by medical practitioners completely by day five, while the control and corticosteroid
to aid wound healing. Corticosteroids, unfortunately, can groups required the full 14-day experiment period to reach
cause adrenal suppression and subsequent kidney grade 1 healing status. The German chamomile group also
malfunction when they are used over a long period of time. exhibited low rates of abscess formation in vivo during
Because Matricaria recutita’s chemical constituents are healing, demonstrating the antibacterial activity of the plant.
known to possess antibacterial, anti-inflammatory, and Martins et al. (2009) inferred these results were due to
antifungal capabilities, Martins et al. (2009) decided to test, chemical constituents of German chamomile such as
via in vitro and in vivo studies, the plant’s potential as a chamazulene, flavonoids, etc. as documented by other studies.
wound-healing drug. The cytotoxicity of the plant was also Although German chamomile demonstrated the lowest cell
examined. viability during the in vitro study, researchers believe results
For both the in vitro and in vivo studies, five test groups were could have been influenced by said antibacterial activity.
created: control, German chamomile, and three different Therefore, German chamomile could serve as an alternative
forms of corticosteroids. For the in vitro study, cells were wound treatment that is safer and faster with fewer side
cultured under nutritionally deficient conditions to simulate effects than corticosteroids.
the environmental stress on cells during wound healing. Cell
mitochondrial activity and cell viability were measured in the
presence of no drugs, chamomile, or the corticosteroids. For Clinical Studies
the in vivo study, 125 male albino rats were evenly divided Most recent clinical studies have focused on testing Matricaria
amongst the five test groups. After mild anesthetization, recutita as an alternative therapy for the treatment of
experimenters inflicted traumatic ulcers on the rats’ tongues. depression and/or anxiety. Other clinical trials, as examined
No drugs, chamomile, or corticosteroids were administered at by McKay and Blumberg (2006), have demonstrated positive
effects of topical applications and inhalation treatments. and determined that administration of oral chamomile extract
McKay and Blumberg (2006) reports on a study that resulted in lowered HAM-A and HAM-D scores over time.
demonstrated German chamomile’s topical application effect
German chamomile’s method of action for these anxiolytic and
was equal to that of .25 percent hydrocortisone cream in the
antidepressant results is unknown, however researchers have
treatment of atopic dermatitis, eczema, radiation therapy, and
several hypotheses. The anxiolytic effect may be a result of M.
erythema. McKay and Blumberg (2006) also examined two
recutita’s flavonoid content acting on γ-amino butyric acid,
studies that showed German chamomile’s essential oil
noradrenalin, dopamine, and serotonin neurotransmissions or
potential to alleviate pain and create a “comfortable feeling”
modulating hypothalamic-pituitary-adrenocortical axis
when inhaled.
function. Another hypothesis is that apigenin may bind to
benzodiazepine receptors and reduce γ-amino butyric acid-
Anxiety and Depression activated activity. Researchers believe the anti-depressant
mechanism of action could be a result of flavonoid content
Amsterdam et al. (2009) and Amsterdam et al. (2012) are two modulating central noradrenalin, dopamine, serotonin, and γ-
studies that examine the potential anxiolytic and anti- amino butyric acid neurotransmission (Amsterdam et al.,
depressant activity in German chamomile. The search for an 2009; Amsterdam et al., 2012).
herbal therapy for anxiety and/or depression is relevant
because many patients decide not to seek treatment for
various reasons such as cultural (many societies have a stigma Contraindications
towards these two mental disorders), financial (psychiatric
The FDA (Food and Drug Administration) categorizes
treatment is often costly), or personal reasons. In addition,
Matricaria recutita, German chamomile, as GRAS (Generally
modern conventional therapies such as selective serotonin
Recognized as Safe) and ADRs (Adverse Drug Reaction) to the
reuptake inhibitors and benzodiazepines can cause
plant are rare. However, a small amount of ADR cases have
undesirable side effects (Amsterdam et al., 2009).
been recorded in the form of allergic reactions. Most reactions
Although the researchers responsible for these two studies to M. recutita occurred in patients with preexisting allergies to
mention various caveats present in their methods, they do other members, such as mugwort or ragweed, of the
believe their results still show potential for Matricaria recutita Asteraceae family (McKay & Blumberg, 2006).Therefore, those
as a possible treatment. Both clinical trials were randomized, with said allergies should avoid interaction with M. recutita.
double blind, and placebo-controlled. All patients included had Oral ingestion, topical application, and use as an eye rinse of
a standardized diagnosis of Generalized Anxiety Disorder or M. recutita can cause severe hypersensitivity and anaphylaxis,
Depression. Those patients who had major mental co-morbid allergic conjunctivitis, and contact dermatitis (Rodriguez-
disorders, unstable medical conditions, or allergies to the Fragoso, Reyes-Esparza, Burchiel, Herrera-Ruiz, & Torres,
Asteraceae family or chamomile were excluded. Researchers 2008). Cases of anaphylaxis are extremely rare and of the few-
examined the mean scores of HAM-A and HAM-D scoring tests recorded ADRs most were associated with conditions of the
skin and its deeper subcutaneous layers (Jeschke et al., 2009).
Cases in which Matricaria recutita was prescribed: Current Use in Allopathic and CAM Therapies
Conditions, Diseases, Infections Modern day uses of German chamomile are diverse and far-
Respiratory: reaching across the globe. German chamomile is one of the
• Acute upper respiratory infections most consumed herbs worldwide, with over a million cups of
• Acute lower respiratory infections its herbal tea consumed on the daily (Srivastava et al., 2010).
• Chronic lower respiratory diseases Because most clinical studies on the plant are fairly recent and
• Other diseases of the respiratory system have not been replicated, there are no conventional
• Other diseases of the upper respiratory tract chamomile-derived or synthetically modified chamomile
Digestive distress drugs on the market today. In fact, Matricaria recutita is still
Other infectious diseases typically consumed/utilized in its traditional preparation
Diseases of oral cavity, jaw, and salivary glands forms: teas, tisanes, tinctures, eye rinses, and topical skin
Non-infective enteritis and colitis applications. German chamomile for tea brewing is sold in
Diseases of middle ear and mastoid dried flower heads or tea bags made from powdered M.
Table 1. Cases in which German allopathic physicians recutita alone or in combination with other popular medicinal
prescribe Matricaria recutita. Adapted from Jeschke et al. herbs. Drinking of the tea or inhalation of the essential oil is
(2009). common for German chamomile’s reported overall calming
effect and alleviation of depression, anxiety, insomnia
(Srivastava et al., 2010). In Germany, M. recutita is the most
An additional potential cause of ADRs among patients is prescribed herb of the Asteraceae family by allopathic
contamination of chamomile supplements and products with a physicians (Jeschke et al., 2009). See Table 1 for a list of cases
similar species known commonly as “dog chamomile” in which M. recutita was prescribed for treatment. According
(Srivastava, Shankar, & Gupta, 2010). to "Matricaria chamomilla (German chamomile)" 2008)
courtesy of the Alternative Medicine Review, the
There are no scientifically proven drug interactions for M. recommended dosage is 1 dried flower head prepared via
recutita however several theories for potential interactions infusion and consumed orally. Chamomile is also a common
exist. It is thought that M. recutita’s coumarin content may ingredient in aromatherapy, cosmetic, and hair products
increase the power of the drug Warfarin by interfering with (Srivastava et al., 2010).
the blood coagulation process. In addition, M. recutita may add
blood thinning effects to the existing anti-platelet effects of
aspirin, NSAIDs (Non-steroidal Anti-Inflammatory Drug), and Discussion
acetaminophen and increase the effects of several central
nervous system depressant sedative drugs (McKay & German chamomile, Matricaria recutita, is a plant with a
Blumberg, 2006). detailed ancient history in cultures across the world, but is a
relatively new plant in the world of western medicinal
research. Patients using both eastern and western traditional
forms of medicine (Unani, Aberëshë, etc.) have reported Asadi-Shahmirzadi, A., Mozaffari, S., Sanei, Y., Baeeri, M., Hajiaghaee,
ethnomedical and ethnobotanical benefits for centuries. In R., Monsef-Esfahani, H. R., & Abdollahi, M. (2012). Benefit of
particular, German chamomile seems to be one of the most Aloe vera and Matricaria recutita mixture in rat irritable
frequently used traditional herbal remedies for overall bowel syndrome: Combination of antioxidant and
spasmolytic effects. Chin J Integr Med. doi: 10.1007/s11655-
gastrointestinal distress and anxiety relief. These herbal uses
012-1027-9
of the plant appear across cultures that developed an ocean
apart. It’s surprising to find that more older scientific studies Barnes, P. M., Powell-Griner, E., McFann, K., & Nahin, R. L. (2004).
are not available on the plant, but logical as well. With western Complementary and alternative medicine use among adults:
medicinal struggles such as antibiotic resistance, conventional United States, 2002. Adv Data(343), 1-19.
drug side affects, and the costliness of healthcare emerging Carmona, M. D., Llorach, R., Obon, C., & Rivera, D. (2005). "Zahraa", a
only in the past few decades, it makes sense that most Unani multicomponent herbal tea widely consumed in Syria:
research on alternative therapies is fairly recent. German components of drug mixtures and alleged medicinal
chamomile’s biological activity presents the exciting potential properties. J Ethnopharmacol, 102(3), 344-350. doi:
for safer and less expensive therapies for conditions involving 10.1016/j.jep.2005.06.030
oxidative stress, bacterial infections, cancer cell and tumor Chandrashekhar, V. M., Halagali, K. S., Nidavani, R. B., Shalavadi, M.
proliferation, and much more. It has also presented itself at H., Biradar, B. S., Biswas, D., & Muchchandi, I. S. (2011). Anti-
the forefront of research on new therapies for mental distress allergic activity of German chamomile (Matricaria recutita
(depression, generalized anxiety disorder, and insomnia). L.) in mast cell mediated allergy model. J Ethnopharmacol,
These exciting findings and claims of both past and present 137(1), 336-340. doi: 10.1016/j.jep.2011.05.029
should encourage more research on the plant’s phytochemical Guimaraes, R., Barros, L., Duenas, M., Calhelha, R. C., Carvalho, A. M.,
constituents for potential new drugs and whole herb Santos-Buelga, C., . . . Ferreira, I. C. (2013). Infusion and
treatments. decoction of wild German chamomile: bioactivity and
characterization of organic acids and phenolic compounds.
Food Chem, 136(2), 947-954. doi:
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Melaleuca alternifolia Cheel, Myrtaceae
Elizabeth M. Cappello
Introduction
Melaleuca alternifolia Cheel is an angiosperm in the Myrtaceae
family. The common names of Melaleuca alternifolia are tea
tree and paperbark tree. M. alternifolia has many different
uses, both traditional and modern, including flavoring,
antiseptic, antibiotic, antiviral, anti-inflammatory, antifungal
and topically for skin abrasions (Brophy et al., 1989; Carson et
al. 2002; Hammer et al., 2004). M. alternifolia has been used as
a natural preservative in both pharmaceutical and cosmetic
products (Cox et al., 2000). Halberstein noted that M.
alternifolia has been prescribed as an antibiotic and is similar
to Elecampane flower (2005). The main constituents are
terpinen-4-ol, 1,8-cineole and α-terpineol (Carson et al.,
2002). The essential oil extracted from M. alternifolia has
become popular within the last century and is an economically
significant essential oil (Homer et al., 2000).
The Myrtaceae family is known for its popular genus,
Eucalyptus, and also includes Psidium guajava L. (common
guava) and Syzygium aromaticum L. (clove). M. alternifolia Figure 1. Melaleuca alternifolia (Source: http://toptropicals
(Figure 1) is a small evergreen tree found in New South Wales .com/catalog/uid/melaleuca_alternifolia.htm)
and Queensland and is native to Australia, found in the low
and swampy areas near the Clarence and Richmond rivers were seen mostly in northern New South Wales, low levels of
(Butcher et al., 1994; Carson and Riley., 1993). A correlation terpinen-4-ol (high levels of 1,8-cineole) were seen near
has been observed between the composition of tea tree oil Grafton and terpinolene was seen in abundance in M.
(TTO), the essential oil of M. alternifolia, and the geographic alternifolia populations in Queensland (Homer et al., 2000). It
location of the tree in Australia; high levels of terpinen-4-ol has been hypothesized that this chemical distribution
according to geographic location is because of genetic rather wounds (Carson et al., 2006). M. alternifolia has also been
than environmental pressures; the close proximity of these used for cleansing and dressing wounds (Carson and Riley,
trees may have caused a type of “inbreeding” effect allowing 1993). Medicinally in Aboriginal culture, the crushed leaves
for a more “pure breed” within each geographic area (Homer were inhaled for coughs and colds while an infusion of the
et al., 2000). M. alternifolia has very small white flowers and a leaves were used for treatments of sore throats (Carson et al.,
papery, black bark with narrow leaves, growing up to 22 1993; 2006). The Aborigines also noted sacred healing rivers
meters in length. The evergreen grows to about 5 meters in in which leaves of the M. alternifolia fell in the river, creating a
height (Carson and Riley, 1993). The essential oil of M. simple infusion; these rivers were used for healing (Carson et
alternifolia, famous for its biological activity, is pale, yellow, al., 1993; 2006). It is unlikely that the Aborigines used
viscous oil with a pungent odor (Carson and Riley, 1993). extractions of M. alternifolia for its essential oil, but they were
aware of the plant’s medicinal benefits (Carson et al., 1993).
Traditional Uses There was no documentation of medicinal uses of M.

alternifolia prior to colonization of Australia as the Aborigines
The use of M. alternifolia has been a part of the had an oral tradition (Carson and Riley, 1993). Due to this oral
Australian Aboriginal tradition, particularly the Bundjalung tradition, there are no ancient texts documenting the
Aborigines (Budhiraja et al., 1999; Hammer et al., 2003). medicinal uses of M. alternifolia. The oral tradition of the
When traditionally used by Aborigines, the leaves and Aborigines influenced modern physicians to look more closely
branches were crushed or decayed leaves were placed in at M. alternifolia that led to the increase of scientific
water (Carson and Riley, 1993). The collection of M. knowledge of the tea tree in the past century.
alternifolia was originally done by coppicing process, a
method of cutting down the plant to its tree stump and The use of M. alternifolia has changed over time. The raw
allowing it to grow back (this make take up to 10 years) materials were originally used, but now the focus is on the
(Carson et al., 2006). The use of the essential oil, tea tree oil, essential oil that is extracted through steam distillation. It is
became popular within the 20th century. Prior to the scientific now harvested for its oil (Butcher et al., 1994). The traditional
discoveries of the benefits of TTO from M. alternifolia in the uses of M. alternifolia are still relevant today. These uses
1920s and 1930s, the raw materials of M. alternifolia were provide scientists and physicians with an idea of what it could
used (Carson et al., 2006). A steam distillation is preformed of be used to treat. Since the Aboriginal culture has relied on M.
the leaves to extract the essential oil, which is now in demand alternifolia for so long, this indicates that there must have
today (Carson and Riley, 1993). In a more crude process of been some efficacy associated with its medicinal use.
extracting the essential oil, people would simply break off the
leaves and terminal branches and do a very simple steam
distillation over a temporary wood fire (Carson et al., 2006).
The essential oil of M. alternifolia, tea tree oil (TTO), is the
The Aborigines used M. alternifolia for skin infections, bruises, focus of research and is extracted by steam distillation from
insect bites and cuts by sprinkling the crushed leaves over
the evergreen’s leaves (Brophy et al., 1989). This essential oil
is similar to nutmeg oil and contains terpinen-4-ol (Figure
2A), 1,8-cineole (Figure 2B) and α-terpineol (Figure 2C)
(Borphy et al., 1989; Carson et al., 2002). Tea tree oil from M.
alternifolia is insoluble in water (Carson and Riley, 1993).
There are actually three different varieties of M. alternifolia
according to the concentration of cineole; low, medium and
high, with low being the most sought after for medication
(Brophy et al., 1989). The essential oil of M. alternifolia is
composed of monoterpenes, terpinen-4-ol, cineole and various Figure 2. Chemical structures of (A) Terpinen-4-ol, (B)1,8-
hydrocarbons (Carson and Riley, 1993). Of the monoterpenes, cineole, and (C) α-terpineol – all main constituents of
50% are oxygenated and 50% are hydrocarbons (Cox et al., Melaleuca alternifolia oil. (Source: http://pubchem.ncbi.nlm.
2000). The International Standard of M. alternifolia oil is a nih.gov.proxy.library.emory.edu/summary/summary.cgi?cid=2724161&lo
minimum of 30% terpinen-4-ol and a maximum of 15% 1,8- c=ec_rcs)
cineole (Homer et al., 2000). The composition of the oil of M.
alternifolia may change if not stored properly (the proper
These effects from TTO lead to cell death (Cox et al., 2000).
storing requires a cool, dry, dark setting in a container with as
TTO has also been observed to increase potassium ion leakage
little air as possible) (Carson et al., 2006).
from cells (Cox et al., 2000). TTO can permeate skin very
easily, but this also dependent on how it is applied to the skin
Biological Activity (an ointment will permeate the skin more than a cream for
example) (Reichling et al., 2006).
The essential oil of M. alternifolia known as tea tree oil
(TTO) is the main constituent that contributes to the biological TTO has demonstrated a variety of uses ranging from
activity of M. alternifolia. While there is still speculation antibacterial and antifungal to antiviral and anti-inflammatory
regarding how TTO is able to disrupt the cell membrane (Carson et al., 2002; 2006). M. alternifolia is even used for
functions, it is hypothesized that there is not one single flavoring and an antiseptic for mouthwashes (Brophy et al.,
mechanism of action due to its heterogeneous composition 1989). M. alternifolia has been shown to be great for treating
and structure (Carson et al., 2002). The essential oil of M. oral infections, such as oral candidiasis, but is not very useful
alternifolia is able to disrupt cell membrane function by as a preventative measure (Hammer et al., 2003). While TTO
increasing permeability, disrupting homeostasis and has demonstrated a variety of uses, there have not been many
inhibiting cell respiration (Carson et al., 2006). TTO and other investigations displaying these uses in vitro (Carson et al.,
terpenes have been shown to affect cell respiration, leading to 2006).
the hypothesis that it has an adverse effect on the M. alternifolia has demonstrated to be effective against
mitochondria organelles within cells (Hammer et al., 2004). furunculosis, wood-destroying fungi, vaginitis, oral vaginitis,
dermal infections, ulcers and cuts (Brophy et al., 1989; infection by inhibiting both aerobic and anaerobic respiration
Budhiraja et al., 1999). TTO can penetrate body tissues and (Kessel et al., 2003). This treatment was also estimated to be
shows high biological activity with low irritation effects of low cost to the patient ($2.00 - $20.00 per day) (Kessel et
(Budhiraja et al., 1999). White blood cells were activated after al., 2003).
interacting with TTO (Budhiraja et al., 1999).
M. alternifolia is an effective treatment of fungal infections
As an antibacterial, TTO was shown to kill Staphylococcus such as dandruff or oral candidiasis, a yeast infection that
aureus during its stationary phase within the host (Carson et allows for fungal growth on the mucous membranes of the
al., 2002). During one investigation of antiviral uses of the mouth typically the tongue (Hammer et al., 2004). In an in vivo
essential oil of M. alternifolia, TTO was tested on tobacco study of M. alternifolia against Candida albicans, terpinen-4-ol
plants with tobacco mosaic virus (Carson et al., 2006). of TTO was showed to be the main contributor to treatment of
Tobacco plants treated with TTO did show a decrease in the fungal infection and eliminating the fungus within three
lesions in comparison to controls (Carson et al., 2006). Tea weeks (Mondello et al., 2006). The use of M. alternifolia for
tree oil was also studied for antiprotozoal activity, showing a treatment of C. albicans would be cost effective because the
50% decrease in growth primarily due to terpinen-4-ol found only active compound is terpinen-4-ol, allowing for faster
in TTO (Carson et al., 2006). M. alternifolia is best when production and lower costs to patients (Mondello et al., 2006).
attacking “free” viruses that have not yet infected a cell
TTO showed antioxidant activity during an investigation by
(Carson et al., 2006). In vitro studies of TTO have shown both
Kim et al. (2004) using two assays to determine the activity:
antimicrobial and anti-inflammatory activity (Carson et al.,
2,2-diphenyl-1-picrylhydrazyl and hexanal/hexanoic acid. The
2006). TTO has been difficult to evaluate for antimicrobial
assays confirmed antioxidant activity due to α-terpinene, α-
activity because it is not soluble in water (Carson et al., 2006).
terpinolene and γ-terpinene, rather than the expected
While investigating the antibacterial use of TTO on Escherichia terpinen-4-ol (Kim et al., 2004). The antioxidant activity of M.
coli, Staphylococcus aureus and Candida albicans, it was alternifolia oil is similar to butylated hydroxytolene (BHT), a
concluded that TTO was able to inhibit cell respiration and synthetic antioxidant used as an additive to food and cosmetic
increased the permeability of the bacterial cytoplasm and products; this suggests that TTO may be a good, natural
yeast cell membrane through the increased uptake of alternative to butylated hydroxytolene (Kim et al., 2004).
propidium iodide, which is normally impermeable to the cell
M. alternifolia is used topically for infections of the skin
(Cox et al., 2000). Potassium ion leakage of E. coli and S. aureus
(Carson et al., 2006). Several investigations have been
cells was observed when exposed to TTO (Cox et al., 2000).
conducted to observe the effect of tea tree oil on mild acne. Oil
One in vitro study of TTO investigated the effect on bacterial was extracted from M. alternifolia and made into a gel (Magin
vaginosis, which is a growth of fungus within the vagina, not et al., 2006). This was compared to 5% benzoyl peroxide, a
to be confused with a yeast infection (Kessel et al., 2003). A typical compound used in skin care products (Magin et al.,
capsule composed of a few drops of TTO and gelatin inserted 2006). While 5% benzoyl peroxide was better at controlling
into the vagina overnight for six days was able to control the inflammatory lesions, M. alternifolia oil was able to reduce
non-inflammatory lesions and provides less side effects such effective (Barker and Altman, 2010).
as itching, redness and stinging, etc. (Carson and Riley, 1993;
TTO has also been used in a clinical study to evaluate double-
Magin et al., 2006).
blind testing (clinical trials where both the investigator and
Hammer et al. investigated resistance of Staphylococcus research volunteers are unaware of receiving the control or
aureus, S. epidermidis and Enterococcus faecalis (all Gram- treatment) (Carson et al., 2008). TTO is difficult to use in
positives) to TTO and rifampicin (an antibiotic) (2008). Low clinical trials due to its distinctive odor (Carson et al., 2008).
resistance of S. aureus, S. epidermidis and E. faecalis to TTO Carson et al. investigated the use of deception by looking at
was observed (<10-9), indicating that single-step mutants of TTO as an effective treatment of recurrent herpes labialis
these bacteria have low resistance to TTO (Hammer et al., (cold sores) (2008). Carson et al. concluded that double-
2008). Recently, Hammer et al. investigated resistance of S. blinding is not ineffective (only 50% of volunteers in each test
aureus and Escherichia coli to TTO (2011). In this study, multi- group were able to correctly identify if they received a placebo
step mutants were evaluated and Hammer et al. concluded product or TTO product) (2008).
that TTO has little effect on the development of resistance of S.
aureus and E. coli (2011).
Contraindications
TTO has been seen to be effective against cancerous
melanoma cells (Buzzoto et al., 2011). One reason that The long history of use of M. alternifolia and its essential oil
melanoma is so deadly is because it is resistant to has led to a general consensus that it is safe and because of
chemotherapy and radiation treatment (Buzzot et al., 2011). this, there is very little scientific documentation of its safety
TTO has been observed to inhibit the growth of melanoma with the exception of case studies (Carson et al., 2006). While
cells by overcoming their resistance of apoptosis (Buzzoto et the essential oil of M. alternifolia was shown not to be
al. 2011). This data shows how TTO is a possible alternative to mutagenic by the Ames test, there are still cases of toxicity
chemotherapy and radiation to treatment of melanoma. (Carson and Riley, 1993). That being said, ingestion of the
essential oil, especially orally, can result in toxicity but there
have yet to be any human deaths due to the oil of M.
Clinical Studies alternifolia as of yet (Carson et al., 2006). There are dangers of
Barker and Altman investigated the efficacy of TTO, lavender toxicity when TTO is ingested orally as it has been shown that
oil, suffocation product and pyrethrin products against head even a modest intake of M. alternifolia has resulted in toxicity
lice (2010). Lavender oil and TTO was almost four times more symptoms (Budhiraja et al., 1999; Carson and Riley, 1993;
effective than products containing pyrethrin in killing lice Jacobs and Hornfeldt, 1994). Toxicity due to TTO ingestion
after one day of treatment (Barker and Altman, 2010). These was observed in a 23-month-old after found with an empty
results show that not only could TTO be used in place of bottle of T36-C7, which is made up of entirely tea tree oil
pyrethrin-containing products for individuals that would have (Jacobs and Hornfeldt, 1994). The child was described to have
an adverse effect to pyrethrin, but also that TTO is more decrease motor coordination and was disoriented. Physicians
were able to treat the patient and release him from the
hospital relatively quickly, but this case did show that a small several plants.
amount (the bottle was 10ml) of oil extracted from M.
Some more obscure current uses of M. alternifolia include its
alternifolia could be toxic when ingested orally (Jacobs and
use for ceasing cannibalism among chickens (Carson and
Hornfeldt, 1994). This has raised concern because of the
Riley, 1993). Not only did M. alternifolia heal the wounds of
prevalence of tea tree oil in soaps, lotions, creams, cleaning
chickens, but also the constituents within the plant created an
products and toothpaste (Jacobs and Hornfeldt, 1994).
irritant to chickens causing them to stop eating other chickens
Any skin irritation due to using TTO topically is mostly due to because of taste (Carson and Riley, 1993).
its improper storage and production rather than the
constituents themselves (Carson et al., 2006). It is difficult to
store TTO because plastics absorb the oil quite readily (Carson Discussion
et al., 2006). Melaleuca alternifolia is an economically important plant that
has a variety of medicinal uses. M. alternifolia has been a
central part of Australian Aborigine medicine and is now a
sought after plant for its essential oil. TTO has shown to be
You can currently purchase an array of products with TTO as a beneficial for a variety of treatments and as more clinical
constituent. You can also find tea tree oil in soap, shampoos, investigations are conducted, we will have a greater
skin care products, etc. (Jacobs and Hornfeldt, 1994). One understanding of TTO’s power to be used medicinally.
commercial product of tea tree oil is Melasol (Carson and
TTO is used as an antibacterial, antimicrobial, antifungal and
Riley, 1993). The production of Melasol was so important
antiviral. It also is useful for skin abrasions, mild acne and
during World War II that those employed to collect M.
cuts. Further research should be done of how the Aboriginal
alternifolia were not required to enter the service (Caron and
culture used M. alternifolia and see how those traditions and
Riley, 1993).
methods can still be applied to medicine today. The many
M. alternifolia is marketed as “tea tree oil.” It may be studies discussed here show how M. alternifolia and more
purchased as just the oil, but is also part of many skin care and specifically, TTO, can be beneficial for human health,
hair care products. The Body Shop has a complete “Tea Tree” providing more cost effective treatments than those currently
line including facial washes, concealers and exfoliants. The tea used.
tree oil used in these products is M. alternifolia that is
From its use as an antibiotic to another therapy in battling
cultivated in Africa. Typically tea tree oil is marketed as 100%
melanoma, TTO has great potential. Tea tree oil is more than
pure essential oil and is advertised to be part of first aid kit to
just an essential oil to be purchased at a health food store, but
be used on cuts and abrasions. Other companies, including
instead an oil that has a wealth of opportunities to help human
Desert Essence market tea tree oil skin ointments and creams,
health.
but the products are not entirely composed of the essential oil
from M. alternifolia and are instead a mixture of oils from
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Tree) Oil: A Review of Antimicrobial and Other Medicinal
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Lyall R. Williams. "Gas Chromatographic Quality Control for
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Journal of Agricultural and Food Chemistry 37 (1989): Warmington and S.G. Wyllie. "The Mode of Antimicrobial
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Budhiraja, Shalini S., Malford E. Cullum, Susie S. Sioutis, Lucio
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d=12031
Momordica charantia L., Cucurbitaceae
Soraya Chanyasubkit
Introduction
Many plants serve a dual role as food and medicine. With a
majority of the world’s healthcare system based in traditional
medicine, up to 80% dependency in some regions according to
the World Health Organization, plants are critical in health
promotion and disease prevention. The term “functional food”
refers to a modified food or specific food ingredient that can
provide a health benefit beyond basic nutrition (Hasler, 2002)
and can be applied to the many herbs and plants used in
traditional healing. Momordica charantia is such an exemplary
plant that is widely consumed in the tropics of Asia, the
Caribbean, Africa, and the Amazon (Figure 1). It is in the
Cucurbitaceae family, which also includes melons, squashes,
and gourds. The plant’s defining characteristic is its bitter
taste, hence its common names like bitter melon, bitter gourd,
balsam apple, balsam pear, sorosi, karela (Hindi), and
ampalaya (Tagalog) (Kumar et al., 2010; Grover and Yadav,
2004).
Aside from its culinary use, M. charantia is also employed in
traditional medicine due to its hypoglycemic, antibacterial,
antioxidant, wound-healing, and other therapeutic properties.
It is typically prepared as a tea or bath by soaking the leaves,
stem, and fruit in water or directly eating the juice or the fruit Figure 1. Momordica charantia as the fruit and the plant.
itself (Behera et al., 2010). The key anti-diabetic compounds (Image source: http://kookiecurious03.files.wordpress.com
are charantin and momordicin, but bitter melon is known as a /2010/10/ampalaya.jpg)
health-promoting vegetable due to the presence of many kinds
of chemical compounds such as phenolic acids, saponins, continues to be an integral part of diet, ceremonies, and health
triterpenes, and proteins (Kumar et al., 2010). It has been worldwide (Behera et al., 2010; Taylor, 2002).
incorporated into many cultures for over 3,000 years and
The most well-known part of Momordica charantia is its
edible fruit which has an oblong shape, similar to a large
cucumber, but with a rough surface full of ridges and warts.
Unripe, it has varying shades of green but matures into a
brilliant yellow-orange fruit that bursts to reveal the vibrant
red seeds within. In a cross section of the fruit, the flesh is
crisp and full of water and has a mostly hollow cavity similar
to a bell pepper. In this cavity, a mesh, white pith suspends its
flat seeds (Figure 2).
The fruit of M. charantia can be categorized into three groups
which are described in Table 1. Depending on the phenotype, A B
the fruit can range from a smoother, pale green (Chinese) to
an incredibly warty and spiky surface of deep green (Indian).
The size of the fruit can range from 9-12cm to 30-60cm, again
depending on variety. However, a more recent categorization
for Indian and Southeast Asian bitter melons is by diameter: C D
M. charantia var. minima (< 5cm) and M. charantia var.
maxima (> 5cm) (Behera et al., 2010). Figure 2. The growth and phenotypes of M. charantia.
Bitter melon is a tendril-bearing vine with jagged leaves and
This herbaceous, tendril-bearing vine has leaves with jagged yellow flowers (A). At maturation, the fruit is a brilliant
edges hence the genus name Momordica which means “to bite” yellow-orange and bursts to expose the seeds (B). The
in Latin. The plant itself can grow to a height of 2-4 meters. M. phenotypes of Chinese and Indian bitter melons are easily
charantia is monoecious and its flowers have five petals and distinguishable (C and D).
are typically yellow. Bees are the primary pollinators. All parts
of Momordica charantia are bitter (Taylor, 2002). (Image sources: A - http://www.herbal-supplement-
M. charantia can tolerate a variety of environments from resource.com/images/bitter_melon_herb_img.jpg; B - http://
tropical to subtropical climates but it grows best in hot, humid www.whitetigernaturalmedicine.com/wp-content/uploads
areas. The cultivation of bitter melon is similar across /2010/10/Herb__0109.jpg; C - http://yourhomegarden
countries except for the spacing between plants. Frost can kill blog.com/wordpress/wp-content/uploads/2009/03/chinese-
the plants, and cooler weather can slow development. Ideally, bitter-melon.jpg; D - http://farm4.static.flickr.com/3318/
it is grown in a sunny, warm area with well-drained sandy soil 3475604705 _27b918fed6.jpg)
at pH 6.0 – 6.7 (Behera et al., 2010).
Small fruit Long fruit Triangular
type type fruit type
(var. (var. (var.
charantia - charantia - muricata)
Indian) Chinese)
Size 10-20 cm in 30-60 cm in 15-25 cm in
length/ length/ length/
5-8 cm in 3.5-6.0 cm in 9-12 cm in
width width width
Weight 0.1-0.3 kg 0.2-0.6 kg 0.3-0.6 kg
Color Dark green Light green Light-dark
green
Bitterness Extremely Slightly bitter Medium- Figure 3. Origin and movement of M. charantia. Bitter
bitter strongly bitter melon is believed to originate in Asia near China and India,
Table 1. Categories of Momordica charantia. The and its domestication spread to Africa and later the New
phenotypes of M. charantia can be classified due to the distinct World via the transatlantic slave trade.
appearances of each type. The most commercial is the Chinese
bitter melon due to its more suave bitter flavor.
fries, or is stuffed or pickled. Before culinary use, the bitter
melon is typically boiled, blanched, or soaked in salt water to
Traditional Uses attenuate the bitter flavor (Behera et al., 2010).
The origin of M. charantia is unknown, though the Historically, the plant has been used all over the world as an
domestication of the plant is thought to be in Asia, namely edible plant product to treating a variety of ailments from
China or India. The first mention of the bitter melon is in gastrointestinal to veterinary to, most famously and
Ayurvedic texts dating back 2000-200 BCE by Indo-Aryans in universally, diabetes. Though its use has been primarily
India. The ancient Chinese medicinal book Pen Ts’ao (or Ben medicinal, the exact applications differ from region to region.
Cao in pin-yin) referenced the bitter vegetable later in 1370 Preparation across cultures typically involves extracting juice
AD (Walter and Decker-Walters, 1988; Yang and Walter, from the unripe fruit and leaves or soaking and boiling the
1992). The use of M. charantia moved westward through the plant in water to create tea or a bath (Basch, 2003).
African continent toward the New World into the Americas via
the slave trade as one of many domesticates introduced from
the Old World as early as the 16th century (Figure 3). The Africa
melon is a versatile vegetable used in soups and curries, stir-
M. charantia has a variety of uses to both traditional healers
and the general population. According to Beloin et al. (2004),
in Togo, bitter melon is used primarily not only to combat
gastrointestinal diseases and childhood viral infections like conducted by Sonibare et al. (2009). The primary methods of
chicken pox, but also to treat infections and skin afflictions. extraction are juicing the leaves or boiling the leaves and
The groups soaked the vine in water for several hours and the ingesting or bathing in the juive. According to recipes
resulting liquid was drunk or bathed in, sometimes using gathered from Nigerian herbalists, fresh leaves of M. charantia
vines as a sponge if necessary. The seed is applied locally in (local name: ejinrin) are washed and squeezed to extract juice.
gynecological circumstances. It is notable that traditional Two tablespoonfuls of this liquid is taken orally three times a
healers and the villagers used the plant to treat the same day and in bathing morning and evening. In another recipe the
diseases, except for diabetes where none of the general leaves of ejinrin are boiled with the leaves of Newbouldia
population uses the plant as a treatment and 33% of healers laevis Seem. (Bignoniaceae), Vernonia amygdalina Chevallier
do. Healers use all parts of the plant except for seeds which (Asteraceae) and Ocimum gratissimum (Lamiaceae) and the
47% of healers agree that they are toxic. It is also notable that resulting concoction is drunk three times daily as well.
many healers hold university degrees and a few even have
medical degrees and still rely heavily on plant-derived
remedies and therapy. The Americas
Bitter melon also has strong spiritual and ritual properties in Generally, across the Americas and the Amazon, locals and
Togo. It is used to provide protection against evil spirits, indigenous peoples grow bitter melon in their gardens as a
diseases, malignant, intentions, and madness. It is viewed as a source of food and medicine. Some applications are similar in
purifying plant and used in ceremonies involving sacred use and purpose and other remedies are more highly
objects. The vine itself is worn as jewelry or a crown during emphasized depending on the region. In Mexico, the most
traditional rituals. This custom is likely derived from the mid- common afflictions are diabetes and dysentery. Peruvian
1600s when the Guin tribe moved to current Togo due to shamans use the plant mainly to treat different types of
warfare and the slave trade and wore the vines to protect inflammation (Taylor, 2002).
themselves from enemies and ensure a safe journey (Beloin et However in Brazilian herbal medicine, the whole plant or
al., 2004). various parts are used to combat many skin infirmities such as
In the Democratic Republic of Congo, whole plant decoction is scabies, eczema, and leprosy, in addition to tumors,
used to treat many gastrointestinal afflictions such as inflammation, allergies helminthiasis, rheumatism, diarrhea,
intestinal worms, colic, diarrhea, dysentery, constipation and dandruff, and wounds (de Albuquerque et al., 2007; Taylor,
for general ailments like, diabetes, cold, hypertension, malaria, 2002). In Colombia, it is taken as an oral infusion to treat
fever, anemia, psoriasis, and jaundice. It can also be used as a intestinal parasites, fever, and pruritic ailments (Gomez-
laxative and an aphrodisiac (Mesia et al., 2008). Estrada et al., 2011). Various Amazonian Bolivian indigenous
groups also use the mashed leaves for skin infirmities and
M. charantia is also one of the more frequently used plants in
considers M. charantia a valuable medicinal plant (Boudary et
the treatment of measles in Nigeria and Cucurbitaceae is the
al., 2000; Thomas et al., 2010).
most widely mentioned family according to interviews
In eastern Nicaragua, bitter melon is used extensively in
fertility health and childbirth among the Rama midwives.
Taken orally or applied topically, M. charantia can relieve
abdominal and back pain, post-partum abdominal pain,
menstrual hemorrhage and pain, fever, vaginal infections,
weakness and anemia and promote contraception and induce
abortions (Coe, 2008).
The Caribbean
Trinidadian hunters use botanical and zoological methods to
stimulate their hunting dogs, typically foxhounds, or to
enhance their sense of smell to ensure more successful
hunting trips. Lans et al (2001) interviewed a hunter who uses
M. charantia to help his dogs acclimate to hunting for larger
game, specifically wild hogs. First, he bathes the dog in congo
lala (Eclipta prostrate L., Asteraceae) and the dog will begin
hunting the small matte lizard. Next, the dogs are bathed in M.
charantia (caraaili in Trinidadian Creole) and barbadine leaf
(Passiflora quadrangularis L., Passifloraceae) and they will
hunt for bigger game. Finally, the dog is bathed with Figure 4. Doctrine of Signature. Comparison of the agouti
unspecified plants that promotes hunt for wild hogs (Lans, et rodent and M. charantia which Trinidadians use in hunting
al., 2001). (Image source: http://plantecology.files.wordpress
.com/2010/05/agouti.jpg; http://upload.wikimedia.org/
M. charantia usage is also based on the doctrine of signatures wikipedia/commons/5/54/Momordica_charantia_003.JPG)
which dictates that a specific plant trait resembles the desired
outcome; thus after application of this plant, the foxhound dogs infected with mange, or parasitic mites, and then a
would want to hunt for the particular animal the plant poultice of other plant species can be applied to the affected
corresponds to (Figure 4). In this case, there is an association areas. Aside from veterinary use, the vine is steeped in water
between caraaili and agouti, a type of rodent similar to the to create a “cooling” tea for individuals who have too much
guinea pig (Lans, et al., 2001). “heat” or impurities in their system e.g. blood. In the
Another use of caraaili by Trinidadian hunters for dogs is for Caribbean as a whole, M. charantia is used as an abortifacient,
medical treatment rather than improved hunting. Crushed to treat diabetes, and to lower high-blood pressure (Lans,
leaves and vines of M. charantia are steeped in bathwater for 2006).
China Moradabad district of northern India, it serves an
Traditional Chinese Medicine is one of the oldest whole ethnoveterinary role (Ali, 1999). The fruit is mixed with onion
medical systems beneath the umbrella of complementary and (Allium cepa L., Amaryllidaceae) and vinegar and the resulting
alternative medicine founded on the principle of balance paste is applied to the forehead, horns, and legs of cattle with
between yin and yang. If they are out of balance, this leads to ephemeral fever. Boiled in equal quantities with Boerhavia
disease. In the case of diabetes, a yin deficiency results in diffusa L. (Nyctaginaceae), Luffa acutangula L.
dryness in the body that can be remedied by eliminating the (Cucurbitaceae), onion, and sugarcane, it is an oral remedy for
heat and promoting fluid (Li et al., 2004). This can be achieved stomach disorders and fever.
by the incorporation of a common traditional Chinese plant In the northwestern state of Rajasthan, karela treats a variety
into the diet of the patient. M. charantia is one of 13 plants of afflictions. The whole plant is combined with cinnamon,
listed in Liu et al. (2004) study and has been used to treat long pepper, rice and Hydnocarpus wightiana Blume,
diabetes in China for thousands of years through oral (Achariaceae) oil for topical application of scabies and other
administration of the extract or fruit juice. skin disorders. The leaf juice is externally applied around the
In addition, many plants in the Cucurbitaceae family are eyes for night blindness. The paste of its roots is also used
mentioned in ancient Chinese texts including M. charantia. topically over piles. Of course, ingestion of one spoonful of
Even in modern-day China, use of bitter melon is still highly fruit paste in water can reduce blood sugar (Namsa et al.,
prevalent to treat rheumatism, gout, dysentery, and 2011).
toothaches (Yang and Walters, 1992). In tea form, it is also Other miscellaneous applications of karela across India
used to stimulate appetite and treat gastrointestinal infections include a topical snakebite antidote when mixed with olive oil
(Kumar et al., 2010). (Samy et al., 2008), topical paste when mixed with lime for
skin diseases like dhobis itch and ringworm (Mahishi et al.,
2005), and as a blood purifier for diabetes and eye infections
India (Jain et al., 2005)
As one of the countries with the longest tradition of M.
charantia use, India has extensive applications for the plant.
This exhaustive list includes but is not limited to “antidiabetic, Chemistry and Pharmacology
abortifacient, anthelmintic, contraceptive, antimalarial and Momordica charantia has a variety of phytochemicals
laxative and is used for treatment of dysmenorrheal, eczema, dispersed throughout the plant anatomy, totaling to 228
emmenagogue, galactagogue, gout, jaundice, kidney (stone), known compounds. The leaves are rich in alkaloids,
leprosy, leucorrhea, piles, pneumonia, psoriasis, rheumatism, flavonoids, hecogenins, steroidalglyscoside, saponins, and
and scabies” (Grover and Yadav, 2004). tannins. Many minerals like iron, calcium, copper, and zinc are
In specific regions of India, use of the M. charantia (local present in the roots (Bakare, 2006). The essential oil from the
name: karela) is more specialized. For example, in the
seeds is comprised mostly of trans-nerolidol (61.6%) and Plant Chemical Constituents
apiole (8.9%) and many trace compounds (Braca et al., 2007). Part
Momordicoside K, L, two acylglycosylsterols-3-O-[6%-O-
The fruit, the most used part of the plant, contains glycosides, palmitoyl-b-D-glucosyl] stigmast-5,25(27)-diene and 3-O-[6%-
saponins, alkaloids, triterpenes, proteins, and phenolic O-stearyl-b-D-glucosyl]stigmasta-5,25(27)-diene, benzyl
Fruits
alcohol, myrtenol, cis-3-hexenol, trans-2-hexenal, 1-penten-3-ol,
compounds and steroids, which contribute to the range of
cis-2-penten-1-ol, charantin, stigmast-5,25-diene-3b-O-
medicinal uses. Namely, charantin (a steriodal saponin), glucoside
momordicin (an alkaloid), and protein P-insulin demonstrate Octacosane, 1-triacontanol, 7-stigmasten-3b-ol, 7,25-
anti-diabetic activity (Figure 5). Phenolic compounds have an Leaves stigmastadien-3b-ol, 5,25-stigmastadien-3b-ol glucoside,
antioxidant, anticarcinogenic, and anti-inflammatory effects. phytosphingosine, momordicine I, II, III
Benzyl alcohol, myrtenol, cis-3-hexenol, trans-2-hexenal, 1-
The protein MAP-30 shows potential anti-HIV properties. The Tendrils
penten-3-ol, cis-2-penten-1-ol
plant in general is rich in vitamin A, vitamin B, and vitamin C b-sitosterol-b-D-glucoside, stearic acid, two lectins, two new
(Kumar et al., 2010, Singh et al., 2011). A more exhaustive list triterpene glycosides – momordicosides A and B, characterized
of known chemical constituents in M. charantia can be found as 3-O-b-gentiobioside and 3-O-b-D-xylopyranosyl (1.4)-[b-D-
in Table 2. glucopyranosyl (1.6)]-b-D-glucopyranoside, respectively, of
cucurbit-5-en-3b,22(S),23(R),24(R),25pentaol; momordicosides
C, D and E characterized as 3-O-b-gentiobiosides of cucurbit-5-
en-3b,23,24,25-tetraol, cucurbit-5,24-dien-3b,22,23-triol and
3b-hydroxy-23.24,25,26,27-pentanor-20(j) cucurbit-5-en-22-al,
respectively; two cytokinins – zeatin and zeatin riboside –; two
Seeds
proteins a and b momorcharins, p-cymene, hexadecanol,
menthol, nerolidol, pentadecanol, and squalene, 10a-cucurbit-
5,24-dien-3b-ol, 24-methylencycloartanol, taraxerol, b-amyrin,
campesterol, cycloeucalenol, 24b-ethyl- 5a-cholesta-7-trans-22-
Charantin dien-3b-ol, 24b-ethyl-5acholesta-7-trans-22,25(27)-trien-3b-ol,
lophenol, 4a-methylzymosterol, obtusifoliol, spinasterol,
stigmasterol, stigmasta-7,25-dienol and stigmasta- 7,22,25-
trienol, momordica anti-protein (MAP 30), ribosome-
inactivating-proteins (RIPs)
Momordicosides G, F1, characterized as 3-O-b-D-allopyranoside
and 3-O-b-D-glucopyranoside, respectively, of 5,19-epoxy-25-
methoxy-5b-cucurbita-6,23-dien-3b-ol, momordicosides F2, I
Unripe
characterized as 3-O-b-D-allopyranoside and 3-O-b-D-
fruits
Momordicin glucopyranoside of 5,19-epoxy-5b-cucurbita-6,23-dien-3b,25-
diol, 3-O-[6%-O-palmitoyl-b-Dglucosyl]-stigmasta-5,25(27)-
Figure 5. Structures of Charantin and Momordicin. diene and stearil derivative
Table 2. Chemical constituents of Momordica charantia by
plant part. Courtesy of Scartezzini and Speroni, J of Ethnopharmacology
71 (2000).
Biological Activity less damaged pancreas compared to control untreated rats.
Hypoglycemic activity Thus, the authors concluded “MCE [Momordica charantia
Since its initial documented use thousands of years ago, extract] exhibited promising anti-diabetic activity in alloxan
Momordica charantia has been associated with reducing blood diabetic rats” (p 7). In this study, the researchers suggested
sugar levels. The compounds involved in this process have that the extract increased pancreatic beta cells insulin
come to light, though the exact mechanisms of action are still stimulation.
under debate. Charantin, a steroidal saponin, momordicin, an New literature proposes that M. charantia extract possesses
alkaloid and protein P-insulin all have structures similar to 11β-hydroxysteroid dehydrogenase type 1 inhibitor (11β-
animal insulin, leading to the hypothesis that their makeup HSD1) which is involved in the etiology of obesity and thus
plays a hypoglycemic role. Unfortunately, there is a dramatic type 2 diabetes. 11β-HSD1 has been implicated in regulating
lack of standardization among the studies, and concrete obesity: 11β-HSD1-deficient mice have better lipid and
conclusions are difficult to glean. There are discrepancies glucose profiles and overexpressed-11β-HSD1mice are obese
among concentrations, extraction procedures, experiment and have diabetes. Blum et al. (2011) suggests that the
duration, and model organisms used; though for the most part, presence of this inhibitor contributes to M. charantia’s anti-
there is a consensus that M. charantia does reduce plasma diabetic activity and opens another avenue for future
glucose levels (Basch et al. 2003). research.
Some proposed methods include stimulation of pancreatic
insulin secretion, attenuation of hepatic gluconeogenesis, or
Antioxidant/Anticarcinogenic activity
rise in hepatic glucagon synthesis. Application of M. charantia
fruit juice increased the number of functional beta cells which Aside from its strong hypoglycemic activity, Momordica
produce insulin in the pancreas though not to the normal charantia has also been implicated in having antioxidant and
amount. Other literature suggests an extra-pancreatic antitumor properties as well. Though there is no evidence to
mechanism of action, resulting in increased glucose suggest that bitter melon can treat cancers, research suggests
breakdown in the liver, inhibition of glucose-6-phosphatase, that it can retard or suppress tumor growth. Pitchakarn et al.
or enhanced GLUT4 transporter protein in muscles (Kumar et (2010) observed bitter melon leaf extract reduced cell growth,
al., 2010, Singh et al., 2011). invasion, and migration in rat prostate cancer cell line PLS10
in vitro. The authors also observed reduced metastatic lesions
Fernandes et al. (2007) attempts to provide experimental
in lung cancer, though not in incidence in rats. This study
evidence for hypoglycemic activity by using a well-
significantly showed the anti-metastatic activity of M.
standardized M. charantia extract in alloxanic diabetic rats
charantia in vitro and in vivo.
compared to glibenclamide, a current anti-diabetic drug. The
sample was obtained through an ethanolic extract and Crude extracts have also shown anticancer effects in leukemia,
received as 10% processed powder. Their results showed an lymphoma, melanoma, breast cancer, and many other cancers.
increase in insulin serum, a decrease in plasma glucose, and a Methanol extract has demonstrated cytotoxicity in human
cancer cell lines. The mechanisms of action for this property subjects. The human subjects underwent glucose tolerance
include inhibition of guanylate cyclase, disruption of G2 and M tests (GTT) as a standard test and after consumption of 50 ml
phases of cell cycle, activation of NK cells, or instigation of of bitter melon juice and eight to 11 weeks of consuming fried
apoptosis (Kumar et al., 2010). bitter melon. In both instances where the subjects ingested M.
charantia regardless of modality, the blood sugar level
declined. There appears to be a significant decrease in plasma
Antimicrobial/Antiviral activity glucose level between the standard and the consumption of
Another property of M. charantia that makes it a widely-used the juice. However, it is not apparent if the authors conducted
and beneficial plant is its ability to fight off nearly any type of a statistical analysis between consumption of the fried
infection. The leaf extracts of bitter melon have demonstrated vegetable and the standard or the juice. They conclude their
a wide-range of antimicrobial effects including activity against study demonstrated M. charantia’s hypoglycemic properties.
Escherichia coli, Salmonella paratyphi, Helicobacter plyori and Basch et al. (2003) compiled the literature of previous clinical
Myobacterium tuberculosis. It also has demonstrated studies in a review article including Leatherdale et al. (1981)’s
antihelminitic properties against Ascaridia galli worms, study and noted the many shortcomings that were common in
antiprotazoal properties against Trypanosoma brucei brucei, all the previous research conducted: not randomized and
and antifungal properties against Candida albicans and double-blind, lack of standardization and controls, poor
Cryptococcus neoformans (Grover and Yadav, 2004). Such experimental set-up, and establishment of patient history and
infections are common in the developing world and the value proper baselines. The authors suggested that though the
and benefit of bitter melon is immediately obvious in these research has shown M. charantias’s antidiabetic activity, these
circumstances. are only preliminary studies.
Notably, protein MAP 30 has potential as antiviral drug, A more recent study, however, provides more conclusive data
specifically in HIV treatment. This activity can be credited to and results. In Thailand, Fuangchan et al. (2011) conducted
inhibition of HIV-1 integrase and viral reverse transcriptase. the first multi-week, randomized, large sample size, double-
M. charantia extract has also been shown to combat herpes blind, active-control trial in four paralleled treatment groups
and the polio virus, likely by inhibiting protein synthesis to determine the minimum effective dose of M. charantia in
(Grover and Yadav, 2004). newly diagnosed type 2 diabetes patients. Headache,
dizziness, and increased appetite in the highest concentration
group were noted as low-incident side effects and bitter
Clinical Studies melon was generally well tolerated. This study concluded that
Few clinical studies have been conducted to verify, quantify 2000 mg/day of bitter melon significantly lowered
and explore the mechanism of action of glucose tolerance due fructosamine levels and had a modest hypoglycemic effect.
to Momordica charantia. Leatherdale et al. (1981) conducted a
study with nine non-insulin-dependent diabetic Asian
Contraindications lowering effects have been reported when bitter melon was
Though Momordica charantia is widely eaten and consumed while the patient was taking sulfonylureas, a class
incorporated into many diets around the world, it should be of antidiabetic drugs that stimulate insulin production (Basch
avoided in certain circumstances. Bitter melon has historically et al., 2003).
been used as an abortifacient and should not be ingested
during pregnancy as it might result in premature birth or
accidental abortion. In general, it has been shown to reduce
fertility in females and sperm production in males. Thus, Generally, the current market for Momordica charantia is
couples trying to get pregnant should avoid eating this directed to promoting healthy blood sugar levels, reducing
vegetable (Basch et al., 2003). hyperglycemia and stimulating the immune system (Figure
6). According to Birdee and Yeh (2010) in Clinical Diabetes,
A large-scale study has not been conducted investigating the
approximately a third of adults with diabetes use some type of
potential harmful effects of bitter melon, but rather isolated
cases of strong side effects have been reported. Of course, any
individuals with known allergies to the Cucurbitaceae family
such as melon, pumpkin, or squash should avoid consumption
of bitter melon (Basch et al., 2003). Fruits in this family have
been reported to be one of the most allergy-causing fruits in
the United States (Figueredo et al., 2000). Similarly, people of
Mediterranean or Middle Eastern descent or that have a
glucose-6-phosphate dehydrogenase deficiency should take
caution in the ingestion of bitter melon seeds which has the
compound vicine that can cause favism, or hemolytic anemia.
The red arils enveloping the seeds are also toxic to children
and can cause headaches (Basch et al., 2003). All parts of the
plant register low toxicity, but extracts administered
intravenously or intraperioneally in high doses can cause
death in laboratory animals (Gover and Yadev, 2004). Figure 6. Example of how M. charantia is marketed today
Due to its hypoglycemic effects, it has had great success as a as an herbal supplement. Rather than the traditional method
possible treatment for diabetes. However, this property can be of eating the whole vegetable, pharmaceuticals have
exacerbated when used in conjunction with other anti- condensed the plant and marketed it as convenient, easy-to-
diabetic medication. Two incidences of hypoglycemic coma swallow capsules. However, there is no mention of potential
and convulsions have been reported in children after side effects or a consultation with a certified physician.
consumption of bitter melon tea. Also, additive-glucose Courtesy of http://www.ayurvedatoday.org/karela.htm
CAM therapy, which can include botanical sources, dietary components of this versatile plant. The one grave deficit in
supplements, and mind-body medicine. Many diabetes this vegetable’s history is the lack of reliable, conclusive
journals suggest M. charantia reduces blood glucose but also clinical trials in humans. The studies thus far have been poorly
cautions its use due to lack of conclusive clinical studies executed and thus have not effectively showed that the
(Birdie and Yeh, 2010; Yeh et al., 2003; Krawinkel and Keding, research conducted in mice, rats, and rabbits can be translated
2006). Bitter melon can come in many forms. The to human subjects.
encapsulated extract dosage is usually 100-200 mg 2-3 times
Such conclusive research would be invaluable to current
daily or liquid form is 50-100 mL/d and the dry powder can
human health with the global increase in obesity, type 2
range from 3-15g daily (Najm and Lie, 2010).
diabetes, and cancers. Incorporation of this vegetable into the
In Traditional Chinese Medicine, M. charantia is dried, daily diet, with certain restrictions of course, and purification
powdered, and placed into capsules to make pills. This is the of the active compounds into medication could produce more
most common form that is available in the herbal remedy potent and efficacious resources in the future.
market (Covington, 2001). In local communities across the
globe that have a long history with bitter melon, it is
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Nepeta cataria L., Lamiaceae
Erika Burgess
Introduction
Nepeta cataria L. of the Lamiaceae family (also known as the
Labiatae family) is colloquially known as “catnip,” “catmint,”
“catnep,” “catwort,” or “field balm.” The genus name is derived
from the city of Nepi (historically referred to as Nepete) in
Italy and the species name from the late Latin word for cat,
“cattus” (Coffey, 1993). Catnip is generally thought of in
relation to its feline-attracting properties and the euphoric
effect that the plant induces on cats. However, the herb has a
long history of medical use, most prominently in treating
fevers, anxiety, and gastrointestinal ailments (Grognet, 1990).
The biological activities of catnip are generally attributed to
the chemical nepetalactone, a monoterpenoid, and related
stereoisomers (D’Amelio, 1999; Frohne & Pfander, 2005).
Although neither the herb itself nor its active compounds are
medically researched today, the compounds in N. cataria Figure 1. A flowering Nepeta cataria plant.
could have potential uses in insect repellants, including one (Source:http://companionplants.com/catalog/product_info.php?pr
for the malaria mosquito (Birkett, Hassanali, Hoglund, oducts_id=981
Pettersson & Pickett, 2011). These applications of the plant especially in the United Kingdom, and may now even be
can still relate, however indirectly, to human health extinct in Ireland (Stace, 2010). Catnip has been historically
prevention and treatment. cultivated in North America and is thought to have been
introduced to the continent by European settlement (Grognet,
1990). Today, it is particularly prominent in the United States
and Canada, located nearly everywhere in the States and the
Geography & Related Plants lower Canadian provinces, especially in the northeast and
Nepeta cataria L. (Figure 1) is a perennial herb that grows up north central states (Figure 2) (Sih & Baltus, 1987; Swerdlow,
to three feet in height. It is indigenous to most of Europe, as 2000). The plant grows in open fields and meadows and is
well as to Southwestern and Central Asia. It has been reported adept at growing in dry, drained areas such as along
that the plant was once much more common in some areas, roadsides, in waste lands, and in calcareous, rough soils
Figure 3. Nepeta cataria leaves. (Source:
http://www.missouriplants.com/Whiteopp/Nepeta_cataria_page.ht
Figure 2. Growth range of Nepeta cataria in the United ml)
States and Canada. (Source:
http://plants.usda.gov/java/profile?symbol=NECA2)
over 67 species are endemic to Iran (Domokos, Peredi, &
Halasz-Zelink, 1994; Zomorodian, et al., 2012). Given that N.
(Meuninick, 2008; Stace, 2010). One variation of the basic cataria is part of the Lamiaceae family, it is also more distantly
catnip plant is Nepeta cataria var. citriodora, or lemon catnip, related to many commonly used, aromatic culinary herbs such
which contains a higher level of the compound citronellal, as basil (Ocimum basilicum), mint (Mentha spicata), and thyme
giving this variety its distinct citrus scent (Baranauskiene, (Thymus vulgaris) (Duke, 1985).
Venskutonis, & Demyttenaere, 2003). The term “catmint” can
be used to describe the Nepeta genus as a whole, which
includes several other cat-attracting herbs related to N. Herbal Description
cataria such as dwarf catmint (Nepeta racemosa) and giant
Nepeta cataria L. has grey, quadrangular, erect stems with
catmint (Nepeta grandiflora). The different species of the
many branches and a downy texture (D’Amelio, 1999;
Nepeta genus are similar in leaf and flower structure and most
Grognet, 1990; Meuninick, 2008). The heart-shaped leaves
are aromatic. The genus is also extremely diverse; over 150 of
have a velvet-like quality to them; the blades have serrated
them are indigenous to temperate regions of Central Asia and
edges and are green-grey in color with a grey underside,
which often gives them a white appearance (Figure 3)
(Meuninick, 2008; Stace, 2010; Swerdlow, 2000). The small
flowers of the plant grow in large clusters (Meuninick, 2008).
The petals are usually white with purple spots and can also
have violet or purple hues (Figure 4) (Crellin & Philpott,
1990; Stace, 2010). The flowers have four stamens with red
anthers, which are shorter than the surrounding corolla
(Stace, 2010; Swerdlow, 2000). N. cataria blooms starting in
summer, from late June to September (Foster & Duke, 2000).
All parts of the plant have a mint-like odor. The leaves have a
sharp, bitter flavor that is also reminiscent of mint (D’Amelio,
1999; Grognet, 1990). A typical catnip plant will remain alive
for four years after planting; a plant dies after its seeds ripen
(Domokos, et al., 1994). The herb is typically pollinated by
bees including honey bees (Apis mellifera) and bumble bees
(Bombus spp.) (Sih & Baltus, 1987).
Traditional Uses
Non-medicinal Uses
Nepeta cataria L. has a long history of both medicinal and non-
Figure 4. A Nepeta cataria flower cluster (Source:
medicinal use. The herb is best known for its euphoria-
http://www.missouriplants.com/Whiteopp/Nepeta_cataria_page.ht
inducing effect in cats, producing a state resembling sexual ml)
excitement. Domestic cat owners have often grown the plant
as a stimulant treat for their pets or for use in cat toys. In
ancient Egypt, the plant was sacred to the cat goddess, Bast. cheeses, and soups in Iranian cuisine (Duke, 1985;
Because the “catnip response” is also shown in larger, wild Zomorodian, 2012).
cats, the essential oil of catnip has historically been used as In the 1960s, catnip began to be experimented with as a
bait for trapping bobcats and mountain lions (Duke, 1985; hallucinogen, though the outcomes are not well-documented
Swerdlow, 2000). The taste and smell of catnip has appealed (Swerdlow, 2000). N. cataria was sometimes used in
to humans as well as cats, however, due to its close relation to conjunction with or as a replacement for marijuana (Cannabis
other aromatic, culinary herbs. The aerial parts of the plant sativa). It could be mixed with tobacco or an alcohol tincture
have been used as a spice or flavoring, especially for sauces, of the herb could be sprayed on the tobacco and smoked,
which supposedly gives a stronger effect than smoking the leaf
alone. It is claimed that the effects of smoking catnip are were mentioned. The treatments mentioned in relation to N.
similar to the relaxing, euphoric “high” induced by smoking cataria around this time included those for gastrointestinal
marijuana; visual or auditory hallucinations also might occur ailments, uterine disorders, and nervousness (Crellin &
(Grognet, 1990). However, catnip is reported to be less potent Philpott, 1990). Before it temporarily fell out of use, catnip
and quicker-burning than marijuana, meaning more catnip was thought to induce fierceness in users; hangmen
would have to be consumed in order to conjure an effect reportedly chewed the root of the herb before being led to
equivalent to that of cannabis. Little mention of any their executions (Swerdlow, 2000). The supposed stimulating
hallucinogenic effects were reported before the 1960s and the effect of the plant’s root was opposite the sedative effects
findings are mostly based on case studies. Most individuals traditionally associated with catnip’s leaves and flowers
report uplifted moods after smoking N. cataria, as well as an (Grognet, 1990). By 1847, catnip was administered in the form
appreciation for music. Some researchers have suggested that of a tea in Europe, parts of Asia, and the Americas, where it
the effects of catnip as a recreational drug are more similar to was cultivated for its ability to calm infant colic (Swerdlow,
LSD than to marijuana (Jackson & Reed, 1969). 2000). The herb was also traditionally thought to help with
digestive issues, insomnia, headaches, and as a refrigerant
(Grognet, 1990).
Medicinal Uses
By the 1800s, catnip had become naturalized in America and
Aside from the herb’s obvious feline-entrancing qualities, was commonly mentioned in medical books (Crellin &
Nepeta cataria L. has been mentioned in medical texts since Philpott, 1990). Among Americans living in the Ozarks, leaves
the 16th century. The herb has been and still remains common were chewed to soothe toothache, and catnip tea was used as
in peasant gardens across Europe (Domokos, et al., 1994). a nerve tonic and to cure colds, hives, fevers, and stomach
Many uses were especially listed in early English literature; ailments. Dried leaves were often also smoked as respiratory
John Gerard, a British herbalist, mentioned “nep, catmint, and treatments (Duke, 1985). Besides its use by early colonists,
small catmint” in his 1597 herbal, claiming the plant had the herb was also used widely among different Native
deobstruent properties (Crellin & Philpott, 1990). The American tribes across the States for a variety of ailments.
frequent mentions of catnip were likely related to the fact that Table 1 shows a range of uses and preparations of N. cataria
teas made out of the N. cataria plant were popular in England traditional to several of these tribes; the use of the herb was
until black tea was introduced from China in the late spread across all parts of the United States throughout
seventeenth century. Nicholas Culpeper, an English scientist, different tribal regions. Among Native American groups,
prescribed catnip as a remedy for bruises, hemorrhoids, and catnip is commonly cited for its use as a febrifuge, a medicine
head scabs (Swerdlow, 2000). The herb was also used as an for children, and a general cold and cough remedy. The leaves
English folk remedy for inflammatory conditions (Prescott, and flowers are often prepared into a tea or other infusion,
Veitch, & Simmonds, 2011). However, around the time of the but other ways of preparation such as smoking the dried
eighteenth century in Europe, few writers mentioned catnip as leaves or topically using the leaves have also been reported
an herbal remedy and in the several accounts given, few uses (Moerman, 2009). The plant’s common use as a febrifuge
correlates to the plant’s use in the Menominee tribe as a Tribe (Cardinal Uses for N. cataria Traditional Preparations
diaphoretic. In Europe as well as the Americas, catnip was location in US) (if known)
mentioned for its ability to induce sweating without raising
the body temperature; this helps to disperse the body heat Iroquois (N, NE, Analgesic (headaches)
centr.) Antiemetic (from unknown
associated with a fever (Swerdlow, 2000). Throughout its use cause)
worldwide, catnip has been frequently used in the treatment Cold remedy
Tribe (Cardinal Uses for N. cataria Traditional Preparations Cough medicine
location in US) (if known) Febrifuge
Gastrointestinal aid
Laxative
Cherokee (S, centr.) Abortifascient Used in infusion Oral aid (excess salivation)
Antihelmintic Pediatric aid
Anticonvulsive Sedative
Throad aid
Cold remedy Mixed into a syrup with
Cough medicine honey
Shinnecock (NE) Antirheumatic Dried leaves are smoked
Dermatological aid (hives)
Menominee (N) Diaphoretic
Dermatological aid (boils, Used in infusion
Pulmonary aid Applied to chest for
swelling) Leaves applied to skin
Sedative pneumonia
Febrifuge
Ojibwa (N) Blood purifier
Raises body temperature Used in baths
Gastrointestinal aid (colic,
stomachaches) Used in infusion
Table 1. Traditional uses and preparations of Nepeta cataria
Pediatric aid in various Native American tribes (Moerman, 2009)
Sedative
Stimulant
Tonic
of infant colic and gastrointestinal issues (including diarrhea,
flatulence, and stomach cramps), often in the form of infusion,
Chippewa (N, NW) Febrifuge Concoction of leaves
as well as for bronchial and pulmonary conditions, fevers, and
insomnia (D’Amelio, 1999; Duke, 1985). The herb is
Delaware (N, Pediatric aid Used with peach seeds commonly mentioned for its supposed sedative effects in
centr.) humans (unlike the stimulant effect induced in felines) and
Keres (SW) Stimulant Used in baths for tiredness therefore has been used in easing headaches, menstrual
cramps, muscle spasms, anxiety, stress, and sleep disorders
Hoh (NW) Pediatric aid
(Meuninick, 2008). Catnip tea was once recommended as a
treatment for scarlet fever and smallpox (Duke, 1985).
Cosmetically, the herb can be mixed with other plants such as
wintergreen and chaparral in a concoction that is used to
soothe puffy eyes. The cooling effects of the herb have also
contributed to its use as an antidandruff treatment (D’Amelio,
1999).
Though N. cataria has been cited for use in the treatment of a
wide variety of conditions and ailments and became
widespread in America after colonization, the herb began to
be dismissed in the nineteenth century as a simple folk
remedy. The Dispensatory of the United States in 1836 noted
that catnip was used most often in domestic practices for colic,
amenorrhea, and anemia, but was not used in formal medicine
(Crellin & Philpott, 1990; Jackson & Reed, 1969). One source
quotes that, in 1847 Pennsylvania, the herb was a popular
medicine among “good ladies who deal in simples,” suggesting Figure 5. The molecule structure of nepetalactone, the
that the herbal remedy was used more often by uneducated primary active compound in Nepeta cataria. (Source:
homemakers rather than physicians or other healers (Coffey, http://www.creaturecomfortsinc.com/ThePetZone/CatnipInfo.htm
1993). )
Chemistry and Pharmacology Eisenbraun, 1967). Nepetalactone is found in various amounts

in all Nepeta species; some species also contain
The main constituents in Nepeta cataria L. are a non- epinepetalactone, a related compound with a structural
glycosidic iridoid, nepetalactone, and several related difference in one hydrogen group (Regnier, et al., 1967).
compounds, including nepetalic acid, nepetariaside, and Nepetalactone is believed to be the main cat-attracting
nepetol rosemarenic acid (D’Amelio, 1999; Frohne & Pfander, compound in N. cataria and is thought to induce the mild
2005). Nepetalactone (Figure 5) is a methylcyclopentane cooling and sedating effects in humans. It is synthesized from
monoterpenoid found in the essential oil of catnip, which can mevalonic acid and related compounds such as mevalonic acid
constitute up to one percent of the fresh, flowering tops of the phosphate; these precursors are also involved in the
plant (Downing & Mitchell,1974; Duke, 1985). The essential biopathways that synthesize terpenes and steroids (Downing
oil consists mostly of sesquiterpines and monoterpines & Mitchell, 1974). The plant contains other terpenoids often
(Heuskin, et al., 2008). Of the essential oil, up to 99% can be found in the Lamiaceae family, including carvacrol
nepetalactone, though many studies using gas (characteristic of oregano) and thymol (found in thyme)
chromatography have shown the nepetalactone content to fall (Duke, 1985). These monoterpenoids contribute to the
around 75% (Crellin & Philpott, 1990; Regnier, Waller & distinct aromas of the herbs. A monoterpenoid found
especially in N. cataria var. citriodora, or lemon catnip, is aphids as a pheromone during the sexual mating phase.
citronellal, which contributes to the lemony odor of the plant Because catnip is a common target for aphid attacks, it is
(Baranauskiene, et al., 2003). Several other compounds hypothesized that the plant produces this compound in order
recently isolated from the catnip plant have showed to play a to attract aphid predators in order to reduce the levels of
role in regulating inflammation. The caffeoyl phenylethanoid infestation (Kelly, 1996).
glycosides known as verbascoside and lamiuside A inhibit
The mechanism of action that results in the feline euphoria
calcineurin, a protein phosphatase which regulates the gene
related to N. cataria is relatively unknown. While cats
expression related to T cells in the human immune system.
sometimes ingest the leaves and stems of the plant, the “catnip
This process leads to decreased immune response and could
effect” can be induced simply by smell. The response to the
account for some of the traditional plant uses related to
herb’s aroma is characterized by actions similar to those
decreasing inflammation (Prescott, et al., 2011). The seed oils
shown in female cats in estrous; these displays include rolling
are also high in linoleic and linolenic acids, fatty acids that
on the ground, head shaking, rubbing the face and head on the
have antioxidant properties (Domokos, et al., 1994).
ground and plant (Figure 6), chewing, and scratching (Kelly,
1996). Although these actions resemble females in heat, male
Biological Activity cats also show these behaviors after being exposed to N.
Nepeta cataria L. displays biological activity in organisms

other than humans and cats. The essential oil of the plant has
been studied for its antimicrobial, antifungal, and antibacterial
properties. This effect is believed to be related to the high
concentrations of nepetalactone in the herb and its essential
oil. The essential oil has bacteriostatic and bactericidal effects
against Salmonella and Shigella species, Staphylococcus aureus,
and Escheria coli. (Zomorodian, 2012). The oil inhibits gram-
positive bacteria in lower concentrations than gram-negative
bacteria. Ants, cockroaches, Afro-tropical mosquitoes
(Anopheles gambiae and Culex quinquefasciatus, vectors of
malaria and West Nile virus, respectively), the brown ear tick
(Rhipicephalus appendiculatus), the red poultry mite
(Dermanyssus gallinae), the stable fly (Stomoxys calcitrans)
and the house fly (Musca domestica) have all been shown to be
repelled by the essential oil in N. cataria (Birkett, et al., 2011; Figure 6. A housecat exhibiting the “catnip response” to
Regnier, et al., 1967; Zhu, et al., 2009). Nepetalactone and Nepeta cataria. (Source: http://www.vaswim.org/wp/wp-
related compounds are released by certain species of female content/uploads/2011/04/cat_catnip2.jpg)
cataria (Palen & Goddard, 1966). The tendency for this Catnip oil, which mainly consists of nepetalactone, has shown
reaction to catnip is governed genetically; the response is a to increase sleeping time in rats as well. This may be related to
dominant autosomal trait found in about two-thirds of all the sedating effects of the compound which is evident in
domestic cats (Foster & Duke, 2000). This effect is said to be humans (Harney, Barofsky, & Leary, 1978).
similar to the effect of cannabis on cats. Similar activity is
found for female cats in response to the urine of tomcats,
which contains feline pheromones that may induce sexual Clinical Studies
receptivity in females. However, because the catnip response Few clinical studies have been performed with Nepeta cataria
is also characteristic of male cats, it cannot be assumed that L. or its active compounds, most likely due to the herb’s
nepetalactone and related compounds are mimicking these declared status as a home remedy rather than a medical
pheromones (Mabberley, 2008). The effects of N. cataria in treatment. Rather than testing the biological effects of catnip
male cats do not result in characteristic sexual excitement; in humans themselves, one study investigated the insect-
male cats show no mounting or aggression when presented repellent effects of two isomers isolated from the essential oil
with a cat-sized object after exposure to catnip (Palen & of catnip, E,Z- and Z,E- nepetalactone, along with whole catnip
Goddard, 1966).These catnip-induced behaviors are also oil. In this study, using human volunteers, the biting activity of
evident in larger members of the cat family. Lions and jaguars Aedes aegypti, the red eye Liverpool mosquito, was measured.
have shown high excitability in response to catnip, yet The effects of nepetalactone were compared to effects from
bobcats, tigers, and cougars showed little characteristic N,N-diethyl-3-methylbenzamide (the common, yet reportedly
response. This same study also showed that the catnip toxic, insect repellent, deet) and chiral (1S,2S)-2-
response is higher in these larger felines around reproductive methylpiperidinyl-3-cyclohexene-1-carboxamide (a new
age than older or immature cats. Therefore, the catnip repellent isolated by the same lab, known as SS220). Repellant
response differs not only with species of feline, but also with activity was tested both in vitro, using human blood, and in
relative age of an individual (Hill, et al., 1976). vivo using skin treatments with each chemical on six human
In addition to the cat family, N. cataria has shown to induce volunteers. Catnip oil and both forms of nepetalactone were
excitatory effects in male rats (Frohne & Pfander, 2005). The shown to repel over half of the mosquitos (measured by the
penile erections of rats have been shown to increase after the proportion of mosquitoes not biting) and were equally as
animals are fed catnip leaves. However, the overall activity of effective as deet. The new compound SS220, however,
the rats reduces after ingesting N. cataria, except for a slight repelled more mosquitoes than any catnip extract or deet
increase in sexual activity (Bernardi, Kirsten, Lago, Giovani, &, (Chauhan, Klun, Debboun, & Kramer, 2005). These data
Massoco, 2011). This differs from the feline response in that suggest catnip oil and its extracts as a safe and effective
there is a direct effect on the sexual organs of the animal, yet alternative to deet as a topically-applied insect repellent.
little effect on overall euphoric behaviors. It is hypothesized Aside from these possible uses as a mosquito deterrent,
that sexual arousal is increased due to N. cataria’s action on however, the United States Pharmacopeial Convention has
the dopaminergic system of the rat (Bernardi, et al., 2011). declared that the plant has no therapeutic value other than
that of an aromatic (Coffey, 1993). Overall, N. cataria has wild. In these mountainous regions, the plant is also still used
received little attention from the medical community, despite as a remedy for colds, skin infections, anxiety, and digestive
evidence for its antimicrobial and antibacterial activities issues (Duke, 1985). However, because of its lack of medical
(Crellin & Philpott, 1990). attention, the herb is mostly used and researched for its non-
medical properties, such as the insect repellent compounds
found in its essential oil and its popularity as a treat and toy
Contraindications for domestic cats.
It is recommended that pregnant women do not use Nepeta
cataria L. treatments (Meuninick, 2008). Case studies have
reported headache and a distorted sense of reality after Discussion
smoking catnip; however, this was in relation to catnip as a Most modern research on Nepeta cataria L. has focused on
hallucinogenic drug and not as a medical treatment (Jackson & studying the effects of compounds in the plant on non-human
Reed, 1969). Few side effects to using catnip have been animals and insects. Although the herb has been long-
reported, likely due to the fact that the plant only has a mild abandoned in way of its medical legitimacy, catnip still has
effect on humans in regular doses. The LD-50 of catnip oil is potential to make an impact on human health. The repellant
reported to be around 1300 mg/kg, meaning it would require effect of catnip’s essential oil towards several species of
ingestion of over 90 grams of pure essential oil to kill the mosquitos and flies could help slow the spread of diseases
average human (Harney, et al., 1978). The FDA has classified carried by these insects, including malaria, West Nile virus,
N. cataria as an “herb of undefined safety” (Duke, 1985). and filariasis. Using the plant as a lure for wild cats may not
only save human lives by relocating these big cats from
dangerous areas, but may also assist in the conservation and
Current Use in Allopathic and CAM Therapies protection of these great felines. The herb has also shown
Nepeta cataria L. is still used in alternative medicine promise in stopping the growth of or killing certain bacteria,
communities as a natural remedy for many of its traditional fungi, and microbes. This may be applicable in future research
uses. Catnip is sold in many countries worldwide in its whole for use as a topical or ingestible treatment, although the drug-
plant form, as dried leaves and flowers, and in extracts of its resistant capabilities of catnip essential oil have not been
essential oil. The plant is still used as an allopathic treatment researched. Even though N. cataria may not currently have
for fevers and headaches because of its cooling, sedating, and much of a future in medical research, the plant can still impact
mild analgesic effects (D’Amelio, 1999). The tea has been used human health as it has done historically, whether through its
to stimulate the gallbladder and digestion. Catnip is mixed effects on other organisms or through its use as a mild home
with elderberry to treat infections and used in tincture for remedy.
arthritic joins when applied topically (Meuninick, 2008). The
leaves are still chewed as a mild painkiller for toothache,
especially in Appalachia where it grows abundantly in the
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nfo.htm
Panax ginseng C.A. Mey., Araliaceae
Mengshi Dai
Introduction
Panax ginseng C.A. Mey, otherwise known as Asian ginseng or
Chinese or Korean ginseng, is an important medicinal plant in
the Araliaceae family (Duke, 2012). Asian ginseng is called ‘ren
shen’ (man plant) in Chinese, due to the root’s forked shape
which resembles a man’s body. The genus Panax, derived from
the Greek word ‘panakos’ (panacea) meaning ‘all healing’,
refers to the many inclusive curative properties attributed to
this plant (Swerdlow, 2000). Not to be mistaken for its
American counterpart (Panax quinquefolius L.) or Siberian
ginseng, (Eleutherococcus senticosus (Rupr. ex Maxim.)
Maxim.), which belong in the same family, Asian ginseng is
solely native to China and Korea. However it is also cultivated
in Japan, Russia, and parts of North America. Asian ginseng
has been used for centuries in Asia, but was introduced to the
West in the 1700s by Father Jartroux who advocated its use in
the treatment of fatigue, pleurisy, and convalescence.
Ginseng’s primary constituents are ginsenosides and
panaxans. Ginsenosides stimulate the cardiovascular and
central nervous systems to enhance physical and mental
performance. Panaxans are polysaccharides derived from
ginseng extract which lower blood sugar, strengthen the Figure 1. Panax ginseng. (Source: http://foodspeople.com/wp-
immune system, and treat diabetes (Swerdlow, 2000). Ginseng content/uploads/2011/05/ginseng1.jpg)
also has antioxidant, antiaging, and appetite-stimulating
properties. In addition, the Chinese and Koreans use this plant Botanical Description
for almost every ailment ranging from sexual potency to colds
and even to cancers in the forms of teas, tonics made from Panax ginseng (Figure 1) grows on mountainous or hilly
decoctions, and infusions of the roots or powdered extracts forest slopes in the Manchurian region of China, and North
(Harriman, 1973). Korea. It thrives in small patches in climates with cold and dry
air, especially in wooded regions where the shady forest
Figure 3. Fruit of Panax ginseng. (Source:
http://www.herbs.org/greenpapers/panaxq.jpg)
rare and elusive, contributing to extremely high prices for

roots of good quality. The plant is a perennial shrub, growing
up to two and a half feet tall with an erect stem and a single
cluster of greenish yellow or pink flowers in groups of 15 to
Figure 2. Stem, Leaves, and Flowers of Panax ginseng. 30 shooting up each spring. The leaves are thin and finely
(Source: http://i01.i.aliimg.com/photo/v0/269775813/ serrated, clustered in groups of three to five, which grow up to
plant_extract_panax_ginseng_P_E_ginsenoside.jpg) eight inches long (Figure 2). The fruits are scarlet, smooth,
and glossy (Figure 3). The root is cream-colored or white,
resembling a parsnip with rootlets branching in the form of a
canopy offers protection from wind, rain, and sun. Asian human body shown in Figure 4 (hence the indigenous name
ginseng grows among hardwoods rather than conifers, and ‘ren shen’, or man plant). Ginseng root extracts and tea have a
often grows together with basswood (Tilia tomentosa) and distinctive sweet taste mixed with underlying bitter tones.
royal paulownia (Paulownia tomentosa) (Harriman, 1973). In There is little or no odor and the root is starchy with small
addition, Asian ginseng requires rich, moist soil and around amounts of resin, volatile oils, and the medicinally active
five to seven years to mature fully (Swerdlow, 2000). These compound, panaquilon (Harriman, 1973).
difficult growing requirements cause ginseng to remain quite
sexual amulet to increase sexual potency. Folklore has it that
an emperor once paid $10,000 to buy a particularly shapely
root. To be able to afford fine ginseng was sign of wealth and
commanded respect because it was used by wealthy Oriental
aristocrats to keep concubines satisfied. Even now, men take
ginseng before and after intercourse to enhance performance
and to replenish his sapped energy and sexual potency after a
taxing encounter (Harriman, 1973). According to Jartroux, the
man who introduced Panax ginseng to the West, ginseng was a
necessity in all the prescriptions set by the Chinese physicians,
and only the Emperor had the right to collect its roots
(Swerdlow, 2000). Ginseng was, and still is, a scarce,
expensive, and highly prized possession.
Religious Uses
Figure 4. Root of Panax ginseng. (Sources: During the 18th and 19th centuries, several reports of ginseng
http://www.bouncingbearbotanicals.com/images/ginseng_root.jpg, found their way back to America from missionaries and
http://www.buzzle.com/img/articleImages/489358-262329-53.jpg) officials serving in Asia. They discovered that the Chinese and
Koreans attributed stimulating and restorative properties to
Traditional Uses Asian ginseng, and that this plant has been held in high esteem
for centuries. A report in 1900 from a president of one of the
Increased sexual potency largest trading companies in the Orient said that the Chinese
Panax ginseng has been used in China for thousands of years. used ginseng for thousands of years for medicinal and
It was documented for its life-prolonging effects in one of the religious purposes. He also elaborated that its use has been
ancient medical texts, Shen Nong Ben Cao Jing (Shen Nong’s firmly established in their religion for generations. Due to its
Materia Medica) as early as 502-557 in the Liang Dynasty seemingly supernatural powers, it was also worshipped
(Yun, 1996). Aside from its inherent medicinal properties, (Harriman, 1973). Owing to its long history of use, several
ginseng was used to increase potency. In Chinese medicine, folklores exist about ginseng. One tale from the 6th century
health is holistic. The balance of yin (feminine attributes) and attributes ginseng with human qualities. One day, a general
yang (masculine attributes) and humans with nature was coming back from war stopped to stay at a stranger’s house to
essential to good physical, mental, and spiritual health. rest. That night, he heard the cries of a man coming from a
Ginseng was considered the most “yang” of all the herbs. As close distance. The strange cries continued for several nights
such, true believers wore a well-shaped ginseng root as a with the entire house searching for the source of the voice. At
last, the general followed the voice to a distance of about half a Tuberculosis Dysentery
kilometer from behind the house, and there he found a single Fitful coughs Enuresis
ginseng plant. He dug until the root was exposed, and was Nausea Gout
startled by its human-like appearance. In fact, it had been this Diabetes Suppurating sores
root that had been calling out in a man’s voice over the Thirst accompagnied by dry Degeneration of the kidneys,
skin and flushed throat characterized by continual thirst,
previous nights (Harriman, 1973). Stories where dreams or polynuria, and pain in renal area
voices led to the discovery of wild patches of ginseng are Indigestion Rheumatism in lower limbs
common in China. The people believe that if someone finds Diarrhea Sexual potency
wild ginseng, they will be blessed and luck and fortune will Table 1. Conditions and diseases involving the use of
come their way (Harriman, 1973). Ginseng in traditionally prescribed remedies in China
(Harriman, 1973).
Medicine
tools against stomach and bowel pains as well as gas, coughs,
Panax ginseng remains famous in the East and West for its
and chest and lung problems (Harriman, 1973). Aside from
numerous and ubiquitous health benefits, ranging from colds
Shen Nong Ben Cao Jing, ginseng medicinal recipes are found
to cancers and everything in between. Even now, Chinese
in additional ancient texts in China and Korea, such as Ben Cao
people believe in corresponding ginseng body parts to the
Kang Mu and Pang Yak Hap Pyung (Harriman, 1973). These
actual limbs that are hurting. For example, taking medication
formulas serve as guides and healers adapted them to fit the
derived from part of the root that looks like an arm will be
specific cases of their patients. Some examples of these
beneficial to that individual’s ailing arm (Harrison, 1973). The
medicinal recipes include a tonic decoction using equal parts
root was, and still is, often used as a tonic. One can chew a bit
of several herbs, including ginseng; a tincture of ginseng using
of root or take a spoonful of extract each morning on an empty
powdered ginseng root fermented with rice and yeast; date
stomach to help the body gain vigor and resilience.
and ginseng pills made by pounding together fresh ginseng
Preparation of ginseng tonic involves ginseng extract, which is
root with dates and others plants. One Cantonese ginseng
produced by soaking the root in water and evaporating the
tonic uses ginseng in combination with several other
solution. The extract is then kept in a tightly sealed container,
ingredients to treat loss of vitality, loss of appetite, fever,
and no metal except silver may come into contact with it
weakness of legs, jaundiced appearance, and laborious
(Harriman, 1973). Ginseng extract can be used alone or in
breathing. It is also used to strengthen the spleen and stomach
conjunction with several other ingredients, which will
and to increase yang forces. Since ancient times, ginseng has
enhance the individual healing properties of each drug. Most
been used as a panacea, treating many serious illnesses. A list
Chinese medicines are decoctions or infusions of various
of conditions and diseases involving the use of ginseng in
ingredients, and certain plants are frequently used with
traditionally prescribed remedies in China is shown in Table
ginseng. These herbs are ginger, licorice, fou ling, cassia, and
1, and in Korea is shown in Table 2 (Harriman, 1973).
huang ch’i. Taken together, these decoctions are powerful
Acute gastritis Endometritis
Infant diarrhea Nipple infection resulting from
nursing
Excessive thirst accompanying fever Suppuration
Chronic cough Furuncle
Anemia Toothache
Alcoholism Malaria
Abnormality of the blood Hysteria
Table 2. Conditions and diseases involving the use of
Ginseng in traditionally prescribed remedies in Korea
(Harriman, 1973).
Figure 5. Chemical Structures of Ginsenoside (A) 20(S)-
Chemistry and Pharmacology Rg3 and (B) 20(R)-Rg3. (Source:
http://ars.sciencedirect.com/content/image/1-s2.0-
Panax ginseng has many constituents. The primary ones are
S0006295211009555-gr1.jpg)
ginsenosides (Figure 5), which stimulate the cardiovascular
and central nervous systems to enhance physical and mental
performance. Panaxans, polysaccharides from ginseng Biological Activity
extracts, are also important compounds. They lower blood In Vitro
sugar, strengthen the immune system, and treat diabetes
(Figure 6) (Swerdlow, 2000). Ginsenoside-RB-1 is present in Many studies have been conducted evaluating the potency of
5000 ppm in the ginseng root, offering antiamnesic, antistress, Panax ginseng extracts on cancer. One study evaluated the
and antipsychotic activities. Ginsenoside-RB-2 is present in cytotoxic potency against a variety of cancer cells by
2000 ppm in the root and has calcium-antagonist and using ginseng ethanol extracts (RSE), protopanaxadiol
hypocholesterolemic properties. Ginsenoside-RC is present in (PPD/PPT)-type ginsenosides fractions, and their
3000 ppm in the roots and is also a calcium-antagonist. Other hydrolysates. Cytotoxic potency of the hydrolysates of the
constituents in the root with biological activity include extracts and ginsenoside fractions was much stronger than the
ascorbic acid, beta-carotene, beta-sitosterol, calcium, original control. Using two synthesized derivatives of the
magnesium oleonolic-acid, pathothenic acid, and selenium. fractions and the original ginsenosides, a comparative study
These compounds contain analgesic, antiaging, anticancer, and was performed on various cancer cell lines. The results
antibacterial properties. They are also anticarcinomic, suggest that compounds with less polar chemical structures
antiarrythmic, antiarthritic, antiaggregant, and antiangial. have more cytotoxic activity towards cancer cells, and are
Many more chemical compounds exist in the plant in lower involved in suppressing tumors and mediating cell growth
concentrations, and a full list of the constituents is shown in (Dong et al., 2011).
Table 3 (Duke 2012).
Plant
Chemicals/Molecules ppm Plant Part Chemicals/Molecules ppm Part Chemicals/Molecules ppm Plant Part
Carbohydrates 834000 Root Ginsenoside-RG-1 2000 Root Chromium 11 Root
Fiber 72000 Root 15000 Leaf Panthothenic-acid 6.6 Root
ASH 50000 Root 2000 Flower Riboflavin 1.8 Root
Fat 17700 Root 200 Fruit Thiamin 1.7 Root
Calcium 2880-4140 Root Ginsenoside F-1 4000 Leaf Biotin 0.9 Root
Ginsenoside-RB-1 5000 Root Ginsenoside-F2 2000 Leaf Ascorbic Acid Root
2000 Bud Ginsenoside-F3 2000 Leaf Beta-Carotene Root
1000 Leaf Carbon-disulfide 1500 Root Beta-Flemene Root
Ginsenoside-RB-2 2000 Root Choline 1000-2000 Root Beta-Sitosterol Root
4000 Leaf Panaxynol Root Beta-Sitosterol Glucoside Plant
Camptesterol-6'-
2000 Flower Water 788000 Root linolenylglucoside Root
Camptesterol-6'-
200 Fruit Protein 109000 Root linolenylolglucoside Root
Camptesterol-6'-
Ginsenoside-RB-3 50 Root Disaccharides 33000 Root oleylglucoside Root
Camptesterol-6'-
Ginsenoside-RC 3000 Root EO 500 Root palmitylglucoside Root
2430- Camptesterol-6'-
2000 Flower Potassium 10700 Root stearylglucoside Root
2000 Leaf Magnesium 481-1950 Root Citric Acid Root
1000 Fruit Iron 180 Root D-Fructose Root
Heptadeca-1-EN-4,6-
Ginsenoside-RD 2000 Root Dien-3,9-Diol 150 Root D-Glucose Root
15000 Leaf 2-Glucoginoside-RF 50 Root Fumaric Acid Root
2000 Flower Zinc 27 Panaxene Root
1000 Fruit Aluminum 22 Root Panaxic Acid Root
Ginsenoside-RE 2000 Root Manganese 19-180 Root Panaxin Root
15000 Leaf Tin 16 Root
25000-
60000 Fruit
28000 Flower
Table 3. List of active chemicals and biological molecules in ppm in Panax ginseng (Duke 2012).
Another study was conducted on the immunological effects of separated into fractions. Preliminary immunological tests
ginseng on cells. Water-soluble ginseng oligosaccharides suggest that WSGO were potent T and B-cell stimulators and
(WSGO) were obtained from extracts of ginseng roots and
could be taken to achieve immortality (Harriman, 1973). In a
modern experiment, the effect of fermented Panax ginseng
extract (GINST) on oxidative stress and antioxidant activities
in major organs of aged rats was studied. Oxidative stress
throughout life is the major cause of aging. The study found
that administration GINST to aged rats resulted in increased
activities of superoxide dismutase, catalase, and glutathione
peroxidase as well as levels of ascorbic acid and α-tocopherol.
Levels of malondialdehyde, aspartate aminotransferase, and
Figure 6. A Panaxoside in Panax ginseng. (Source: urea were lowered, on the other hand. These findings indicate
http://actanaturae.ru/article.aspx?id=190) that ginseng extract can decrease oxidative stress and age-
related disorders due to free radicals (Ramesh, 2012).
Another research study also showed ginseng to possess
were effective towards lymphocyte proliferation (Wan et al., antioxidant effects. The ginsenoside RG3 inhibited Cy-induced
2011). oxidative stress by increasing levels of catalase and
superoxidase dismutase while lowering activities of xanthine
oxidase and nitric oxide (Wei et al., 2012).
In Vivo
So far, there has been no research supporting issues of the
Research has shown Panax ginseng extracts, specifically
development of drug resistance. Ginseng is mainly taken as a
ginsenosides, have a positive effect on lowering hypertension
‘bu yao’ and ‘bu yin,’ which are herbs or plants used to
in rats. The extract stimulated nongenomic Akt-mediated
enhance and nourish the body (Guo, 1961). Even when
endothelial NO synthase (a regulator of systematic blood
ginseng extracts are used to target biological receptors in the
pressure) activation. It also enhanced NO production and
body, they are not used to fight microbiological agents, which
vessel wall thickening, and alleviated hypertension in
is why there have been no instances documenting drug
hypertensive rats (Hong et al., 2012). Ginseng is also proven to
resistance to ginseng.
protect against influenza. One study shows that mice infected
with the H1N1 virus that were treated with ginseng
polysaccharides (GP) had higher survival rates than the Clinical Studies
control mice. Mice exposed to GP had lower levels of lung viral
titers and inflammation (Yoo et al., 2012). Ginseng can also Although Panax ginseng has been used for thousands of years
suppress asthma through the inhibition of lung inflammation for its obvious health benefits, not many controlled clinical
by the ginsenoside RG-II (Jung et al., 2012). studies have been carried out. One study, however,
investigates experimental and epidemiological evidence of
One traditional use of ginseng was for the purpose of cancer-preventive effects of ginseng on humans. The
antiaging. In ancient China, people used to believe ginseng relationship between ginseng consumption and cancer was
evaluated by interviewing 905 human pairs of case and what is reducing cancer risks. However, further studies need
control subjects matched by various factors, such as age, sex, to be carried out to support this theory and to identify
and date of admission to the hospital. Ginseng extract and unknown constituents that may have anticarcinogenic effects
powder were more effective at fighting and reducing cancer (Yun et al., 1996).
than fresh sliced ginseng, ginseng juice, or ginseng tea (Yun et Aside from reducing cancer, ginseng has also been shown to
al., 1996). lower hypertension in humans. One study compared blood
A later experiment was carried out to further study the effects pressure from two groups of adults. One group took 200 mg
of types of ginseng products that have the most cancer- daily extract of ginseng and the other group took 200 mg daily
prevention. The study also investigated the duration of of the placebo. The study showed that taking ginseng extract
ginseng consumption, types of preventable cancers, and effect reduced blood pressure by 5 mm Hg in two hours after
of ginseng on cancers related to smoking. Ginseng intake was ingestion (Caron et al., 2002). There are also studies of
found to decrease risk of cancer and there was an inverse ginseng on diabetes. Although used traditionally to treat this
relationship between cancer risk and frequency and duration disease, there are mixed results from experiments regarding
of ginseng intake.The longer and more often an individual its effect on diabetes. Some studies have found ginseng extract
ingests ginseng, the lower risk of developing cancer. There to reduce diabetes while others did not produce conclusive
was an effect on lung, lip, oral, and liver cancer, but no effect evidence. A study investigating the effect of red ginseng
on breast, uterine cervix, or thyroid gland cancers. With (heated Panax ginseng) on type 2 diabetes did not yield
regards to smokers, cancer of the lung, lip, and oral cavity supporting data for the effectiveness of red ginseng on glucose
decreased as opposed to smokers who did not intake ginseng control (Kim et al., 2011). Other studies investigating ginseng
extract. These findings show that ginseng intake can decrease and cardiovascular illness also produced mixed conclusions.
cancer at various sites (Yun et al., 1996) One experiment showed taking ginseng extracts did not lower
deaths related to cardiovascular disease, but did decrease
The mechanism for this anticancer effect is still not
mortality overall (Yi et al., 2009). Although the results were
understood. However, it is hypothesized that saponins are the
not definite, this study supports the holistic practice of taking
active components of ginseng, giving this plant its
ginseng to enhance and nourish the body rather than to treat
anticarcinogenic effects. Saponins have been shown to have
specific diseases (Guo 1961).
antimutagenic activity, growth inhibition activity against
several mouse tumor cells lines, growth inhibition of human Like most medicinal plants, clinical evidence of ginseng
ovarian cells, and immunomodulating activity in mice. efficacy in treating various diseases are contraindicating and
Polysaccharides, another main active constituent in ginseng, sometimes produce no conclusive evidence in the benefits of
have anticomplementary activity, reticuloendothelial system- ginseng intake. However, this problem is mostly due to the
potentiating activity, and alkaline phosphatase-inducing scarcity of well-designed, randomized, and controlled clinical
activity. Also, polyacetylenes extracted from ginseng have trials rather than to any problems related to the plant
been shown to have cytotoxic activity. It is reasoned that the (Karmazyn et al., 2011).
synergy of the combination of these different constituents is
Contraindications syndrome (which can lead to arrhythmias) during periods
when she was consuming large amounts of ginseng (Torbey et
Harriman states in 1973 that no studies so far have shown any
al., 2011). Another report of an elder man developing
toxicity related to Panax ginseng intake. In fact, of all the
bradyarrhythmia after prolonged exposure to ginseng (Liao et
research done on ginseng, not one has shown even the
al, 2011) also calls into question the potential toxicity of
slightest deleterious side effect of this gentle “Queen of the
ginseng.
herbs” (Harriman, 1973). Toxicology and carcinogenesis
studies of ginseng were made in rats, mice, and other
microbes. Genetic toxicology studies were performed in Current Use in Allopathic and CAM Therapies
Salmonella typhimurium, Escherichia coli, and mouse
peripheral blood erythrocytes, as well as on live mice and rat The current uses of Panax ginseng have not changed much
subjects. The mice and rats all survived in 2-week, 3-month, from the thousand-years-old traditions of the ancient people.
and 2-year studies. No increases in the incidences Ginseng is one of the most important herbs used in traditional
of neoplasms or nonneoplastic lesions were attributed to the Chinese medicine. According to a study asking elderly Chinese
administration of ginseng. Almost 30 years later, in modern patients in America to list their medications, ginseng was
studies contradictions exist in data regarding ginseng toxicity. listed as a home remedy benefitting the lungs and spleen, used
In a genetic toxicity study, ginseng was not mutagenic in against weakness with chronic illnesses, vaginal bleeding,
either of the two independent bacterial mutagenicity assays. diabetes, and palpitations (Guo, 1961). Ginseng is still used by
Under the conditions of these 2-year studies, there was no modern people to fight colds and chronic illnesses, amongst
evidence that ginseng was carcinogenic in male or female rats many other traditional uses. The preparations of decoctions
(National Toxicology Program, 2011). and tonics have not changed since earlier times. The roots are
still soaked in water then kept in an airtight container for later
However, another study found that Rg3, a ginsenoside, use. Ginseng roots are still being sought after, and prices on
suppresses normal physiological responses in vitro and leads the market vary according to the quality. Fine ginseng costs
to vascular remodeling in rats, which is surprising concerning many times more than rougher forms. Eastern people regard
ginseng’s proven protective effects on vascular function the root shape (how closely it resembles a man) as the
(Karmazyn et al., 2011). Potential embryotoxic effects exist for defining factor in quality while Westerners look for
mice embryos that were directly exposed to the Re ginsenoside content. Table 4 shows the difference in prices of
ginsenoside, but no side effects were found in embryos various grades of ginseng. Asian ginseng costs more than
exposed to the Rc ginsenoside (Chan et al., 2004). In general, American or cultivated ginseng. Ginseng is a highly priced and
ginseng has relatively few adverse effects although this could popular root that has spread from Asia to the Western
be due to low reporting instead of low incidences (Karmazyn hemisphere. Even in the United States, all oriental drugstores
et al., 2011). The other recorded side effects were provided carry the root or extracts of it. The harvesting and processing
mostly through case reports and were not conclusive data of Korean and Chinese ginseng is done entirely under
taken from controlled experiments. A female without supervision and the seal on packaged products ensures the
cardiovascular risk factors reported developing long QT
Grade Price (per Catty) ginseng extract on cancer and tumor cells are especially
Chinese Wild Imperial $5000.00 exciting, with studies documenting favorable results
Korean and Chinese Red $26.50 supporting the anticancer properties of this herb. Research
Korean White $196.50 data is favorable in the use of ginseng as a possible herb
American Wild $133.30 against cancer, and future anticancer drugs containing ginseng
Japanese and American Cultivated $36.60 is possible. However, the pathways in which ginseng suppress
Table 4. 1971 Hongkong wholesale prices of ginseng cancer still remain to be elucidated. The main theory involves
according to grades (Harriman, 1973). the synergy created by the various components acting
together although this hypothesis has not been proven yet.
Although new studies are emerging in the potential adverse
identity of this herb. Whole roots are shipped to the US in
effects of ginseng, these cases are few and far between.
boxes weighed in cattys, with one catty equal to 1.33 lbs.
Ginseng has been used for over two thousand years as a
There have been many attempts (now successful ones) to
medicinal plant, and traditional techniques in preparing
cultivate this precious herb outside of its native Chinese and
ginseng decoctions remain almost unchanged to this day.
Korean forests, in America, Japan, and Russia. The popularity
Ginseng acts as a panacea, restores energy, and nourishes the
of this herb maintains the use of tonics and decoctions found
body. In addition, its antihypertensive and anticarcinogenic
in traditional Chinese medicine and herbal teas, and powdered
properties are most exciting, as these can be utilized to treat
forms can be taken as drugs in the form of capsules
chronic diseases for which Western medicine still lacks a cure.
(Harriman, 1973).
The potential for the active constituents to be made into drugs
is high and favorable, as in vivo, in vitro, and clinical studies
Discussion continue to support ginseng’s various positive effects on
health.
Panax ginseng has been an important plant in the treatment of
a broad range off diseases and illnesses since ancient times.
Today, it continues to be one of the leading herbs used in References Cited
traditional Chinese medicine. Its active biological constituents
Caron, M. F., Hotsko, A. L., Robertson, S., Mandybur, L., Kluger, J., &
include various ginsenosides and polysaccharides. Research White, C. M. (2002). Electrocardiographic and hemodynamic
has been done on this herb to classify its active constituents effects of Panax ginseng. [Clinical Trial Randomized
on biological pathways and diseases, with results showing Controlled Trial Research Support, Non-U.S. Gov't]. Ann
antihypertensive, anti-inflammatory, and anti-carcinogenic Pharmacother, 36(5), 758-763.
effects. As with the use of all plants and herbs, well-controlled
Chan, L. Y., Chiu, P. Y., & Lau, T. K. (2004). Embryotoxicity study of
and effective studies are few in number. Further research still ginsenoside Rc and Re in in vitro rat whole embryo culture.
needs to be made in clinical trials, as well as continued in vitro Reprod Toxicol, 19(1), 131-134. doi:
and in vivo studies. The preventive and curative effects of 10.1016/j.reprotox.2004.06.001
Dong, H., Bai, L. P., Wong, V. K., Zhou, H., Wang, J. R., Liu, Y., . . . Liu, L. Lee, J. Y., Lim, K. M., Kim, S. Y., Bae, O. N., Noh, J. Y., Chung, S. M., . . .
(2011). The in vitro structure-related anti-cancer activity of Chung, J. H. (2010). Vascular smooth muscle dysfunction and
ginsenosides and their derivatives. Molecules, 16(12), remodeling induced by ginsenoside Rg3, a bioactive
10619-10630. doi: 10.3390/molecules161210619 component of ginseng. [In Vitro]. Toxicol Sci, 117(2), 505-
514. doi: 10.1093/toxsci/kfq201
Duke, J. (n.d.). Chemicals and their Biological Activities in: Panax
ginseng C. A. MEYER (Araliaceae) -- Chinese Ginseng, Liao, W. I., & Tsai, S. H. (2010). Letter regarding bradyarrhythmia
Ginseng, Korean Ginseng, Oriental Ginseng. GRIN National caused by ginseng in a patient with chronic kidney disease
Genetic Resources Program. Retrieved March 9, 2012, from response. American Journal of Emergency Medicine, 28(8),
http://www.ars-grin.gov/cgi-bin/duke/farmacy2.pl 978-979. doi: Doi 10.1016/J.Ajem.2010.07.003
Guo, Z. (2000). Ginseng and aspirin : health care alternatives for Nag, S. A., Qin, J. J., Wang, W., Wang, M. H., Wang, H., & Zhang, R.
aging Chinese in New York. Ithaca, N.Y.: Cornell University (2012). Ginsenosides as Anticancer Agents: In vitro and in
Press. vivo Activities, Structure-Activity Relationships, and
Molecular Mechanisms of Action. Front Pharmacol, 3, 25.
Harriman, S. (1973). the Book of Ginseng. New York: Pyramid Books.
doi: 10.3389/fphar.2012.00025
Hong, S. Y., Kim, J. Y., Ahn, H. Y., Shin, J. H., & Kwon, O. (2012). Panax
Ramesh, T., Kim, S. W., Sung, J. H., Hwang, S. Y., Sohn, S. H., Yoo, S. K.,
ginseng Extract Rich in Ginsenoside Protopanaxatriol
& Kim, S. K. (2012). Effect of fermented Panax ginseng
Attenuates Blood Pressure Elevation in Spontaneously
extract (GINST) on oxidative stress and antioxidant
Hypertensive Rats by Affecting the Akt-Dependent
activities in major organs of aged rats. [Research Support,
Phosphorylation of Endothelial Nitric Oxide Synthase. J Agric
Non-U.S. Gov't]. Exp Gerontol, 47(1), 77-84. doi:
Food Chem, 60(12), 3086-3091. doi: 10.1021/jf204447y
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. Kang, S. M. (2012). Protective effect of ginseng
Papaver somniferum L., Papaveraceae
Ben Jarvis
Introduction
Papaver somniferum L., commonly known as the opium poppy
or the poppy plant, belongs to the family Papaveraceae. The
opium poppy is one of the most well known plants because of
its many uses. It has a long history throughout the world as
being one of the most useful as well as one of the most abused
plants. In fact, opium is perhaps one of the oldest narcotics
known to man with evidence of its use found in limestone
caves in Spain from about 55,000 years ago (Schultes 1995).
The earliest writings of the opium poppy date back to about
4000 B.C., where the Sumerians refer to it as the “joy plant”
(Lewis 2003). The opium poppy has a range of uses from the
commonly used food ingredient, the poppy seed, to one of the
most effective pain relievers, morphine. Other common drugs
derived from the opium poppy include codeine, noscapine,
thebaine, and papaverine. Because of the addictiveness and
abuse caused by this plant’s effect on the central nervous
system, there has been a lot of conflict and controversy over
its growth and cultivation. In fact, the Opium Wars that took Figure 1. The basic parts of the opium poppy are shown
place between England and China in the nineteenth century above. The opium poppy consists mainly of a stem, leaves,
were over this very plant. Even today, with the United States flower and flower buds, peduncle, tiller, and typically three
and other countries battling a war front in Afghanistan, Opium seed pods with a crown. (Image Source: poppies.org)
farming and its funding of the Taliban remains a key issue in
the war. The opium poppy has many therapeutic uses in around the globe. The seeds and their oil contain very low
humans, but its addictive nature also brings about a great deal levels of opiates and are considered to be safe ingredients for
of controversy and concern. all ages.
The two most common food ingredients of the opium poppy P. somniferum also has many medicinal uses that have had a
are poppy seeds and poppy seed oil. They provide a unique great impact on anesthesia and healthcare as a whole. There
flavor that can be found in many cuisines from cultures are over 25 alkaloids that come from the opium poppy, the
most common of which is morphine. Morphine, a
benzylisoquinoline alkaloid with two additional rings, is
derived from the poppy’s latex, or milky fluid commonly found
in angiosperms, and is commonly sold under 125 different
brand names worldwide.
Description
The plant species, Papaver somniferum, can be found in fields
and flower gardens throughout the world. The opium poppy
consists mainly of a stem, leaves, flower and flower buds,
peduncle, tiller, and typically three seed pods with a crown
(Figures 1 and 2). It is these seed pods which contain the
valuable latex that is so commonly used in codeine, morphine
salts, and other drugs derived from the plant. The plant
secretes this thin latex as a response to mechanical damage,
but it is still unclear why the opium poppy produces the latex
in the first place. Most recent evidence shows that the
metabolism of morphine to bismorphine serves as a defense
mechanism in the opium poppy (Morimoto 2001). Morphine
comes from two molecules of the amino acid L-tyrosine
through a series of at least 17 enzymatic steps (Grothe 2001). Figure 2. The image above shows another view of the
Perhaps the most commonly seen poppies are in the movie major parts of the opium poppy. Notice the different color
“The Wizard of Oz,” where Dorothy and her friends travel flowers. (Image Source: botanical.com)
through the poppy fields (Figure 3). It is in that movie that
many people learn about the sedative effects of the opium fall under a thin moist layer of soil. The opium poppy grows
poppy. The opium poppy is not only grown in fields. Many very quickly and a seedling can be seen within a week or two.
growers include the opium poppy as an ornamental flower in The pods of the poppy plant contain the seeds and the latex
their gardens. The flowers of the opium poppy can be found that are commonly sought after.
in many different colors, but are most frequently seen as red,
white or pink flowers. The flowers have two sepals that fall P. somniferum also has over 75 close relatives which are
off as the flower blooms. The exact number varies, but the grown as weeds or flowers. A few common relatives are the
poppy flower can usually be seen with four to six petals. The corn poppy, Papaver rhoeas, the Western poppy, Papaver
seeds of the poppy plant are most commonly planted in the californicum, and the Oriental poppy, Papaver orientale.
Some of the earliest writings focused on the opium poppy
show that it was used in anesthesia. In the Roman Empire, a
sponge was soaked with the latex from the opium poppy and
placed under the nose of the patient. The vapors that were
released when the sponge was moistened would induce sleep.
Mandrake wine and other concoctions containing morphine
were also used to induce sleep, but it was quickly noted that
high dosage could cause negative side effects and often lead to
death (Carter 1996). William Shakespeare referred to the
poppy’s sedative effects in two of his most common plays, in
Othello and in Romeo and Juliet. It was from the opium poppy
that the potion was made that put Juliet to sleep.
Throughout recorded history, there is evidence of the use of
the opium poppy for anesthesia and for its sedative effects.
The opium poppy has also been used to treat many other
Figure 3. In this popular scene from the “Wizard of Oz,”
ailments and as an aphrodisiac. Papaverine, one of the
Dorothy and her friends pass through the poppy fields on
alkaloids from the opium poppy, has been used as an antiviral
their journey. (Image Source: joewmccord.com)
to combat cytomegalovirus (CMV), measlesvirus, and human
immunodeficiency virus (HIV) and has potential to help AIDS
Although less common, there have been medicinal uses found patients who also have CMV disease. Papaverine has also
in these other species as well. been used to treat conditions of the nervous system, peptic
In P. somniferum, most of the flowers are planted by humans ulcers, painful menstruations, gastrointestinal complications
in controlled environments where they can keep a close watch and spasms among many other things. Cryptopine, a colorless
on the plant. Because of the value obtained from the latex in alkaloid obtained from the opium poppy, has shown to control
the opium poppy, growers pay close attention to the growth arrhythmias and slow myocardium tissues. Protopine,
and harvesting of the crop. another alkaloid found in the opium poppy, has been shown to
inhibit histamine inhibitors and show bradycardial action. A
powder from the poppy seed has also been shown to relieve
Traditional Uses toothache (Lewis 2003). The most common use of alkaloids
Papaver somniferum is used not only as one of the most from Papaver somniferum has been to relieve pain. Codiene
common analgesics and narcotics, but it is also commonly has been used in cough syrups as an antitussive. Amorphine,
used in food, gardening and recreational drug use. The an emetic derived from morphine, has been used in the
majority of its influence, however, has been because of its removal of poisons from the stomach and in aversion therapy.
drug effects.
Figure 4. The chemical structure for morphine Figure 5. The chemical structure for codeine (C18H21NO3).
(C17H19NO3). Notice the ring structure bearing nitrogen, Like morphine, codeine is an alkaloid. (Image Source:
which is a common characteristic of alkaloids. (Image Source: pubchem. ncbi.nlm.nih.gov)
pubchem.ncbi.nlm. nih.gov)
Many famous drug related deaths have been attributed to
Some of the common analgesics previously mentioned heroin.
including morphine, codeine, noscapine, thebaine, and
papaverine also have addictive tendencies associated with A safer and very common use of the opium poppy includes the
their use. Both mental and physical addictions are common use of poppy seeds and poppy seed oil. Poppy seed and their
with the abuse of these drugs. Overcoming the addiction, oil are used to add flavor and texture to many foods. The
however, is not easy and can often require professional help. seeds are commonly used in many baked goods, casserole
Withdrawal symptoms can be quite severe and include dishes, and in several types of Indian curry.
nausea, vomiting, and diarrhea among many other things
(McClung 2006).
Perhaps one of the most addictive drugs, heroin, comes from
Alkaloids are commonly identified by their ring structure
the opium poppy. Heroin, or diacetylmorphine, is a semi
bearing nitrogen. Morphine (Figure 4) and codeine (Figure
synthetic drug created from morphine. In some countries,
5) are both alkaloids. Morphine has the chemical formula
heroin is used to treat severe acute pain (van den Brink 2003).
C17H19NO3 and a molecular weight of 285.338 g/mol. The
Unfortunately, the recreational use of heroin is much more
crystal structure of an anti-morphine antibody and its
popular than the medical uses. Heroin is a commonly sought
complex with morphine are shown in Figure 6. Codeine has
after drug due to the induced euphoria effects. Tolerance
the chemical formula C18H21NO3 and a molecular weight of
forms quickly in heroin users and creates a need for more.
Alkaloid Chemical Molecular
Formula Weight
Noscapine C22H23NO7 413.421 g/mol
Thebaine C19H21NO3 311.375 g/mol
Papaverine C20H21NO4 339.385 g/mol
Table 1. Chemical formulas and molecular weights of

some common drugs derived from the opium poppy.
299.364 g/mol. The chemical formula and molecular weight

of thebaine, noscapine, and papaverine are shown in Table 1.
Figure 6. The crystal structure of an anti-morphine
Biological Activity antibody and its complex with morphine are shown.
(Image Source: pubchem.ncbi.nlm.nih.gov)
There has been a great deal of research surrounding the
opium poppy and it uses. In 1988, an in vitro study showed
initiate a series of intracellular signals that affect many
how thebaine, an intermediate of morphine and codeine
hormones and neurotransmitters throughout the body and
biosynthesis in the opium poppy, could be transformed to
can often cause respiration depression (Pattinson 2008).
oripavine, codeine, and morphine by rat liver, kidney, and
While the effects of many of the opiate drugs are well studied,
brain microsomes. (Kodaira 1988). In 1995, Lenz and Zenk
the mechanisms of actions for many of them are still unclear.
showed the properties of codeinone reductase (NADPH),
Although the mechanism of action for papaverine remains
which catalyzes the production of codeine from codeinone,
unclear, some researchers have found evidence that it is a
another step in the biosynthetic pathway shown in Figure 7
strong inhibitor of cyclic-3’,5’-nucleotide-phosphodiesterase
(Lenz 1995).
(Kukovetz 1970).
Morphine and other opiate drugs greatly affect the central
nervous system (CNS). There are four major receptive sites
found in the brain and spinal cord of most vertebrates, known Clinical Studies
as the opioid receptors. The four opioid receptors are New drugs, such as Kadian, are in clinical trials to determine
identified as MOP (µ), KOP(k), DOP(δ) and the nociceptin the effectiveness of low dosage or sustained release morphine
receptor (NOP). Each of the four receptors has a different capsules. There are also clinical studies to determine more
location in the brain and spinal cord and has a different effective means of overcoming addictions to morphine and
function affecting the reception of pain (Dreborg 2008). A other narcotics. A current, ongoing study sponsored by the
stimulation can activate these receptors, which will then Norwegian University of Science and Technology is trying to
Figure 7. Codeinone reductase (NADPH), which catalyzes the production of codeine from codeinone is shown above. (Image
Source: Lenz 1995)
determine if it is possible to switch from morphine treatments interactions and the addictive nature of the drugs. Pregnant
to methadone in patients with advanced cancer or short life women should be especially careful to avoid the abuse of
expectancy. morphine. Babies born from mothers addicted to morphine
often have the physical addiction themselves (Becker 2005).
Contraindications
There are many interactions to watch out for with the use of Current Use in Allopathic & CAM Therapies
drugs from the opium poppy. Some of the more common Because of the addictive nature of the drugs and the
interactions include alcohol, barbiturates, antidepressants, widespread abuse, opiates are not commonly used in
muscle relaxants, antihistamines, sleep medications, complementary and alternative medicine therapies. Codeine
antipsychotics, and other narcotics. Morphine itself does not can be found in some combination preparations such as
interact with grapefruit juice, but codeine, on the other hand, Tylenol with codeine and antitussives. There are many drugs
will cause an interaction. The two most common dangers derived from morphine, but in nearly every country, they are
associated with alkaloids from the opium poppy include closely regulated by the government to prevent such abuse.
Morphine and other opiate drugs are often administered in Becker, Daniel E. and James C. Phero. 2005. Drug Therapy in Dental
hospitals and clinics to manage post-operative pain. Many Practice: Nonopioid andOpioid Analgesics. Anesthesia
doctors will choose to use NSAIDs instead of opiate analgesics Progress. 52: 140-149.
because there is less risk involved, both in addiction and Carter, Anthony J. 1996. Narcosis and Nightshade. British Medical
respiratory depression. NSAIDs are a good for mild to Journal. 313: 1630-1632.
moderate pain, but it is recommended that practitioners “use Dreborg, Susanne, Görel Sundström, Tomas A. Larsson, and Dan
opioid therapy for the short-term management of Larhammar. 2008. Evolution of Vertebrate Opioid Receptors.
breakthrough pain that is not responsive to NSAIDs or Proceedings of the National Academy of Sciences. 105 (40):
acetaminophen” (Becker 2005). 15487-15492.
Facchini, Peter J. and Vincenzo De Luca. 2008. Opium poppy and
Madagascar periwinkle: model non-model systems to
Discussion
investigate alkaloid biosynthesis in plants. The Plant Journal.
Papaver somniferum has generated many medicinal uses that 54: 763-784.
have greatly impacted human health over the years. The Grothe, Torsten, Rainer Lenz, and Toni M. Kutchan. 2001. Molecular
controversy surrounding the opium poppy, however, has Characterization of the Salutaridinol 7-O-Acetyltransferase
often overshadowed its positive effects. The highly addictive Involved in Morphine Biosynthesis in Opium Poppy Papaver
nature of heroin and other opiates can even be passed on somniferum. The Journal of Biological Chemistry. 276 (33):
through pregnancy. Over-dosage of opiates, like most 30717-30723.
narcotics, can often lead to death. Many lives have been Kodaira, Haruyoshi and Sydney Spector. 1988. Transformation of
improved and many lives have been lost over the opium thebaine to oripavine, codeine, and morphine by rat liver,
poppy plant. With proper use and direction, morphine and kidney, and brain microsomes. Neurobiology. 85: 1267-1271.
codeine can help alleviate pain, spasms, coughs and many
Kukovetz, W.R. and G. Pöch. 1970. Inhibition of Cyclic-3′,5′-
other conditions. Even when used correctly, one must be very Nucleotide-Phosphodiesterase as a Possible Mode of Action of
careful to avoid addiction. While many drugs have been Papaverine and Similarly Acting Drugs. Naunyn-
derived from the opium poppy, there is still a lot of research Schmiedeberg's Archives of Pharmacology. 267: 189-194.
surrounding this plant.
Lenz, Rainer and Meinhart H. Zenk. 1995. Purification and
properties of codeinone reductase (NADPH) from Papaver
somniferum cell cultures and differentiated plants. European
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Suemune, Yasuyuki Shimohigashi, and Yukihiro Shoyama.
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Passiflora incarnata L., Passifloraceae
Ronni Shalem
Introduction
Passiflora incarnata (Figure 1) is from the Passifloraceae
family. It is most commonly known as the purple
passionflower but alternate names include: apricot, ground
ivy, Holy Trinity flower, mayapple, maypop, or mollie cockle
(McGuire, 1999). P. incarnata is indigenous to warm
temperate and tropical North America (Dhawan, Dhawan, &
Sharma, 2004). It has a perennial vine (present at all seasons
of the year) with white and blue or purple flowers, and an
edible fruit. The fruits are berries and oval in shape (Figure
2). The main constituents include flavonoids, flavonoid
glycosides, alkaloids, cyanogenic glycosides, carbohydrates, Figure 1. Passiflora incarnata L. (Image source:
amino acids, benzopyrone derivatives and volatile http://www.wildflower.org/plants/result.php?id_plant=PAIN6)
constituents (Elsas, Rossi, Raber, White, Seelay, Gregory,
Mohr, Pfankuch, & Soumyanath, 2001).
Passiflora has been used traditionally as a sedative, anxiolytic,
antispasmodic, analgesic, anticonvulsant, and for the
treatment of whooping cough, bronchitis, and asthma
(Dhawan, Kumar, & Sharma, 2002). Topically, it is has been
used for hemorrhoids, burns, bruises, and inflammation. More
recently, P. incarnata has been recommended for insomnia,
neuralgia, seizures, menopause, and as an anti-diabetic (Tovar
& Petzel, 2009; Tenney, 2007).
The pharmacological effects of P. incarnata include
anticonvulsant, anti-asthmatic, antitussive, and anxiolytic
activities (Grundmann, Wang, McGregor, & Butterweck, 2008). Figure 2. Fruit of Passiflora incarnata L.
Although there is a vast use of P. incarnata, the (Image source:
pharmacological work on this plant has been insufficient and http://www.duke.edu/~jspippen/plants/passiflora.htm)
inconclusive in determining the mode of action of the plant as
and new shoots grow each spring from buds on rhizomes and
roots that live over from one season to the next (McGuire
1999).
P. incarnata's wild growth, branching, and underground
spreading can make it very difficult to manage in cultivation.
The stems are not self-supporting, so plants must be bolstered
in cultivation to protect the foliage and developing fruits from
pests. The petioles, up to eight centimeters long, have two
nectaries (gland that secretes nectar) attached at the base of
the laminae (expanded part of a foliage leaf). Laminae of adult
leaves are moderately to deeply three-lobed, and are 6-15 cm
long along the mid vein. Two meristems (plant tissue that
Figure 3. Juice with Passionflower allow cells to differentiate and produce tissues and organs) in
(Image source: http://tastesfromaroundnz.co.nz/4-x-325ml-teza- the axil of each leaf allows for the possible upper development
peach-passionflower-juiced-teas.html) into a branch, and the lower into a tendril, or a tendril and a
flower (McGuire 1999).
well as the phyto-constituents responsible for the anxiolytic Flowers are born individually on the stalks up to ten
and sedative effects of the plant (Soulimani, Younos, Jarmouni, centimeters long. Three leaves, each bearing two nectaries,
Bousta, Misslin, & Mortier, 1997). circle the base of the floral bud. Floral buds grow two to three
The passionflower fruit is widely eaten today and is used in centimeters long before opening. Open flowers are up to nine
juice drinks (Figure 3), beverages, baked goods, cereals, centimeters wide and have the complex floral structure typical
yogurt, ice cream, candy, jams, and jellies (Ngan & Conduit, of the Passiflora genus. The sepals and petals are white to pale
2011). It is currently used in complementary and/or lavender on their displayed surface. The prominent corona
alternative medicine for its treatment of anxiety, asthma, (crown) consists of five or six series of thin and flexible
insomnia, nervousness, neuralgia and more (Tenney, 2007). appendages. The outer two filaments are 10-20 mm long,
colored white, pink, lavender, and/or purple, and variously
banded. The remaining series of corona filaments are much
Botanical Description shorter (two to four millimeters long) (McGuire 1999).
Passiflora incarnata is an herbaceous perennial vine that At maturity, fruits separate at the region of articulation on the
climbs with the support of tendrils. Individual shoots are peduncle, and the floral parts and a portion of the peduncle
unclassified, grow up to ten meters long, and are usually remain at the base of the separated fruit. The fruits are
branched. The plants often develop additional shoots from the berries, oval in shape, and up to seven centimeters long.
underground roots and rhizomes. The shoots die in autumn, Immature fruits have smooth, green rings that at maturity
germination percentages. Root or rhizome fragments lose
their capability to grow, develop and even live very easily if
they are not kept moist (McGuire, 1999).
There are four important aspects of P. incarnata's
reproductive biology that could affect fruit and seed set in
cultivation. Firstly, P. incarnata is typically self-incompatible.
Secondly, insect pollinators (generally Xylocopa spp.) are
required to deposit compatible pollen on stigmas. Thirdly,
flowers must have both male and female reproductive organs
(hermaphrodites) to receive pollen, and plants vary
hermaphroditic flower production in response to resource
status. Finally, when pollinator visits are not frequent, seed set
may cause a relatively long delay between flower opening and
effect the way the plant bends (McGuire, 1999).
P. incarnata is a native of temperate and tropical North
Figure 4. Passiflora incarnata is native to southeastern America (Figure 4). P. incarnata seeds occur in many human
North America. archaeological sites from the Late Archaic (3500- 800 B.C.E.)
(Image source: http://plants.usda.gov/java/profile?symbol=pain6) to Historic (1550-1800 C.E.) periods in the southeastern U.S.,
indicating that Native Americans were consuming the fruit.
Moreover, seed abundance increases over time in the
sometimes become wrinkled, yellow, and eventually brown.
archaeological record. This suggests that human fruit
Some plants bear fruits with three longitudinal maroon stripes
consumption rose at this time. During the same time period,
originating at the juncture of the peduncle and fruit and
agriculture expanded in southeastern North America, and
continuing down partially to the end of the fruit. Within the
increased human consumption of P. incarnata fruits may
thin skin are three longitudinal parietal placentae, and the
indicate an increased cultivation of this plan. It is also possible
fruit interior contains up to 120 seeds, dark brown at
that since P. incarnata prefers disturbed habitats, fruit
maturity, four to five nun long, three to four mm wide, and
consumption may have risen simply because the plant became
individually enclosed. The arils (exterior covering) vary in size
more common, as it invaded the disturbed habitats associated
among fruits and contain an edible, aromatic, creamy yellow
with an expanding agriculture (McGuire, 1999).
juice (McGuire, 1999).
Early European travelers in North America noted that
P. incarnata can reproduce asexually from stem cuttings and
Algonkian Indians in Virginia and Creek people in Florida ate
root or rhizome fragments. Root or rhizome fragments four to
P. incarnata fruit gathered from cultivated, semi-
eight cm long have nearly 100 percent germination when
domesticated, or wild plants. The European settlers
planted one cm deep, but shorter fragments have lower
themselves also consumed the fruit and praised its flavor dysmenorrhea, epilepsy, insomnia, neurosis, and neuralgia. It
(Dhawan, Dhawan, & Sharma, 2004). Since then, inhabitants of has been used to cure hysteria and neurasthenia in Poland. P.
the U.S, as well as people globally, have continued to eat wild incarnata has also been used to treat morphine addiction in
and cultivated P. incarnata fruits. India (Dhawan, Dhawan, & Sharma, 2004).
The Houma, Cherokee and other Native American tribes used
Traditional Uses P. incarnata for food and medicinal purposes. In 1612, Captain
Smith reported that Native Americans in Virginia planted the
The discovery of seeds dating back to thousands of years from vines of Passiflora in order to produce the fruit of the plant.
archaeological sites in North America provides evidence of the They were eaten raw, boiled to make syrup, and squeezed to
historic use of the fruit by the ancient Red Indians. Early make a drink from the juice. The roots were used in a tea
European travels in North America (particularly Southeastern infusion to treat boils, inflammation, and to cure liver
parts) documented the consumption of the fruit of Passiflora problems. The plant was also used as a sedative to treat
by the Algonkian Indians in Virginia and the Creek peoples in nervousness and hysteria (USDA).
Florida. These fruits were eaten from cultivated as well as
wild sources (Dhawan, Dhawan, & Sharma, 2004). The Native The above ground (aerial) parts have been used as a sedative,
Americans also used passionflower as a tonic for bruises and anxiety reliever, pain reliever, as well as a convulsion
injuries. The Aztecs used it as a sedative and for pain relief preventative and reliever for epilepsy. Aqueous extract
(Tenney, 2007). (extract prepared by evaporating a watery solution of the
soluble properties to a semisolid or solid consistency) of P.
The use of Passiflora as a medicine was documented for the incarnata roots has been used topically on ulcers and
first time in 1569 by Spanish researcher Monardus in Peru. hemorrhoids. The whole plant has also been used in the
The Matrica Medica Americana, published in Germany in treatment of insomnia, anxiety, and other central nervous
1787, mentions the use of P. incarnata to treat epilepsy for system disorders (Dhawan, Kumar, & Sharma, 2001; Dhawan
older people. An ancient report also describes its use in & Sharma, 2001). However, to date, there is little scientific
spasmodic disorders and insomnia in infants and the elderly validated evidence for the constituents of P.incarnata that are
(Dhawan, Dhawan, & Sharma, 2004). responsible for the sedative and anxiolytic effects (Ngan &
P. incarnata is a popular traditional European remedy and a Conduit, 2011).
homoeopathic medicine for insomnia and anxiety. In North P. incarnata is currently listed in the pharmacopoeias of Great
America, it has a history of use as a sedative tea. In America, it Britain, United States, India, France, Germany, Switzerland
is used to treat diarrhea, dysmenorrheal, neuralgia, burns, and others. The active ingredients have not been conclusively
hemorrhoids, and insomnia. In Brazil, Passiflora has been used defined. Most available data suggests flavonoids and indole
as an analgesic, anti-spasmodic, anti-asthmatic, wormicidal, alkaloids as possible active components (Elsas et al., 2010).
and sedative. In Iraq, it has been used as a sedative as well as a
narcotic. In Turkey, Passiflora has been used to treat
Figure 6. Indole alkaloids chemistry structure (Dhawan,
Figure 5. Flavonoid compound chemistry structure 2004).
(Dhawan et al, 2004).
derivative maltol and ethyl-maltol (0.05%) (Table 1).

Passionflower fruit is widely eaten today and is used in juice
drinks, beverages, baked goods, cereals, yogurt, ice cream, Other constituents include carbohydrates such as raffinose,
candy, jams, and jellies (Ngan & Conduit, 2011). sucrose, d-glucose, and d-fructose; essential oil with hexanol
(1.4%), benzyl alcohol (4.1%), linalool (3.2%), 2-phenylethyl
alcohol (1.2%), 2-hydroxy benzoic acid methyl ester (1.3%),
Chemistry and Pharmacology carvone (8.1%), trans-anethol (2.6%), eugenol (1.8%),
isoeugenol (1.6%), β-ionone (2.6%), α-bergamotol (1.7%) and
The constituents of Passiflora incarnata include flavonoids,
phytol (1.9%). The constituents responsible for the odor are
flavonoid glycosides, alkaloids, cyanogenic glycosides,
limomene, cumene, prezizaene, zizaene, amino acids; and
carbohydrates, amino acids, benzopyrone derivatives and
cyanogenic glycoside gyanocardin (Dhawan, Dhawan, &
volatile constituents, as well as coumarins from the roots
Sharma, 2004).
(Soulimani et al., 2007).
The pharmacological effects of P. incarnata include
The main chemical constituents of Passiflora incarnata are
anticonvulsant, anti-asthmatic, antitussive, and anxiolytic
flavonoids (0.25%). These include vitexin, isovitexin, orientin,
activities (Grundmann et al., 2008). Although there is a vast
isoorientin, apigenin, and kampferol, luteolin, quercetin,
use of P. incarnata, the pharmacological work on this plant
schaftoside, isoschaftoside (Figure 5). The greatest
had been insufficient and inconclusive in determining the
accumulation of flavonoids is found in the leaves (Dhawan,
mode of action of the plant as well as the phyto-constituents
Dhawan, & Sharma, 2004). The simple indole alkaloids (0.1%)
responsible for the anxiolytic and sedative effects of the plant
such as harman, harmin, harmalin, harmol, and harmalol are
(Soulimani et al., 1997).
also active compounds (Figure 6). The medicinal extra of the
plant has 10-20 ug/100 ml of harman and harmine. P. Researchers have proposed different theories on the bioactive
incarnata also contains the active compounds y-benzo-pyrone chemicals of P. incarnata. However, there has been no
Active Compounds inclusive pharmacological studies on P. incarnata by
Flavonoids (0.25%) Soulimani et al. (1997) ruled out the main phyto-constituents
Vitexin of flavonoids and indole alkaloids as the sources of
Isovitexin psychotropic activity. Although the sedative and anxiolytic
Orientin properties of the plant were shown in their studies, the mode
Isoorientin of action of both the aqueous and hydroalcoholic extracts
Apigenin
were not found.
Kampforel
Luteolin
Quercetin
Schaftoside Biological Activity
Isoschaftoside In vitro
Indole Alkaloids (0.1%)
Harman Passionflower fruit, which is used to produce mark, jams, and
Harmin juices, has shown to contain a considerable amount of
Harmalin lycopene. This finding shows that passionflower fruit products
Harmol may serve as a good alternative for those people who do not
Harmalol or cannot eat tomatoes and tomato products (which is known
Maltol and ethyl-maltol (0.05%) to have a high amount of lycopene). Lycopene, a carotenoid
Table 1. Constituents of Passiflora incarnata. antioxidant, has been shown to protect against oxidative
damage in many epidemiological and experimental studies. In
consensus regarding the exact mode of its pharmacology. addition to its antioxidant activity, other metabolic effects of
Some researchers have highlighted the role of the flavonoid lycopene have also been demonstrated (Mourvaki, Gizzi, Rossi,
chrysin and even the b-pyrone derivative maltol to be & Rufini, 2005).
responsible for the CNS effects of the plant (Movafegh, Dhawan, Kumar, and Sharma (2001) show that roots of P.
Alizadeh, Hajimohamadi, Esfehani, & Nejatfar, 2008). The incarnata do not have anxiolytic effects, but act as natural
indole alkaloids and flavonoids have been speculated to be the adulterants and should be separated from the aerial parts
main bioactive constituents of the plant. They are believed to prior to any pharmacological, phytochemical and
be so due to their MAO enzyme inhibiting properties (Dhawan, standardization studies on P. incarnata. The presence of
Dhawan, & Sharma, 2004). Some findings have attributed the flowers along with leaves and stems is also undesirable. Using
sedative and anxiolytic activities in P. incarnata to the whole plant for pharmacological studies (both commercial
benzodiazepine and GABA receptors in the body. By and medicinal purposes) is not optimal for finding the CNS
increasing levels of GABA in the brain, lowering the activity of effects of P. incarnata. Although the separated leaves afford
some brain cells, one feels more relaxed (Dhawan, Kumar, & the best possible results, the selection of the entire aerial parts
Sharma 2001). Yet contrary to many of these reports, the (except for the flowers) may prove to be the best approach for
identifying the bioactive parts of the P. incarnata plant. prepared from the herb of Passiflora incarnata induced an
anxiolytic-like effect in mice, since it increased the number of
entries and the time spent in open arms in the EPM test at a
In vivo dose of 375 mg/kg. Although the anxiolytic effects of various
Studies in animal models show efficacy of Passiflora incarnata extracts from Passiflora have been demonstrated in animals
extracts and flavonoid fractions against pentylenetetrazol and in humans, the mode of action and the identity of the
(PTZ) induced seizures. It is possible that Passiflora inhibits active constituents of the different Passiflora species remained
the benzodiazepine site antagonist Ro 15-1788, suggesting the unclear.
involvement of GABAA receptors. Flavonoids bind to the In Dhawan and Sharma (2001), the methanol extract of the
benzodiazepine site of the GABAA receptor, but appear to leaves of P. incarnata was shown to be significantly active in
alter GABAA and also GABAC receptor currents by a different suppressing the SO2 -induced cough in mice. These results
mechanism than benzodiazepines (Elsas et al., 2010). This provide evidence for the folklore claims on the effectiveness of
finding suggests that the anticonvulsant activity of the plant is the plant in managing “tough” cough conditions. Moreover,
attributed to the benzodiazepine and GABA receptors this finding showed that P. incarnata, having no reports to
mediated biochemical processes in the body (Dhawa, Dhawa, possess an addictive quality, could be an optimal alternative to
& Sharma, 2004). cough-suppressants opiates, which have several negative
Soulimani et al. (1997) examined the potential anxiolytic and effects including CNS depression, dryness of the mouth,
sedative effects of aqueous and hydrocoholic extracts of blurred vision, and severe gastrointestinal effects.
Passiflora on mice. The aqueous extract appeared to induce The ethanolic extract of P. incarnata showed anti-
sedative effects at 400 and 800 mg/kg. It reduced activity in inflammatory properties at a dose of 125 to 500 mg/kg in rats
the staircase and free exploratory tests. The hdyroalcoholic when inflammation was induced by cotton pallets, dextran
extract did not have such sedative effects, rather, it appeared and carrageenin (Borrelli, Pinto, Izzo, Mascolo, Cappaso,
to enhance activity and have an anxiolytic effect at 400 mg/kg. Mercati, Toja, & Autore, 1996). This provides evidence for the
Singh, Singh, and Goel (2001) used hydroethanolic extracts of plant’s anti-inflammatory properties.
Passiflora to explore the anticonvulsant effects of the plant.
Treatment with the extract significantly decreased seizure
severity at 300 and 600 mg/kg. This finding suggests that the Clinical Studies
presence of flavonoids, which act by agonizing the GABA- Although the effects of Passiflora incarnata have been studied
benzodiazepine receptor may be responsible for the less in humans, Akhondzadeh, Naghavi, Vazirian,
anticonvulsant activity. Since depression in the mice was Shayeganpour, Rashidi, and Khani (2001) and Movafegh,
induced by seizures, the anti-depressive effect can be due to Alizadeh, Hajimohamadi, Esfehani, and Nejatfar (2008), are
the suppression of seizures. two clinical trials that have demonstrated Passiflora’s efficacy
In Grundmann et al. (2008), oral administration of an extract in the treatment of anxiety. The findings of the studies
attribute the effectiveness of the treatment to the anxiolytic Contraindications
and sedative actions of the passionflower extract (Ngan &
The FDA lists Passiflora incarnata as a safe herbal sedative.
Conduit, 2011). Akhondzadeh, Naghavi, Vazirian,
Since the mode of CNS depressant activity has not been
Shayeganpour, Rashidi, and Khani (2001) also explored the
conclusive, it is advised to take caution when taken with other
use of the plant in the treatment of opiate withdrawal and
CNS depressants or stimulants. The neuromuscular relaxing
attention‐deficit hyperactivity disorder (ADHD).
effects of the extract have synergetic effects with
Akhondzadeh et al. (2001) study on anxiety used the Hamilton aminoglycoside antiobiotics such as clindamycin (Dhawan,
anxiety rating scale to assess the anxiety levels of 36 Dhawan, & Sharma, 2004).
outpatients diagnosed with generalized anxiety disorder. The
The use of the plant up to one month is considered safe.
anxiety scores indicated that passionflower (45 drops of P.
However, negative affects associated with the plant include
incarnata extract per day) was just as effective as the positive
dizziness, confusion, sedation, and a lack of coordination
control condition (30 mg of oxazepam per day) in reducing
(Tovar & Petzel, 2009).
anxiety levels at the end of the 28-day treatment. In another
study, Movafegh et al. (2008) used a numerical rating scale to There has been a report about a woman who developed
assess the anxiety levels of 60 ambulatory surgery patients severe nausea, vomiting, weakness, drowsiness, slower heart
during the 90 minute period between premedication (placebo rate, and ventricular arrhythmia, after two days self-
or 500 mg of passionflower tablets) and surgery. They found administration of an herbal remedy containing P. incarnata
that the group that received passionflower had significantly (Fisher, Purcell, & LeCouteur, 2000). A case of hypersensitivity
lower anxiety ratings than the placebo group after with skin vasculitis (inflammation of blood vessels) and hives
premedication. These clinical findings indicated that P. after ingestion of tablets containing Passiflora extract has been
incarnata may be effective in reducing short term as well as reported (Movafegh et al., 2008). Five patients have been
long term, heightened anxiety (Ngan & Conduit 2011). reported to suffer altered consciousness after taking an herbal
preparation from P. incarnata called Relaxir (Dhawan,
Akhondzadeh et al. (2001) study on opiate withdrawal
Dhawan, & Sharma, 2004).
randomly assigned 65 opiate addicts to treatment of Passiflora
extract and clonidine tablet or a placebo and clonidine tablet. In an in vivo study, no acute toxicity was observed after an
Although both were effective in treating the physical injection into the peritoneum of mice in doses larger than 900
symptoms of withdrawal, Passiflora in addition to clonidine mg/kg (Movafegh et al., 2008).
had a significant increase in managing mental symptoms than Passiflora may induce uterine contraction so its use is
clonidine on its own. These results suggest that Passiflora contraindicated during pregnancy (Movafegh et al., 2008). The
extract may be effective for the management of opiate use of Passifora is also highly discouraged in lactating
withdrawal. mothers. There is also a severe contraindication of the plant
with the synthetic MAO inhibitor drug Phenelzine (NARDIL)
(Dhawan, Dhawan, & Sharma, 2004).
Passiflora incarnata is currently used primarily to treat
alcoholism, asthma, insomnia, nervousness, anxiety, eye
tension, headaches, menopausal symptoms, and neuralgia
(acute pain). It’s secondary applications include bronchitis,
depression, muscle spasms, seizures, convulsions, diarrhea,
epilepsy, pain (for example, menstrual) and restlessness
(Tenney, 2007). It is available as a liquid extract, capsule, tea,
and tincture (Figure 7). The recommended dose for anxiety is
45 drops (90mg) daily (Tovar & Petzel, 2009).
Gupta, Kumar, Chaudhary, Maithani, and Singh (2011) showed
the anti-diabetic properties of the Passiflora incarnata. This
study explored the hypolygemic and hypolipidemic effects of
the methanolic extract of P. incarnata on induced diabetic
mice. At a dose of 200 mg/kg, the mice had significantly
increased tolerance in glucose. This depicts that the leaf can Figure 7. Herb, extract, and capsule form of Passiflora
be a good alernative medicine for diabetes as it has significant incarnata. (Photo by Ronni Shalem).
anti-hyperglycemic activity in streptozocin-induced diabetic
mice. Discussion
Frontier markets the herbal supplement to naturally promote Passiflora incarnata was an important plant for the Native
relaxation. To make the tea, you boil 1-2 teaspoons of the Americans in traditional medicine. It served many purposes
herb, cover it, and let it seep for 5 to 10 minutes. Gaiia markets including food and beverage as well as having medicinal
the passionflower to support the nervous system, to promote properties. After being introduced to the Europeans, P.
calm and relaxation, and to support healthy sleep. Its incarnata became a popular traditional European remedy and
recommended dose is 1 capsule, 2 times daily between meals. a homoeopathic medicine for insomnia and anxiety. It is now
Gaia also makes an extract of the passionflower, and its used all over the world. This is evident by the fact that it is
suggested use is 40-60 drops in a small amount of water, three listed as an official plant drug in the British Herbal
times daily between meals. Pharmacopoeia (1983), Homeopathis Pharmacopoeia of India
The Passionflower fruit itself is eaten globally and is widely (1974), United States Homoeopathic Pharmacopoeia (1981),
used in juice drinks, beverages, baked goods, cereals, yogurt, Pharmacopoeia Helvetica (1987), as well as the
ice cream, candy, jams, and jellies (Ngan & Conduit, 2011). pharmacopoeias of Egypt, France, Germany, and Switzerland
(Dhawa, Dhawa, & Sharma, 2004).
The importance of the plant is exemplified in its use all over anxiety and insomnia, they can turn to P. Incarnata as a
the globe. In Brazil, Passiflora has been used as an analgesic, natural remedy. In addition, people can incorporate the
anti-spasmodic, anti-asthmatic, wormicidal, and sedative. In passionflower fruit in their diets for its lycopene content,
Iraq, it has been used as a sedative as well as a narcotic. In which is extremely notable for its antioxidant activity. To do
Turkey, Passiflora has been used to treat dysmenorrhea, so, the fruit can simply be blended into a juice.
epilepsy, insomnia, neurosis, and neuralgia. It has been used
to cure hysteria and neurasthenia in Poland. P. incarnata has
also been used to treat morphine addiction in India (Dhawan, References Cited
Dhawan, & Sharma, 2004). Akhondzadeh, S., Naghavi, H.R., Vazirian, M., Shayeganpour, A.,
Almost every component of the plant has shown to have some Rashidi, H., & Khani, M. (2001). Passionflower in the
form of pharmacological activity. There have been many treatment of generalized anxiety: a pilot double-blind
randomized controlled trial with oxazepam. Journal of
studies on the plant both in vivo and in vitro, although mostly
Clinical Pharmacology and Therapeutics, 26, 363-367.
in vivo, to explain the chemical activities of P. incarnata.
Studies in animal models show efficacy of Passiflora extracts Akhondzadeh, S., Naghavi, H.R., Vazirian, M., Shayeganpour, A.,
and flavonoid fractions against pentylenetetrazol (PTZ) Rashidi, H., & Khani, M. (2001). Passionflower in the
induced seizures. In Grundmann et al. (2008), P. incarnata treatment of opiates withdrawal: a double-blind
randomized controlled trial. Journal of Clinical
extract induced an anxiolytic-like effect in mice when
Pharmacology and Therapeutics, 26, 369-373.
administered orally. In Dhawan and Sharma (2001), the
methanol extract of the leaves of P. incarnata was shown to be Borelli, F., Pinto, L., Izzo, A.A., Mascolo, N., Capasso, F., Mercati, V.,
significantly active in suppressing the SO2 -induced cough in Toja, E., & Autore, G. (1996). Anti-inflammatory activity of
mice. Although the effects of P. incarnata have rarely been passiflora incarnata L. in rats. Phytotherapy Research, 10,
104-106.
studied in humans, two clinical trials have demonstrated its
efficacy in the treatment of anxiety. It has also been shown to Dhawan, K., Dhawan, S., & Sharma, A. (2004). Passiflora: a review
be effective in opiate withdrawal. P. incarnata, serving so update. Journal of Ethnopharmacology, 94(2004), 1-23.
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world of medicine. extracts of passiflora incarnata linneaus. Journal of
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consider holistic lifestyles of alternative medicine, P. incarnata Dhawan, K., Kumar, S., & Sharma, A. (2001). Anxiolytic activity of
will be an important plant to turn to for its variety of aerial and underground parts of Passiflora incarnata.
medicinal applications. Its various uses to treat conditions Fitoterapia 72, 922-926.
from fevers to neuralgia and seizures to diarrhea, the Dhawan, K., & Sharma, A. (2001). Antitussive activity of the
multiplex applications of the plant are pretty remarkable. For methanol extract of passiflora incarnata leaves. Fitoterapia,
someone who is not comfortable taking synthetic drugs or 73(2002), 397-399.
synthetically derived drugs to treat medical ailments such as
Dhawan, K., Kumar, S., & Sharma, A. (2002). Comparative anxiolytic Mourvaki, E., Gizzi, S., Rossi, R., & Rufini, S. (2005). Passion fruit: a
activity profile of various preparations of p. incarnata new source of lycopene. Journal of Medicinal Food, 8(1), 104-
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Elsas, S.M., Rossi, D.J., Raber, J., White, G., Seelay, C.A., Gregory, W.L., anxiety in ambulatory surgery patients: a double-blind,
Mohr, C, Pfankuch, T., & Soumyanath, A. (2011). Passiflora placebo-controlled study. Anesthesia & Analgesia, 106(6),
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hippocamal neurons in vitro, and show anxiolytic and
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anticonvulsant effects in vivo, varying with extraction
investigation of the effects of Passiflora incarnata
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Persea americana Mill., Lauraceae
Corinne Grady
Introduction
Persea americana Mill. of the Lauraceae family is commonly
known as the avocado tree. This edible fruit is also called the
alligator pear, el aguacate in Spanish, and e li in Chinese
("Persea americana (Mill),"). The English name avocado is
derived from the Spanish aguacate, which in turn comes from
the Nahuatl, or Aztec, name ahuacatl (Popenoe, Zentmyer, &
Schieber, 1997). As depicted in Figure 1, P. americana is a tall,
green leafy tree with single seeded fruit. The plant originates
from the tropical and subtropical climate regions of Central
and South America, where indigenous people first cultivated
it. For thousands of years, the fruit, leaves, and seeds of the
avocado tree have been used as a food source and for
medicinal purposes. The uses of P. americana range from
emollients for the skin to treatments for hypertension. The
main chemical constituents that lend to the activity of avocado
are aliphatic acetogenins, flavonoids, terpenoid glycosides,
and furan-ring derivatives (Yasir, Das, & Kharya, 2010).
Figure 1 Persea americana Mill (Source:
Today, the flesh of the fruit is cultivated and consumed
http://www.public.asu.edu/~camartin/plants/Plant%20html%20f
worldwide and is generally recognized as safe as a food source iles/perseaspecies.html)
(Morton, 1987).
tolimanensis, and zentmyerii. Each subspecies has distinct

Botanical Description botanical features as described in Table 1. Three of these
The genus Persea contains 8 species, which are all trees or varieties (the West Indian, Mexican, and Guatemalan avocado)
shrubs ("Persea americana Mill, avocado,"). A polymorphic have been domesticated and are used commercially for their
tree native to Central America, Persea americana has a variety fruits, which all slightly differ in size, shape, and color. The
of subspecies, which include the commercial varieties of necessary climate and soil type for each subspecies varies. For
avocado. The varieties of P. americana are americana, example, the Mexican variety is the hardiest and can survive in
drymifolia, floccosa, guatemalensis, nubigena, steyermarkii, the coldest weather (25°F). The Guatemalan variety
Subspecies Common Distinctive botanical features
name Tree Leaf Fruit
P. americana var. americana West Indian Small to large, low N/A 10-15cm long green mature fruit with flesh more
avocado elevation than 1 cm thick
P. americana var. drymifolia Mexican Small to large N/A <5cm long purple-black mature fruit with little
(rare in Guatemala, common in avocado flesh, anise flavored
Mexico)
P. americana var. guatemalensis Guatemalan N/A N/A Nearly round fruit >4cm diameter, 2-3 cm of
avocado flesh, rough to smooth exocarp, green to black
P. americana var. floccosa N/A Native to eastern Young growth of floccose Thick green to black exocarp, not much longer
Mexico pubescent than broad
P. americana var. nubigena N/A N/A Secondary veins 30-50° Thick green to black excocarp, little flesh <4cm
divergent, glaucous diameter
P. americana var. steyermarkii N/A N/A Secondary veins 45-75° Thick green to black excocarp, little flesh <4cm
(rare) divergent, glabrous diameter
P. americana var. tolimanensis N/A Branching begins Dull foliage Round to oblong fruit 6-8cm diameter, bitter
high on trunk taste, irregular rough green exocarp
P. americana var. zentmyerii N/A N/A N/A 3.5-5cm diameter, little flesh, thick green to black
(very rare) exocarp covered with corky ridges
Table 1: Key features of the subspecies of P. americana (Whiley et al., 2002)
originated in the subtropical highlands of Central America and seasons. The leaves are glossy and dark green on top with a
while not as hardy as the Mexican variety, it is tougher than paler bottom surface. They vary from oval to oblong and
the West Indian race, which only grows in tropical or near rounded to obtuse in shape. The flowers of P. americana are
tropical climates like southern Florida and Puerto Rico. small in comparison; only reaching from a few millimeters to a
Although the avocado tree needs a particularly humid and couple of centimeters long. They are small, yellow or pale
non-windy climate, it can grow in an assortment of different green in color, and do not have petals. Instead, the flowers
soil types. Some soil types include red clay, volcanic soil, sand, have sepals, whorls of perianth lobes and nine stamens
limestone, and slightly alkaline soils. The pH level preferred (Figure 2). The female and male organs of the flower do not
operate simultaneously. Unlike all other flowering plants, the
by P. americana is between 6 and 7, however avocados in
southern Florida can grow on land with pH levels between 7.2 avocado’s flowers first function as only female – accepting
and 8.3. Good drainage is also essential for tree growth. The
trees can grow up to 30 meters tall with leaves up to 20
centimeters long and 24 centimeters wide. The trees are
almost evergreens, only losing their leaves briefly during dry
Figure 2. Avocado Flower (Source:
http://www.doyletics.com/images/avocflwr.jpg)
pollen but not producing any from their stamen. This stage
only lasts for two to three hours and is the only time in which
sperm from another flower can fertilize the egg. Bees and
sometimes other large insects are the pollinators for the
avocado flower in addition to its self-pollination capabilities.
Once the two to three hours have passed, the flower’s sepals
close for about twenty-four hours. When the flower reopens, it Figure 3. A single fruit on a P. americana tree
sheds pollen rather than receiving it until the flower closes (Source:("Persea americana Mill, avocado,")
again. This second closing is permanent and if fertilization is
successful, an avocado will begin to grow. Cross pollination is pollen to fertilize the female flowers during both parts of the
able to occur because every plant has two different varieties of day. When temperatures fall below 70°F, however, the
flower – the A type and the B type. Usually, the A type flowers flowers’ cycles become irregular and the plant produces less
open as female in the morning and are male the following fruit.
afternoon while the B type do the opposite so that there is
In general, P. americana produce fruit, called avocados Central America used avocado, or ahuacatl, in the dish
(Figure 3). These single seeded berries range in size from 3.5 ahuacamulli, which is now known as guacamole. This term
cm to 20 cm long, can have smooth to rough skin, and vary in “mulli” means sauce or soft dish in the Nhuatl language. So the
color from green to purple-black. The fruit does not ripen until Aztec compound word for guacamole is a description of the
removed from the tree due to inhibition from the stem. Some dish, which is made by mashing up the avocado fruit into a
related species include Persea schiedeana (Lauraceae) and soft paste and adding other ingredients. Ahuacachiaualloti,
Beilschmiedia anay (Lauraceae). These are both trees native to meaning avocado oil, was also used by Aztec people thousands
Central America. They can grow up to 20 meters high, which is of years ago (Popenoe et al., 1997). Indigenous American
slightly shorter than P. americana. Both produce fruit similar peoples also eat avocados whole with salt and tortillas. Today,
to varieties of the avocado, however, their flowers are very avocados are served with salads, in sandwiches, and are added
different. P. schiedeana produces yellow-green, downy flowers to hot dishes just before serving. The avocado becomes very
with stamens that redden over time. B. anay produces 5-inch bitter when cooked due to a significant amount of tannins in
long green flowers. The fruit of P. schiedeana is marketed the flesh so the fruit is normally served cold. In Brazil, New
locally while the fruit of B. anay is not (Bergh, 1973; Morton, Zealand, Hawaii, and Java the avocado is treated more like a
1987; Whiley, Schaffer, & Wolstenholme, 2002). fruit than a vegetable like in the Americas. The fruits are used
in milkshakes, ice creams, and fruit salads sweetend with
sugar (Morton, 1987).
Traditional Uses
Food Uses
Ethnomedicinal Uses
Avocados have been used as a food source in the Americas,
particularly in Central America, for approximately 10,000 P. americana has been, and continues to be, used for a variety
years. The three types of edible avocados consumed by the of ailments as a traditional medicine. The leaves of P.
indigenous people are Persea americana var. drymifolia, P. americana are used in traditional medicine to treat
americana var. americana, and P. americana var. hypertension in Trinidad and Tobago (Lans, 2006). In Togo, a
guatemalensis (Williams, 1977). These three subspecies were decoction of P. americana leaves and Theobroma cacao leaves
selected and cultivated by indigenous populations of Mexico, are taken orally as an antihypertensive agent. In addition, a
the Pacific coast of Central America, and Guatemala combination of Lippia multiflora leaves, Stachytarpheta
respectively (Whiley et al., 2002). In addition, avocados were angustifolia leaves, Allium sativum bulbs and P. americana
intentionally taken from their centers of origin to other places fruit are made into a powder and taken orally for the
throughout Central and South America for cultivation treatment of hypertension (Karou et al., 2011). In the
purposes even before Europeans landed in the Americas. Philippines, the seeds or a decoction of P. americana are used
Evidence for the cultivation of avocado trees was discovered to relieve toothaches by applying them to tooth decay (Lewis
in excavations in Peru which revealed avocado remains dating & Elvin-Lewis, 2003). In the Dominican Republic, the seeds
back to 4000BC (Whiley et al., 2002). The Aztec people in are fried and mashed along with several other plants to treat
lice (Lewis & Elvin-Lewis, 2003). Avocado are also used to lipids. With up to 864,000 ppm in the fruit, fat makes up a
treat snakebites through neutralizing the hemorrhagic effect significant portion of avocado chemistry (Duke, 2012). The
of snake venom (Lewis & Elvin-Lewis, 2003). main form of glycolipids and phospholipids in P. americana
are oleic and linolenic acids. There is a different composition
of the lipids in the fruit and in the seed; the most significant
Other Uses difference being a higher oleic acid content in the fruit
Different parts of P. americana are utilized for nonfood and compared to the seed (Pacetti, Boselli, Lucci, & Frega, 2007).
non-medicinal purposes. For example, the bark of P. While many of the chemicals in P. americana are well
americana is used to set the color of dyes in Guatemala. Wood understood and defined in terms of their biological activity,
from avocado trees is used in construction. During the time of there are even more compounds with unknown activity and
the Spanish conquistadores, documents were written with the more studies are needed to elucidate a fuller picture of the
red-brown ink expelled from avocado seeds (Morton, 1987). avocado’s chemical and biological effects within the human
In cosmetics, avocado oil is used an emollient and sunscreen body.
(Swisher, 1988).
Biological Activity
Chemistry and Pharmacology There is extensive biological activity among the constituents
The main chemical components that have been identified in of Persea americana. Several studies have examined the effects
Persea americana include alkanols (or aliphatic acetogenins), of various extracts of different parts of P. americana, both in
flavonoids, terpenoid glycosides, furan-ring derivatives and a vivo and in vitro. These studies can be classified into several
coumarin. These chemical groups all contain different categories based on the type of activity found, including
functionality, which enable diverse biological activity (Yasir et analgesic, anti-inflammatory, anticonvulsant, anticancer,
al., 2010). There are over six hundred biological activities antioxidant, and hypotensive activity, among others.
known for the compounds identified in P. americana (Duke,
2012). As described in Table 2, most of the known
compounds in avocados have multiple activities ranging from Analgesic and anti-inflammatory
antibacterial and antiviral to hypotensive and antidiabetic Adeyemi et. al found in an in vivo study with mice, that an
effects (Duke, 2012). Persin, Figure 4, is an alkanol aqueous extraction of dried avocado leaves, which were
constituent of avocado leaves that has been studied rather processed through boiling, filtration, and drying, had
extensively. Persin was first studied due to its observed toxic significant analgesic and anti-inflammatory effects. For
effects on animals, especially among lactating mammals example, a 1600mg/kg dose of the extract inhibited acetic
(Oelrichs et al., 1995). Later research found that persin has in acid-induced pain (evaluated based on the writhes of the
vitro activity against breast cancer, as later described (Butt et mice) equivalent to a 100mg/kg dose of acetylsalicylic acid. An
al., 2006). Other major components of P. americana fruit are 800mg/kg dose inhibited pain response to heat equivalent to
Plant Antibacterial Anticancer Antioxidant Colorant Multiple activities1 Unknown
Part
Ascorbic-acid2 Alpha- Alanine2 Alpha- Alpha-tocopherol, arginine, 1-acetoxy-2,4-
Proanthocyanidi carotene2 Histidine2 cryptoxanthi aspartic-acid, beta-carotene, dihydroxyheltadeca-16-ene,
ns2 Alpha- Lecithin2 n2 biotin, boron, caffeic acid, abscisic acid, ash, carbohydrates,
tocopherol2 Manganese2 Violaxanthin2 calcium, carnitine, d-erythro-d-galacto-octitold-
Folic acid 2 Methionine2 chlorogenic acid, copper, erythro-l-gluco-nonulose, d-
Linoleic acid2 P-coumaric fiber, folacin, glutamic acid, glycero-d-galacto-heptitol, d-
Lutein2 acid2 glycine, glycerol, iron, glycero-d-galacto-heptose, d-
Oleic acid2 Palmitic acid2 isoleucine, lysine, glycero-d-galacto-octulose, d-
Serine Riboflavin2 magnesium, mufa, niacin, glycero-d-manno-octulose, d-
Tartaric acid2 nonacosane, pantothenic mannoketoheptose, d-
Threonine2 acid, phylloquinone, taloheptulose, dopamine, fat,
Tryptophan2 phytosterols, potassium, hentriacosane, heptacosane,
propionic acid, pufa, isolutein, leucine, linolenic acid,
pyridoxine, salicylates, myo-inositol, p-coumaryl-quinic
serotonin, stearic acid, acid, pentacosane,
thiamin, tyramine, tyrosine, phenylalanine, phytate,
valeric acid, valine, zinc proanthocyanidin-a-2, proline,
sfa, triacosane
Fruit3 N/A 4,8- N/A N/A N/A avocadene, avocadenofuran,
biscatechin avocadenone-acetat,
avocadineofuran, avocadyne,
avocadynofuran, avocadynone-
acetate, avocatins, d-arabitol,
galactitol, isoavocadienofuran,
perseitol
Seed4 Pinene2 N/A Tannin2 N/A anethole, estragole, beta- N/A
sistosterol, methyl-chavicol,
quercetin,
Leaf5 N/A N/A N/A N/A N/A n-caffeoylputrescine
Flower N/A N/A N/A N/A Anethole N/A
Estragole
Bark 1,2,4- Catechol2 Campesterol2 Epsilon- Phosphorus 24-methylene-cycloartenol
trihydroxyhepta Cholesterol carotene Subaphyllin Feruloyl-putresine
deca-16-ene
Cycloartenol
Table 2: Chemical composition of Persea americana Source: (Duke, 2012)
1. Compounds with 3 or more biochemical activities are listed here. The activities for an individual compound may include those listed in the
table or any of the 630 known activities for P. americana compounds.
2. Compounds also have multiple biological activities, however they are listed under one of their significant activities.
3. Also contains: citrostadienol which is an antirheumatic; /cryptoxanthin which is antimutagenic; cystine which is antihomocystinuric;
palmitoleic acid which makes soap; sodium; vit-B6; and vit-D.
4. Also contains volemitol, which is a sweetener.
5. Also contains paraffin, an emollient.
a 2mg/kg does of morphine. Swelling and inflammation receptors in the EGFR/RAS/RAF/MED/ERK1/2 cancer
induced by carrageenan, a compound extracted from seaweed, pathway. The two compounds work together to produce this
was also inhibited by a previously administered dose of the anticancer effect (D'Ambrosio, Han, Pan, Kinghorn, & Ding,
extract (Adeyemi, Okpo, & Ogunti, 2002). In another study, 2011). Another study investigated the cartenoid content of
polyhydroxylated fatty alcohols from avocados were found to avocado fruit and found that an acetone extract of the fruit
suppress inflammatory response (Rosenblat et al., 2011). inhibited prostate cancer cell growth in vitro. The main
carotenoid in the extract was lutein, at 70%, but alone it did
not have the anticancer effects that the extract possessed. A
Anticonvulsant mechanism of action involving the monounsaturated fat
P. americana aqueous leaf extracts were tested on mice for the content of avocado and the relationship with absorption of the
extract’s ability to delay and reduce seizures induced by phytochemicals into the bloodstream was proposed but has
pentylenetetrazole, picrotoxin and bicuculline. In each type of yet to be verified (Lu et al., 2005). Another chemo-protective
induced seizure, the aqueous leaf extracts yielded positive effect was discovered with avocado fruit extracted using
results indicating that the extract has some effect on methanol. This effect works with regard to the anticancer drug
GAGAergic action and/or neurotransmission involved with cyclophosphamide, which may have genotoxic effects on
seizures (Ojewole & Amabeoku, 2006). healthy cells (Paul, Kulkarni, & Ganesh, 2011). A study on the
effects of persin found that both in vivo and in vitro the
compound is cytotoxic for mammary epithelium for mice and
Anticancer human breast cancer cells, respectively. Applications of persin
to human breast cancer cells in vitro result in a halt of the cell
Extracts of avocado have been found to inhibit cancer growth
cycle, preventing further division, and apoptosis due to
and have some chemo-protective effects. In one study, a
interference with microtubules (Butt et al., 2006).
chloroform soluble extract of the avocado fruit flesh was
found to have activity inhibiting oral cancer cell growth. The
mechanism of action of two aliphatic acetogenin compounds
isolated from this extract was found to involve the blocking of
phosphorylation of protein kinases and growth factor
experienced a significant and does- dependant antiulcer effect
when ulcers were induced (Yasir et al., 2010).
Antiviral
An infusion and an ethanol extraction of P. americana were
Figure 4 Chemical Structure of Persin. (Source: compared regarding their inhibitory effects on viral
http://upload.wikimedia.org/wikipedia/commons/thumb/f/f6/Per replication. The infusion had activity against the three viruses
sin_Structural_Formulae_V.1.svg/400px-
AD3, HSV-1, and ADV whereas the ethanol extract was only
Persin_Structural_Formulae_V.1.svg.png)
active against HSV-1 and ADV (Yasir et al., 2010).
Antioxidant
P. americana contains many chemical compounds that have
antioxidant capabilities. Wang et al. investigated the Hypoglycemic
antioxidant capacity of avocado along with its phenolic In one study, areduction in blood glucose level was found to
content and proyanidins. The seeds had the highest occur when aqueous leaf extract of avocado was administered
antioxidant capacity and proyanidins and phenolic content to normal rats (Yasir et al., 2010).
while the fruit flesh had the lowest antioxidant capacity
(Wang, Bostic, & Gu, 2010). Another study found that the
catechins, proyanidins and hydroxycinnamic acids in the peels Hypotensive
and seeds were present in larger amounts and were more
antioxidant in vitro compared to those constituents in the pulp Dose-dependent hypotensive activity was discovered for
(Rodrı́guez-Carpena, Morcuende, Andrade, Kylli, & Estévez, intravenous doses of P. americana aqueous and methanol leaf
2011). An in vivo study on rats found that a methanol extract extracts in normotensive rats. Doses used ranged from
of avocado probably has an antioxidant effect on intracellular 6.25mg/kg to 50mg/kg with those above 12.5mg/kg having
defense mechanisms used to cope with increased oxidant hypotensive activity when compared to the control group
stress. This mechanism supports the finding that the extract (Adeboye, Fajonyomi, Makinde, & Taiwo, 1999).
could protect against oxidative stress and paracetamol toxicity
by increasing the activity of the particular defense enzymes
Vasorelaxant
during hepatic damage (Yasir et al., 2010).
There are several different mechanisms of action proposed for
the vasorelaxant effects of aqueous P. americana extracts. In
Antiulcer an in vivo study examining the aortas of rats, it was found that
An in vivo study of albino rats, it was found that the rats the vasorelaxation response occurs due to the administration
treated with an aqueous leaf extract of P. americana of the extract and is concentration related (Yasir et al., 2010).
osteoarthritis. All of these findings require further study for
Wound healing confirmation, whether positive or negative, concerning ASUs
ability to modify osteoarthritis symptoms (Ameye & Chee,
Normally, 17 days are required for an excision wound to heal 2006).
in rats. However, in a study by Nayak et al. complete healing of
an excision wound occurred in 14 days after oral or topical Research investigating the antidiabetic and cholesterol-
treatment with P. americana fruit extract at 300mg/kg/day lowering capabilities of P. americana has found positive
(Nayak, Raju, & Chalapathi Rao, 2008). results in clinical trials. For example, a study by Lerman-
Garber et al found that a diet high in monounsaturated fatty
acids from avocados and olive oil for patients with non-
insulin-dependent diabetes patients resulted in minor
decrease in cholesterol and a 20% decrease in plasma
Clinical Studies triglycerides (Lerman-Garber, Ichazo-Cerro, Zamora-González,
Although there has been extensive research into the biological Cardoso-Saldaña, & Posadas-Romero, 1994). Another study
activity of Persea americana, few clinical studies have been comparing an avocado enriched diet high in monounsaturated
done examining the avocado’s effects in humans. There have fatty acids and a high carbohydrate diet also found that the
been four clinical studies investigating the use of the non- avocado enriched diet was more effective in lowering total
soap-forming, or unsaponifiable, extract of P. americana cholesterol levels and low-density-lipoprotein (Colquhoun,
combined with the unsaponifiable extract from soybeans, Moores, Somerset, & Humphries, 1992). These clinical trial
known as avocado/soybean unsaponifiables (ASUs), to treat results coincide with the hypocholesterolemic activity of some
osteoarthritis. These studies focused on osteoarthritis of the of the chemical constituents in P. americana (Duke, 2012).
hip and/or knee. In two of the studies, 300mg of the extracts
taken each day for three months resulted in lower use of non-
steroidal anti-inflammatory drugs for pain and inflammation. Contraindications
There was no significant difference found between 300 and Although the fruit of Persea americana is widely cultivated and
600mg/day doses. In a 6-month study, a two month delayed consumed safely as a food source, there are contraindications
onset of effects was observed and effects continued for two for the avocado. Avocado hypersensitivity, while rare, is one
months past the end of treatment. No long-term effects on the contraindication. Possible symptoms include anaphylaxis,
prevention of joint narrowing were observed. The fourth angioedema, bronchial asthma, rhinoconjunctivitis, urticaria
study investigated effects of ASUs on hip osteoarthritis with and vomiting (Blanco, Carrillo, Castillo, Quiralte, & Cuevas,
two years of treatment. With a 300mg/day treatment, no 1994). In a study of avocado hypersensitivity, an allergic
statistically significant difference was found between the ASUs reaction usually occurred when the patient had a preexisting
and placebo concerning levels of pain and NSAID usage after allergy to latex, chestnut, and/or other fruit, such as banana
one year. Despite these negative results, ASUs may have (Blanco et al., 1994). Interactions with Warafin, an
symptom-relieving effects for the most severe hip anticoagulant, have been documented although the
mechanism through which avocado prevents the Persea americana has been used for thousands of years as
anticoagulant effects of Warafin is unknown (Blickstein, both food and medicine. The beneficial activity of avocado
Shaklai, & Inbal, 1991). In addition, the leaves of P. americana occurs due its composition of bioactive compounds, which
contain a toxic compound, persin, which has been found to affect a myriad of pathways in the human body. Further
cause necrosis of lactating mammary glands and the studies are needed, especially clinical studies, to verify the
myocardium in mice (Oelrichs et al., 1995). Instances of efficacy of traditional uses of P. americana. The many
poisoning have been reported in rabbits, horse, cattle, goats, biological activities found in laboratory studies also need to be
fish and canaries (Lewis & Elvin-Lewis, 2003). These investigated with clinical studies to determine the
poisoning are most likely due to the persin content present in effectiveness of specific activities in humans. Since instances
the avocado plant (Yasir et al., 2010). of cancer and diabetes have become more widespread threats
to human health worldwide, the avocado’s activity in
preventing and treating these diseases needs to be further
Current Use in Allopathic and CAM Therapies researched. In particular, the development of cancer
The only major current use of Persea americana in allopathic treatments should be studied since P. americana has shown
medicine is as an osteoarthritis treatment in which the activity against so many different types of cancer. In addition,
unsaponifiable portions of the fruit are added to soy bean the many chemical components with unknown biological
unsaponifiables (Ameye & Chee, 2006). These ASUs (avocado- effects must be studied for complete understanding of the
soybean unsaponifiables) are also used as dietary effects of P. americana in the human body (Table 2). As a
supplements in complimentary and alternative medicine widely consumed food, whose cultivation has spread globally
therapies for the treatment of arthritis and have support for in more recent years, the avocado will continue to remain an
effectiveness from positive results in clinical trials (Soeken, important food source that provides nutrition along with
2004). Another current use of avocado is the preparation of flavor (Whiley et al., 2002). With proper investigation and
skin products with the oil due to the strong emollient drug development, the avocado has the potential to provide
properties of avocado oil. The oil is also a component of hair much needed medicines for a wide range of ailments in the
products. Some CAM treatments for skin disorders, like future.
sclerosis, include the use of avocado oil (Khan & Abourashed,
2010). Although there are not many targeted medicinal uses
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Phenolics, In Vitro Antioxidant and Antimicrobial Activities,
and Inhibition of Lipid and Protein Oxidation in Porcine
Petroselinum crispum (Mill.), Apiaceae
Ellen Chiang
Introduction
Petroselinum crispum Mill. commonly referred to as parsley,
belongs to the Apiaceae (Umbelliferae) family, which includes
other popular plants such as carrot, coriander, and celery
(Anthony & William, 1977). Parsley has a unique aroma that
distinguishes it from other leafy, green herbs (Stace, 1991).
The aromatic herb is used worldwide to garnish and flavor
dishes. The perfume industry also uses the plant’s essential
oil, which is responsible for the aroma, in fragrances
(Teuscher, 2005). The essential oil contains the most
medically significant compounds, mainly terpenes and
phenolic compounds (Taiz & Zeiger, 1998). These compounds
contribute to the efficacy of the herb as a diuretic,
immunomodulator, antioxidant, abortifacient, and
hypoglycemic agent. P. crispum is one of the most widely
known herbs, especially in the U.S. where it is found fresh in
most supermarkets or in supplements, dietary pills, and
essential oil extracts (Peter, 2004).
Dioscorides named P.crispum “rock celery” because the Figure 1. Flower umbels of flat-leaved parsley
undomesticated plant grew amongst rocks (Peter, 2004). P. Image source:
crispum is native to the Mediterranean but naturalized http://www.dispatch.com/content/stories/home_and_garden/201
throughout Europe. Parsley is now heavily cultivated, 2/06/03/1-plant03-gm4hh52o-1.html
especially in the U.S., Europe, and western Asia (Navazio,
2012). Two of the most popular parsley varieties are
Parsley is a biennial herbaceous plant; the herb foliage grows
Petroselinum crispum var. crispum, also known as curly-leafed
in the first year and sets seed in the second year (Navazio,
parsley, and Petroselinum crispum var. neapolitanum, referred
2012). If parsley is being cultivated for its leaves, stems, or
to as flat-leaf parsley or Italian parsley (Teuscher, 2005).
Figure 2. Flat-leaved parsley Figure 3. Fool’s Parsley
A close up of the morphological traits of Italian parsley leaves. Fool’s parsley leaves are structurally similar to flat-leaved
Image source: http://www.sunlandherbs.com/wp- parsley.
content/uploads/2010/07/parsley.flatleaf.HZell2009.WikiCom.jpg http://www.biolib.cz/en/taxonimage/id133998/?taxonid=40297
roots then these are collected the first year. However, seed accelerated by soaking the seeds in hot water a day prior to
collection occurs in the second year after the flowering period. sowing in order to soften the seed coat (Peter, 2004).
P. crispum forms yellow-green flowers in 10-20 compound
P. crispum grows up to 60 to 120 cm tall in sunny or slightly
umbels (Anthony & William, 1977) (Figure 1). Wasp and
shaded areas that have humid soil with a pH level of 5.3 to 7.3
hoverfly species cross-pollinate the parsley florets, each of
(Navazio, 2012). P.crispum var. neapolitanum has dark green
which have five stamens, two styles, and a two-celled ovary.
triangular leaves, which are flat and divided into 2-3 leaflets.
This type of ovary produces two seeds, one from each cell
The leaflet edges are pinnately separated (Polunin, 1969)
(Navazio, 2012). The ideal temperature for pollination and
(Figure 2). Fool’s parsley, Aethusa cynapium, also has flat,
subsequent seed production is 65-85 degrees Fahrenheit;
triangular leaves with similar pinnation. These similarities
therefore, the flowering period typically occurs during the
often result in misidentifying A. cynapium as P. crispum var.
warmer months of June and July (Teuscher, 2005). Parsley
neapolitanum (Figure 3). A. cynapium also belongs to the
seeds take about 3 weeks to germinate. This process can be
Apiaceae family but is poisonous (Stace, 1991). The
unpleasant odor of fool’s parsley helps distinguish it from
Figure 4. Curly-leaved parsley Figure 5. Hamburg Root
Curly-leaved parsley displays a voluminous and ruffled Hamburg parsley variety has significantly larger roots.
appearance. Image source:
Image source:http://www.sunlandherbs.com/wp- http://www.mariquita.com/images/photogallery/umbelliferfamily.
content/uploads/2010/07/parsley.leaf_.WikiCom.jpg jpg
parsley, which has a sharp, grassy aroma (Tisserand, 1995). P. parsley worms. They feed on both celery and parsley foliage
crispum var. cripsum is similar to the neapolitanum variety for several weeks before pupating. Parsley worms do not
except that there are more leaflets per stem and the leaves cause any major damage to the plant and can easily be dealt
have a ruffled appearance (Figure 4). Parsley roots grow up with by manually picking them off the plant (Schrock, 2004).
to 20 cm in length and 5cm in width. The roots are a faint
yellow color and carrot-shaped. However, P. crispum var.
radicosum, or Hamburg root parsley, has much larger roots Traditional Uses
(Figure 5) and is commonly used in European cuisine Symbolic
(Teuscher, 2005).
The ancient Greeks believed that parsley originated from the
P. crispum does not have many predators. The most common blood of Archemorus, the “Forerunner of Death” (Scoble &
pest is the larva of Papilio polyxenes asterius, the black Field, 2001). The herb was a symbol of imminent death and
swallowtail butterfly. The larvae are often referred to as was used in funeral rites. For example, parsley was given to
the terminally ill and parsley garlands were placed on corpses. Parsley Leaf Oil Parsley Seed Oil
Compounds
Parsley also eventually became associated with Satan and was (% composition) (% composition)
dedicated to the queen of the underworld, Persephone (Peter, α-pinene 26.42 15.73
2004). Virgins were warned not to plant parsley, for doing so Sabinene 1.1 0.64
would result in losing their virginity to Satan. The Greeks β-pinene 18.04 10.01
believed that the parsley seed traveled to and from the Myrcene 4.24 0.22
underworld several times before germinating (Scoble & Field, α-phellandrene 0.51 0.12
2001). Due to these negative associations, parsley was not
β-phellandrene 6.48 2.14
consumed or incorporated into dishes. Interestingly, the
Terpinolene 2.52 0.01
Greeks began to crown athletic victors with parsley garlands
in memory of important predecessors. Over time, parsley p-mentha-1,3,8-triene 16.41 0.12
shifted from a symbol of death and Satan to a symbol of Myristicin 11.92 39.65
strength (Castleman, 2009). Elemicin 2.71 4.84
2,3,4,5-tetramethoxy-
0.72 7.82
allybenzene
Deodorant Apiol 0.27 18.32
Table 1. Essential oil content of parsley leaves and seeds
The Romans had a less superstitious view of parsley, but they
The table shows the percentages of each compound found in
also did not widely consume the herb. However they often
the essential oils of parsley leaves and seeds.
chewed on parsley to hide the lingering smell of garlic from
their meals (Castleman, 2009). This may have contributed to
the use of parsley to garnish plates of food. The Romans also topically and internally (Lis-Balchin, 2006). In 1850 the U.S.
believed that wearing parsley garlands would prevent pharmacopeia documented parsley as a laxative, diuretic, and
intoxication and were thus worn at large banquets and parties quinine substitute (Castleman, 2009). Many communities
(Peter, 2004). continue to implement traditional medicinal practices. For
example, Colombian immigrants of London continue to use
parsley as a condiment for its digestive and cleansing
Medicinal properties. They also use parsley infusions to treat and
P. crispum has a long history of medicinal use. Hippocrates regulate menstrual pain (Ceuterick, Vanderbroek, Tony &
classified parsley as a diuretic. During the Medieval period, Pieroni, 2008). The powder of parsley seeds has also been
parsley compresses were used to treat arthritis and chest pain massaged into the scalp in order to stimulate hair growth.
was addressed by drinking wine boiled with parsley. In the Additionally, parsley juice was used to prevent and treat
17th century, an English herbalist expanded on the medicinal insect bites (Peter, 2004).
relevance of parsley and recommended using P. crispum to
alleviate menstrual symptoms. Parsley was administered both
Culinary
The first uses of parsley as seasoning trace back to Europe
during the Middle Ages. Charlemagne, who grew the herb on
his property, is often credited for increasing the popularity of
incorporating parsley in food (Peter, 2004). The plant’s
distinct aroma and flavor explains its many culinary
applications (Polunin, 1969). The raw leaf stalks and roots can
flavor food or can be eaten as a side dish (Teuscher, 2005).
Because parsley originated in the Mediterranean region, the
herb is commonly associated with Italian cuisine, hence the Figure 6. The chemical structure of myristicin.
name “Italian parsley” (Stace, 1991). In the U.S., the curled Myristicin’s structure is directly related to its significant
leaves of P.crispum var. crispum are used as a garnish or plate functions.
decoration. In Germany, parsley is the most commonly used Image source: http://en.wikipedia.org/wiki/Myristicin
herb in cooking. Tabbouleh, a very popular Middle Eastern
dish, uses parsley as the main ingredient (Teuscher, 2005). triene act as pest control. The terpenes are responsible for the
The Jewish Passover Seder has parsley in the dishes to characteristic parsley aroma. This aroma is meant signal the
symbolize a new beginning (Peter, 2004). presence of compounds that are toxic to several insects.
However, some aphids are able to feed on parsley in a way
that specifically avoids ingestion of the toxins. Due to this
Chemistry and Pharmacology adaptive mechanism, the parsley aroma now serves as a food
Secondary products function as plant defense mechanisms or signal to these pests (Rosenthal & Berenbaum, 1991).
pollinator attractants (Sumner, 2000). These compounds have Myristicin is a toxic phenolic compound that has
various medicinal applications. In parsley, the essential oil hallucinogenic properties (Figure 6). Nutmeg contains higher
(Table 1) and seed coating primarily contain terpenes and levels of myristicin and, at high intake levels, can act as a
phenolic compounds, which are responsible for parsley’s anti- psychoactive (Hallström & Thuvander, 1997). Vitamin C,
oxidant, anti-inflammatory, anti-microbial, diuretic, and vitamin A, vitamin K, and folate are also found within the
hypoglycemic properties (Taiz & Zeiger, 1998). parsley leaves (Teuscher, 2005).
Leaves Seeds
The leaves of P. crispum are made up of 0.02-0.9% volatile oil. Parsley’s seeds contain 2-8% volatile oil and 13-22% fixed oil.
The main components of the oil are α-pinene, β -pinene, p- The major compounds are α-pinene, β-pinene, myristicin, and
mentha-1,3,8-triene, and myristicin (Peter, 2004). The apiol (Peter, 2004). Apiol is a phenolic compound that is
monoterpenes: α-pinene ,β –pinene, and p-mentha-1,3,8- responsible for parsley’s abortifacient properties (Figure 7).
Figure 7. The chemical structure of apiol. Figure 8. Apiin Structure
Apiol is similar to myristicin but has an additional methoxyl The chemical structure of apiin, an important compound in
group. parsley.
Image source: http://en.wikipedia.org/wiki/File:Apiol_acsv.svg Image source: http://en.wikipedia.org/wiki/File:Apiin.svg
These compounds stimulate the uterus and can also be used to (Peter, 2004). Additionally, apiin makes up 0.2-1.6% of the
induce the beginning of a menstrual cycle (Castleman, 2004). roots and is from a large subset of phenolic compounds
Furanocoumarins, such as oxypeucedanin, account for a large known as flavonoids (Taiz & Zeiger, 1998) (Figure 8). Apiin is
part of the seed coat (Maderfeld et al, 1997). a glycosidic form of apigenin, which has been shown to help
Furanocoumarins are simple phenolic compounds that inhibit prevent chemoresistance (Gupta & Seshadri, 1952).
DNA transcription after exposure to UV-A light causes the Phthalides including: ligustilide, senkyunolide, and
compounds to enter a high-energy state. These compounds butylphthalide as well as polylines such as falcarinol and
are therefore believed to have allelopathic effects via the falcarindiol also make up parsley’s roots (Teuscher, 2005).
regulation of weed and other plant germination (Roenthal &
Berenbaum, 1991). In fact, these compounds may inhibit
parsley itself, thus explaining the tough seed and long Biological Activity
germination period (Kato et al., 1978). In vitro
Antioxidant
Roots Free radicals lead to oxidation of biomolecules which then
Essential oil makes up 0.2-0.75% of parsley’s roots. The oil lead to cell damage or death. Antioxidants mitigate the effects
mainly consists of terpinolene, β-pinene, apiol, and myristicin of oxidative stress by scavenging these free radicals and
donating electrons to them in order to keep biomolecules Ahmed, & Ebraheim, 2010). Similarly, parsley is susceptible to
intact and undisturbed (Wong & Kitts, 2006). Myristicin and Erysiphe heraclei, which causes growth of powdery mildew on
apiol are believed to be the major contributors to the the leaves (Koike, Gladders, & Paulus, 2007). P. crispum has
observed antioxidant properties of parsley, which are also been shown to reduce the growth of Listeria
characteristic of phenolic compounds (Taiz & Zeiger, 1998). monocytogenes, L. innocua, Escherichia coli O157:H7, E. coli Bs-
1 and E. carotovora (Wong & Kitts, 2006).
The research of Zhang et al. supported this hypothesis by

testing antioxidant capabilities through three in vitro assays: Anti-inflammatory
β-carotene bleaching assay, 2,2-diphenyl-1-picrylhydrazyl free The immune system protects humans from foreign antigens,
radical scavenging assay and Fe2+-metal chelating assay. While wards off microbes, etc. However, chronic activation of the
the metal chelating properties where insignificant, parsley’s immune system results in inflammation and is linked to tissue
essential oil showed activity in β-carotene bleaching and free damage, neuropathological diseases, and autoimmune
radical hunting. Apiol showed more free radical scavenging disorders. Myristicin found in parsley has been shown to
activity than myristicin despite being present in lower reduce inflammation, by inhibiting the production of nitric
concentrations. The presence of an additional methoxyl group, oxide and cytokines, inflammatory proteins released by the
a prominent electron donor group, most likely contributes to immune system, through the calcium pathway (Lee & Park,
this observed difference (Zhang, Chen, Xi & Yao, 2006). 2011).
Yousofi et al. treated mice splenocytes, white blood cells from
Anti-microbial the spleen, with phytohemagglutinin (PHA) or
lipopolysaccharide (LPS) in order to stimulate an immune
Parsley has evolved defense mechanisms against microbial
response from the T and B cells respectively. In the
predators such as bacteria and fungi. The secondary plant
experimental group treated with PHA, parsley essential oil
phenolic compounds such as apiol, myristicin, and
suppressed T-cells proliferation and therefore inhibited the
furanocoumarins play important roles in these functions
growth of the splenocytes. Parsley’s essential oil displayed
(Manderfeld, Schafer, Davidson & Zottola, 1997). One study
similar suppression of B-cells but only at higher
extracted parsley leaves in a 70% alcohol solution after they
concentrations. Therefore parsley seems to be more efficient
were washed, dried, and ground up. The solution then
at targeting T-cells. These researchers also found that parsley
underwent filtration and evaporation to obtain a semi-solid
suppressed nitric oxide concentrations without toxic effects
residue. This parsley extraction showed significant inhibitory
(Yousofi, Daneshmandi, Soleimani, Bagheri, & Karimi, 2012).
activity against Staphylococcus aureus. Additionally, the
addition of fresh parsley leaves to Kareish cheese showed
reduced levels of yeast after two hours. However, parsley was
less effective in reducing the proliferation of mold (Wahba,
In vivo GSH levels, therefore protecting and reducing damage to the
liver tissue (Ozsoy-Sacan et al., 2006).
Diuretic
In traditional medicine, parsley is most used as a diuretic. One
study examined the effect of parsley seed extract on the urine Clinical Studies
output of rats. The rats alternated between drinking aqueous Parsley has been shown to have abortifacient effects when
parsley seed extract and water without any additives. The taken in high doses (Lis-Balchin, 2006). A retrospective study
results show that when the rats drank the P. crispum extract, was conducted in Montevideo, Uruguay where calls to the
they had significantly higher levels of urine output every 24 poison control center were made after ingesting an herb with
hours compared to when they only drank water. Parsley the intention to abort a fetus. Of the 86 reported cases, 13
increases urine output by inhibiting the activity of the Na+- K+ involved the use parsley either in a single herb infusion or in a
ATPase. This inhibition increases the K+ concentration in the homemade mixture with other herbs. Three cases of taking
lumen, therefore leading to increased water flow into the parsley with Ruta graveolens lead to multiple organ failure in
lumen via osmosis. This process results in increased urine the women. In 7 cases, where parsley was either taken by
flow and output (Kreydiyyeh & Usta, 2001). itself, with prescription drugs, or in addition to self-mutilation,
the end result was abortion. Although causation between
ingestion of parsley and abortion cannot be conclusively
Hypoglycemic Agent
determined, this study addresses the need for greater
As traditionally used in Turkey, parsley displays hypoglycemic awareness when using herbal medicines at home without the
effects (Patel, Kumar, Laloo & Hemalatha, 2012). One in vivo supervision or guidance of someone that is knowledgeable in
study compared the effectiveness of parsley extract versus the field (Carmen & Laborde, 2003).
gilbornuride, an anti-diabetic treatment, in diabetic rats. One
The antioxidant properties of parsley have been studied in
group of diabetic rats received parsley extract for 28 days. The
humans. One clinical trial focused on the potential antioxidant
second group of diabetic rats took gilbornuride for 28 days. All
properties of apiin, a flavonoid glycoside found in P.crispum.
of the rats had lower body weight, which may indicate the loss
The 14 subjects were both males and females. Those in both
of tissue due to oxidative damage from diabetes. However the
the control group and the experimental ate the same meals
gilbornuride treatment group had higher body weight
with the exception that fresh and microwaved parsley was
compared to the parsley treatment group. This difference may
added to the experimental group’s meals. The subjects’ urine
be attributed to the herb’s diuretic effects. The diabetic rats
outputs were measured for apiin concentration. Low
treated with parsley showed decreased blood glucose levels
concentrations of apiin in the experimental group indicated
and decreased lipid periodization in the liver. Liver
that the intestine readily absorbs apiin. However, the high
glutathione (GSH) functions as an antioxidant to diminish the
variability of apiin concentrations between subjects suggests
effects of high levels of free radicals caused by oxidative stress
that there are different aptitudes for apiin absorption. Two
from diabetes. Parsley treatment in rats showed increases in
antioxidant enzymes, GR and SOD were monitored In order to
determine whether apiin ingestion results in antioxidant parsley components should be avoided by those with allergies
activity. The subjects that consumed parsley in their diets to plants in the Apiaceae family (Castleman, 2009).
showed increased activity levels of these two enzymes
(Nielsen et al., 1998).
Drug Interactions
Those who are taking Warfarin, a blood thinner, should
Contraindications closely monitor parsley intake, which may reduce the
General Safety Guidelines effectiveness of the drug (Heck, DeWitt, & Lukes, 2000).
Additionally, those taking diuretic drugs may want to refrain
There is a common misconception, especially among
from taking parsley because both treatments work to increase
Westerners, that plant based therapies have negligible or no
water excretion. Too much water loss can lead to dehydration,
side effects. However, herbal remedies also carry dangers
dizziness, and low blood pressure. Those with parsley
related to dosage, application method, and drug interactions.
allergies should avoid taking aspirin with parsley because the
Traditionally, the society’s healers carried the knowledge of
aspirin will increase the body’s sensitivity to the herb and may
these safety and efficacy parameters. However, botanical
result in increased bleeding risk (Grossberg & Fox, 2008).
medicine is now a global industry. In the U.S. and many other
countries, there is a need for further regulation on the sale and
distribution of herbs. Universal parameters are necessary in Current Use in Allopathic and CAM Therapies
order to ensure the quality, safety, and efficacy of these
natural products (Lewis & Lewis, 2003). U.S. physicians do not prescribe P. crispum as a medicinal
treatment. However, many people use parsley in place of
Most people purchase the fresh herbal form of parsley but water pills because the herb is a cheaper diuretic. Parsley’s
supplements, teas, and oils are also for sale. Parsley seed oil ability to increase urine output makes it a popular herb to
has high levels of myristicin and apiol; therefore, the seeds recommend for treating congestive heart failure and high
and oil should not be used in cooking. At high doses, the oil blood pressure (Kreydiyyeh & Usta, 2001). In Germany,
content may lead to gastroenteritis, headache, kidney and parsley seed tea is a very popularly proscribed high blood
liver damage, shock and coma. Additionally, high quantities of pressure treatment. For optimal results, it’s recommended to
myristicin and apiol may stimulate the uterus and should drink 3 cups of this infusion per day. However, the therapeutic
therefore be avoided by pregnant women. Babies and young levels can easily be surpassed and reach toxic levels, so the
children have higher susceptibility levels to the toxic dosage must be carefully monitored. Parsley is officially
compounds so exposure to parsley essential oil should be recognized as a diuretic by the German equivalent of the FDA
limited. Parsley leaves, stalks, and roots have low levels of and the German Commission E recognizes parsley as a kidney
these compounds and are safe to consume. Those with stone treatment (Peter, 2004). The diuretic properties of
sensitive skin may experience skin rashes aggravated by the parsley contribute to its detoxifying uses in juice cleansers
plant’s furanocoumarin content (Lis-Balchin, 2006). All and health tonics.
Parsley tinctures, the herb dissolved into alcohol, can also be popular herbs. Data from in vitro, in vivo, and clinical studies
made or bought for around $16 per 2 ounces of tincture. The of parsley provide empirical support for the traditional
recommended dose is 1-3 ml, three times per day (Johnson, remedial applications of the herb as an antioxidant, anti-
2012). Parsley supplements are very common in the U.S. and inflammatory, anti-microbial, diuretic, abortifacient, and
can be bought over the counter at drug stores such as hypoglycemic agent. Myristicin and apiol are the main
Walgreens. The supplements usually come in capsule form. compounds responsible for this array of medicinal properties.
Fresh parsley can be bought at almost all supermarkets for Both chemicals are most concentrated in parsley seeds, which
around $2 /bunch. Most CAM therapies utilize nutrition as contain the highest amount of volatile oils. Apiin has very
disease prevention, therapy, and health promotion. Parsley is interesting properties but has been much less studied.
a perfect example of this type of treatment. Many cultures However, the research that has been conducted on apiin in the
have and continue to use parsley as a condiment or main form of apigenin shows great potential for its biological
ingredient in food preparation and consumption. Although it significance in cancer therapy (Gao et al., 2013). Myristicin
may seem cheaper or more convenient to buy supplements, may also have anticancer effects (Zheng et al., 1992).
the dried form of parsley may have lost most of its biological Incorporating fresh parsley into one’s diet can serve as an
activity and effectiveness and there is risk of product effective, economic, and relatively safe way to boost overall
adulteration due to the weak regulations on herbal products health. However, there is a need for more clinical studies in
(Lewis & Lewis, 2003). Accidental adulteration of parsley order to assess the efficacy and safety of the therapeutic
products with plants of greater toxicity, such as Fool’s parsley, applications of parsley in humans, especially in regards to
poses a very serious risk. pregnant women and children. Safe dosage levels allow
humans to receive therapeutic effects and avoid the
ramifications of excess toxin intake. In the past, parsley was
Discussion
reserved for momentous events such as victory and death, but
Despite the prominence of allopathic healthcare systems in nowadays the herb often goes unnoticed on the corner of our
many countries, patients often refer back to traditional plates. Further research on parsley and its components could
remedies when conventional medicine has proved to be lead to important discoveries that impact both botanical and
ineffective or too expensive. In urban areas, where there are human health.
large immigrant populations, healthcare professionals with
knowledge of these cultural traditions are able to better serve
their patients. Additionally, some immigrants rely heavily on References Cited
traditional treatments because their illegal status limits their Anthony, H., & William, T. (1977). Flowers of greece and the aegean.
access to national healthcare systems (Ceuterick, (p. 110). London:
Vanderbroek, Tony & Pieroni, 2008).
Chatto and Windus Ltd.
P. crispum has a long history of symbolic, medicinal, and
culinary uses and continues to be one of the world’s most
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Rosmarinus officinalis L., Lamiaceae
Kedra Woodard
Introduction
Rosmarinus officinalis, commonly known as rosemary, is a
perennial plant that belongs to the Lamiaceae family. It is also
known in Chinese Pinyin as mi die xiang. The Lamiaceae
family is a large group, rich in aromatic species and is used in
many ways such as culinary herbs, part of folk medicine, and
fragrance. Many of the species of this family are rich in
essential oils. Studies have shown that species of the
Lamiaceae family have antimicrobial, anticarcinogenic,
antioxidant, cognitive-improving, and glucose level lowering
properties due to the essential oils that are typically secreted
by glandular trichomes (Okoh, Sadimenko, & Afolayan, 2011). Figure 1. Picture on the left is of (A)peltate trichome and
Trichomes are present in most plants and are specialized the picture on the right is of (B)capitate trichome. Source:
http://www.knottybits.com/jftrich/trichome.htm
epidermal cells. Glandular trichomes, found in most species in
the Lamiaceae family, contain secretions produced by plants
including volatile oils. There are typically two types of areas near seashores, which makes the Mediterranean
trichomes in the leaves and stems of plants, peltate and seashore a perfect growing location. R. officinalis received its
capitate. An illustration of both can be found in Figure 1. R. common name from where it can be found in abundance, near
officinalis was first cultivated in the Mediterranean and was the sea. The term rosemary means “dew of the sea” (González-
then transplanted in China. Today, R. officinalis is cultivated Trujano et al., 2007). Rosemary has been recorded in an
worldwide (Waggas & Balawi, 2008). Italian herbal, circa 1500 (Foley 1974). The picture from this
document of R. officinalis can be seen in Figure 2. Rosemary
can be identified by its dark green leaves, small blue, violet, or
Botanical Description white flower, and minty odor.
Rosmarinus officinalis is an herb with ever-green needle-like The primary pollinators of rosemary are honeybees because
leaves. It is indigenous to the Mediterranean where it grows rosemary is rich in highly concentrated nectar. Studies have
wild. It can especially be found near the Mediterranean shown that when compared to nine other plants of the
seashore in Spain, Portugal, Morocco and Tunisia where it can Lamiaceae family, rosemary is one of the most preferred by
grow up to 6 feet high. Rosemary thrives best in warm, sunny honeybees (Zer & Fahn, 1992). One study discusses the
Cultivars Description
Albus White flower
Arp Leaves light green, lemon-scented
Aureus Leaves speckled yellow
Benenden Blue Leaves narrow, dark green
Blue Boy Dwarf, small leaves
Golden Rain Dark green leaves, with golden streaks
Gold Dust Low and lax, trailing, intense blue flower
Irene Procumbent selection from Tuscan Blue
Lockwood de Shrubby
Forest
Ken Taylor Pink flowers
Majorica Pink Distinctive tall fastigate form with wider leaves
Miss Jessop’s Pink flower
Upright
Pinkie Lower groundcover
Prostratus Fastigate form, pale blue powers
Pyramidalis Pink flowers
Roseus Pale blue flowers, cold hardy similar to Arp
Salem Spreading, low-growing, with arching branches;
flowers deep violet
Severn Sea Traditional robust upright form
Wilma’s Gold Yellow leaves
Table 1. Rosemary cultivars and descriptions (Mulas,
Figure 2. Rosemary illustration from an Italian herbal, Brigaglia, & Cani 1997).
circa 1500
Image Source: http://en.wikipedia.org/wiki/Rosemary
Gold, are frequently sold in grocery stores and nurseries
(Mulas, Brigaglia, & Cani 1997). Table 1 is a chart illustrating
percentage of dry matter in the nectar of rosemary in varying more frequently sold cultivars and their varying descriptions.
locations in the summer. The amount found in Israel may be
as high as 62-65% and about 44% in Jerusalem. The sucrose:
glucose: fructose ration is about 2-83:1:1-85 however amino Traditional Uses
acid levels are pretty low (Dafni et al., 1988). Because Rosmarinus officinalis is used topically in Mexico to relieve
honeybees pollinate based on the amount of nectar that can be rheumatic pain. The rosemary is prepared by maceration,
found, rosemary in these areas are preferred. which is the process of softening using an alcohol, in ethanol.
There are several common cultivations of rosemary. Many of This mixture is applied externally and directly to the skin
these cultivations, such as Albus, Arp, Salem, and Wilma’s
Chemical Plant Part Present Percent per million improvement of circulation, hyperglycemia and skin care
(ppm) (Hamedo, 2009). Rosemary tea, as a folk remedy, can be used
(+) Limonene Plant 16-76 for nervous headaches and healing colds. Some studies have
Acetic Acid Esin, Exudate, Sap
Alpha Terpineol Plant 24-1555 reported its use as an effective diuretic and mood stabilizer
Ascorbic Acid Plant 612-673 (Haloui et al., 2000).
Betulinic Acid Leaf
Cadalene Plant
Rosemary was believed to strengthen memory in ancient
Caffeic Acid Plant Greece. Rosemary was consumed often in hopes to avoid
Calcium Plant 10919 - 16150 forgetting. It was also very popular to see Greek students
Camphor Plant 60 - 5800 wearing rosemary leaves in their hair as they studied so they
Carbohydrates Plant 640,600 - 704660 could remember reviewed information. Rosemary became a
Carnosic acid Leaf, Plant 448.4- 5000
Chlorogenic Acid Plant
symbol of remembrance (Foley 1974).
Copper Plant 5–6 Rosemary was cultivated in many of the ancient European
Ethanol Plant countries, including France, Germany, Denmark, England, and
Fenchone Plant 250
Fiber Plant 165420 - 206338 parts of Scandinavia. It was too cultivated in ancient Central
Glycolic Acid Plant America, Venezuela, and the Phillippines. This plant has been
Iron Plant 220 – 400 associated with love and marriage as well as birth and death
Lavandulol Plant 7 – 34 in many of these cultures. In Shakespeare’s Hamlet, it is used
Limonene Plant 1,950 as a symbol of love (al-Sereiti, Abu-Amer, & Sen, 1999).
Methyl Ether Plant
Rosmaric Acid Plant 3,000 - 3,500
Rosmarinic Acid Leaf 3,500
Plant 25,000 Cosmetic Uses
Shoot 13,500
Tissue Culture 38,957
Rosmarinus officinalis is commonly used as a fragrant additive
Rosmarinol Plant in soaps and other cosmetic products. Rosemary is used in
Safrole Plant 32 – 95 these products for treating cellulite, wrinkles, and normalizing
Salicylates Leaf 70 – 680 excessive oil secretion from the skin (Hamedo & Abdelmigid,
Sodium Plant 462 – 592 2009). Rosemary can also be found in hair dyes and rinses to
Tannin Plant
Zinc Plant 30 – 38
darken and retain color and in oils and shampoos to prevent
Zingiberene Resin, Exudate, Sap premature balding.
Table 2. A few important constituents found in Rosmarinus
officinalis.
(Ventura-Martínez, Rivero-Osorno et al., 2011). Rosemary is

also used in ethnomedicine as a general stimulant, for
Figure 4: Chemical structure of caffeic acid.
Figure 3. Chemical structure of rosmarinic acid.
cineole as a main component (Stojanović-Radić, Nešić, Čomić
& Radulović, 2010) though, there are not many studies that
Culinary Uses discuss the role of this compound. Table 2 displays several of
Rosemary is an ancient spice. Because it is native to the the constituents found in rosemary, as well as its plant
Mediterranean, it is extremely common in Mediterranean location, and abundance. The synergy of the constituents helps
cuisines. Extracts produced from the leaves of rosemary can to produce the odor, appearance, and nutrients of rosemary.
also be used in food production to keep materials from Rosemary extracts are effective in relaxing the smooth
spoiling due to its antioxidant properties. Its effectiveness in muscles of the trachea and intertine. It has choleretic,
food preservation can be witnessed in many different types of hepatoprotective, and anticarcinogenic properties. Recently,
foods including refrigerated beef and frozen pork patties scientists seem to be particularly interested in three of the
(Lara, Gitierrez, Timón & Andrés, 2011). acids found in rosemary: carsonic acid, caffeic acid and one of
its derivatives, rosmarinic acid. All of these compounds have
antioxidant effects (al-Sereiti, Abu-Amer, & Sen, 1999).
Other Uses Figures 3 and 4 illustrate the structure of rosmarinic acid and
When combined with other herbs, the chemical activity of caffeic acid, respectively.
Rosmarinus officinale can be increased. For example, a mixture Carnosic acid is a carbon dioxide solution found in many plant
of its leaves and juniper berries were burned in hospitals molecules. It can be found in abundance in rosemary. Carnosic
around France to kill germs during World War II (Foley 1974). acid has been found to promote weight loss. Ibarra et al.
Also, using rosemary leaves mixed with myrrh can be effective discovered this phenomenon while observing its effects in
in treating bleeding gums. mice. In this study, standardized 20% carnosic acid rosemary
leaf extract was used to identify its effects on weight gain,
glucose level, and lipid homeostasis in mice (2011). Three
Chemistry and Pharmacology groups were observed: mice given a high-fat diet, mice given a
Rosmarinus officinalis has many important constituents with low-fat diet, and mice given a high-fat diet supplemented with
important biological activity. Some studies reported 1,8– 500mg of the standardized rosemary leaf extract since
juvenile. The mice were monitored for sixteen weeks. The leukrotriene B4, a fatty signaling molecule, and inhibits the
rosemary extract reduced cholesterol level. This was visibly complement system (al-Sereiti, Abu-Amer, & Sen, 1999). PGE2
noted when the group given a high-fat diet and the extract is important in childbirth labor because it softens the cervix
were compared to those only given a high-fat diet. There was and causes the uterine to contract; however if activated early
too, a direct correlation between fecal fat excretion and can be an abortifacient. Many of the activities rosmarinic acid
rosemary extract. This, however was not witnessed with is involved with have therapeutic potential. For example,
decreased food intake (Ibarra et al. 2011). Though further relaxing the bronchial and intestinal smooth muscles can treat
studies are needed for this one to be conclusive, this study bronchial asthma and be antispasmodic. Reduction of
shows that perhaps rosemary rich in carnosic acid can be used leukotrienes and the increase of PGE2 production can also
for weight loss. treat bronchial asthma, peptic ulcers, and inflammatory
Caffeic acid is a naturally occurring compound that can be diseases.
found in most plants. This compound may contribute to the The three constituents of rosemary discussed, caffeic acid,
prevention of cardiovascular disease (Olthof, Hollman, & carnosic acid, and rosmarinic acid, are also found to have
Katan 2001). Margreet Olthof, Peter C. H. Hollman, and Martjin therapeutic potential in treatment. These constituents are able
B. Katan conducted an experiment to determine the amount of t inhibit lipid peroxidation which can then treat hepatotoxicity
caffeic acid absorbed in humans (2001). This was determined atherosclerosis and inflammatory diseases. They also prevent
through a cross-over study using four healthy female and the formation of the carcinogen-DNA adduct which gives
three healthy male subjects. The calculation used to determine rosemary its anticarcinogenic property (al-Sereiti, Abu-Amer,
the amount absorbed was the amount ingested minus the & Sen, 1999).
amount excreted. Eleven percent of the caffeic acid absorbed
was excreted in urine (Olthof, Hollman, & Katan 2001).
Accounting for human error, almost all of the caffeic acid Biological Activity
intake will be absorbed by humans. In vitro
Rosmarinic acid, the ester of caffeic acid and 3,4- Rosmarinus officinalis was tested in a study conducted by Vina
dihydroxyphenyllactic acid, is a compound commonly found in Yang and Carol Clausen for its effectiveness in controlling
the Boraginaceae family but unique to rosemary in the mold growth on wood (2007). Moisture is the most critical
Lamiaceae. In the plant, rosmarinic acid behaves as a defense component to consider when controlling mold growth,
compound (Petersen & Simmonds 2003). Rosmarinic acid is a however when moisture cannot be controlled, one must
phenolic compound; it has one phenolic ring from consider what to do to control mold growth. In this
phenylalanine via caffeic acid and one phenolic ring from experiment, seven plants, rich in essential oils were test for
tyrosine via dihydroxyphenyl-lactic acid. Rosmarinic acid can their antifungal effects including rosemary. Petri dish tests
be well absorbed through membranes such as the and tank test chamber gave similar results. Rosemary
gastrointestinal tract and the skin. It is capable of increasing essential oil extract was among the group of essential oils
the PGE2, prostaglandin E2, and reducing the production of
shown to have promising antifungal effects in this experiment due to the aqueous and ethanol extracts of rosemary
(Yang and Clausen 2007). (Hosseinzah & Nourbakhsh 2003). This study introduced the
possibility of using rosemary extractions to treat morphine
withdrawal syndrome.
In vivo
Fawzia A. Fahim and Amr Y. Esmat conducted an experiment
to study the antimutagenic and hepatoprotective effects of the Clinical Studies
essential oil of Rosmarinus officinalis and ethanolic extract Moss and Cook conducted an experiment using human
(1999). They used carbon tetrachloride as hepatotoxic and subjects to test the cognitive effects of Rosmarinus officinalis
cyclophosphamide as mutagenic compounds. For three weeks, and lavender (Moss & Cook 2003). Many nontoxic herbal
rats were administered rosemary ethanolic extract (0.15 spices from Europe are traditionally used to treat cognitive
g/100 g BW). This produced the better hepatoprotective deficiency. This experiment, however only tests two. Moss and
results than when compared to silymarin. Mice were Cook assessed the olfactory impact of the two plants on
pretreated for seven days with rosemary essential oil cognitive performance and mood. Rosemary was found to
(1.1mg/g BW) and later injected with cyclophosphamide. This produce enhancement in secondary memory factors and
significantly reduced the induced mitodepression of bone terms of overall quality of memory. However, it was found to
marrow cells in the mice. The presence of high percentages of impair the speed component of memory (Moss & Cook 2003).
phenolic compounds within the rosemary essential oil extract This could be due to rosemary’s essential oils; they produce a
contributed to its antioxidant effects (Fahim & Esmat, 1999). soothing effect.
Hossein Hosseinzah and Mahnaz Nourbakhsh investigated the Rosemary essential oils were found to moderately inhibit
effects of aqueous and ethanol extracts of R. officinalis on acetyl-cholinesterase (Orhan et al., 2008). The inhibition of
morphine withdrawal syndrome in mice (2003). The aqueous acetyl-cholinesterase by rosemary essential oil can be
and ethanol extraction of rosemary induced significant activity explained by the synergy produced by the interaction between
in the writhing test that showed a decline in sensitivity to 1,8 cineole and 2-pinene. Inhibition of acetyl-cholinesterase is
painful stimuli and this activity was then inhibited by currently one of the treatment strategies against several
naloxone, am opioid antagonist drug, pretreatment. The mice neurologic disorders such as Alzeimer's and other dementias.
developed dependence to morphine by being induced daily for Because rosemary was found to have this activity, it is now
three days usimg subcutaneous injections of morphine. Day being further investigated to see how it can potentially treat
four, the mice were injected two hours prior to the these diseases (Orhan et al., 2008).
intraperitoneal injection of naloxone with morphine. The
effects of the withdrawal syndrome was observed in the mice
and were then measured by the number of jumps within the Contraindictions
30 minute period after the naloxone injection was Rosmarinus officinalis is not known to be toxic. However, a
administered. It was found that the number of jumps reduced large intake of the plant or its oils could pose a threat to
on PGE2. Also, a frequent intake of rosemary can cause iron
deficiency in susceptible individuals.
Current Uses in Allopathic and CAM Therapies

Extracts from Rosmarinus officinalis are presently used in
herbal medicine today, such as in the drug Gastroplex.
Gastroplex is used for the treatment of dysbiosis, the rapid
overgrowth of yeast, parasites, and bacteria. Gastroplex is
used to regain the proper function of the gastrointestinal tract
and reclaim its health. This drug cannot be taken during
Figure 5. Gastroplex pregnancy or lactation. A photograph of the drug can be found
Image source: in Figure 5.
http://www.google.com/imgres?q=Gastroplex&um=1&hl=en&sa=N&biw
=1441&bih=747&tbm=isch&tbnid=kRZczBPNBrnZrM:&imgrefurl=http://b
Because of the high concentration of volatile oils, rosemary is
iomedicine.com/products-page/biomed- used in aromatherapy. It has also been effectively in use in
supplements/gastroplex%25E2%2584%25A2&docid=yr_hRbG4MT6qfM massage therapy. Its scent has the effect of producing a
&imgurl=http://biomedicine.com/wp- relaxing sensation. Other uses of rosemary include its use as a
content/uploads/2011/07/11080.jpg&w=600&h=480&ei=c91aT7baBsq9t diuretic. Teas with rosemary extract are used by the general
weB_OSEDA&zoom=1
public and are widely marketed and can be purchased with
convenience.
pregnant women (al-Sereiti, Abu-Amer, & Sen, 1999). A study
was conducted on mice to see the dietary effects of rosemary
on the fertility of adult rats. It was reported that sperm Discussion
motility and density decreased. In addition, the number of Rosmarinus officinalis is an amazing plant with many health
aborted fetuses was increased. It was concluded that the benefits. It is anti-inflammatory, anticarcinogenic,
increased amount of rosemary given caused infertility (Nusier antibacterial (Jarr et al., 2010), and an antioxidant. It is rich in
et al. 2007). Because humans are much larger, it would take a phenols and tannins. It can be used medicinally and used in
lot more rosemary to cause this effect. The amount to cause cuisines. Though originating in the Mediterranean, today this
such effects, however are not known due to lack of studies. plant can be found in all parts of the world. This plant can
There is no evidence that the intake of a moderate amount of even be grown in indoor pots inside the home. By simply
rosemary could be harmful to breast-feeding women or their incorporating R. officinalis into the diet, many bacterial
children. There is potential for the oil to act as an infections can be avoided while gaining nutritious benefits.
abortifacient, which is an agent that may induce abortion (al-
Sereiti, Abu-Amer, & Sen, 1999). This is only due to its effects
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acrylamide. American-Eurasian Journal of Scientific Research, Zer, H., & Fahn, A. (1992). Floral nectaries of Rosmarinus officinalis
3(2), 163-171. L.) structure, infrastructure and nectar secretion. Annals of
Botany, 70, 391-397.
Yang, V., Clausen, C., (2007). Antifungal effect of essential oils on
southern yellow pine. International Biodeterioration &
Biodegradation 59 (2007) 302–306
Salix alba L., Salicaceae
Kinsey McMurtry
Introduction
The plant being investigated in this paper has the scientific
name Salix alba L., which is in the plant family Salicaceae.
Salix alba L. is commonly called white willow, catkins willow,
European willow, salicin willow, and withe withy (Highfield &
Kemper, 1999). The white willow contains salicin, which is
metabolized into salicylic acid in the body. Synthetic salicylic
acid is used to make Aspirin by acetylating the synthetic
salicylic acid. The discovery of Aspirin can be attributed to the
knowledge of the medical uses of willow bark. Willow bark is
used as an analgesic and anti-inflammatory due to its main
constituents such as flavonoids, polyphenols, tannins, and
salicin (Vlachojannis, 2011). While it is mostly known for its
use in Aspirin, the use of the white willow tree dates back to
the ancient Egyptians who used it to treat pain and
inflammation. Its use has been well documented by many
healers including Hippocrates, Dioscorides, and Pliny the
Elder. White willow bark, roots, and leaves are also well Figure 1. White willow tree (http://www.herbal-
documented in Native American medical rituals for a variety supplement-resource.com/white-willow-bark.html)
of ailments including hair loss to healing skin lesions
(Moerman, 1998).
male flowers and green female flowers. The white willow tree
is native to North America, Asia, and Europe. It can survive in
Botanical Description cold temperatures and can grow in a variety of climates. The
bark of young branches from the tree is usually harvested
The willow family, Salicaceae, has four genera containing trees
during spring (Highfield & Kemper, 1999). As far as the
and shrubs. These 350 species are found in northern
willow tree’s habitat, typically the white willow must grow in
temperate climates. Salix alba originated from Europe and
an environment near water for its seeds to germinate.
contains tannins and salicin (Pfister, 1992). The white willow
Moisture is critical during seed dispersal because the seeds of
is a tree that grows 6-18 meters high. It blooms with yellow
the willow tree are only viable for a few weeks. However,
after the plant has taken root in the soil constant moisture is Traditional Antipyretic and Anti-inflammatory Uses
not necessary. The seeds of the willow tree can travel great
Galen, a Roman physician, first described the antipyretic and
distances because they are lightweight and have hair-like
anti-inflammatory properties of willow leaves (Mueller &
attachments (Kuzovkina, 2004). See Figure 1 for a picture of
Scheidt, 1994). Salix alba has been recorded as a traditional
the tree in its typical habitat.
use for treating fever and malaria in Epirus, Greece as well
(Vokou, Katradi & Kokkini, 1993). Similarly, Cherokee Indians
Traditional Uses in North America used white willow to create infusions to
treat fevers (Moerman, 2009). In England, before disease and
The modern use of white willow dates back to 1763 when its infection were fully understood it was common to think that
antipyretic effects from the dried and powdered bark was first illnesses were related to the geographic locations in which
reported (Vlachojannis, 2011). However, the use of willow they occurred. Therefore, it was argued that remedies could
bark dates much further back. be found where the diseases were. This is the case for white
willow. Because white willow is found near water the bark
was used as a cure for agues (chills and fevers) because agues
Traditional Analgesic Uses typically occurred in people living near water (Porter, 2006).
The Ancient Egyptians used the white willow tree bark to In 1757 Edward Stone began to search for a new antipyretic
treat pain and inflammation. Willow bark was also used as a drug to replace quinine. Upon tasting the bark of the willow
remedy for gout and rheumatic joint diseases during the eras tree he noticed the similarity in the extreme bitter taste
of Hippocrates and Dioscorides (Highfield & Kemper, 1999). between the cinchona bark and the willow bark. Stone
Hippocrates recommended chewing the leaves of the willow performed studies to test the anti-inflammatory effects and
tree during childbirth because of its analgesic effects. He also reported his positive findings in a letter to the Royal Society in
recommended using the juices of the tree for eye diseases. 1763. In addition, Stone’s findings gave scientific evidence to
Dioscorides also reported the analgesic effects of willow the already well-known use of willow bark for the treatment
leaves and he similarly suggested its use to treat gout. Pliny of fevers and inflammatory illnesses. His work allowed for
the Elder, a Roman encyclopedia writer, described the science to take the next step in analysis by isolating and
analgesic effects and other uses of the gum, leaves, and bark of purifying the active constituents of the white willow bark for
the willow tree (Mueller & Scheidt, 1994). Native Americans clinical study and production (Mueller & Scheidt, 1994). In
also used willow for its analgesic properties. Willow bark’s 1829 a French pharmacist, H. Leroux, identified willow’s
traditional uses include rheumatic pain, back pain, toothache, active chemical constituent salicin. Salicylic acid was
headache, menstrual cramps, relieving sore throats, fever, and prepared in pure form in 1838. Both Salicylic acid and salicin
headaches associated with flu and upper respiratory were a popular treatment for rheumatic fever and gout in the
infections (Highfield & Kemper, 1999). 19th century. The benefits and therapies of willow bark were
also known in Italy. Bartolomeo Rigatelli used willow bark
extract as a therapeutic agent in the early 1800s. In 1838
Raffaele Piria, an Italian chemist, extracted the salicylic acid Active Chemical Constituents Percentage
compound from the white willow bark. In 1855 Cesare Glycosides 1.5-11%
Berganini published a detailed report about the adverse
Tannins 8-20%
events that are caused by a salicylate overdose (Marson &
Aromatic aldehydes and acids
Pasero, 2006).
Salycil alcohol
Flavonoids
Traditional Antidiarrheal Uses Table 1. Active chemical compounds in Salix alba
(Highfield & Kemper, 1999).
Cherokee Indians used white willow as an antidiarrheal by
creating an infusion with the bark. The infusion was taken to
check the bowels (Moerman, 2009). Traditional uses in teas
In west Bosnia and Herzegovina Salix alba is used in herbal
teas. One tea is used for the treatment of renal ailments.
Traditional Respiratory Uses
Another tea is used for the treatment of restlessness (Saric-
Cherokee Indians chewed the roots of white willow as a Kundalic, Dobes, Klatte-Asselmeyer & Saukel, 2010).
respiratory aid while playing sports. White willow is also
used as a throat aid. Cherokee Indians also made infusions
with the inner bark of the willow tree to treat a lost voice and Chemistry and Pharmacology
the root was chewed to treat hoarseness (Moerman, 2009). The active chemical constituents of the white willow bark
include glycosides (1.5-11%), tannins (8-20%), aromatic
aldehydes and acids, salicyl alcohol, and flavonoids. The
Traditional Cosmetic Uses
glycosides include salicylates such as salicin, salicortin,
Cherokee Indians used the white willow as a dermatological populin, fragilin, and tremulacin. The aromatic aldehydes and
aid. A decoction or infusion of the bark was used as a wash to acids include salidroside, vanillin, syringin, salicylic acid,
make hair grow. The Blackfoot tribe created tonics for caffeic, and ferulic acids (Highfield & Kemper, 1999). See
dandruff and to straighten the hair by soaking the dried, Table 1 for an organized representation of the chemical
crushed willow roots in water and adding grease. The constituents.
Costanoan tribe created a hair rinse by making an infusion of
Using decoctions of herbs and plants, like willow bark and
the willow leaves. The leaves were also used to treat balding
leaves, containing salicylates, as anti-inflammatory therapies
by creating a paste that was rubbed on the scalp. Creek
have been well documented and used throughout history. The
Indians treated swellings by creating an infusion with willow
creation of synthetic salicylate led to the acetylated form of
roots that was then used as a wash. The Isleta tribe used a
salicylic acid. This drug, known as Aspirin, has anti-
decoction of willow leaves as a skin bath (Moerman, 1998).
inflammatory, analgesic and antipyretic actions. Aspirin
than the meadowsweet and chamomile but all three showed
positive results (Drummond, Harbourne, Marete, Martyn,
Jacquier, O'Riordan & Gibney, 2012).
Another study investigated the anti-inflammatory mode of
action in rosehip, willow bark, and nettle leaf. The study was
performed as an in vitro model of primary canine
chondrocytes. The extracts from the rosehip, willow bark, and
nettle leaf all showed anti-inflammatory and anabolic
effectiveness on chondrocytes (Shakibaei, Allaway, Nebrich &
Mobasheri, 2012).
Since the discovery of Aspirin, studies on the white willow
Figure 2. The Creation of Aspirin have declined greatly due to Aspirin’s magic bullet
http://www.mdidea.net/products/herbextract/salicin/data0 characteristics. However, in one study the final objective was
2.html to determine if white willow and meadowsweet could be used
to create a beverage with anti-inflammatory properties. The
first part of the study investigated which type of herb drying
inhibits the activity of the cyclooxygenase (COX) enzyme. This allowed for the phenolic compounds to remain effective. The
enzyme leads to the creation of prostaglandins (PGs), which herbs were air-dried, freeze-dried, and oven-dried. The
cause inflammation, swelling, pain and fever (Vane & Botting, results showed that freeze-drying and oven drying had no
2003). See Figure 2 for a graph of the molecular structures. significant effect on the phenolic constituents for both
meadowsweet and white willow. The temperature used was
30 degrees Celsius but when the temperature was increased
Biological Activity to 70 degrees Celsius the herbs dried faster but there was a
In vitro loss of some phenolic compounds (Harbourne, Marete,
Jacquier & O’Riordan, 2009). This study is important because
Anti-inflammatory Effects
an anti-inflammatory beverage that contained plant
A study of the inhibition of pro-inflammatory biomarkers in constituents could be very beneficial and could be used to
THP1 macrophages by polyphenols in willow, chamomile, and circumvent the ill effects of current popular NSAIDs.
meadowsweet showed that willow bark had the greatest anti-
inflammatory activity. This was achieved by using aqueous
herbal extracts and isolated polyphenolic compounds. These Anti-proliferative and Proapoptotic Effects
were incubated with THP1 macrophages. Interleukin (IL)-1β, Salicin is known for its anti-inflammatory and analgesic effects
IL-6 and tumor necrosis factor-alpha (TNF-α) were measured. in willow bark. It was used to create acetylsalicylic acid, but
The willow bark reduced IL-6 and TNF-α production more
this synthetic non-steroidal anti-inflammatory drug (NSAID) significantly reduced the occurrence of tumors in the rats
and other NSAIDs have shown to have anti-proliferative (Davis & Patterson, 1994).
effects on cells. A study was done to investigate the possible
anti-proliferative and proapoptotic effects of willow bark on
the cells of the lining of the colon. A water extract (STW 33-I) Clinical Studies
and a polyphenolic rich fraction of willow bark were tested by Headaches
using the colon-carcinoma cell line (HT-29). The willow bark
extract (STW 33-I) contained 23-26% total salicin derivatives In a clinical study to investigate the effects of salicin cream on
and therefore was an effective analgesic and anti- headaches, it was found that the salicin worked better than
inflammatory drug. It also contained flavonoids, condensed the placebo. In the study, 54 patients were given anticephalgic
tannins and polyphenols. The in vitro experiment photo protective premedicated masks to treat migraines.
demonstrated that the willow bark extract had pro-apoptotic They were also given bottles of topical medication that either
effects on the HT-29 cancer cells. This experiment showed contained salicin or a placebo. They were instructed to apply
that willow bark extract is similar to other NSAIDs in its anti- the medication to their foreheads, put the mask on, and lie
proliferative and pro-apoptotic effects. This is important for down. They were then told to rank the relief using a scale of 0
the prevention of side effects such as gastric erosion that is to 10. Seven of the 20 patients who had placebo reported the
common in NSAID use (Bonaterra, Kelber, Weiser, Metz & medication and mask helped. 28 of the 34 patients who used
Kinscherf, 2010). salicin reported that the treatment was effective in relieving
the pain (Hyson, 1998).
In vivo
Blood Thinner
The acetylation of salicylate, a naturally occurring anti-
inflammatory found in Salix alba, is how Aspirin is produced. In another study, the effects of salicylates on the hemostatic
There have been many studies to investigate the effects of properties of platelets in males were investigated. According
Aspirin on cancer prevention (Burn, Chapman, Bishop & to the results, aspirin has a more significant effect on the
Mathers, 1998). One such study investigated the effect of bleeding time in six normal males in comparison to sodium
aspirin on colonic carcinogenesis in rats. Groups of rats were salicylate. This is due to the finding that aspirin prolongs
given daily doses of aspirin for 18 weeks. The dosages given bleeding time because it inhibits the release of platelet ADP
were 0, 5, 30, or 60 mg/kg. Half of each of the four groups was while sodium salicylate does not (Weiss, Aledort & Kochwa,
given 18 x 30 mg/kg/wk injections of dimethyl hydrazine 1968). This information is important for those who take
(DMH) colonic cancer. The results showed that the doses of 5, aspirin daily and therefore have much thinner blood, which
30, or 60 mg/kg/dy had a progressive effect on the reduction can cause problems when combined with other drugs or when
of the number of tumors. The dosages also reduced the size of an injury occurs.
the tumors. Aspirin doses of 30 and 60 mg/kg/dy
Lesion Improvement by Percentage of patients
Therapies percentage who didn't need
4 weeks 6 weeks Dosage Tramadol
Conventional therapy 62.60% 89.90% 120 mg Salicin
Herbal therapy with acid 42.90% 61.30% 393 mg of dry willow bark extract 21%
Herbal therapy without 240 mg Salicin
acid 55.10% 87.80% 2 pills of 393 mg of dry willow bark
Table 2. Results from The Effect of Clove Bud, Nigella and extract 39%
Salix alba on Wart and Comparison with Conventional Table 3. Results from chronic lower back pain trial (Setty &
Therapy (Rezaei, Jebraeili, Delfan, Noorytajer, Meshkat & Sigal, 2005).
Maturianpour, 2008).
with or without acid is significantly efficient (Rezaei, Jebraeili,
Warts Delfan, Noorytajer, Meshkat & Maturianpour, 2008).
Salicylic acid is commonly used to treat warts. Clove bud,
Olive, Nigel, and Salix alba are all disinfectants, anesthetics,
analgesics, and have wound healing properties. Because of Back Pain
these properties, one study investigated the effects of these A randomized double blind study investigated the efficacy of
plants on wart treatment in comparison to conventional willow bark extract for the treatment of chronic lower back
treatments. The investigation was performed as a pain in 210 patients. These patients either received a twice-
randomized double blind study on 291 female students. The daily dose of 120 or 240 mg of salicin per day or a placebo.
students were organized into three groups. One group was Patients in the low dose group also received a pill of 393 mg of
treated with the conventional treatment of Salicylic acid dry willow bark extract and the high dose group received 2
(16.7%), lactic acid (16.7%) in a collodione body. The second pills of 393 mg of dry willow bark extract. A rescue
group was treated with herbal medicine in olive oil that medication of tramadol was available. The end goal of the
contained no acid. The third group was treated with herbal study was to see how many patients were pain free and did
medicine along with salicylic acid (1%) and lactic acid (1%) in not need tramadol for at least 5 days in the last week of the
olive oil. The results showed that after four weeks the study. The results showed that 39% of the high dose group
improvement of the wart was 62.6% for conventional therapy, and 21% of the low dose group were able to go five days
42.9% for herbal therapy with acid, and 55.1% for herbal without tramadol by the end of the study. More tramadol was
therapy without acid. At six weeks the improvement of the required for the patients in the placebo group (Setty & Sigal,
wart was 89.9% for conventional therapy, 61.3% for herbal 2005). See Table 3 for a visual representation of these
therapy with acid, and 87.8% for herbal therapy without acid results.
(Table 2). This study showed that the use of herbal therapy
Osteoarthritis Contraindications
Another study was done to investigate the efficacy of willow Willow bark has a high concentration of tannins, and because
bark for the treatment of osteoarthritis of the hip or knee. of this, it usually leads to gastrointestinal toxicity before a
There were 78 patients in this double blind, placebo therapeutic concentration of salicylates is reached. However,
controlled study. Patients were given two doses of willow it is safe as an analgesic and wart remover when applied
bark tablets that were equivalent to 240 mg salicin/day or a topically. Along with tannins, salicin and salicortin are also
placebo. Additional NSAIDs were not allowed in the study. potentially toxic compounds. Allergies to willow bark are
The Western Ontario and McMasters University Osteoarthritis possible. Toxicity from Aspirin is more common than with
Index was used to score the pain. The patient’s pain index was willow bark because willow bark has much lower levels of
lowered by 14% after 2 weeks of treatment. There was a pain salicylates. High doses can cause gastric and renal irritation,
index increase of 2% in the placebo group. The results nausea, vomiting, and gastrointestinal bleeding. There are no
showed that there was a moderate analgesic effect (Setty & reported interactions with other herbs or pharmaceuticals
Sigal, 2005). (Highfield & Kemper, 1999).
While Aspirin inhibits the formation of prostaglandins, which
Oral Administration cause inflammation, swelling, pain, and fever, Aspirin also
inhibits the formation of physiologically important PGs. Some
One study evaluated the effectiveness of salicin when it is of these PGs are responsible for the protection of the stomach
given orally as a willow bark extract. Ten volunteers ingested mucosa from hydrochloric acid damage. They also maintain
240 mg of salicin twice in a period of 24 hours. Throughout kidney function and amass platelets when needed (Vane &
the 24 hours, urine and serum levels of salicylic acid and its Botting, 2003).
metabolites were measured. Renal excretion rate, elimination
half-life and total bioavailability of salicylates were also
measured. The results showed that salicylic acid was the main Current Use in Allopathic and CAM Therapies
metabolite of salicin that was detected in the serum at 86%.
Acetylsalicylic acid was first synthesized in 1853 and was
The peak levels of salicylic acid occurred less than two hours
rediscovered by the Bayer Company in Germany. See Figure
after ingested. Renal elimination occurred mainly as
3 for a visual representation of the key plants used in the
salicyluric acid. The peak serum levels of salicylic acid
making of Aspirin, the chemical compounds, and who
averaged at about 1.2 mg/l. This study concluded that the
discovered these elements. Today, Bayer Aspirin is one of the
current therapeutic dose of willow bark extract leads to much
most popular drugs sold worldwide. Synthetic acetylsalicylic
lower serum salicylate levels than analgesic doses of synthetic
acid is used as an analgesic and antipyretic. Aspirin is also
salicylates. According to this study, the formation of salicylic
acid alone cannot explain the analgesic or anti-rheumatic
effects of willow bark (Schmid, Kotter & Heide, 2001).
informants in Jordan were asked about the typical plants used
for certain illnesses, Salix alba was mentioned. According to
these informants, Salix alba is most commonly used for
intestinal colic, gastric disturbances, and renal calculi (Al-
Qura’n, 2007). White willow bark is usually dried and
prepared in creams, ointments, tablets, liquids, and capsules
(Highfield & Kemper, 1999).
Discussion
Salix alba has a long history of use throughout Europe, North
America, and Asia. Its use was widely known and documented
by healers like Dioscordes, Hippocrates, y Pliny the Elder. Its
early use as a treatment for pain, fever, and an anti-
inflammatory led to further research by scientists in the early
1800s. Salix alba is one of the first herbal remedies that lead
to a synthetic drug. Salicin had long been known for its
curative powers and with advancements in science; chemists
began to experiment with the chemical structure of Salicin.
Salicylic acid was first isolated from meadowsweet, which led
to the creation of acetyl-salicylic acid. Bayer “rediscovered”
the acetyl-salicylic acid and created aspirin. After the creation
of Aspirin there was a decline in research on the white willow
because Aspirin treated so many illnesses.
Figure 3. Chart of the salicylates and how they make There are a couple studies such as the study by Rezaei (2008)
Aspirin (Mueller, 437) and Hyson (1998) that show the efficacy of the almost
forgotten herbal form of salicin. Salicin is a strong anti-
inflammatory and anesthetic but medical uses in its natural
used to prevent myocardial infarctions, strokes, and colorectal form are not very common because of the invention of Aspirin.
cancer. Some herbalists believe willow bark extract can be
More studies need to be done to further investigate the
used as a natural substitute for aspirin. This belief is used in
potential uses of salicin. There also needs to be more studies
Germany where willow bark is typically taken with aspirin in on its use as a cancer treatment. Because of Salicin’s apoptotic
order to minimize side effects and enhance therapeutic effects effect on the cell lining of some organs, it could be used as a
(Highfield & Kemper, 1999). In a study done where
potential drug for cancer treatment. In the study done by
Bonaterra et al., the dangers of overuse of NSAIDs are shown meadowsweet (Filipendula ulmaria) and willow (Salix alba).
but it would be interesting to see what further investigation LWT – Food Science and Technology, 42(9). 1468-1473.
could indicate (2010). As much of a wonder drug the white Highfield, E. S., & Kemper, K. J. (1999). White Willow Bark (Salix
willow has proved to be it still has potential to be even more alba). Long Wood Herbal Task Force: www. mcp.
beneficial. Further study should also be done on how the edu/herbal/default. htm, Revised July, 13, 1.
Native Americans use white willow. There are very distinct Hyson, M. I. (1998). Anticephalgic photoprotective premedicated
differences in how Europeans historically used salicin and mask. A report of a successful double-blind placebo-
how the Native Americans used the white willow. Many tribes controlled study of a new treatment for headaches with
use the willow tree as more than just a pain reliever but few of associated frontalis pain and photophobia. Headache, 38(6),
these methods have been investigated scientifically 475-477.
(Moerman, 1998). Kuzovkina, Y A. (2005). Willows beyond wetlands: Uses of salix l.
species for environmental projects. Water, air and soil
pollution, 162(1-4), 183.
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http://www.mdidea.net/products/herbextract/salicin/data02.html
Sambucus nigra L., Adoxaceae
Katie Nelson
Introduction
Sambucus nigra L., commonly known as Elderberry, belongs to
the Adoxaceae family. Other common names include European
Elder, Black Elderberry, Elder Flower, Elder, Flor de Novia
(Peru) (Tropicos, 2001), Cinta de Novia (Peru) (Tropicos,
2001), Savuchə or Shtog (Arbëreshë) (Quave, 2009; Quave and
Pieroni, 2005), Saúco (Spain) (Cavero et al., 2011), Savucu
(Calabria) (Tagarelli et al., 2010), Sambuco (Italy), Sureau
(France) and Sabugueiro (Brazil) (Charlebois, 2011). The
origin of Sambucus is believed to be from the Greek word
sambuca, which was a triangle-shaped instrument made from
the bark. (Austin, 2004; Watts, 2007).
Elderberry is most commonly used today in Europe to treat
colds and influenza (Anderson, 2007; Watts, 2007; Zakay-
Rones et al, 2004). Other suggested uses include use as a
laxative, for dropsy or for topical skin treatments of wounds, Figure 5: Sambucus nigra. (Image source: http://irapl.altervista.org
burns or insect bites (Picon et al, 2010; Quave and Pieroni, /nit/viewpics.php?title=Sambucus+nigra)
2005; Uncini-Manganelli et al, 2005; Watts, 2007). Modern-
day products of Elderberry extract include Sambucol and Keightley, 1850; Morgenstern, 2000; Notes and Queries, 1907;
phytotherapic Brazilian tea. Studies have shown Elderberry Watts, 2007).
extract to have antioxidant, antiviral and antibacterial activity
and insulin-like properties (Gray et al, 2000; Heinrich et al,
2004; Roxas and Jurenka, 2007; Swanston-Flatt et al, 1991;
Uncini-Manganelli et al, 2005; Wu et al, 2004). Its main Elderberry is a deciduous shrub that can range from 4m to
constituents are comprised of cyanogenic glycoside, 10m in height. The shrub initially grows straight and vertical
flavonoids, triterpenoids and anthocyanidins (Atkinson and from the base and has arching branches (Atkinson et al, 2002;
Atkinson, 2002; Duke, 1992; Roxas and Jurenka, 2007). The Kabuce et al, 2006). The bark of the shrub is moderately acidic
Elderberry tree is referred to extensively in European folk- and is highly capable of holding water (Atkinson et al, 2002).
lore. (Anderson, 2007; Burne, 1914; Grimassi et al, 2011; The branches contain porous white pith. Individual leaves
grow up to 20cm in length and are oval shaped with a pointy subspecies canadensis is known as American Black Elderberry
tip. The flowers are a creamy white color and 5mm in and is predominately found in eastern United States (Austin,
diameter. The flowers commonly have 5 petals and have 2004; Charlebois et al, 2007; Tropicos, 2001). Another
cream colored anthers (Figure 1). The fruits of this shrub are subspecies is cerulea, which is known as the Blue Elderberry
spherical black berries that grow in clusters and contain 3-5 in primarily found in western United States (Austin, 2004;
seeds (Atkinson et al, 2002; Kabuce et al, 2006). They have a Tropicos, 2001).
lifespan of up to 25 years (Atkinson et al, 2002).
Elderberries are believed to be native to continental Europe Traditional Uses
but are cultivated as far north as the Scandinavian countries,
as far south as northern Morocco, Algeria and Tunisia, but it is Medicinal/Ritual
also grown in North America, areas of Australia, New Zealand Elderberry is mentioned in ancient texts and appreciated for
and east Asia (Atkinson et al, 2002). American elder its medicinal properties. Hippocrates is said to have called the
(Sambucus canadensis or S. nigra subsp. canadensis), a close elderberry a “medicine chest” in 400 BC. Additionally,
relative of S. nigra, is more commonly cultivated in North Pedanius Dioscorides, author of De Materia Medica (50-70
America and is sometimes confused with S. nigra (Charlebois AD), and Theophrastus used and wrote about elderberry as a
et al, 2007). medicinal plant (Krawitz et al, 2011).
Elderberry shrubs are commonly found in either naturally or The medicinal uses of elderberry are numerous and span
unnaturally disturbed sites. These sites tend to have eutrophic across Europe. In general the flowers were used to heal sore
soils or nutrient-rich soil (Atkinson et al, 2002). Disturbances or red eyes and gastrointestinal tract problems, and the fruit
can refer to woodland margins, hedgerows, neglected gardens, was used as a laxative (Uncini-Manganelli et al, 2005).
floodplain terraces, roadsides and building sites. The shrubs
show stunted growth under shade, which suggest that they Primarily in the United Kingdom, tea was made from the
prefer sun-lit habitats (Atkinson et al, 2002; Kabuce et al, leaves of S. nigra to treat diabetes (Gray et al, 2000; Swanston-
2006). Flatt et al, 1991). Elderberry tea was also used for the
treatment of colds, coughs, fevers and influenza (Anderson,
The only pollinators known to impact elderberry are birds. 2007; Watts, 2007). In medieval England, berry juice or tea
They spread the seeds either by regurgitation or defecation was used for dropsy. In England, elderberry leaves were also
after eating the berries (Atkinson et al, 2002; Charlebois et al, used on wounds and lacerations, and were especially effective
2007; Kabuce et al, 2006). if picked in April (Uncini-Manganelli et al, 2005). Also, the
leaves were used to heal insect bites (Watts, 2007). The inner
bark was used to treat burns (Quave and Pieroni, 2005; Watts,
Subspecies 2007). It was common in England to use elder flower water,
In this monograph, Sambucus nigra subsp. nigra is being the inner bark or flower lotions to clear freckles and
addressed, but another subspecies is canadensis. This blemishes, whiten skin and heal sunburn (Watts, 2007).
Elderberry was also used in treating witchcraft that came in In Spain, communities in the Middle Navarra had traditionally
the form of wounds from animals or plants. One such remedy used elderberry for multiple purposes. Fourteen such uses
ritual involved placing the pus of the wound into a hole in the were documented by Cavero et al. (2011). The inner bark and
side of the elderberry tree and covering it with elderberry the inflorescence were used together or separately for the
material (Notes and Queries, 1907). topical treatment of wounds, burns, blisters and animal bites.
In the Arbëreshë communities in Italy, there are numerous The plant material was roasted then mixed in either oil or
uses of elderberry to treat foot sores and blisters, toothache, wax, forming an ointment which was applied topically. The
sore throat, abscess and headache, and worked as an anti- inflorescence had additional uses for toothaches, catarrhs,
inflammatory, anti-rheumatism and anti-pruritic. Flowers are sore throat and as an expectorant. For the previously
used for sore throat, foot sores and blisters. For insect bites, mentioned purposes the inflorescence was boiled and the
wounds, inflammations, rheumatisms and abscesses the smoke inhaled with the exception that a tea was made for sore
leaves on are topically. The community also smokes the dried throats. The researchers also noted that this community was
stems to relieve toothache (Quave, 2009). A cream made from aware that some medicinal usage knowledge about elderberry
elderberry bark, olive oil and bees-wax was used to treat ‘cigli has already been lost (Cavero et al., 2011). Adjacent to the
alla testa’, which is characterized by a headache on the top of Navarra region is the Pyrenees area which separates Spain
the head. Part of the healing ritual for ‘cigli alla testa’ includes and France. In this area, elderberry was used for medicinal
a prayer being said under the elderberry (Quave, 2009; Quave purposes as well (Akerreta et al., 2007). Another nearby
and Pieroni, 2005). Another Arbëreshë ritual using Elderberry region where the medical use of elderberry was prevalent was
in conjunction with other plants (Malva sylvestris, Matricaria that of Catalonia. Here, elderberry was used to reduce blood
recutita and Parietaria diffusa) is used to treat ‘mal vjnt’, or thickness and as an anti-pneumonic (Agelet and Vallés, 2003).
‘wind illness’. In this community ‘mal vjnt’ is identified as a In North America, the subspecies canadensis was used by the
skin rash and he four plants are bundled together and brushed Native American tribes Cherokee, Menominee, Iroquois, Creek,
over the rash while a specific prayer is said (Pieroni et al., Choctaw and Houma. The Cherokee and Seminoles prepared
2002). tea from the bark for stomach complaints. The Houma
In the region of Calabria (southern Italy), elderberry was however, used bark tea for difficult childbirths, as analgesic
traditionally used as an anti-rheumatic and purgative, to treat and anti-inflammatory. The Iroquois also used elderberry as
swollen breasts and legs, insect bites, toothache, colic and an anti-inflammatory. Among the Iroquois bark was used to
conjunctivitis. The plant materials used include the treat headaches, cuts and measles. They used a mixture of
inflorescence, fruit, leaves, bark and dry flower heads roots and bark as poultice for newborn infant navels.
(Tagarelli et al., 2010). Additionally, fresh leaf bunches were Branches or bark could be used as a laxative and the pith from
used to attract flies so could them kill them (Passalacqua et al., stems treated heart disease and gonorrhea within Iroquois
2006). culture Berry tea was used for rheumatism among the
Cherokee and for fevers in Menominee and Cherokee. The
Creeks treated swollen breasts with water soaked roots, the
Figure 6. Example of one type of elderberry wine. (Image Figure 7. Elder flower fritters. (Image source:
http://utmarketgarden.files.wordpress.com/2011/03/elder-flower.jpg)
Source: http://heatherhillfarms.com/proddetail.php?prod=manischewitz-
elderberry-wine)
Culinary
Choctaw mixed leaves with salt for headaches (Austin, 2004; Culturally, elderberry was most commonly used in the
Banks, 2004; Moerman, 1998). culinary arts. During the nineteenth and twentieth century
The subspecies cerulea was commonly utilized by western elderberry was used to make soup, jam, wine and juice in the
Native American tribes including the Thompson and Kawaiisu Polish countryside (Luczaj, 2010; Luczaj and Szymański,
and selectively used by eastern tribes Choctaw and Houma. 2007). In traditional Europe and United States, elderflowers
The Kawaiisu used a mixed of leaves and flowers in a steam were used to make elderberry beer and the berries to make
bath for headaches and colds. Additionally, leaf tea is used to elderberry ale or Ebulon. The recipe for elderberry beer calls
wash blood poisoned appendage among Kawaiisu. The for fresh or dried elderflowers, water, sugar and yeast.
Thompson tribe treated arthritis with boiled bark, from a Elderberry ale is made with elderberries, water, malt extract
nonmetal pot otherwise will be poisonous. Bark was also used and yeast (Buhner, 1998). Elderberry wine was also a popular
for toothaches and dried flowers treated syphilis in Thompson in England, possibly due to the belief that it was beneficial for
tribe. The Choctaw used leaves topically for swollen hands and sore throat, asthma, sciatica and longevity (Figure 2) (Watts,
internally as a purgative. The bark is used by the Choctaw to 2007). In Germany, a recipe called Hollerküchln, encompassed
treat diarrhea and the Houma as an analgesic (Austin, 2004; elderflowers deep fried and the leftover oil was used further
Moerman, 1998). for the treatment of ear infections (Figure 3) (Buhner, 2004).
This same recipe is used in the Calabria area of southern Italy
too; there the flower fritters are called ‘pitte cu majiu’
(Passalacqua et al., 2006).
The berries of both subspecies cerulea and canadensis were
used in many tribes to make wine, pie, jelly and sauce and in
one instance as a fish marinade (Moerman, 1998).
Folk-Lore
There is much folk-lore associated with the elderberry tree
throughout Europe and America in traditional beliefs of
Christianity, Wicca and others. In England, Germany, Scotland
and Denmark it was considered bad luck to burn or cut an
elderberry tree without asking permission (Burne, 1914;
Keightley, 1850; Morgenstern, 2000; Notes and Queries, 1907;
Watts, 2007). It was bad luck to burn the tree because by
doing so the tree would release evil. Each culture had a
different specific prayer or saying for the proper way to ask
permission of the Elderberry, but all cultures had expressed a
bargain to return wood to the elderberry (Keightley, 1850;
Notes and Queries, 1907). In Germany and Denmark, if you did
not ask permission before using the wood to make a cradle,
the entity within the tree would torment the baby (Keightley,
1850; Notes and Queries, 1907; Watts, 2007). Additionally, in
the areas near the Rollright Stones and Wales, people believed
that the elderberry would bleed when cut (Blaine and Wallis, Figure 4. Illustration of Hyldemoer (Elder-Mother Tree)
2007; Burne, 1914; Notes and Queries, 1907; Watts, 2007). from a Hans Christian Anderson story. (Image Source:
This stemmed from the belief that the entity within the tree http://polarbearstale.blogspot.com/2010/06/sct-hans-and-elderflowers
was injured. The name of the entity was different in various .html)
countries: in England it was Old Lady, Old Girl or witch and in
Denmark it was Hyldemoer, which translates to Elder-Mother One of the protective activities associated with the Elderberry
(Figure 4) (Anderson, 2007; Blaine and Wallis, 2007; Burne, was as a safeguard against lightning because it was never
1914; Grimassi, 2000; Keightley, 1850; Morgenstern, 2000; struck. In some Christianity sects, this was believed because
Notes and Queries, 1907; Watts, 2007). Judas Iscariot hung himself from an Elderberry tree and the
Other
Compound Class The flowers of S. nigra were used as a dark yellow dye for
Flavonoids (<3%) quercetin, rutin, isoquercitrin, kaempferol, white doilies in the Latíum area of Italy. The fruit juice was
astragalin, nicotiflorin and hyperoside used as blackish ink and as a blackish dyeing agent for must
Triterpenes Ca 1% α- and β- amyrin, occurring mainly as fatty (result of first step in wine making) in Latíum, Abruzzo and
acid esters; Triterpene acids: Ca 0.85% oleanolic
Marche areas. These three areas are in the central portion of
and ursolic acids, 20β-hydroxyursolic acid
Volatile Oil 65% of free fatty acids including palmitic acid and Italy adjacent to one another (Guarrera, 2006). The berries
(.03-.14%) linoleic acid. 7% alkanes. Others include ethers, have been used as a dye to color wine since Greek and Roman
oxides, ketones, aldehydes, alcohols and esters. times and their dying properties were utilized in other
Caffeic acid chlorogenic acid materials as well (Austin, 2004; Morgenstern, 2000; Watts,
derivatives (3%)
2007).
Sterols β-sitosterol, stigmasterol, campesterol and
cholesterol The subspecies canadensis and cerulea were used by the North
Minerals potassium American Indian tribe Houma, to make blowguns. Canadensis
Other constituents tanin, muclilage, plastocynin (protein), pectin and
sugar
specifically was used by the Menominee to make toy guns. The
Table 1. Compounds and their percentages found in Elder Kawaiisu used the subspecies cerulea to make a flute after
flowers. (Image Source: http://www.ema.europa.eu/docs/en_GB/docu removing the pith and making six holes in the wood
ment_library/Herbal__HMPC_assessment_report/2009/12/WC500018238 (Moerman, 1998).
.pdf)
cross used during Jesus Christ’s crucifixion was an elderberry Chemistry and Pharmacology
tree (Morgenstern, 2000; Notes and Queries, 1907; Watts,
The main constituents of elderberry are cyanogenic glycoside,
2007). Additionally, it became a common practice to place a
flavonoids, triterpenoids and anthocyanidins (Table 1).
stick of elderberry over a grave, because if it grew into a tree
Sambunigrin is the main cyanogenic glycoside and is found in
then the soul of the deceased was happy (Morgenstern, 2000;
the leaves (Figure 5). The common flavonoids found are rutin,
Watts, 2007). In Wicca, standing beneath the elderberry tree
which is found in the flower and berry, and quercetin, which is
and inhaling the scent of its flowers was believed to reveal the
found in the berry and leaves (Atkinson and Atkinson, 2002;
fairies that live there (Grimassi, 2000; Watts, 2007).
Duke, 1992; Roxas and Jurenka, 2007). There are numerous
Elsewhere, a pregnant woman standing under the elderberry
triterpenoids found in elderberry: ursolic acid, oleanolic acid,
tree would have an abortion (Notes and Queries, 1907). In
α-amyrin and β-sitosterin (Atkinson and Atkinson, 2002;
England, boys beaten with wood from elderberry were
Christensen et al, 2007; Duke, 1992). The latter is classified as
believed to have stunted growth (Notes and Queries, 1907;
a subtype called steroid alcohols (Heinrich et al, 2004). The
Watts, 2007).
two anthocyanidins present in the berries are cyanidin-3-
sambubioside and cyanidin-3-sambubioside-5-glucoside
and Streptococcus pyogenes, and in Gram-negative bacteria
including Branhamella catarrhalis and Haemophilus influenza.
However, in the study using Rubini, the extract did not inhibit
bacterial growth of Staphylococcus aureus, Streptococcus
mutans and Haemophilus parainfluenzae. Rubini was also used
in cell cultures where it decreased grow of avian type-A
influenza virus (H5N1) and type B influenza virus (Krawitz et
al, 2011).
Elderberry fruit extract was used in an in vitro study to
Figure 5. Sambunigrin is one of the chemical constituents determine the flavonoids effect on type-A influenza virus
of Sambucus nigra. (Image Source: http://www.awl.ch/heilpflanzen (H1N1). The extract was more effective in inhibiting H1N1
/sambucus_nigra/index.htm) infection compared to when each flavonoid was used
individually. The flavonoids used were a type of quercetin and
dihydromyricetin because they were bound to the virus. It
(Charlebois, 2007; Duke, 1992; Roxas and Jurenka, 2007). The was suggested that either of these flavonoids bound to the
berries also contain the sweetener compounds dextrose and domain of the virus responsible for binding to a host cell
levulose (Duke, 1992). The noteworthy fatty acids present in (Roschek et al, 2010). A different study used dried elderberry
the flower are linoleic acid and α-linolenic for their activity on flower boiled in water in an in vitro for insulin-like properties.
peroxisome proliferator-activated receptor (PPARγ) The compounds lectin, rutin and β-sitosterol were identified
(Christensen et al, 2007; Duke, 1992). in the extract. The extract significantly increased glucose
The elderberry’s antioxidant capacity is due to the flavonoids uptake, glucose metabolism and insulin secretion from
and anthocyandins, which are responsible for the color of the pancreatic β-cells. The suggested mechanism of action was
flower (Heinrich et al, 2004; Roxas and Jurenka, 2007; Wu et sulfonylureas receptor activity on β-cells, which depolarizes
al, 2004). Cyanogenic glycosides are toxic and thus, thought to membrane and causes an influx of calcium ions. Diazoxide,
be a defense against herbivore. Triterpenoids contain steroid which inhibits sulfonylureas activity, decreased insulin
type compounds and are useful in mammals (Heinrich et al, secretion by the extract (Gray et al, 2000). The effectiveness of
2004). elderberry extracts used for inhibition of H1N1 and insulin-
like properties were dose-dependent (Gray et al, 2000;
Roschek et al, 2010).
Biological Activity Additional antiviral properties were studied of elderberry
There have been many studies addressing the biological bark with the feline immunodeficiency virus (FIV) in vitro. The
activity of elderberry. In bacterial liquid culture standardized boiled bark extract significantly inhibited syncytia formation
elderberry extract (Rubini) was effective in decreasing growth (formed by virus) (Uncini-Manganelli et al, 2005).
in Gram-positive bacteria such as, group C and G Streptococci
The insecticidal activity of Elderberry is due to the plant
protein type-2 ribosome-inactivating protein (RIP) of
Sambucus nigra agglutinin I’ (type-2 RIP SNA-I’) found in the
bark. In bioassays, tobacco plants (Nicotiana tabacum) were
transformed with type-2 RIP SNA-I’ and were found to be toxic
for tobacco aphids (Myzus nicotianae) and pea aphids
(Acyrthosiphon pisum) when ingested (Shahidi-Noghabi et al.,
2008). In an additional study, transgenic tobacco plants
(Nicotiana tabacum) with type-2 RIP SNA-I were harmful
when ingested by tobacco aphids (Myzus nicotianae) and beet
armyworm (Spodoptera exigua). The mechanism of action of
RIP is proposed to inactivate eukaryotic ribosomes. The B-
chain RIP binds to the cell surface receptors which allows the
A-chain of the RIP to enter the cell where it inactivates
ribosomes (Shahidi-Noghabi et al., 2009).
Figure 6. A variety of Sambucol products. (Image Source:

Clinical Studies http://www.nutranutra.com/nutraport/?cat=15&paged=3)
In a Norwegian clinical study, patients who took the nigra juice and berries and two sets of tablets, one made from
elderberry product Sambucol syrup showed a faster recovery S. nigra and the other Asparagus officinalis. This diet regiment
from influenza type A and B compared to placebo (Figure 6). consisted of 370mg flavonol, 150mg hydroxycinnamates and
The patients also reported no adverse effects after taking the 1mg anthocyanin from S. nigra and 19mg saponins from A.
syrup (Zakay-Rones et al, 2004). officinalis. The participants had significantly decreased body
In Brazil, a mixture of Pimpinella anisum, Foeniculum vulgare, weight and improvement of blood pressure, emotional and
Cassia augustifolia and S. nigra prepared as a tea is used to physical well-being (Chrubasik et al., 2008).
treat constipation. The efficacy of this mixture was supported.
The patients had significant increases in evacuations per day
(after day 2), and self-reported improvement of bowel Contraindications
functions. There were no reported adverse effects, but it was There are very few dangers associated with elderberry plant
not recommended to be used with diuretics (Picon et al, material use. The unripe berries can be toxic and might cause
2010). nausea, vomiting and severe diarrhea in the worst cases
A clinical study addressed the before and after differences (Morgenstern, 2000). It is also recommended that elderberry
when obese people ingested a combination of psyllium, S. extracts not be taken in conjunction with diuretics (Picon et al,
2010).
Discussion
Elderberry has widespread traditional and modern-day uses
and great treatment potential for colds, influenza and
constipation. The modern-day uses are based on some of the
traditional uses, but there are many more traditions that have
yet to be explored. There are few clinical trials supporting the
efficacy of extracts for colds and influenza and no clinical trials
for laxative use. Additionally, a majority of the mechanisms of
action of the elderberry extract’s compounds have yet to be
identified or replicated. While there is support for elderberry’s
antiviral and antibacterial activity, the same cannot be said for
its laxative and insulin-like properties. Furthermore, its
traditional use as a topical skin healing treatment has not been
Figure 7. Example of laxative tea made with elderberry, addressed. The alternative medicinal products mentioned
not necessarily the same one from the study. (Image Source: previously are only available in Europe and Brazil, and are
http://oilnatural.com/product_info.php?cPath=42&products_id=31)
largely unknown to the America public. For the most part,
Current Use in Allopathic and CAM Therapies Americans are unaware that its health benefits rival those of
other berries, which is a shame because of all its wonderful
Today there are some elderberry extract products used in medicinal properties and culinary uses.
CAM therapies but they are primarily used in Europe. One
such product is Sambucol, a syrup used to alleviate and
shorten duration of colds and influenza. In a clinical trial there References Cited
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Silybum marianum (L.) Gaertn., Asteraceae
Annelies Carl
Introduction
Silybum marianum (L.) Gaertn, commonly known as Milk
thistle, St. Mary’s thistle, and Blessed Thistle, is a member of
the Asteraceae family, commonly known as the daisy family
(Abenavoli et al., 2010). Historically, milk thistle was
administered to treat liver aliments, hemorrhoids, and used as
a diuretic. Today this plant is still used in the same manner,
and the isolated active compounds have a myriad of
applications including anti-toxin properties and liver
cleansing. This plant is also suggested as a panacea on many
herbal Internet sources, reflecting milk thistle’s popularity
and frequency of usage. The main active ingredient in milk
thistle is silymarin, which is found in the highest
concentrations in the seeds of the plant but other parts of the
plant like the leaves and fruit are also used. Milk thistle seeds Figure 1. Milk thistle. Note the milky white veination
or the isolated compound silymarin are sold in many products patterns. (Source: http://altmed.creighton.edu/MilkThistle/What%20Is
from biomedical pharmaceuticals to herbal supplements, %20It.htm)
which range in price. Although many clinical trials have been
conducted that showed numerous positive effects of milk among cereal crops. Removing milk thistle can be a costly
thistle components, many of the studies provide contradictory effort for those farmers who consider milk thistle to be a
results because of unstandardized concentrations and prickly annoyance, since the milk thistle is a very hardy plant.
preparations of milk thistle. Milk thistles with well-developed root systems can be grown
in light soils with periods of water deficiency. Milk thistle will
also grow in heavier clay soils and will tolerate a wide variety
Botanical Description of pH levels ranging from 5.5 to 7.6 (Karkanis et al., 2011).
Milk thistle is native to the Mediterranean basin but has Although milk thistle is obvious highly adaptable, it prefers
spread throughout the world, and in some areas this plant is fertile soils. Also reflective of its adaptability, milk thistle can
now considered to be a noxious and invasive weed that can grow as an annual or biennial.
often be found growing along roadsides, in waste ground, and
The stem of milk thistle can grow from 40cm to 200cm tall.
The stem itself grows vertically and is slightly downy.
Towards the upper part of the plant the stem becomes
branched. When the stem branches, the lowermost leaves are
large and alternate with spiny edges. These large leaves grow
from 50cm to 60cm long and from 20cm to 30 cm wide
(Karkanis et al., 2011). Milky white veins, a distinguishable
characteristic, found on milk thistle leaves are what give the
plant part of its name. Due to the white veins, tradition says
that milk thistle was given the name ‘marianum’ based on the
legend that the milk from the Virgin Mary landed on the plant
when she was sheltering under a bower formed from milk
thistle leaves, and this milk is what turned the veins of the
milk thistle white (Figure 1).
The leaves on the stem are smaller than the leaves on the base.
At the end of each stem, a flower head will form that is around
5cm in diameter with reddish–purple coloration. The seeds
have a white pappus, are about 5 to 8 cm long, and range in
color from brown to black. On average, each flower head
produces about 190 seeds. While in the soil, the milk thistle
seed can remain viable for nine years. It has not been
observed that the seed needs dormancy (Karkanis et al., 2011)
(Figure 2).
Many pests and diseases can threaten milk thistle. There have
been reports of rust fungus (Puccinia punctiformis (F.Strauss)
Rohl.) in the U.S, smut fungus (Microbotryum silybum Vanky &
Berner) in Greece, and cucumber mosaic virus (CMV) in Spain.
Milk thistle is also a host for the tomato spotted wilt virus. In
addition, there are many insects that feed on milk thistle
including the seed-head weevil in Egypt and aphids (Dysaphis
lappae cynarae and Aphis fabae cirsiiacanthoidis) in Iran and Figure 2. Botanical drawing of Silybum marianum. (Source:
Greece (Karkanis et al., 2011). Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland, Österreich und der
Schweiz 1885, Gera, Germany. Permission granted to use under GFDL by
Kurt Stueber. www.biolib.de)
Traditional Use
The seeds of the milk thistle have been used for over 2,000
years in the treatment of liver aliments and gallbladder
disorders including hepatitis, cirrhosis, and jaundice. Although
other parts of the plant like the flowers are occasionally used,
medicinally the seeds are most commonly used. Milk thistle
was also used to protect the liver from damaging poisons from
sources like snakebites, insect stings, mushroom poisoning,
and alcohol (Abenavoli et al., 2010).
In the 4th century B.C. Theophrastus described milk thistle
under the name Pternix. Milk thistle was later included in
Dioscorides De Materia Medica in the 1st century A.D. All parts
of this plant have been historically eaten as vegetables with no
toxic side effects (Karkanis et al., 2011) and the root was also
eaten as a nutritional supplement. Milk thistle was used in the
Mediterranean and across Europe. Milk thistle was also used
in Indian and Chinese medicine. In Traditional Chinese
Medicine (TCM), milk thistle is thought to restore balance by Figure 3. The components of silymarin: silibinin,
fortifying yin, which is helpful in treating illness since illnesses silydianine, and silychristine. (Source: http://www.medscape.
com)
that drain yin, the dark force that opposes yang (Bensky,
1986).
In Dr. Finley Elingwood’s 1919 classic, American Materia
Medica, Therapeutics and Pharamacognosy, milk thistle was Most of the medicinal compounds found in milk thistle are
used to improve the general bilious conditions like jaundice, present in high concentrations in the seeds. These compounds
hepatic pain, and swelling. In a study conducted in Mujib include silymarin, which is composed of three isomer
region of Jordon on the medicinal plants of the area, milk flavonolignans: silybin, silydianin, and silychristin (Karkanis
thistle was found to be an extremely important plant used for et al., 2011). Silymarin is 50 to 70% silybin. Silymarin has
the treatment of liver diseases. The flowers and seeds were been shown to have the most biological activity and is a strong
made into either decoctions or infusions (Hudaib et al., 2008). antioxidant. The seeds are about 20 to 35 % fatty acids and
A different study conducted in the Calabria region (Southern other polyphenolic compounds (Ramasamy and Agarwal,
Italy) found that milk thistle leaves are made into a decoction 2008). Seeds of milk thistle have also been discovered to
to treat hemorrhoids or make into an infusion as a diuretic contain other flavonolignans including isosilybin,
(Passalacqua, Guarrera, and Fine, 2007). dehydrosilybin, desoxysilycristin, silandrin, silybinome,
silyhermin, and neosilyhermin (Karkanis et al., 2011). shown to promote neuronal differentiation in vitro (Kittur et
Silymarin has very low toxicity, and silymarin is not water- al., 2002). Another study suggested that silymarin inhibits
soluble, so it is usually given in capsules that contain about 70 leukotriene formation by Kupffer cells in vitro (Dehmlow et al.,
to 80% silymarin (Karkanis et al., 2011) (Figure 3). 1996). In addition, silymarin has been shown to increase the
expression of growth factor beta-1 and c-myc in mice (He et
al., 2002). Other in vivo studies have shown that silymarin may
Biological Activity protect the pancreas from damage due to cyclosporine (von
There are many hypotheses regarding the mechanism of Schonfeld et al., 1997), protect the kidney from
action; the multitude of explanations concerning the acetaminophen, cisplatin (Platinol), and vincristine (Oncovin)
mechanism of actions causes confusion and debate in the (Sonnenbichler et al.,1999), and protect the liver from damage
literature. Silymarin is absorbed orally and from there is due to carbon tetrachloride by reducing lipid peroxidation
distributed into the alimentary tract, which includes the liver, (Kravchenko et al., 2001). In baboons, silymarin was shown to
stomach, intestine, and pancreas (Karkanis et al., 2011). One slow the progression of alcohol-induced liver fibrosis (Lieber
theory is that silymarin’s hepatoprotective action is due to its et al., 2003). Many other in vitro and in vivo studies suggest
anti-free radical and anticarcinogenic ability, but its that milk thistle might have anti-cancer properties against
heptoproductive action may also be due to other actions like cancers of the prostate, breast, skin, colon, tongue, and
its antioxidant, anti-lipid, peroxidative, antifibrotic, anti- bladder (Tyagi et al., 2002, Zi et al., 1998, Kohno et al., 2002).
inflammatory, immunomodulatory, and liver regenerating
activity (Karkanis et al., 2011). Silymarin is a toxin-blocking
Clinical Studies
agent, which inhibits how toxins bind to hepatocyte cell
membrane receptors (Abenavoli et al., 2010). In addition, Most clinical trials have been done in patients with either
silymarin has shown anti-inflammatory and immune- hepatitis or cirrhosis, although other studies have been
modulation activity in various structures and pathways in the conducted concerning hyperlipidemia, diabetes, and Amanita
cell. phalloides (death-cap mushroom) poisoning. Overall, clinical
trials have found lower bilirubin serum levels, which are a
The anti-inflammatory properties of silymarin may be due to
sign of an improved liver because high bilirubin levels are an
the way it regulates inflammatory mediators like the tumor
indicator of liver inflammation, damage, and disease. One
necrosis factor (TNF), tumor necrosis factor-alpha, nitrous
study on patients with hepatitis A and B found that silymarin
oxide, interleukin-6, and interleukin-1 receptors (Manna et al.,
helped lower levels of AST, ALT, and bilirubin in five days
1999, Zi X et al., 1997, and Tager et al., 2001). This
(Magliulo, Gagliardi, and Fiori, 1978). On the other hand,
information suggests that silymarin may help to prevent and
many clinical trials have shown that silymarin has no effect on
treat infectious disease.
liver disease or liver enzyme levels (Flisiak and Prokopowicz,
With regards to the cytoprotective activity of milk thistle, 1997)
several mechanisms have been observed. Milk thistle has been
There is debate regarding whether or not silymarin has a claims that it is the only effective antidote for patients
direct effect on the hepatitis C virus, with contradictory suffering from liver damage due to Amanita phalloides related
evidence from various clinical trials. In a trial conducted by poisoning (Enjalbert et al., 2002). In addition, a meta-analysis
the National Institute of Diabetes and Digestive and Kidney of herbal supplements on glycemic control, silymarin was
Diseases, users who were given silymarin reported fewer shown to increase insulin resistance when used for eight
symptoms from their chronic liver disease and had a better weeks (Suksomboon et al., 2011).
quality of life than those who did not use the products
Although milk thistle is arguably one of the most researched
containing silymarin. One report found that silymarin helped
plants in the treatment of liver disease (Karkanis et al., 2011),
inhibit a tumor necrosis factor and increased peripheral blood
studies done on silymarin and/or silybin are often
mononuclear cells (Polyak et al., 2007). In addition, silymarin
controversial and are constantly reassessed (Kren and
has also shown prophylactic and therapeutic effects against
Walterova, 2005). Many studies have shown that constituents
hepatitis C virus infection and helped increased the inhibitory
in various parts of milk thistle, most often the seeds, help the
ability of interferon-alpha against hepatitis C virus replication.
function of the liver but not all studies agree (Kren and
This evidence shows that silymarin has both anti-
Walterova, 2005). Studies concerning milk thistle also suffer
inflammatory and antiviral properties for patients who suffer
from undefined mechanisms of action, undefined disease
from hepatitis C.
populations, different formulations of active components, and
Trials conducted on patients with chronic liver disease have varying length of therapy (Kren and Walterova, 2005). Other
also been promising. In a large study of over 2,500 patients studies are poorly designed. Overall, the undefined
with chronic liver disease, an eight week treatment of 560 composition of silymarin preparations that are used in the
mg/day of silymarin produced reductions of serum AST, ALT, studies is the most common cause of controversy (Kren and
and gamma-glutamyltranspeptidase (a sign of bile duct Walterova, 2005). This lack of standardization is because
disease) and decreased the occurrence of palpable there is variation in the proportions of components in
hepatomegaly (Albrecht et al., 1992). silymarin that depends on the source of the milk thistle seeds
Trials have discovered that silymarin may be useful in the including the specific plant under cultivation and the
treatment of cancer. In two case reports silymarin was used in conditions of cultivation (Kren and Walterova, 2005). In
individuals with cancer as a treatment and additional therapy. addition, silymarin extract and the pure compound of
In one case a 34-year old woman with leukemia was given 800 silymarin are often confused in the literature (Table 1).
mg of silymarin during maintenance therapy, which helped
reduce the number of breaks in therapy due to abnormal liver
Contraindications
enzyme levels (Invernizzi et al., 1993). In another case, a 52-
year-old man with hepatocellular carcinoma was given 450 In general, silymarin and silybin are thought to be safe with
mg of silymarin per day and his tumor regressed although he rare adverse effects. One study, Jacobs et al., 2002, reported
had not started anticancer therapy (Grossmann, Hoermann, three serious side effects. After being given a combination
Weiss, et al., 1995). A report conducted on the use of silybin herbal formula which contained milk thistle one of the
concentrations in vivo. Although silybin and its related
Efficacy Acute and chronic viral hepatitis, alcoholic liver flavonolignans showed inhibition of the catalytic activities of
disease: conflicting evidence. Cytoprotection: rigorous cytochrome P450(CYP) isoenzymes in vitro, the
randomized controlled trials ongoing; limited concentrations required to achieve this are almost
evidence suggests benefit. Anticarcinogen: clinical
physiologically impossible (Kren and Walterova, 2005). These
trials ongoing Amanita phalloides poisoning:
insufficient data
findings suggest that the likelihood of drug interactions
Adverse Generally well tolerated; infrequent reports of involving silymarin and silybin are lower, although further
effects gastrointestinal disturbances; rare reports of pruritus, studies are required to better determine the mechanisms of
eczema, rash, and anaphylaxis*CAUTION: do not use actions in order to better understand the adverse side effects
in patients with allergies to members of the aster (Kren and Walterova, 2005). On the other hand, other studies
family. suggest that interactions between silymarin and other
Interactions No significant drug interactions prescriptions may lead to serious clinical reactions. Milk
Dosage Milk thistle seed extract, 150- to 175-mg capsule, thistle constituents may have negative reactions when taken
standardized to 80 percent silymarin, three times with nifedipine, iriontecan, metronidazole, indinavir,
daily. Ultrathistle (seed extract bound to pyrazinamide, digoxin, rosuvastatin, and ranitidine (Wu et al.,
phosphatidylcholine), 360-mg capsule, three times
2009).
daily
Cost $15 to $30 per month at 150 to 175 mg three times
daily$42 per month at 360 mg three times daily
Bottom line Safe, no known drug interactions; insufficient data to Current Use in Allopathic & CAM
recommend for treatment of liver disease; under Milk thistle is sold in many herbal products for the treatment
investigation for anticarcinogenic and of various aliments but mainly for liver problems. These
chemoprotective effects products can be found online and in many stores from herbal
specialty stores to supermarkets. Commonly, these products
*—Three nonfatal case reports, only one of which is sufficiently contain either the dried milk thistle seeds or extracted
attributed to the herb silymarin. Silymarin is sold under a wide variety of trade
Table 1. Key points about milk thistle (Rainone, 2005). names including Legalon, Silipide, and Siliphos (Figure 4).
These products can cost anywhere from three dollars to
patients in the study suffered from gastroenteritis symptoms. seventy dollars, but theses costs can change dramatically
Jacobs et al. also reported anaphylactic reactions after depending on the supply of milk thistle that year.
drinking milk thistle tea. Other smaller reactions have been
In allopathic medicine, milk thistle, and the associated
reported, the most common of which being gastrointestinal
chemical silymarin, is mainly used in clinical settings for the
symptoms, dermatological effects, and headaches, but these
treatment of hepatitis and cirrhosis (Post-White et al., 2007).
symptoms were also reported in the placebo groups. Due to
The main constituent, silymarin, is given as a milk thistle seed
the low solubility of silybin, it is very difficult to reach toxic
extract, 150 mg to 175 mg per capsule with a standardization
panacea, but these claims should used with care until more
research can be completed. Although milk thistle may be as
effective as herbal supplies describe, milk thistle is a relatively
safe plant with low toxicity.
Currently, information on how milk thistle was traditionally
prepared is rare in the scientific literature, perhaps because
knowledge on the use of this botanical was spread by word of
mouth. Studies that do include traditional uses of milk thistle
lack detail, listing the part of the plant and the type of
preparation made but not how that preparation is made.
Historically, milk thistle was also reputed to help nursing
mothers produce milk and eaten as a nutritional supplement,
but these claims are not supported by the scientific literature
Figure 4. Legalon – one of the tradenames that silymarin although one study has suggested that milk thistle spouts may
is marketed under. (Source: http://www.poisoncentre.be/ article. be a good source of nutrients and antioxidants (Vaknin, 2008).
php?id_article=223) Milk thistle is used to improve liver function and often
administered when certain diseases result in decreased liver
of 80 percent silymarin three times daily (Rainone, 2005). function. There has been promising research that milk thistle
Milk thistle is also taken in other forms like liquid extracts and might have many anti-cancer properties and also help relieve
tinctures. This is taken to treat liver disease and used in the liver damaging effects of many cancer treatments.
conjunction with other treatments that may have liver Negative side effects of milk thistle are rare although there
damaging effects. Milk thistle may also be given to reduce may be significant drug reactions, so consultation with a
damage from a variety of poisons. physician is important when combing milk thistle with
biomedical drugs.
Discussion Future studies on milk thistle might clear up confusion
regarding the effectiveness of milk thistle constituents. Milk
Milk thistle has been an important botanical throughout the
thistle’s most biologically active set of compounds found in
world, especially in Europe and Asia, but also in the U.S in the
silymarin may be found to have greater effects in the
growing herbal market for people interested in more natural
alternatives to biomedicine. It is incorporated in many treatment of various liver diseases, cancers, and anti-toxin
abilities. New treatments for these problems will become
treatments, both allopathic and CAM, for liver aliments and
increasingly important as toxins build up in the environment,
other various health problems like diabetes, hemorrhoids, and
which will lead to increased cancer rates. As history has
liver damage from alcohol abuse. Like many other botanicals,
shown, cancer and chronic disease are on the rise due to many
there are many online sources that suggest milk thistle is a
factors, some determined while others are unknown. The rise
in rates of liver disease and diabetes may be due to increased Grossmann M, Hoermann R, Weiss M, et al.: Spontaneous regression
alcoholism and obesity, and there is potential for milk thistle of hepatocellular carcinoma. Am J Gastroenterol 90 (9):
to be used to combat the side effects from both diseases. Since 1995. 1500-3.
milk thistle has a long historical use and numerous current He Q, Osuchowski MF, Johnson VJ, Sharma RP. Physiological
applications, it should be tested further. Such studies may lead responses to a natural antioxidant flavonoid mixture,
to new treatments for these health problems and many others. silymarin, in BALB/c mice: I. Induction of transforming
growth factor beta1 and c-myc in liver with marginal effects
on other genes. Planta Med. 2002; 68:676–9.
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Solidago virgaurea L., Asteraceae
Alisha Morris
Introduction
Solidago virgaurea (European goldenrod) belongs to the
Asteraceae family. The herbal substance consists of the dried,
flowering parts of the plant. It has been used for treatment of
different diseases such as arthritis and diabetes. Today, it is
mostly used as an aquaretic agent. Studies have found that the
active constituents help reduce inflammation, relieve muscle
spasms, fight infections and cancer, lower blood pressure, and
have antioxidant effects (UM Medical Center).
Description
European goldenrod is a perennial found along roadsides and
in open fields. It has a single woody stem that grows to heights
of 3 to 7 feet. It has yellow flowers, about 1/4 of a inch wide
and come in large clusters. They appear mainly in August and Figure 1. Picture of Golden rod, Solidago virgaurea (Source:
September (Figure 1). The leaves alternate between toothed Naturephoto-cz.eu).
and smooth edges. The plant is native to Europe and the Asia
mainland. Different species of the goldenrod can be found in wounds. It may be taken in a variety of forms, including the
many locations outside of Europe because of its ability to dried herb; for teas and capsules, tincture (a medicine
crossbreed with other plants. Its pollen grains are meant to be consisting of an extract in an alcohol solution), or fluid extract
carried by insects because of their heaviness in comparison to (UM Medical Center). It also used frequently in Europe as a
plants with airborne pollens (UM Medical Center). treatment for urinary tract infection and to prevent or treat
kidney stones. It has been approved by the German
Commission E as a diuretic, anti-inflammatory, and
Traditional Uses
antispasmodic for the treatment of urinary tract disorders
The goldenrod has been used to treat tuberculosis, diabetes, (Vitamin for life 2002). In the Appalachian Mountain region of
enlargement of the liver, gout, hemorrhoids, internal bleeding, the U.S., its leaves have been used to prepare tea, which is
asthma, and arthritis. Topically, it is used to treat taken as a treatment to combat fatigue and physical
inflammation of the mouth and throat as well as slow-healing exhaustion (Annussek 2001).
European goldenrod contains about 1.5% flavonoids
(quercetin, kaempferol, astragalin, and rutoside) and
antocyanidins. Others constituents include about 2% of
triterpene saponins, between 0.08% and 0.48% bisdesmosidic Figure 2. European goldenrod flavonoids (Dzyubak).
phenol glycosides leiocarposide and virgaureoside A,
diterpenoid lactones of cis-clerodane type phenolic acids
including caffeic acid and chlorogenic acid (0.2-0.4%), and edema and the volume of the arthritic paw (El-Ghazaly et al.
small amounts of essential oils (Figures 2). The 1992). Phytodolor (composition of S. virgaurea, Fraxinus
pharmacological effects of goldenrod have been described in excelsior and Populus tremula) was tested for an anti-
several researches and reviews. A synergistic action of several inflammatory, analgesic, and antipyretic activity in rats.
components of the S. virgaurea are proposed. Therefore, the Activity was similar to that of the reference substances
herbal substance or herbal preparations from goldenrod must salicylic alcohol and indomethacin. All of the extracts
be considered as the active ingredient (European Medicines displayed considerable efficacy (Okpanyi et al. 1989).
Agency, 2008).
Antibacterial activity
Biological Activity Nine clerodone diterpenes were isolated and characterised
Anti-inflammatory activity from ethanol-ethyl acetate extract of S. virgaurea. Many of
these showed moderate antibacterial activity against
Anti-inflammatory influence of goldenrod extracts from Staphylococcus aureus (Starks et al. 2010). Antimicrobial
Phytodolor N on the activity of myeloperoxidase liberated by activity of the extracts from S. virgaurea were tested in vitro
the activated granulocytes was estimated in in vitro by use of free-dried biomass from 4 week old callus cultures of
experiments. Goldenrod extract did not inhibit the plant. The minimal bactericidal concentrations of the
myeloperoxidase activity at concentrations up to about 1%. It extracts estimated with the agar diffusion assay method
proved that its anti-inflammartory and anti-rheumatic showed moderate activity (Thiem and Goslinska 2002).
properties were comparable to non-steroidal anti-
inflammatories, but with little or no side effects (Von
Kruedener et al. 1995). Extracts of S. virgaurea Antifungal activity
(aqueous/alcoholic) were tested individually for anti-
Triterpenoid glycosides obtained from S. virgaurea and Beallis
inflammatory activity using carrageenan induced edema and
perennis inhibited the growth of human pathogenic yeasts.
adjuvant induced arthritis of the rat paw as well as Extracts of
The intensity of growth inhibition is influenced particularly by
Populus tremula and Fraxinus excelsior were also tested. All
the carbohydrate chains of the glycosides. Monodesmosidic
of the extracts showed significantly reduction of the carrageen
and bisdesmosidic glycosides of polygalacic acid exert
fungicidic effects (Bader 1990). Glycosides of polygalacic acid significant inhibition of radioligand binding for bradykinin
are isolated from the aerial parts of S. virgaurea. The receptors (Sampson et al. 2000).
glycosides were tested against humanpathogenic strains of
Candida albicans, C. glabrata, C. krusei, and C. tropicalis using a
micro-dilution assay. The antifungal action can influence the Spasmolytic activity
variation of the etherglycosidically bonded carbohydrate nits Extract of leaves from S. virgaurea inhibited muscarinic M2
at C-3 and the acylglycosidically bonded oligosaccharide at C- and M3 receptor-mediated contraction of rat and human
28 of the aglycone (Bader et al 2000). bladder muscle strips. 0.01% concentrations appeared to
result from non-competitive muscarine receptor antagonism.
0.1% concentrations might have a non-specific inhibitor effect.
Antioxidant activity
However, the relationship between in vitro concentrations
Ethanolic extracts of S. virgaurea, Potentilla anserina, Radix and therapeutic doses remained unclear due to unknown
Rubiae tinctorum, Equisetum arvense, Oleum juniperi and bioavailability of the active ingredients of the extract
Petroselini sativi fructus mixtures were used in vitro to (Borchert et al. 2004). According to Westendorf and
estimate glucose consumption by rabbit brain slices. With an Vahlenieck (1981), S. virgaurea ethanolic extract induced
increase of glucose consumption and the aerobic formation of spasmolytic activity in the range of 14.7% of papaverin in an
lactic acid, the swelling of the brain slices was significantly in vitro experiment on isolated smooth muscles of intestines
diminished (European Medicines Agency, 2008; Dittmann of guinea pig (European Medicines Agency, 2008). According
1973). Extracts (aqueous/ethanolic) from Fraxinus excelsior, to Racz et al. (1980) and Duarte et al. (1993), the presence of
Populus tremula and S. virgaureaI, all carriers of phytodolor, flavonoids in goldenrod preparations may contribute to
were tested in vitro for antioxidant activity. The activity of explain vascular smooth muscle relaxation. The vasodilatory
xanthine oxidase, diaphorase, lipoxygenase, riboflavin and action depends on the inhibition of protein kinase C, inhibition
rose bengal were studied. The results showed inhibition of of cyclic nucleotide phosphodiesterase, or decrease of calcium
production of reactive oxygen species that were mentioned uptake (European Medicines Agency, 2008). The
above (Meyer et al. 1995). phytotherapeutic product (Extr Rad. Rubiae tinct. Spir, Extr.
Sem Ammeos visnagae spir., Extr. Herb. S. virgaurea spir., Extr.
Rad. Taraxaci) and aescin exhibited spasmolytic activity in
Analgesic activity vitro in acetylcholine pretreated urinary bladder of the rat
The analgesic activity of S. virgaurea was tested in vitro for (European Medicines Agency, 2008, Westendorf and
affinity to three neuropeptide receptors involved in the Wahlensieck 1983).
mediation of acute pain in mammals. The receptors were
bradykinin (expressed in Chinese hamster ovary cells),
neurokinin 1 (expressed in astrocytoma cells), and calcitonin
gene related peptides. The results showed there was
Anticancer activity (European Medicines Agency, 2008; Chodera et al. 1985a,
In a study using mice with an allogenic sarcoma-180model 1985b; Budzianowski 1999). The compound exhibited
and syngenic sacroma model, significant tumor inhibitory diuretic activity in rats: only 75% lower than furosemide
action against Virgaurea saponin E was found (European (European Medicines Agency, 2008; Chodera et al. 1985a).
Medicines Agency, 2008; Bader et al. 1996; 1998b). In another The diuretic action was delayed but, began 5 hours after
series of experiments the antitumor effects of polysaccharides administration and lasted up to 24 hours (European
were demonstrated. In an SCID mouse model antineoplastic Medicines Agency, 2008; Chodera et al. 1985b). The flavonoid
activity of S. virgaurea on prostatic tumor cells was texted and fraction of S. virgaurea was administered to rats and showed
cytotoxic activity on various tumor cell lines were an increase of diuresis. Decrease of an overnight excretion of
demonstrated. The active fraction of the extract potassium and sodium and an increase of excretion of calcium
corresponding to a molecular weight of about 40,000 grams ions was observed (European Medicines Agency, 2008;
per mole, was administered intraperitoneal or subcutaneous Chodera et al. 1991).
every 3 days for 25 days in an experimental tumor model in According to the European Medicines Agency (2008),
mice. Tumor growth was inhibited at 5mg/kg (European Schilcher et. al (1989) demonstrated that leiocarposide
Medicines Agency, 2008; Gross et al 2002). diuretic activity was reduced by the presence of flavonoids
and saponins. In contrary, some researchers suggest that
diuretic activity of goldenrod is exerted by the mixture of
Immunobiological activity flavonoids and saponins. Others demonstrated in animal
According to European Medicines Agency, Plohman et. al studies that relative inactivity of the flavonoid mixture
(1997,1999) stated that the immunomodulatory and present. After 6 weeks of administration of leiocarposide, a
antitumor activity of triterpene saponins were shown in in significantly decreased of growth of the renal calculi was
vitro experiments (Plohman et al. 1997, 1999). Choi et. al observed in experimentally induced renal calculi models in
(2005) used in vitro mouse peritoneal macrophages to rats (European Medicines Agency, 2008; Chodera et al. 1988).
showed that two compounds from S. virgaurea exhibited After oral administration of an infusion of S. virgaurea,
stimulation macrophage function that suggested potential use significant increase of diuresis in rats together with an
in the treatment of infectious diseases and tumors (European increased elimination of sodium, potassium and chloride ions
Medicines Agency, 2008). was observed. The lower dose was more efficient though
(European Medicines Agency, 2008; Schilcher and Rau 1988).
Active flavonoides of S. virgaurea inhibit NEP and the
Diuretic activity converting enzyme activity of angiotensin (European
Medicines Agency, 2008; Schilcher and Rau 1988; Melzig et al.
The diuretic properties are prevalence in studies performed
2001a; Melzig and Major 2000; Major 2001). According to
on the European goldenrod. Leiocarposide was isolated from
Melzig and Major (2000), the mechanism of beneficial renal
S. virgaurea var. leiocarpa (European Medicines Agency, 2008;
and cardiovascular activity of S. virgaurea can depend on
Hiller et al. 1979) and was found in Solidago virgaurea L
modulation of neutral endopeptidase activity. By increasing of cystitis (European Medicines Agency, 2008; Schmitt 1996).
water and sodium excretion and arterial and venous The efficacy of the S. virgaurea extract was estimated in a
vasodilatation, Solidago treatment can regulate water and postmarketing study performed on 1487 patients with several
sodium balance and cardiovascular homeostasis by blocking urinary tract diseases. Patients were treated in average for 4
the hydrolysis of the vasoactive peptides (European Medicines weeks. 79% of patients reached significance in global
Agency, 2008). improvement when evaluated by physicans (European
Medicines Agency, 2008; Laszig et al. 1999).
Clinical Studies An open multicenter study was performed on 1,487 patients

with chronic recurrent irritable bladder conditions. They were
An ethanolic extract made from fresh S. virgaurea was tested treated for five weeks. The patients received S. virgaurea dry
in an open post marketing crossover study with placebo in 22 extract. In result, 96% of the patients treated showed
healthy patients between the ages 17 and 61. The patients improvement registered in clinical global impressions scale,
received 100 drops/day of the ethanolic extract for 2 days. In and in 80.1% of patient´s estimation of effectiveness was good
Solidago treated groups a significant increase of daily volume or very good. Side effects were not registered (European
of urine was observed (European Medicines Agency, 2008; Medicines Agency, 2008; Melzig et al. 2001b; Pfannkuch and
Klinisch-Experimentelle Studie Nr 23223. P 1. 1992). The Stammwitz 2002). According to Laszig et al. (1999), there was
ethanolic extract of S. virgaurea L., made from fresh plant, was a case report of patients treated with S. virgaurea dry extract
tested in 53 patients in a year long open multicenter for 4 weeks after extracorporeal shock wave lithotripsy
postmarketing study. The patients consisted of 45 females and resulted with spasmolytic effects, and lack of additional
8 males between the ages 6 and 83 with symptoms of urinary spasmolytic treatment needed (European Medicines Agency,
tract inflammation, dysuria, pollakisuria, and tenesmus. 2008).
Patients with renal stones, renal carcinoma, gonorrhoea,
syphilis, AIDS and marked prostate hyperplasia were
excluded, as well as patients with bacterial counts in urine Contraindications
over 104. After treatment, 65.4% of treated patients showed
Solidago virgaurea is contraindicated for patients with the
significant clinical improvement with significant reduction of
following conditions: hypertension, hypotension, and
dysuria, pollakisuria and tenesmus (European Medicines
osteoporosis. This should not be taken if pregnant, breast
Agency, 2008; Klinisch-Experimentelle Studie Nr. 23223.P2.
feeding, or have heart or kidney disease. Goldenrod may
1992). In an open multicenter study, the efficacy of the dry
increase the effects of diuretics, increasing the risk of
extract of S. virgaurea was tested. It was performed by 289
dehydration. It could cause of lithium to build up in the blood,
physicians in 745 female patients between 12 and 94 years of
if taking lithium medication (UM Medical Center). Acute
age with dysuria of different origins. After 14 days of
toxicity of leiocarposide in rats was reported (European
treatment with Solidago extract, 69.2% of patients’
Medicines Agency, 2008; Chodera et al. 1985b).
micturition frequency was decreased as the other symptoms
Current Use in Allopathic & CAM medicinal constituents. Acute toxicity of the leiocarposide in
Solidago virgaurea is used in Pauri Garhawl and Uttrakhand rats was reported (European Medicines Agency, 2008;
for kidney trouble, asthma, and throat infection. It serves as an Chodera et al. 1985b). European goldenrod is a reasonable
alternative to modern medical treatments available to the alternative for treatment of diseases mentioned or can be
local inhabitants who have poor economic conditions (Pala et used as supportive treatment in conjunction with antibiotics.
al. 2010). Phytodolor, an active constituent, is a reasonable
alternative to NSAIDs and to cyclooxygenase-2-inhibitors such
References Cited
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9361.html
Taraxacum officinale F.H. Wigg., Asteraceae
Dhondup Tso King
Introduction Stigmasterol
Taraxacum officinale, commonly known as the common

dandelion, is a member of the Asteraceae family. There are Phenolic Phenolic acid Chicoric acid
nine species of the Taraxacum genus. T. officinale has been compounds Immunostimulatory Monocaffeoyltartaric acid
used as a folkloric medicine for a diverse range of diseases properties Caffeic acid
Chlorogenic acid
such as hepatic disorders, breast and uterus cancers. It was Coumarins p-hydroxyphenylacetic
also used as a diuretic and an anti-inflammatory remedy (Jeon Act on cardiovascular acid
et al., 2008). The genus name Taraxacum is derived from the Storage Inulin
Greek words “taraxis” for inflammation and “akeomai” for carbohydrate Prebiotic activity
curative (Schütz, Carle, & Schieber, 2006). The leaves, flowers Aerial dandelion parts (leaves and stems)
Terpenes Sesquiterpene lactones Taraxinic acid beta-
and the roots of the plant are either collected or bought from
Triterpenes/phytosterols glucopyanoside
the market and have been used for medicinal and culinary 11, 13 dihydro-taraxinic
purposes (Yaldiz, 2012). The main constituents of T. officinale acid
are sesquiterpene lactones, triterpene/phytosterols, phenolic beta glucopyanoside
acids, coumarins, inulin, and flavonoids Table 1 (González-
Castejón, Visioli, & Rodriguez-Casado, 2012). T. officinale is Phenolic Phenolic acid Chicoric acid
compounds Immunostimulatory Monocaffeoyltartaric acid
especially wide spread in temporal regions of the Northern properties Caffeic acid
Hemisphere. Most of the known traditional uses for T. Chlorogenic acid
officinale as an herbal remedy are based on empirical findings Coumarins p-hydroxyphenylacetic
and not scientific studies. Act on cardiovascular acid
Phenolic Phenolic acid Monocaffeoyltartaric acid

compounds Immunostimulatory Caffeic acid
Dandelion Phytochemical Group & Phytochemicals
(dandelion properties Chlorogenic acid
Root Biological Activities
flowers) Luteolin 7-O-glucoside
Terpenes Sesquiterpene lactones Taraxinic acid beta-
Flavonoids Luteolin 7-diglucoside
Anti-inflammatory and glucopyanoside
Antioxidant properties Free luterolin
antimicrobial properties 11, 13 dihydro-taraxinic
Free chrysoeriol
acid beta glucopyanoside
Triterpene/phytosterols Table 1. Phytochemical composition of dandelion. Main
Promote reduced cholesterol Traxasterol purported pharmacological properties of phytochemical
absorption Beta-sitosterol beta-D- components shown in italics. Source: adapted and modified from
glucopyanoside (González-Castejón et al., 2012)
Taraxacum officinale (Figures 1 and 2) in most of the western
countries is seen as a perennial weed that grows up to 15-30
cm in length with large, serrated leaves clustered in a rosette
around the base of the plant (Wright, Van-Buren, Kroner, &
Koning, 2007). T. officinale is native to Europe and Asia and
begins to grow at the beginning of the summer. It is widely
distributed in warm temperate zones of the Northern
Hemisphere, especially in fields, gardens, wild, semi-arid land,
and along roadsides (Steven & Foster, 2008; Wright et al.,
2007). Dandelions prosper in nitrogen rich pasture, gardens
and lawns and are cultivated in Germany and France (Steven
& Foster, 2008). The leaves sprout at ground level with a stem
and are arranged in a rose-like, serrated pattern. Another
common name is lion’s tooth, from the French word “dent-de-
lion” (Schütz et al., 2006). In general, dandelion leaves lack
fuzz, which is another way to distinguish it from other similar
plants with serrated leaves. It blooms bright yellow blossoms
that are about 10 to 30 cm long, sprouting from the middle of
the plant (Escudero, De Arellano, Fernandez, Albarracin, &
Mucciarelli, 2004). The fruit of the dandelion is the spherical,
fluffy seeded heads that helps self-pollinate with the
assistance of wind. Its spherical, fluffy, seeded heads give it
another common name: blowball. The dandelion’s root and
Figure 1. A complete depiction of Taraxacum officinale with its
the leaves secrete bitter, milky latex.
aerial parts (serrated leaves, stem, fluffy blowball seedlings
atop, and root). (Source: http://www.survivalschool.us/wp-
content/uploads/dandelion.jpg)
Traditional Uses
Taraxacum officinale has played a significant role in hepatoprotective effects by decreasing hepatic lesions.
traditional herbal medicine. T. officinale has also been Traditionally, dandelion was used as anti-fibrotic agent in
reported to being used in folk medicine as a “blood purifier” hepatic disorders and recent evidence supports this
and to maintain healthy liver. Studies on animals (mice) traditional practice of treatment (González-Castejón et al.,
revealed that dandelion’s polysaccharides have 2012).
(TCM) and Ayurveda medicine (Clare, Conroy, & Spelman,
2009). Dandelion’s medicinal values were recognized by the
ancient Chinese prior to Arab physicians’ introduction as a
strong herbal medicine to the Western herbal medicine
(Steven & Foster, 2008). In addition, German physician and
botanist Leonhard Fuchs (1543) has provided extensive
records of the medicinal application of T. officinale and
described its uses to treat gout, diarrhea, blisters, and spleen
and liver complaints (Schütz et al., 2006). The French have
several terms for the common dandelion including dent-de-
lion, which refers to the deep jagged shape of the leaves, and
pissenlit which is literally translated as “piss in bed,” a
reference to dandelion’s diuretic effect (Steven & Foster,
2008).
According to Steven & Foster (2008), the first recorded
Figure 2. Taraxacum officinale-plant leaves with flowers. reference to T. officinale in TCM was in 659 A.D. This
Source: (Šaćiragić, 2011) detoxifying herb was used to treat ailments ranging from
digestive disorders, appendicitis, breast inflammation, to
T. officinale has been known since ancient times for its
stimulate milk flow, and uterine and lung tumors (Chatterjee,
curative properties and treatment of a wide range of ailments.
Ovadje, Mousa, Hamm, & Pandey, 2011; Steven & Foster,
T. officinale has traditional uses in Germany, North America,
2008). After its introduction to Europe, European herbalists
Turkey and China (Wright et al., 2007). In Germany, it has a
have used dandelion as remedies for common fever, eye
history of treatment for gout, diarrhea, blisters, and spleen
problems, diarrhea, diabetes, and liver complaints. The East
and liver complaints. In North America, it has been used as a
Indians in the 16th century used T. officinale as a hepatic
treatment for kidney diseases, dyspepsia, and heartburn. In
stimulant, diuretic, and for liver disorders and chronic skin
Turkey, the herb is utilized as a laxative, diuretic, and anti-
diseases (Chatterjee et al., 2011) . The Native Americans used
diabetic medicine. T.officinale has also been reported to be a
dandelion decoctions to treat kidney disease, indigestion,
medicinal treatment for arthritis, rheumatoid arthritis,
swelling, skin problems, heartburn, and dyspepsia (Chatterjee
diuretic and skin conditions such as eczema.
et al., 2011; Steven & Foster, 2008).
According to Schutz et al., (2006), Arabian physicians first
Today, TCM specialists prescribe dandelion for lung and
referred to the therapeutic use of T. officinale during the 10th
breast tumors, jaundice, hepatitis, mastitis, abscesses, and
and 11th centuries to treat liver and spleen ailments.
urinary tract infection (Steven & Foster, 2008). In Western
Taraxacum genus plants have long been employed as a
medicine, dandelion is used in a wide range of conditions.
diuretic for over 2000 years in Traditional Chinese Medicine
Fresh dandelion and dried preparations are used to stimulate
appetite and ease stomach distress. The root of dandelion is al., 2012). Dandelion’s bitterness is due to its sesquiterpene
used as mild laxative to improve digestion, jaundice, and liver lactones found only in the aerial dandelion parts (leaves and
related conditions, skin conditions like eczema and psoriasis. stems) and the root of dandelion. Many of the components of
In addition, the sap from the root is used to treat diabetes. dandelion have been isolated and identified, but the
pharmacological activities from these components are still
under research or have not yet been studied. Figures 3 and 4
Nonmedical Uses provide the chemical structures of the most representative
Taraxacum officinale’s serrated leaves are often eaten as phytochemicals in dandelion. Dandelion contains important
vegetables in salads, or boiled and flavored as a side dish or in mineral salts such as calcium, potassium, iron, magnesium,
soups. The roots can be roasted and utilized as coffee phosphorus, silicon and sodium (Šaćiragić, 2011).
substitutes or fermented into beer, while the flowers have
been used to make wine and other soft drinks (Steven &
Foster, 2008). Although there is a limited amount of sources
supporting the use of dandelion parts as food, a research done
in the Province of San Luis, Argentina by Escudero et al.
(2004) has shown that even though dandelion is not a protein
source, it is still considered a food source due to its high
content of minerals, fiber, vitamins, laxative effects, and low
toxicity Tables 2 and 3. The use of dandelion for weight loss
with experimental diet is due to the T. officinale’s diuretic and
effects of T. officinale in combination with high quantity of
fiber content resulting in increased fecal volume (Escudero et
al., 2004).

The constituents and pharmacological activities in the nine
different species of the genus Taraxacum remain unclear.
However, recent research revealed that ethanol extract of
Taraxacum officinale contains anti-angiogenic, anti-
inflammatory and anti-nociceptive activities (Jeon et al., Table 2. Proximate chemical composition of flour from
2008). The main constituents in T. officinale are Taraxacum officinale leaves. (Source: Escudero et al, 2004)
sesquiterpene lactones, triterpenes/phytosterols, phenolic
acids, coumarins, inulin and flavonoids (González-Castejón et
Figure 3. A general structure and substitution patterns of
Table 3. Mineral and vitamin contents in flour from
Phenolic Acids and Flavonoids from Taraxacum officinale.
Taraxacum officinale leaves. (Source: Escudero et al, 2004) Sources: (González-Castejón et al., 2012)
Dandelion root In vitro studies were done on mice to examine the efficacy of T.
The roots of T. officinale contain sesquiterpene lactones officinale on fatigue and immunological parameters by giving
(Taraxicin acid beta-glucopyanoside, 11,13-dihydro-taraxinic the mice a force-swimming test. The results showed that T.
acid beta-glucopyanoside) which biological activities include offcinale decreased the immobility time in the forced swim
anti-inflammatory and antimicrobial properties (González- test, giving a potential future treatment with immune-
Castejón et al., 2012; Yaldiz, 2012). Triterpenes and enhancing effects. However, more studies are needed to
phytosterols in the roots include teraxasterol, taraxerol, further support this finding (Bo-Ra, Jong-Hyun, & Hyo-Jin,
homotaxasterol, beta-amyrine, beta-sitosterol beta-D 2012). Furthermore, dandelion roots also contain 15.35%
glucopyanoside, and stigmasterol to promote reduced free carbohydrates, carotenoids, fatty acids, minerals and
cholesterol absorption. Other chemical ingredients of pectin (González-Castejón et al., 2012; Olennikov, Tankhaeva,
dandelion are sterine, nicotine acid, choline, various resins & Rokhin, 2009). Dandelion root extract is thick and is the
and waxes (Šaćiragić, 2011). The root also encompasses main component for obtaining the appropriate
phenolic acid such as chicoric acid for its immunostimuulatory pharmaceutical pills (Šaćiragić, 2011).
properties and coumarins that act on cardiovascular system.
flowers is a diester of taraxanthin for which the name
“taraxien” was suggested. The major constituents of
dandelion flowers, roots and leaves are chicoric acid and
monoaffeoyltartaric acid caffeic acid and luteolin 7-
diglucoside, and current research studies have focused on
chicoric acid for its potential immunostimulatory activities
(González-Castejón et al., 2012).
The biological component of sesquiterpene lactones suggested
dandelion’s anti-inflammatory and anticancer effects
(Chatterjee et al., 2011; González-Castejón et al., 2012). T.
officinale also contain several phenylpropanoids, terpenoids,
polysaccharides playing their role in immune regulation,
hepatoprotective effects and antitumoral activity (González-
Castejón et al., 2012). Dandelion is also a rich source of
vitamins and contains a high level of potassium. According to,
the phytochemical composition of dandelion strongly depends
on the season, time of harvesting, ecological factors and varies
among the parts of the plant Table 2. For example,
sesquiterpene lactones that contribute to the bitter taste of
the plant are more prominent in the leaves compared to roots.
However, it is noticeable in the roots when it is harvested in
the spring. Overall, sitosterol is the most abundant sterol in
the leaves.
Figure 4. Chemical structure of some Triterpenes and
Phytosterols of Taraxacum officinale. Source: (González-
Castejón et al., 2012)
Biological Activity
Although it is not very strong in caffeine level, many studies
Dandelion Leaves and Flowers
have mentioned the use of Taraxacum officinale roots as coffee
T. officinale’s aerial parts including the flowers, all contain substitute. Emerging evidence suggests that dandelion and its
polyphenol compounds content. However, the content is much constituents (flavonoids and sesquiterpene lactones) have
higher in the flowers and the leaves of dandelion than in the antioxidant and anti-inflammatory activities that result in
roots. Most of the phenolic compounds found in the leaves diverse biological effects. Many consider it to be an annoying
and the flowers of the dandelions are derivatives of weed and spray it down with herbicide without knowing the
hydroxycinnamic acid. A main carotenoid pigment of the diverse biological activity of this herb. With more research,
activity was determined from chorioallantoic membrane assay
from chicken egg (Jeon et al., 2008). Current anti-angiogenic
strategies are the interference of rapid mitosis of endothelial
cell, obstruction of endothelial cell migration and adhesion.
The retinoic acid plays a significant role in inhibiting
angiogenesis by interfering the expression of factors that
promote the formation of new blood vessels (Jeon et al.,
2008). Figure 5 displays that anti-angiogenic activity from
ethanol extract (TEE) increases with respect to increase in
dosage. Luteolin, a flavonoid compound from T. officinale is
considered as one of anti-angiogenic principles in dandelion
after it increased inhibition in the CAM assay from,(Jeon et al.,
2008)’s research. Therefore, the anti-angiogenic activity of T.
officinale from this study provides a pharmacological basis on
its traditional use in treating various acute anti-inflammatory
Figure 5. The inhibitory effect of the 70% ethanol extract diseases and cancer (Jeon et al., 2008). Anti-nociceptive
(TEE) from Taraxacum officinale. Sources: (Jeon et al, 2008) activity was determined through writhing response after
stimulated with acetic acid and there was also a relative
inhibition pattern revealed from writhing response induced
the benefits of dandelion as an choleretic, diuretic, anti- by acetic acid (Jeon et al., 2008).
rheumatic and anti-inflammatory will be better understood.
Recent studies have paid more attention to dandelion’s
antioxidant activity and its possible beneficial effects against Anti-inflammatory Activity
the development of obesity, cancer, and a number of T. officinale was found to contain anti-inflammatory activity in
cardiovascular risks (Gonzalez-Castejon, Visioli, & Rodriguez- cholecystokinin-induced acute pancreatitis in rats (Jeon et al.,
Casado, 2012; González-Castejón et al., 2012). 2008). There is an indication of an anti-inflammatory activity
from T. officinale in the central nervous system from cultures
of rats astrocytes and that it hinders the production of tumor
In vivo Laboratory Studies
necrosis factor alpha by inhibiting the production of
In vivo experiments was conducted by (Jeon et al., 2008) using interleukin-1 (Jeon et al., 2008).
male imprinted controlled region mice with a room
temperature of 23 ± 2°C, a 12 hour light/dark cycle, and food
supply. Dried parts of T. officinale were grounded under liquid Antioxidant activities
nitrogen and extracted for an entire month. Anti-angiogenic In both in vivo and in vitro laboratory studies on rats,
dandelion exhibit antioxidant activities when dandelion root and hypercholesterolemia (González-Castejón et al., 2012).
and leaf extracts are administered. Due to dandelion’s high Potent inhibitory activity of dandelion on pancreatic lipase
phenolic compounds such as flavonoids and coumaric acids has been evaluated in vitro and in vivo studies for its potential
found in its flowers, the flowers have great potential of being a as an anti-obesity agent (González-Castejón et al., 2012).
source of natural antioxidant (González-Castejón et al., 2012). Flavonoids such as luteolin from dandelion leaves might exert
On the other hand, leaf extract from dandelion contain a pancreatic lipase inhibitory activity (González-Castejón et al.,
greater content of both polyphenol and flavonoid compared to 2012). Pancreatic cancer is deadly and research studies have
the roots and has the prospective protection from free-radical been underway to find alternative treatments for this disease.
formations (González-Castejón et al., 2012). Dandelion tea The efficacy of dandelion root extract in inducing apoptosis
was studied for the ability of its flavonoids to protect V79-4 and autophagy and resistance to pancreatic cancer cells was
cells from free-radical induced toxicity (González-Castejón et evaluated and the research data reveals that dandelion’s root
al., 2012). In vitro studies on mice provide scientific evidence extract led to the collapse of the mitochondrial membrane,
that dandelion’s antioxidant and antiproliferative activities on consequently leading to degradation of cancerous cells with
hepatic cells and gallbladder disorders give grounds for the no significant effect on the healthy, noncancerous cells
use of dandelion in traditional medicinal use (González- (Ovadje et al., 2012).
Castejón et al., 2012). Dandelion also interferes with the
expression of certain proinflammatory mediators. In vitro
studies show that dandelion root methanol extracts and leaf Hypoglycemic effects
extract influence inflammatory mediators, while in vivo The mechanism of action of its hypoglycemic properties gives
studies show that ethanol, aqueous, and methanol extracts controversial results. However, certain dandelion extracts
inhibits the production of inflammatory cytokines in rats. stimulate the release of insulin by pancreatic beta-cells,
Furthermore, in vivo studies in humans with seven herb resulting in reduced blood sugar level (González-Castejón et
combination including dandelion found significantly less al., 2012). More thorough research study is needed to confirm
rectal bleeding and anti-inflammatory activity in which of the dandelion extract initiates the insulin release.
inflammatory bowel disease Table 1. A recent study reveals
that dandelion seem to demonstrate protective anti-
inflammatory effects on an acute lung injury in mice induced Chemotherapeutic potential
by lipopolysaccharide (González-Castejón et al., 2012).
Aqueous extracts of T. officinale have been long used in
traditional medicine throughout Asia, Europe and North
Pharmacological effects America as a treatment for various types of cancer including
breast cancer and leukemia. However, the mechanism of
Animal studies have reported the effects of different action is unknown. In vitro laboratory studies have been done
dandelion extracts on a range of risk factors of cardiovascular to investigate the anti-carcinogenic effects of dandelion on cell
disease such as obesity, hyperlipidemia, hypertriglyceridemia proliferation and metastasis formation. The results conclude
that dandelion extracts kill human hepatitis cells (HepG2) and with methionine and choline deficient diet. Non-alcoholic
exhibit toxicity to the uncontrolled cancerous cell growth in steatohepatis (NASH) is a form of metabolic liver disease,
humans (Chatterjee et al., 2011; González-Castejón et al., which is becoming a serious global health problem. NASH is
2012). Crude extract of dandelion leaves have the benefit of caused by the increasing accumulation of fatty acids triggering
decreasing the growth of breast cancer cells by 40 percent. oxidative stress and inflammation (Munkhtugs et al., 2013).
Meanwhile, root extract was found to block the invasion of Therefore, a developed treatment for NASH includes inhibiting
MCF-7/AZ breast cancer cells while leaf extract block the fatty acid build up, oxidative stress, and inflammation.
invasion of LNCaP prostate cancer cells (Chatterjee et al., Dandelion extract has shown efficiency in reducing oxidative
2011; González-Castejón et al., 2012). Preventing rapid tumor stress and fibrosis that cause liver injuries. Dandelion leaf
cell growth from Taraxacum extracts attributed to extract with its high content of polyphenol and luteolin inhibit
triterpenoids (especially taraxasterol and taraxerol) and lippolysaccharide induced oxidative stress and protect against
sesquiterpenes suggesting chemopreventive agents liver injury (Munkhtugs et al., 2013). Conversely, the
(González-Castejón et al., 2012). mechanisms by which the dandelion leaf extract exert
In test tube studies, dandelion extracts have shown strong hepatoprotective effects are unclear. Another study done
anti-tumor activities against liver, colon, and melanoma recently also shows that the combination formula (HV-P411)
cancer cells (Steven & Foster, 2008). This is important, as of seeds from Vitis vinifera, Schisandra chinesis and T. officinale
melanoma is one of the leading cancers targeting adolescents was used to treat D-Galactosamine (D-Ga1N), hepatotoxicant,
and young adults in North America and its aggressive and showed that the formula did have preventive effect on liver
chemotherapy resistant nature have lead many researchers to fibrosis (Kang et al., 2012).
try to find alternative treatments. Chatterjee et.al (2011) have
investigated the efficacy of dandelion root extraction on
Renal effects
human melanoma cell lines in in vitro laboratory studies and
discovered that dandelion root extract is effective in inducing In traditional folk medicine, T. officinale has been employed as
apoptosis. (González-Castejón et al., 2012) and (Chatterjee et a diuretic throughout Europe, Asian and Americas, and is still
al., 2011) state that the possible mechanism of action is utilized in modern phytotherapy. Dandelion leaves have been
through the activation of caspase-8 by the dandelion root shown to possess diuretic effects in rats and account for 100%
extracts. weight loss in the testing animals Table 4. Studies done on
human subjects given fresh hydroethanolic extracts to assess
urine volume and frequency of urination indicate diuretic
Detoxifying and hepatoprotective effects effects but additional studies are needed (Clare et al., 2009).
Traditional folk medicines have been using Taraxacum
officinale for hepatic disorders as a detoxifying agent. In one
Antimicrobial / antiviral effects
research study, extract from dandelion leaves was
investigated for its hepatoprotective effects by inducing mice In vitro laboratory studies data demonstrate that there are
Compounds Other activities of diuretic locations on the territory of Bosnia and Herzegovina to
compounds investigate the levels of plant contamination with heavy
Ascorbic acid Nutrient metals (Šaćiragić, 2011). T. officinale has been investigated in
Caffeic acid Antiaggregant, anti-inflammatory, this field research due to its bio indicator of the degree of
antioxidant, anxiolytic contamination of the environment with heavy metals
according to (Šaćiragić, 2011). Throughout the research, the
Calcium Nutrient
Chlorogenic acid Anti-inflammatory, antioxidant,
content of heavy metals varied depending on the parts of the
cardio protective plant, the site where the survey was done, the level of
Isoquercitrin Anti-inflammatory, antioxidant, contamination of the environment with heavy metals, and
hypotensive other ecological factors. As a result of the research, dandelion
Luteolin Anti-inflammatory, antioxidant, was classified as a hyper accumulator plant and as bio
hypocholesterolemic, vasodilator
indicator of heavy metals, particularly lead (Šaćiragić, 2011).
Magnesium Nutrient
Mannitol Anti-inflammatory, antioxidant
Potassium Nutrient
Table 4. Diuretic compounds in T. officinale and other Clinical Studies
properties. Source: (González-Castejón et al., 2012) One study was done in which fresh leave hydroethanolic
extract of Taraxacum officinale was given to human volunteers
to assess their urine volume and frequency of urination in the
antiviral effects against the human herpes virus type 1 and subjects (González-Castejón et al., 2012). The results
antimicrobial effects attributed to the flavones from the indicated that the dandelion hydroethanolic extract did exert
dandelion (González-Castejón et al., 2012). Dandelion was diuretic activities in humans. However due to the small
used in traditional medicine in Rize region in Turkey for its sample size of only seventeen subjects, further
antimicrobial activity. The milky sap from the roots and experimentation/data collection is advised.
leaves of dandelion has shown efficacy in removing verruca
and warts on the skin in traditional medicine (Yaldiz, 2012)
and melting gallbladder stones and reducing inflammation. Contraindications
Taraxacum officinale has been found to have low toxicity, and
suggested for dietary supplement and as a food source.
Other activities However, since studies indicate that T. officinale is a heavy
Unfortunate events, like the Deepwater Horizon oil spill, have metal absorber in phytoremediation of agricultural land, it
led to an intense search for hyper accumulating plant species would probably be highly recommended not to pick dandelion
that have the potential to be utilized in absorbing a great grown in recreational parks, off the side of roads, or in
concentration of heavy metals. A field research was backyards due to people’s habit of spreading herbicide in
conducted during the month of May 2008 in several different these areas and pollution in the environment. According to
Discussion
Despite the fact Taraxacum officinale and its related species
are commonly considered as a pesky weed, recent research
findings have discovered significant medicinal and dietary
contribute of dandelions. Emerging evidence and studies
suggest that T. officinale and its constituents have a wide-
range of biological activities such as antioxidant and anti-
inflammatory activities attributing to diverse biological
effects. T. officinale is steadily gaining credibility with the
support of growing scientific research on the plant.
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Taxus brevifolia Nutt., Taxaceae
Wallace Wyeth
Introduction
The Pacific yew tree, Taxus brevifolia, is the source of a very
important drug used in the treatment of cancer. The Pacific
yew, also known as the western yew, is a member of the
Taxaceae family (Lewis and Elvin-Lewis 2003). The discovery
of T. brevifolia as a source of a biologically active
phytochemical resulted from its collection in 1962 by
botanists from the US Department of Agriculture (Kingston
2007). This collection was part of a large scale screening
program then being conducted by the National Cancer
Institute. The tree was among a group of 35,000 plants
screened for bio-active metabolites (Vongpaseuth and Roberts
2007). The biologically active phytochemical found in this
slow growing tree is paclitaxel, a diterpenoid that is extracted
from the bark. The Pacific yew is so slow growing that it takes
approximately 100 years for a tree to be large enough to
harvest. Even then, the yield of anticancer diterpene is very
low, in the range of about 0.01 to 0.02%. With such a low
yield, it takes three 100 year old trees to produce 1 gram of
paclitaxel. Each course of treatment requires 2 grams of the
drug (Heinrich, et al. 2004), resulting in the need for a
tremendous number of trees. Renneberg described the
needed amount of paclitaxel in terms of how many trees
would be required each year to treat the patients with ovarian
cancer. 360,000 trees per year would be needed just to treat
the US patients (Renneberg 2007). In order to protect T.
brevifolia from being over utilized, a renewable source of
paclitaxel would have to be found. Figure 1. Taxus brevifolia in a forest in Canada. The brush
in the foreground and the conifers in the background provide
a sense of scale (Tigner 2008).
Figure 3. Leaves and fruit of Taxus brevifolia. The leaves
and seeds are toxic, but the red aril surrounding the seed
is not (Pacific Yew Taxus brevifolia n.d.).
Figure 2. This photograph of the trunk displays the scaly
nature of the bark and the multiple hues of purple of the species is from southern Alaska to northern California.
described in the text (McDougall 2003). It is sometimes found as far inland as just east of the Oregon
or Washington eastern borders. The largest examples of the
Description species are found along the coast with those further inland
generally diminishing in size. It is found from sea level to an
Taxus brevifolia Nutt. (Taxaceae) is described as a small tree, elevation of 2,200 meters (Francis n.d.). T. brevifolia is usually
or a large evergreen shrub (Figure 1). The bark is thin, scaly, the dominant understory plant, most commonly in coniferous
and is purplish in color (Figure 2). The tree may reach a forests. It sometimes grows exposed at higher elevations and
height of 15 meters in areas conducive to maximum growth also when exposed by logging of the overstory species. It is
such as coastal areas or some low lying inland areas. Trees of generally considered a hardy species (Francis n.d.), but is very
this size are approximately 60 cm (about 2 feet) in diameter at vulnerable to fire, and controlled burns are not recommended
chest height. When conditions are less favorable and at higher in forests where the Pacific yew is found (Tirmenstein 1990).
elevations, the Pacific yew will only reach a height of a few The same report stated that due to its thin bark, Pacific yew is
meters and will be proportionally smaller in diameter as well always killed by even small ground fires. If the species is
(Francis n.d.). Leaves are narrow and vary from 8 to 35 abundant in a given area its presence indicates a significant
millimeters in length (up to 1 1/3 inch). The Pacific yew period with an absence of fire. It was observed that in one
produces an ovoid seed 5 to 6 millimeters long that is part of Idaho where the species was eliminated by fire, a
enclosed in a fleshy cup shaped red aril (Figure 3). The range
period of 6 years transpired before seedlings began to people made a poultice from the ground leaves for use as a
germinate (Tirmenstein 1990). topical dermatological aid that was applied to wounds
The Pacific yew can propagate both by seed and by vegetative (Moerman 2004). Another group made a decoction of the
means. Layering is the primary method of propagation in wood and bark that was used both as a gastrointestinal aid to
some areas (Tirmenstein 1990). Layering is a process where relieve stomach ache and also for other internal ailments.
lower limbs that come into contact with the ground form roots Several other tribes used products from the Pacific yew for
and establish a new plant. Pacific yew is dioecious and male similar treatments as well as using it as an analgesic to relieve
plants produce abundant 3 mm staminate cones. Ovulate pain, for the treatment of bloody urine, to treat internal
cones are green and appear individually on the underside of injuries, to treat sunburn, and as a blood medicine to purify
branches. The fruit is red and berrylike as described above the blood (Moerman 2004). The Tsimshian people used it for
and is regularly consumed by several bird species internal ailments and to treat cancer, though the method of
(Tirmenstein 1990). It is common for birds to disperse the preparation for the cancer medication is not described
seeds of the Pacific yew. Seeds are known to exhibit dormant (Moerman 2004).
behavior. Passage through the avian gut may affect this
dormancy in some way. It takes 250 to 350 years for a Pacific
Other Ethnobotanical Uses
yew to reach maturity and individuals often survive for
several centuries (Tirmenstein 1990). In his book, Native American Ethnobotany, Moerman (2004)
provides a list of the uses made by Native Americans of
various plants. On the list of non food, non medical uses,
Traditional Uses Taxus brevifolia is second on the list with 84 uses, behind only
Ethnomedical Uses Thuja plicata (Cupressaceae), the Western Red Cedar, with
121 uses (Moerman 2004).
People of the Pacific Northwest made a tonic from the Pacific
yew that was used medicinally (Tirmenstein 1990). Moerman The wood from T. brevifolia is fine grained and hard as well as
(2004) lists a number of ethnomedical uses by the various being very strong and decay resistant. The sapwood is light
tribes in that region. It was used either topically or taken yellow whereas the heartwood is orange or a rosy red. The
internally as an infusion or decoction. The Chehalis people wood finishes well and is sometimes used in cabinet making
used Taxus brevifolia as a diaphoretic (Moerman 2004). An or to make tool handles or boat paddles. Despite this, the
infusion was made from the crushed leaves that was then used wood is not considered to be commercially important
as a wash to cause perspiration. These same people also used (Tirmenstein 1990). Native Americans also used the wood of
it as a panacea, a cure all, by making a similar infusion and the Pacific yew to make boat paddles, but additionally used it
using it as a wash to improve general health (Moerman 2004). for making harpoons, spear handles, clubs and, most
The Bella Coola boiled the branches complete with leaves to importantly, bows. Pacific yew is considered to be an
make a decoction used as a pulmonary aid. The Cowlitz excellent source of material for making
The principle active molecule in Taxus brevifolia is paclitaxel.
Originally known as taxol, paclitaxel is a very complex plant
secondary metabolite (Figure 4). Because of this complexity,
it took years to determine the molecules structure and that it
was the active constituent in T. brevifolia.
After its initial collection in 1962, plant extracts from the
Pacific yew underwent testing in 1963. These tests confirmed
the cytotoxicity of these extracts against human KB cells
Figure 4. Structure of paclitaxel. Note the side molecule
(Kingston 2007). This eventually led to a second bark
attached at carbon number 13 (Kingston 2007).
collection in 1965 that was sent to the Research Triangle
Institute (RTI) for further testing. Activity against mouse
bows. The Salish people called it the bow plant (Tirmenstein leukemia was confirmed in 1966, but nevertheless, the active
1990). Pacific yew is still used to make bows. These bows are constituent molecule was not isolated until 1969 (Kingston
very expensive because the wood from which they are made is 2007). Taxol was identified as the isolated active constituent
usually cured for decades (Tirmenstein 1990). Though the (Kingston 2007) but not until 1971 was it confirmed that taxol
Pacific yew is supposedly toxic to domestic livestock, it was the anti-tumor component of the T. brevifolia extracts
provides important browse for wildlife species including deer, (Vongpaseuth and Roberts 2007). This pattern of discovery
elk and particularly moose. It is reported that moose depend and long lapses of time with little progress became the
on Pacific yew over the winter months and from it obtain signature of the investigation of the extracts obtained from T.
approximately 40% of their nutritional requirements during brevifolia.
this period. The claim that Pacific yew is toxic to livestock has
Despite its activity against mouse leukemia that was
not been substantiated. Some livestock owners claim it is not
discovered in 1966, and activity against other leukemia’s and
toxic when eaten as browse, but becomes dangerous if cut and
carcinosarcoma demonstrated later, other available
allowed to decay. There are also claims that the fruit is toxic
compounds worked as well or better in these tests, so interest
to some species, but songbirds and some mammals are known
in the products from the Pacific yew remained low (Kingston
to feed on the fruit (Tirmenstein 1990). Native Americans
2007). There remained just enough interest in taxol, as it was
also ate the fleshy portions of the fruit, but not the seeds
still called then, that more testing was conducted in the early
which are poisonous. Native Americans used the foliage as a
1970’s. These results led to even further testing and the
deodorant due to its fragrance and also used it as a cleaning
eventual selection of paclitaxel as a development candidate in
agent. Some Native Americans associated the Pacific yew with
1977. The end to the start and stop process of investigation
death and bereavement (Tirmenstein 1990).
did not come until the mechanism of action was discovered
(Kingston 2007). It was the discovery of the unique tubulin
Table 1. History of paclitaxel (Vongpaseuth and Roberts 2007).
stabilization mode of action in 1979 (Vongpaseuth and
Roberts 2007) that solidified interest in the molecule (Table
1).
Despite its halting nature, research of the chemical properties
of the T. brevifolia extracts continued through the 1960’s and
1970’s. As earlier stated, Taxol was isolated in 1969.
However, the yield of Taxol from the bark of the Pacific yew
was only 0.01% and the concentration in other parts of the
plant, such as the wood and needles, was even lower so little
Taxol was available for experimentation. It was not until 1971
that the structure of paclitaxel was finally determined after Figure 6. Paclitaxel (green) binding tubulin and
the molecule was degraded by the cleavage of a side chain stabilizing the microtubules (Renneberg 2007).
from the main molecule (Figure 5). The cleavage resulted in
two molecules, 10-acetylbaccatin and β-phenylisoserine ester tumor activity discovered during screening using KB
(Kingston 2007). There were a number of reasons why it was cytotoxicity assay (Kingston 2007). In vivo activity testing was
so difficult to determine the structure of paclitaxel. Magnetic done in 1966 that confirmed the bark extract was active
imaging was not nearly as advanced at that time as it is now. against mouse leukemia. Other in vivo testing was done
The complex nature of the molecule was a contributing factor against other leukemia’s and Walker 256 carcinosarcoma that
as was the extremely limited quantity of paclitaxel that was showed only modest activity. Additional in vivo bio assays
available for analysis (Wall and Wani 1995). Although a were developed in the early 1970’s. The paclitaxel results in
number of crystalline compounds were obtained prior to the B16 mouse melanoma assay led to growing support within
degradation of the main molecule, none of them were suitable the National Cancer Institute to pursue development. New
for x-ray analysis which was necessary to help determine the tests were developed for testing mammary and colon
structure of the molecule. After the cleavage of the side chain, xenografts in mice. Paclitaxel demonstrated good activity in
the resulting smaller molecules were then crystallized and these tests and was selected for development in 1977
were suitable for x-ray analysis (Heinrich, et al. 2004). (Kingston 2007).
Determining the structure of the constituent molecules
Susan Horwitz discovered the mechanism of action of
allowed the structure of the parent molecule to be determined
paclitaxel in 1979. Paclitaxel works by inhibiting mitosis.
(Wall and Wani 1995).
Other products discovered before paclitaxel such as
vincristine and colchicine also inhibit mitosis. However,
Biological Activity paclitaxel works completely opposite those other products.
While vincristine for example inhibits mitosis by binding
Paclitaxel does exhibit biological activity. The extracts from tubulin and preventing the formation of the microtubules
the bark of Taxus brevifolia were first studied because of anti- required for mitosis, paclitaxel stabilizes microtubules and
prevents depolymerization (Heinrich, et al. 2004). Paclitaxel melanoma response to paclitaxel was reported in 1987.
and its analogue docetaxel have their greatest effect on cells Responses in ovarian cancer and breast cancer were reported
that divide rapidly such as cancer cells. It binds to the tubulin in 1989 and 1991 respectively (Kingston 2007). Other clinical
subunits of microtubules (Figure 6) and prevents trials found paclitaxel also effective against advanced breast
disassembly. The interruption of the cell cycle leads to cancer (Vongpaseuth and Roberts 2007). Paclitaxel was
programmed cell death (Renneberg 2007). The novel method approved for use in 1993 under the trade name Taxol
by which paclitaxel inhibited mitosis and initiated cell death (Heinrich, et al. 2004). The initial FDA approval was for use
contributed to the growing interest in the compound and led against refractory ovarian cancer. Additional FDA approvals
to clinical trials (Heinrich, et al. 2004). follow over the next several years. Paclitaxel was approved
Many patients do develop resistance to paclitaxel (Renneberg for use against breast cancer in 1994, Kaposi’s sarcoma in
2007). The mechanisms that result in resistance are complex 1997, and for use against non-small cell lung cancer in 1999.
and included many potentially contributing processes. The FDA approved the marketing of semi-synthetic paclitaxel
Factors listed include rates of expression for cell membrane in 1995 (Vongpaseuth and Roberts 2007).
transporters with increased expression of efflux and Other more recent papers have reported clinical results as
decreased expression of influx transporters. Increased well. Many of these clinical trials compared the use of
expression of resistance associated proteins was also paclitaxel in combination with other medications. Platinum
reported. Other factors include over expression of enzymes compounds are known to be active against ovarian cancer, so
that metabolize paclitaxel, tubulin mutations that reduce testing was done using paclitaxel in combination with
paclitaxel binding, and changes in the signaling pathways cisplatin. Phase I trials provided information that the two
leading to microtubule formation (Kumar, et al. 2010). drugs could be used safely in combination (Kumar, et al.
2010). Subsequent trials have compared cisplatin-paclitaxel
combinations against combinations of other agents. For
Clinical Studies instance, one trial (GOG 111) compared the effectiveness of a
Preclinical toxicology testing of paclitaxel was completed in combination of cyclophosphamide-cisplatin against the
1982. Phase I clinical testing was started in 1984 and phase II cisplatin-paclitaxel combination. The progression free
trials followed in 1985. Serious side effects in the form of survival period (PFS) was increased from 13 to 18 months by
hypersensitivity reactions were encountered. Because of its using the paclitaxel containing combination (Kumar, et al.
low solubility, paclitaxel formulations include a surfactant 2010). This same trial reported a median survival increase
(Cremophor EL). The side effects encountered during clinical from 24 to 38 months. I similar trial (OV-10) reported similar
trials were believed to be caused by Cremophor. Two deaths findings with the cisplatin-paclitaxel combination. These
resulted from these unpredictable hypersensitivity reactions studies established this combination treatment as the first line
and clinical trials were almost ended (Kingston 2007). A 24 therapy for ovarian cancer (Kumar, et al. 2010). Subsequent
hour infusion protocol was developed that avoided the trials such as ICON3, reported in 2002, have not demonstrated
hypersensitivity reactions. Through these clinical trials, the same clear superiority of this combination treatment as
reported by GOG 111. However, though not demonstrating a to increased toxicity or a reduction in the cytotoxic antitumor
superior PFS and overall survival rate, the toxicity profile was activity (Kumar, et al. 2010). Paclitaxel is known to have
superior and the cisplatin-paclitaxel combination remained interactions with several other cytotoxic drugs as well as
the recommended first line therapy for ovarian cancer some non-cytotoxic drugs. Even though cisplatin and
(Kumar, et al. 2010). Since these trials concluded, other work paclitaxel have been demonstrated to be safe to use together,
has resulted in the replacement of cisplatin by carboplatin. dosages have to been altered when doing so. Cisplatin
This is a better tolerated platinum compound that is proven administered prior to paclitaxel is known to increase
equally effective. Most patients will respond to first line neutropenia and reduce the antitumor activity of paclitaxel
therapy, but unfortunately the majority of ovarian cancer (Kumar, et al. 2010). Other cytotoxic drugs with known
patients also suffer recurrence (Kumar, et al. 2010). Work interactions include doxorubicin, etoposide, topotecan and
continues to better understand the complex interactions trastuzumab. Interactions of trastuzumab with paclitaxel
involved. New therapies continue to be tested for both have resulted in increased incidence of congestive heart
platinum sensitive and platinum resistant cancer. failure (Kumar, et al. 2010).
The combination of carboplatin-paclitaxel remains important Known interactions with anticonvulsant drugs such as
for the treatment of ovarian cancer. Recently, clinical trials phenytoin and phenobarbital result in reduced cytotoxic and
have been initiated to evaluate adding a third agent along with antitumor activity of paclitaxel. Cytochrome P450 induction is
carboplatin-paclitaxel (Kumar, et al. 2010). involved in this interaction (Kumar, et al. 2010).
Contraindications Current Use in Allopathic & CAM Therapies

There are a number of toxic side effects related to use of Paclitaxel is currently marketed under the trade name Taxol
paclitaxel. Neutropenia, an abnormally low number of by BristolMyersSquibb. Docetaxel is a semi-synthetically
neutrophils in the blood, is the most common toxic effect. produced variant of paclitaxel that is also a taxane diterpene.
Inflammation of the lining of the mouth and the lining of the Both paclitaxel and docetaxel were produced semi-
gastrointestinal tract are also possible. Muscle pain is a synthetically from 10-acetylbaccatin III. Docetaxel has a
common side effect. Cardiac rhythm disturbances have also modified side chain that is different than the side chain of
been encountered (Georgatos and Theodoropoulos 2001). paclitaxel (Heinrich, et al. 2004). Docetaxel is used for the
Drug interactions with paclitaxel must also be considered. It treatment of breast and ovarian cancer and is marketed under
is important that the dosing level of paclitaxel be relative to the name Taxotere. Both of these medications are
the metabolic capacity of the elimination pathway. If the dose administered intravenously (Heinrich, et al. 2004). Paclitaxel
exceeds this level, toxicity is increased. If the dose is below is approved by the FDA for use against “…breast cancer,
this level, efficacy is decreased. Any interactions that alter the ovarian cancer, non-small cell lung cancer…” and is also used
rate at which paclitaxel is metabolized and eliminated can lead against Kaposi’s sarcoma (Vongpaseuth and Roberts 2007,
219). It is also being studied for use against Alzheimer’s and
as a follow up to angioplasty. It is hoped that paclitaxel can Despite this progress, more research is still needed to derive
limit scar formation to prevent artery narrowing. more analogues that can avoid the problems of dangerous side
effects and acquired resistance.
Discussion
The discovery of taxol in the Pacific yew was a very important References Cited
discovery for the treatment of several forms of cancer. The Francis, John K,. "Taxus brevifolia Nutt. Pacific yew." US Forest
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Kumar, Sanjeev, Haider Mahdi, Christopher Bryant, Jay P Shah,
synthetically from 10-acetylbaccatin III harvested from the Gunjal Garg, and Adnan Munkarah. "Clinical trials and
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is a sustainable process. Still not satisfied, as the process is Journal of Women’s Health, 2010: 411–427.
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Lewis, Walter H, and Memory P. F. Elvin-Lewis. Medical Botany:
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Plants Affecting Human Health. Hoboken, New Jersey: John
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Theobroma cacao L., Malvaceae
Kira Ohmart
Introduction
Theobroma cacao, commonly known as cacao or cocoa,
belongs to the Malvaceae family, or the mallow family, which
includes marshmallow plants, kola nuts, okra, and cotton. T.
cacao is one of the most significant perennial crops due to the
massive manufacture of chocolate, which is how the plant is
almost exclusively used (Almeida and Valle 2007). In 2006,
the estimated world output of the cacao plant was 3.5 million
tons. The plant has been cultivated and exploited for the
seeds, which are used for the manufacture of chocolate
(Almeida and Valle 2007). The main constituents of T. cacao
include the methylxanthines theobromine, a similar
compound to caffeine, and caffeine itself, both of which have
stimulant properties. Other compounds in T. cacao include
flavonoids, which exhibit antioxidative effects among other
effects, lipids, sterols and, interestingly, trans-resveratrol,
Figure 1. Typical flower found on cacao tree. These grow in
which may have significant effects on cancer (Colombo,
clusters directly on the trunk of the tree. Each flower has five
Pinorini-Godly et al. 2012). The plant is native to tropical
fertile stamen and five infertile stamen. (Image source:
regions and can be found in neotropical rainforests,
panoramio.com)
particularly the Amazon basin and Guyana Plateau (Colombo,
Pinorini-Godly et al. 2012). rainfall each year and only within 10 degrees north or south of
the equator (Colombo, Pinorini-Godly et al. 2012). The cacao
tree is an understory tree, reaching 20 to 25 meters in height
Botanical Description in its natural habitat, growing beneath the canopy of taller
Theobroma cacao is a small evergreen tree that is native to plants in the rainforest in shady areas indicating that it does
tropical and subtropical areas, and grows at elevations of 20 not require lots of sunlight to survive (Almeida and Valle
to 400 meters. The cacao tree requires a humid climate, with 2007). There are three different subvarieties of the species
regular rainfall, and healthy soil to survive and produce fruit, that are identified by their physical and genetic
tending to grow in areas with 1000-3000 millimeters of characteristics, and the geographical regions they are located
in. These three subtypes are Criollo, Forastero, and Trinitario
(Almeida and Valle 2007). The cacao tree originates in the
river valleys of Middle and South America. It was originally
used by Central Native American groups including Maya,
Aztecs, and Toltecs. Now that the T. cacao species is cultivated,
however, it has been known to be grown not only in Central
and South America, but also Asia and Africa (Almeida and
Valle 2007).
The cacao plant has two different types of branches: those that
grow vertically (orthotropic) and those that grow laterally
(plagiotropic). In the T. cacao species the vertically growing
branches are known as chupons, and the laterally growing
ones are known as fan branches. The cacao tree is cauliflorous
indicating that it produces flowers on older branches and the
main trunk of the plant (Colombo, Pinorini-Godly et al. 2012),
Figure 1. The leaves of the cacao tree are dark green and
shiny with a leathery texture. The leaves are elliptically Figure 2. Pod of Theobroma cacao tree. The husk or outer
shaped and undivided blades. They grow to be about part is characterized by a yellow color. On the inside, the
approximately 20 to 35 centimeters long and 7 to 8 sweet white mucilage surrounds the seeds of the tree that give
centimeters wide (Colombo, Pinorini-Godly et al. 2012). chocolate its typical flavor. (Source: EcoLibrary.org)
The flowers are tiny, usually just 1 to 2 centimeters in
diameter, and contain a pink calyx. The flowers’ color typically
from where cocoa beans originate, the main ingredient of
ranges from white with a yellowish tinge to a very pale pink.
chocolate (Colombo, Pinorini-Godly et al. 2012).
Unusual for the plants in the Malvaceae family, the flowers of
the T. cacao plant grow throughout the entire year, producing, The pods or berries, as they are sometimes referred to, are an
on average, between 50 thousand and 100 thousand flowers ovular shape, ranging from about 15 to 30 centimeters long
per year, and have no nectar or perceptible scent to them and 8 to 10 centimeters wide. These weigh around 500 grams,
(Colombo, Pinorini-Godly et al. 2012). The flowers are or a little over 1 pound. The color of the pods ranges between
produced in little clusters directly on the trunk and older a yellowish to an orange color. Each pod typically contains 20
branches (cauliflorous), and each has five petals, five fertile to 60 seeds, or what are commonly considered cocoa beans.
stamens, and five infertile stamens. The plant is pollinated by These seeds are enveloped by sweet, white mucilage that is
the Forcipomyia midges species, a tiny fly. Interestingly, when said to have a lemony taste or a taste similar to that of mango
these flowers are pollinated, their morphology makes a drastic (Figure 2). Monkeys and other mammals break the pods open
change from tiny to quite massive, becoming the large pods to eat this sweet mucilage, which is how the seeds of the plant
are dispersed. The seeds or beans have an extremely bitter and the beans are removed and laid out on mats to dry. To
taste to them (Colombo, Pinorini-Godly et al. 2012). create the beverage, the beans are roasted over a fire, and
Present within the T. cacao species, there are fungal then ground between stones on a mortar, creating a paste. The
endophytes, particularly Fusarium species that grow within paste is put into cups made from calabashes, similar to a
the plant tissues. These fungal endophytes do not necessarily gourd, produced from Lagenaria seceraria, mixed with water,
have a harmful effect on the host unless the host is under sometimes spices were added, and then finally drunk
environmental stress. Although they are not harmful, there (Colombo, Pinorini-Godly et al. 2012). The Maya groups
have been no conclusive studies on the benefit of these consider T. cacao a significant ritual food due to the stimulant
organisms in the cacao tree (Colombo, Pinorini-Godly et al. effect of the plant (Kufer, Grube et al. 2006).
2012) Another traditional use of the T. cacao species is by the Choco
Indians. These people originate in the Amazonian forest. They
typically do not make chocolate beverages or even use the
Traditional Uses beans. This group is more interested in consuming the white
The Theobroma cacao species had several different uses in pulp surrounding the beans as a snack between meals (Duke
indigenous cultures, including culinary, medicinal, and even 1970).
monetary uses. It had cultural significance within the Maya A different indigenous group, the Cuna of Panama and
and Aztec cultures, among others. The first European Colombia, also consume T. cacao, in the form of a paste made
encounter with the plant was in 1502, during one of from the beans. The Cuna people eat 25 grams of this paste
Christopher Columbus’s returns to the Americas. By this time, per day as a snack. The Cuna also used T. cacao for medicinal
the cacao plant had already been cultivated for up to 2000 purposes to treat malaria and fever (Duke 1975). The
years. The indigenous peoples gave him the concoction that preparation for these treatments included burning the beans
they usually create from the cocoa beans and his response was ceremonially with hot peppers. Additionally, the fruit pulp will
immediate and momentous. He claimed it a “divine drink be turned into a decoction, and taken by pregnant women to
which builds up resistance and fights fatigue. A cup of this relieve their pregnancy symptoms. The Cuna people also use
precious drink permits a man to walk for a whole day without the leaves of the cacao tree to make an infusion for weary
food” (Colombo, Pinorini-Godly et al. 2012). This reaction may children. In addition, adolescent leaves are applied as
have been due just to the very strong taste that accompanies antiseptics, while flowers are used to treat eye parasites
the consumption of the bitter beans, or due to the small (Duke 1975).
presence of the methylxanthines theobromine and caffeine.
The Aztecs actually used cacao as a form of currency, and
The concoction that Columbus was given was a beverage when consumed, it was as if one was “eating money”. This
drunk by the Mayan peoples. The beverage has an intricate made the cacao plant a luxury only ever drunk or eaten by the
preparation in these cultures. The fruits, or pods, are allowed Aztec nobility because commoners simply could not afford to
to ripen throughout the course of a year, picked when ripe, eat their money (Colombo, Pinorini-Godly et al. 2012).
Component Nib % Shell %
Water 3.2 6.6
Fat (cocoa butter) 57 5.9
Cocoa powder 4.2 20.7
Nitrogen 2.5 3.2
Theobromine 1.3 0.9
Caffeine 0.7 0.3
Starch 9 5.2
Crude fiber 3.2 19.2
Figure 3. Chemical structure of caffeine, one of the purine
Table 2. Table of component percentages found in certain
alkaloids present in Theobroma cacao. Both caffeine and
parts of the cacao plant. Nib refers to internal part of the
theobromine are considered methylxanthines. (Image source:
plant, while shell refers to the external husk (Colombo,
med-chemist.com)
Pinorini-Godly et al. 2012).
been evidence to support the antioxidative properties and

Filipinos have been known to use T. cacao, for specific benefits of phytochemical-rich components of chocolate.
ailments. For example, a decoction of the roots of the plant has
been taken orally when menstruation has resulted in The constituents include a large variety of components that
excessive and unceasing bleeding. Filipino people have also interact with each other. These are varieties of catechins,
used scrapings of the skins of the pod placed around boils for flavonoids, tannins, essential oils, alkaloids, polyphenols,
two or three days to excrete and remove pus (Langenberger, proanthocyanidin glycosides, carboxylic acids, purine
Prigge et al. 2009). alkaloids, and fatty acids (Giorgetti, Negri et al. 2007).
In comparison to all of these seemingly advantageous uses for Cacao is rich in methylxanthines, which are an alkaloid,
different parts of the cacao plant, the modern medicinal particularly theobromine, theophylline, and caffeine (Figure
application for the plant is somewhat wanting. Because of the 3). These can tend to have both negative and positive health
huge chocolate industry, the plant is primarily cultivated for effects, but primarily serve as stimulants. There are also
chocolate production. However, chocolate has been marketed flavonols and flavonoids present in the cacao plant, including
for its antioxidant properties, resulting in increased flavan-3-ols, which exhibit antioxidative effects, protection
production value of the plant. from cardiovascular disease, and anticancer effects (Colombo,
Pinorini-Godly et al. 2012). There are also a large variety of
lipids present, especially in the seeds or beans of the pod.
Chemistry and Pharmacology When ground into a paste, a cocoa butter results along with
fine brown particles that are the main constituents of
Over the past fifteen years, there has been piqued interest in
chocolate (Table 1). The cocoa butter makes up 50 to 57
the potential of the products of the cacao plant, including the
percent of the dry weight of cocoa and contains a significant
cocoa removed from the seeds and dark chocolate. There has
(Colombo, Pinorini-Godly et al. 2012). However, this is not
conclusive and needs more research.
Another in vitro study done has resulted in the discovery that
flavonoids (including epicatechins and isoquercitrin) in cacao
have affected transcription, resulting in enhanced expression
in peripheral blood human mononuclear cells. There was also
Figure 4. Chemical structure of trans-resveratrol, one of a decreased nitric oxide production along with cytokine
the most promising medicinal components found in secretion modulation reported when cocoa extracts were used
Theobroma cacao. (Image source: mhhe.com) rather than using the isolated chemical components
suggesting that the synergism of all of the constituents present
in cacao makes it more effective than isolating the compounds
amount of fat and fatty acids, including saturated stearic acids (Ramiro, Franch et al. 2005).
(35%), saturated palmitic acids (25%), monosaturated oleic Some in vivo studies have indicated the antioxidant effects of
acids (35%), and polyunsaturated linoleic acids (3%) epicatechin as well, enhancing oxidation scavenging activity in
(Colombo, Pinorini-Godly et al. 2012). There are also a plasma. Antioxidant activities of this constituent have resulted
number of sterols, and possibly most significantly, trans- in reduction of the concentration of free radicals, diminishing
resveratrol (Figure 4). Trans-resveratrols have exhibited a of oxidation of lipids, proteins, and nucleic acids. Additionally,
significant amount of anti-inflammatory effects, anticancer other in vivo studies have provided support that caffeine and
effects, and cardioprotective and estrogenic activities theobromine have resulted in reproductive toxicities in
(Colombo, Pinorini-Godly et al. 2012). animals, particularly males, among other toxicities from the
isolated compounds. However, the cacao plant does not have a
high percentage of these methylxanthines, and, in fact, is
Biological Activity known to have less caffeine than a cup of decaffeinated coffee
Several studies have been done involving the compounds (Colombo, Pinorini-Godly et al. 2012).
found in Theobroma cacao. In vitro studies have provided The mechanism of action involved in T. cacao constituents is
evidence that suggest that the flavonols and procyanidins still in debate, but a range of potential mechanisms of the
present in cocoa may possess immunoregulatory effects that flavanols in cocoa has been shown to improve cardiovascular
may help modulate immune responses. Additionally, other health. Some of these possible mechanisms of action include
studies have suggested that the removal of theobromine and nitric oxide activation, as seen in the above in vivo study.
caffeine from the cacao plant has actually enhanced the Additionally, there have been some anti-platelet effects that
antioxidant effects of cocoa. This result provides evidence that tend to improve endothelial function, blood pressure, and
these components may inhibit antioxidative activity thereby other heart conditions (Colombo, Pinorini-Godly et al. 2012).
reducing the effectiveness of the plant as an antioxidant Flavonoids have also shown some bioactivity in the
modulation of cell signaling pathways that regulate several because the primary use of cacao is for chocolate use.
cell functions including survival and inflammatory responses However, the few that have been done have suggested that the
(Giorgetti, Negri et al. 2007). In addition, the presence of polyphenolic compounds present in the cacao have been
sterols also contributes to heart health because they useful in increasing blood flow and perfusion of the brain.
contribute to an improvement of blood lipid profiles through Some clinical studies have discussed the use of flavanols to
the mechanism of competitive inhibition of cholesterol treat neurodegenerative diseases like Alzheimer’s disease.
absorption through the gastrointestinal tract (Colombo, Evidence has supported that flavanols may delay the onset of
Pinorini-Godly et al. 2012). There is no known threat of drug this type of disease (Colombo, Pinorini-Godly et al. 2012).
resistance against the constituents in T. cacao.
In another in vivo study, the biological activity of cacao Current use in allopathic and CAM therapies
proteins were studied and identified. This supported the
The current use of Theobroma cacao is commercial
traditional uses of the plants against tumors and free radical
exploitation of the crop. The cacao plant has had a huge
scavenging, particularly inhibiting murine lymphoma L5178Y,
success in the marketing industry. T. cacao has not only been
a model cancer cell found in mice. It was found that the cacao
used for the manufacture of chocolate, but also derivatives
albumin fraction (a certain protein isolated from the cacao
and byproducts of the plant have been used for cosmetics, fine
plant) had a significant effect on tumor growth that differed
beverages, jellies, and juices (Almeida and Valle 2007).
from the other tested protein fractions, which tended not to be
dose-dependent. The results suggested that antitumor activity The modern process of changing the cacao seeds into cocoa or
was due to the amino acid profile that was present in the chocolate has similarities to the ancient Mayan process. The
albumin fraction, which was rich in cysteine, leucine, arginine, cacao plant is allowed to ripen throughout the year, and once
and lysine. The presence and high percentage of these amino ripe, the pods are harvested. After this process, the cacao pods
acids relates this protein to the trypsin inhibitor potential. are cracked open and the seeds, or beans, are extracted from
There was also a significant correlation between radical the pulp and pod. These are then fermented, dried, and finally
scavenging capacity assays in cacao, and evidence shows that roasted. These steps are what contribute to the typical
the cacao protein fractions can be considered a chain breaking chocolate flavor and color that most people are familiar with.
antioxidant. This indicates that it halts the transfer of The roasted seeds are then ground into a chocolate liquor,
hydrogen atoms, creating a stable radical, rather than one that which contains 55 percent cocoa butter, and cocoa powder,
continues the chain reaction (Preza, Jaramillo et al. 2010). which consists of nonfat, fine, brown particles of the beans.
The cocoa powder is where the flavor of the chocolate
primarily comes from and where the polyphenol antioxidants
Clinical studies are located. This nonfat part of the cocoa liquor is what is
For the development of drugs using the constituents of the actually used in the production of chocolate or the cocoa
cacao plant, few clinical studies have been done, merely powder that is used for culinary and beverage purposes
(Colombo, Pinorini-Godly et al. 2012).
It is important to note that chocolate and cacao are not Discussion
interchangeable terms. Chocolate is actually a combination of
Theobroma cacao is now primarily used for the economical
the cocoa powder, cocoa butter, additional sugars, and other
benefit for the countries that cultivate and produce chocolate.
added chemicals that are made into a food. Different
The chocolate industry provides a powerful incentive for
chocolates have different percentages of cacao, but usually
Mesoamerican and South American countries to distribute this
range from 50 to 80 percent cacao.
cash crop widely. The commercial benefits of chocolate have a
Medicinally, one of the most important constituents in cacao is profound effect on these tropical and subtropical countries.
the trans-resveratrol. This is currently one of the
The cacao plant’s traditional uses have guided researchers and
phytochemicals in cacao with the greatest potential for use as
ethnobotanists to compose research on the possible medicnal
a pharmacological drug. These are intended to prevent or
uses for cacao. These studies have resulted in a multitude of
reduce the risk of certain diseases (Colombo, Pinorini-Godly et
results that provide support for many different potential
al. 2012). Resveratrol is of significant interest because of its
medicinal therapies. It can be used to effectively reduce
antioxidatve, anti-platelet, anti-inflammatory, estrogenic,
oxidation, diminish tumor activity, and improve
anticancer, anti-tumor, and antiviral activities. In one study,
cardiovascular health. Some of the constituents found in T.
trans-resveratrol and its glycoside, trans-piceid, were found in
cacao are also effective anti-inflammatory and estrogenic
dark chocolate extracts. Additionally, the same study
constituents including the trans-resveratrol. Stimulants,
discovered that presence of procyanidins increase the
including but not limited to theobromine and caffeine, also
antioxidant activity of chocolate (Counet, Callemien et al.
contribute to the chemical compounds present in cacao plants.
2006).
As discussed previously, the economic value of the cacao tree
Another study provides strong evidence to support that cacao
has influenced the countries that grow and farm the plant to
husk lignin fractions prepared by acid precipitation and
increase production and actually destroy native forests for the
ethanol precipitation yielded an unexpected amount of anti-
cultivation of cacao. This is problematic for the maintenance
human immunodeficiency virus activity. These activities
of forests and completely hinders the efforts to conserve
amount to almost as much anti-HIV effects as conventional
native rainforests, which are already diminishing quickly with
treatments and popular anti-HIV chemical compounds. The
deforestation due to human expansion and other such reasons
husk lignin fractions have showed anti-flu virus activity as
(Almeida and Valle 2007).
well. However, there was no reported antibacterial activity.
This study also supports that there is stimulation in the In the next ten years, it has been projected that the
generation of nitric oxide by macrophage-like cells, suggesting consumption of cacao will increase by nearly one million tons
the possibility of an effective complementary alternative of cacao seeds. It is expected that there will be an increase in
medicine (Sakagami, Satoh et al. 2008). cacao production in West African countries. However, this
would have an impact on the economy and resources of these
countries. The chocolate industry actually foresees a challenge
in the cacao supply in the future (Almeida and Valle 2007). In
fact, if cacao is not supplemented by another crop, this could Bucheli, P., G. g. Rousseau, et al. (2001). "Developmental Variation of
actually be problematic for the chocolate industry and for Sugars, Carboxylic Acids, Purine Alkaloids, Fatty Acids, and
individuals of certain indigenous groups (Hazlett 1986). Endoproteinase Activity during Maturation of Theobroma
cacao L. Seeds." Journal of Agricultural and Food Chemistry
Besides this, there is also an ethical debate over the cacao 49(10): 5046-5051.
plant and chocolate industry. In the United States, successful
Colombo, M. L., M. T. Pinorini-Godly, et al. (2012). Botany and
chocolate manufacturers, including Hershey’s and Mars, were
Pharmacognosy of the Cacao Tree. Chocolate and Health. A.
reported for using child labor on West African cocoa farms. Conti, R. Paoletti, A. Poli and F. Visioli, Springer Milan: 41-62.
Subsequent investigations revealed the conditions that
children worked under as some of the most atrocious forms of Counet, C., D. Callemien, et al. (2006). "Chocolate and cocoa: New
child labor. Child labor probably produced a massive sources of trans-resveratrol and trans-piceid." Food
Chemistry 98(4): 649-657.
percentage of the chocolate products that Americans consider
affordable luxuries (Mustapha 2010). The result of this Duke, J. (1970). "Ethnobotanical observations on the Chocó
discovery bears the presence of ethical concerns that were not Indians." Economic Botany 24(3): 344-366.
previously considered or even detected by the huge chocolate Duke, J. (1975). "Ethnobotanical observations on the Cuna Indians."
industry. These threats make the cultivation of cacao into an Economic Botany 29(3): 278-293.
entirely other issue, where the moral indications have to be Figueiredo, G., H. Leitão-Filho, et al. (1993). "Ethnobotany of
considered. Atlantic Forest coastal communities: Diversity of plant uses
Although there are some ethical concerns regarding the in Gamboa (Itacuruçá island, Brazil)." Human Ecology 21(4):
cultivation of the T. cacao, the plant is still a delectable treat, 419-430.
with a variety of different medicinal effects in humans. The Giorgetti, M., G. Negri, et al. (2007). "Brazilian plants with possible
traditional uses of cacao have permeated through today, in the action on the central nervous system‚ÄîA study of historical
social aspect of drinking the fine beverages. In addition, the sources from the 16th to 19th century." Journal of
stimulant effects of the plant make it a recharging treat. Ethnopharmacology 109(2): 338-347.
Hazlett, D. (1986). "Ethnobotanical observations from cabecar and
guaymí settlements in central america." Economic Botany
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Thymus vulgaris L., Lamiaceae
Carly McCabe
Introduction
Thymus vulgaris is commonly known as Thyme, however, it
goes by many other names such as common thyme, garden
thyme, tomillo, thym, 0v'tos (by the Greeks) (Andrews, 1958)
and many others (Basch, Ulbricht, Hammerness, Bevins, &
Sollars, 2004). It is a member of the Lamiaceae family, which
is the mint family, and so it is related to common plants like
peppermint, rosemary, and oregano. It is native to the
Mediterranean, however, it can be found in many regions of
the world—these regions include Egypt, Iran, Israel, and the
United States among others (Arraiza, Andres, Arrabal, &
Lopez, 2009). Thyme has many applications and it is highly
valued for its antibiotic, antispasmodic, antioxidant,
antimicrobial and antifungal effects. Thyme has also been Figure 1. Oblong-oval leaves of T. vulgaris (Modzelevich,
purported to possess analgesic, diuretic, carminative and 2008).
stimulant properties. Additionally, it has been used in
flavoring applications within the processed foods industry, as
setting roots (Darlington, 1847). The leaves are small, quite
a soap, detergent and preservative (Arraiza, et al., 2009). Its
short, broad, pointed, and dusky-green (Culpeper, 1955). They
medicinal activity comes from the diverse essential oil
can either be an oblong oval shape or a narrow oval shape
content—two main compounds within the extract are thymol
(Figures 1 & 2), curling on the edges, and bunching at their
and carvacrol (Lee, et al., 2005).
axils (Darlington, 1847). Its flower is commonly small and
light blue or light purple. The calyx is hirsute, strongly ribbed,
Botanical Description and studded with what appears to be tiny dots or holes, while
parts of the lower lip subulate (Darlington, 1847). T. vulgaris
Thyme is a small, shrubby, aromatic plant native to the is considered the garden thyme; wild thyme (Thymus
Mediterranean (Robineau, 1997). It is a branched, woody serpyllum) and lemon thyme are others commonly
plant with numerous stems and fibrous roots that usually encountered among the 100-plus varieties (Figure 3). The
grows to be eight to ten inches in height (Culpeper, 1955). At most suitable environment for thyme growth is one with poor,
the base, the stems grow erect or along the ground without light and dry soil. When found in moist or rich environments,
Figure 2. Long-oval leaves of T. vulgaris (Landing, 2012).
the plant thrives or becomes prolific. However, this causes the

plant to lose many of its characteristic aromatic properties;
nor is it then able to survive the winter (Johnson & Emerson,
1858). The plant also enjoys an environment comfortably
surrounded by other plants, although not crowded. Thyme can
be grown from either seed or rooted slips; if using seeds,
sowing should be done around the middle of March until the Figure 3. Botanical drawing of Thymus vulgaris (Future,
beginning of May. Additionally, it should not be sown thin nor 2010).
should it be more than half of an inch from the surface. During
growth, the seedlings must be kept clear of weeds and should Traditional Uses
be lightly watered two times a week, which should continue
until the plants take root. Thyme is a perennial, however, after The growth of various species and the use of thyme in ancient
three or four years the plant no longer grows productively Egypt, Greece and Rome was primarily to perfume unguents
(Johnson & Emerson, 1858). (a viscous substance uses as an ointment), for embalming and
of course for its medicinal properties (Stahl-Biskup & Sáez,
2002). Bardeau proclaimed thyme as “an indispensable plant, stomachache, diarrhea, and parasitism (Navarro, Villarreal,
which should be consumed to conserve health. Furthermore, if Rojas, & Lozoya, 1996). Each of these prescriptions
one could replace ones’ morning cup of coffee with an infusion (especially ones for respiratory ailments) finds similarity in
of thyme, you would quickly appreciate its positive effects: other cultures and other ancient texts that reference it.
animation of spirit, sensation, lightness in the stomach,
absence of morning cough, and its euphoriant and tonic effect
(Stahl-Biskup & Sáez, 2002).” Thyme earned itself a place in Historical Texts
many ancient cultures, and it is referenced in many ancient Cairo Genizah
texts for a variety of uses.
A millennium ago, Old Cairo (Fustat) was one of the most
important centers of social, economic and religious activity
Medicinal Applications (Amar, 2008). The Perfumers’ Square in Fustat as well as in
Alexandria were centers of the drug and perfume business
The medicinal application of thyme and its essential oil are
(Amar, 2008). The Ben Ezra synagogue was a place of
quite concordant when it comes to the many cultures that
worship for the Palestinian Jews of Fustat. In this synagogue
could take advantage of and had access to the plant. Nicholas
existed a “Genizah” or depository, in which sacred books
Culpeper detailed the use of thyme in his herbal, originally
were stored. Until recently, this treasure trove of historical
published in 1652, for a sundry of applications, which find
and cultural knowledge was kept from the hands of
homology in other traditions. He listed it as a strengthener of
researchers and scholars. However, the manuscripts were
the lungs, a remedy for the chin-cough (whooping cough) in
revealed to the world and later purchased by many
children, it purges the body of phlegm, is a remedy for
institutions. These institutions have installed research efforts
shortness of breath, and as cure for helminthiasis. He
aimed at studying and understanding the texts and the
references it as ‘the notable herb of Venus’ such that it
information retained within them. The Cairo Genizah has its
provokes the terms, gives a safe and speedy delivery to
own materia medica in which it details the medicinal use of
women in labor, and stimulates the afterbirth. When used as
Mediterranean plants in and around Egypt (Amar, 2008).
an ointment, it eases swelling and warts, helps sciatica and
Thyme is mentioned in recipes for stomach ailments, colic,
dullness of sight, and eases the pain and hardness of the
excessive lachrymation, eyelids growth, and as a tonic (Amar,
spleen. It can be useful for gout and pains in the loins and
2008).
hips. Additionally, when ingested it has beneficial effects on
the stomach and expels wind (Culpeper, 1955). The essential
oils have also been recognized for the treatment of The Canon of Medicine
respiratory conditions like bronchitis, whooping cough, as
well as tooth ache (Porte & Godoy, 2008). In México, Thyme Avicenna recommends the use of thyme as a treatment for
is commonly known as Tomillo and is popularly used for fresh wounds, abscesses, spleen swellings, chronic fevers,
bronchial affectations, cough, cold, angina, inflammation, and scorpion stings, and as a diuretic, a purgative and
menstrual stimulant (Amar, 2008).
al-Ghafiqi Compound Concentration
(mg/g)
An important scholar and physician in Andalusia, al-Ghafiqi
Monoterpene hydrocarbons
describes thyme as a diuretic, menstrual stimulant, and as a
α-Terpinene 0.005
cure for wounds, ulcers, bruises, and stings of poisonous γ-Tepinene 0.007
insects (Amar, 2008). p-Cymene 0.013
Oxygenated monoterpenes
1,8-Cineole 0.245
Cooking Camphor 0.148
As mentioned, 0v'tos is the Greek name for thyme. However, 3,7-Dimethyl-1,6-octadien-3-ol (linalool) 0.479
the name was commonly applied to the species Thymbra α-Terpineol 0.291
Borneol 0.244
capitata; many centuries ago this name was carried out of
Sesquiterpene hydrocarbons
Greece by colonists and into southern Italy. From there, the δ-Selinene 0.010
Romans adopted the name in the form thymum and applied it Oxygenated sesquiterpenes
to reference Thymus vulgaris, which grew all along the west β-Eudesmol 0.014
side of the peninsula (Andrews, 1958). The use of thyme in Aliphatic alcohols
ancient Greece is referenced with less frequency, however it (Z)-3-hexenol 0.017
is mentioned for its use in flavoring salt and grating it to Aliphatic aldehydes
flavor drinks (Andrews, 1958). Apicius cataloged the use of (E,Z)-2,4-heptadienal 0.004
thyme by the Romans; he mentions thyme as an ingredient in Aliphatic esters
sauces, whether that is boiled foods or meats, as well as with Methyl 2-methylbutyrate 0.001
fish and vegetables. Today in Italy thyme is called timo and its Aliphatic ketones
dried or fresh versions are used to flavor soups, gravies, Methyl jasmone 0.012
Aliphatic acids
stews, sauces sausages and dressings (Andrews, 1958). These
Octanoic acid 0.004
sources that reference thyme as a culinary supplement Aromatic compounds
provide the appearance of thyme as a fine condiment used, 2-Isopropyl-5-methylphenol (thymol)* 8.554
quite secretively, by chefs. 2-Isopropyl-2-methylphenol (carvacrol)* 0.681
Table 1. Sampling of the compound in Thymus vulgaris
essential oil. Notice the bolded compounds and their
Today concentrations (Lee, Umano, Shibamoto, & Lee, 2005).
Thyme alone or in combination with other herbs such as
sundew is one of the most commonly recommended herbs in It is also used to treat chronic candidiasis and halitosis
use in Europe today; it is used for dry, spasmodic coughs, as (Taheri, Azimi, Rafieian, & Zanjani, 2011). As a result of its
well as whooping cough. It is prepared as a topical salve that antibiotic, anti-fungal, and antimicrobial properties, the
consists of thyme, myrrh, and goldenseal to treat oral herpes.
essential oil of thyme is a very useful preservative in the food
industry for stored food items and even for the preservation
of stored fresh meat, specifically chicken (Kumar, et al.,
2008), (Fratianni et al., 2010).

When inspecting the volatile oil profile and the antifungal,
antibiotic, antimicrobial, and antioxidant activities of thyme
(which exist a result of these oils), one will encounter many Figure 4. Structures of Carvacrol and Thymol (Carvalho et
factors that influence results. Specifically, the level of volatile al., 2003).
oil content differs depending on when the plant is harvested
(month, season), from what part of the region it is collected, used thyme that was purchased from a local market in Davis,
and the country from which it is being surveyed (Torras, Grau, California and identified 43 monoterpenes, 16 sesquiterpenes,
López, & de las Heras, 2007). Another factor to note is the 14 aromatic compounds, 7 alcohols, 3 aldehydes, 4 ketones
method in which the volatile oil is extracted; depending on and esters, and 3 acids (Lee, et al., 2005) as the aroma
which method is chosen, the quality and yield of the essential compounds. Within the entire list of volatile oils there are six
oil can be affected. Steam distillation is a common method compounds with the highest concentration: thymol (72%),
used in the laboratory and in addition to being very efficient it carvacrol (5.7%), linalool (4.0%), α-terpineol (2.4%), 1,8-
typically yields high quality oil. The use of organic solvents for cineole (2.1%), and borneol (2.0%) (Lee, et al., 2005). Thymol
extraction, on the other hand, has a tendency to result in and carvacrol are the most important compounds and
residual solvent in the extracts as well as insufficient solvent collectively they comprise roughly three-quarters of measured
selectivity that allows other compounds to be dissolved in volatile oils (Figure 4) (Lee, et al., 2005). Many studies have
addition to the active substances (Grigore et al., 2010). demonstrated that thymol and carvacrol are responsible for
Learning about the volatile oil in thyme is very important to much of the medicinal activity of T. vulgaris.
understanding its various medicinal activities, for it is within
the oil that the compounds responsible for these effects exist.
Biological Activity
Volatile Oils In vitro
T. vulgaris possess many volatile compounds ranging from In one study, various odiferous angiospermic essential oils
aromatics to monoterpenes (Table 1). Within this list of were tested for antifungal activity against a toxic strain of
volatile compounds, there exists another list of compounds Aspergillus flavus. A. flavus is a type of fungi or mold commonly
responsible for the characteristic aroma of thyme. A study found in food. The presence of said mold is particularly
troublesome when it in occurs in the post harvest stage of 1000 ml; pH, 5.6 ± 0.2) in Erlenmeyer flasks that were
food commodities (Kumar, et al., 2008). In developing inoculated with 1 ml spore suspensions. These flasks were
countries, spoiled food is not only a loss of profit but also a incubated for 10 days. After a variety of other steps, the
loss of sustenance. This type of mold produces a particular researchers then evaluated the aflatoxin content.
class of mycotoxins (any toxic substance produced by a
The results indicated that the essential oil of T. vulgaris
fungus) called aflotoxins, which are extremely poisonous and
showed complete inhibition of inoculums of the toxigenic
can cause liver damage and cancer. Nearly 4.5 billion people in
strain of the test fungus at 1.0µl ml-1 and an MIC of 0.7µl ml-1
underdeveloped countries are exposed to these toxins as a
(Kumar, et al., 2008). T. vulgaris showed better antifungicidal
result of post harvest fungal infections of their cereals and
activity than most synthetic derivatives, mainly because of its
pulses (Kumar, et al., 2008). This study’s aim was to
MIC and its broad-spectrum fungitoxicant activity (which was
investigate possible compounds in various essential oils that
also elucidated in this trial). The authors indicated that thyme
could act as natural preservatives, since many industrial
would be an exceptional replacement for industrial
preservatives have their own slew of toxicities. The thyme
preservatives mainly because it is a natural compound and it
used was collected from Banaras Hindu University, and the
is quite stronger.
essential oil was collected using Clevenger’s hydrodistillation
apparatus. The culture was performed on potato dextrose
agar (PDA). Dissolved oil was added aseptically to different In vivo
pre-sterilized Petri dishes that had 9.5 ml of the PDA in order
to obtain a concentration of 1.0 and 1.5µl ml-1. A fungal disk of In an in vivo study, scientists investigated the antispasmodic
the strain of A. flavus was inoculated aseptically to the center effect of T. vulgaris on guinea-pig ileum. This study aimed to
of the poured Petri plates. The plates were then incubated at evaluate the effectiveness of T. vulgaris and its hydroalcoholic
27±2 °C for seven days, after which the diameter of fungal extract on the motility properties of the ileum and to
colonies was measured and the percentage of mycelial determine the mechanisms by which these motility effects are
inhibition was calculated based on these diameters (Kumar, et elicited (Babaei et al., 2008). After being excised and prepped,
al., 2008). T. vulgaris essential oil showed strong fungitoxicity the ileum was placed in a Tyrode solution, which is an isotonic
and was further analyzed for its minimum inhibitory solution that contains: (mM) NaCl 136.9, KCl 2.7, CaCl2 1.8,
concentration (MIC) at which it showed absolute fungitoxicity. MgCl2 1.0, NaHCO3 11.9, NaH2PO4 0.4, and Glucose 5.0.
They performed this analysis by placing varying Glucose acts as the energy source and bicarbonate acts as the
concentrations of the thyme oil on the PDA plates and buffer. The tissue bath was maintained at 37°C and whole
incubating them with the fungal strain for another seven days segments of the tissue (roughly 3 cm long) were set up to
at 27±2 °C. They then investigated thyme oil’s ability to arrest record isometric contractions while in 50 mL of the Tyrode
aflatoxin elaboration using the same conditions as above solution, which was gassed with 5% CO2 and 95% O2. Each
except they used SMKY medium (Sucrose, 200 g; MgSO4 strip of tissue was bound on one end to a glass holder and on
7H2O, 0.5 g; KNO3, 0.3 g; Yeast extract, 7.0g; Distilled water, the other connected by a silk thread to a strain-gauge
transducer that allowed the scientists to monitor the
mechanical activity of the tissue. The tissue strip was loaded guinea-pig ileum. Therefore, these results also imply that T.
with a resting tension of 0.5g and after equilibration was vulgaris extract could be useful in the treatment of diarrhea
ready for field stimulation with rectangular 1 ms pulses of predominant irritable bowel syndrome (Babaei, et al., 2008).
supramaximal voltage delivered at 0.1 Hz through platinum
electrode 10mm in length and 10mm apart. This electrical
field stimulation of the ilea induced twitch contractions. After Mechanism of action
a control period, thyme extract was added to the bath in a The constituents of thyme that confer biological activity and
volume of 0.5 mL at increasing concentrations. The responses thereby usefulness in medicinal applications and everyday
of the tissue as a result of the addition of the varying employment include its essential oils; specifically, the phenols
concentrations of the extract were recorded for a five-minute of thymol and carvacrol, glycosides, flavonoids, p-cymene,
period. Another experiment was performed that looked at the borneol, linalool, alcohols, rosmarinic acid, saponins, tannins,
contractions of the ileum in the presence of Acetylcholine, and terpenoids (Basch, et al., 2004). Thyme’s antimicrobial
Atropine, Granisetron, Morphine, and Naloxone. The leaves of effects can be attributed to thymol, which expresses activity
T. vulgaris plant used in this experiment were collected from against strains of fungi and yeast including Aspergiullus
Iran and the extract was collected via a methanol extraction parasiticus, A. flavus and Candida albicans via suppression of
(Babaei, et al., 2008). fungal growth and aflatoxin synthesis. Thyme’s spasmolytic
The effect of the extract and of the controls was determined by and antitussive activity is accredited to thymol and carvacrol,
comparing the frequency and amplitude of the test and control while flavonoids relax tracheal and ileal smooth muscles by
materials. There were six different concentrations of the inhibiting acetylcholine and histamine receptors and possibly
extract in which the tissue was tested (0.02mg to 6 mg mL-1), through calcium channel antagonism. It has been shown in
which induced concentration-dependent depression of vitro that the extract of thyme and its volatile oil have relaxing
contraction that was evoked by the field stimulation. In effects by inhibiting phasic contractions. Thyme’s antioxidant
comparison to the control substance, there was a significant, effects are due to a biphenyl compound and flavonoids, which
dose-dependent difference in the action of T. vulgaris on inhibit superoxide anion production and protect red blood
peristalsis. T. vulgaris extract displayed a 50% maximum cells against oxidative damage. Finally, thyme’s anti-
effective concentration value of 1.7 mg mL-1 as well as a inflammatory effects are due to thymol and carvacrol’s
maximum inhibition of 60.1±2.9% This smooth muscle inhibition of prostaglandin synthesis (Basch, et al., 2004).
relaxant effect was determined while in the presence of
Acetylcholine, which induces contractions of the isolated
tissue. Acetylcholine can be blocked by Atropine and the Clinical Studies
extract can consequentially inhibit these types of contractions Many studies have supported the efficacy of Listerine and one
as well (Babaei, et al., 2008). These results and the successful of its active components, thymol, in decreasing plaque
dose-dependent decrease in contractions suggest that thyme formation and gingivitis. However, no evidence has been
essential oil is a potent inhibitor of the contractions in the shown to implicate single therapies of thymol to be effective at
clinical trial used Bronchipret to investigate whether herbal
expectorant remedies were a viable replacement for the
traditional antibiotics. Bronchipret contains 60mg of dried
Primula extract and 160mg if dried T. vulgaris extract. The
clinical study involved 771 German physicians who were
asked to place their groups of patients into “lots” of five. They
were then asked to prescribe one group the Bronchipret
tablets and to prescribe the other group any other secretolytic
drug that qualified for their condition. The groups were
matched according to age, gender, and severity of disease. The
researchers investigated two distinct age groups; those under
the age of twelve and patients twelve years or older. Patients
were seen initially by a physician and thoroughly examined;
after which, they were either prescribed Bronchipret or
another secretolytic drug. The patients returned ten days later
Figure 5. Bronchipret, a syrup comprised of T. vulgaris and were examined in the same manner. Each patient was
and Primula that treats acute bronchitis (Vitamin, 2012). examined for a list of pre-determined criteria prior to taking
the drug and after ten days of treatment. Odds ratios were
this same type of inhibition. A study was performed on a calculated that related to each of these variables for the
group of 110 school children in which they each received a children and adult groups. The odd ratios depict the likelihood
combination product of 1% chlorohexidine and 1% thymol of therapeutic success such that if the odds ratio is low then
varnish. They were to receive this preparation for two years the probability of a patient profiting from a control medication
and the results would be compared to a control group. compared to Bronchipret is low. For example, in the adult
Analysis revealed that there were significant reductions in group treated with a medication called Ambroxol, the odds
bacterial colonization levels and interdental plaque in the ratio for the criteria coughing during the day was 0.51, which
treated children (Basch, et al., 2004). indicates a 49% higher chance for someone on Bronchipret to
symptomatically improve compared to Ambroxol. Overall, in
Another clinical trial was performed that compared a drug the adult and child group, for the three control drugs tested,
called Bronchipret to other pharmaceutical drugs that aim to the odds ratio was continually low, suggesting Bronchipret
treat acute bronchitis (Figure 5) (Ernst, et al., 1997). The use had an overall more effective therapeutic action in treating
of antibiotics for acute bronchitis accounts for nearly 30% of acute bronchitis. Additionally, the adverse drug reactions
all antibiotic prescriptions. This leads to the incurrence of (ADRs) to Bronchipret were generally low, especially
large costs, which can be exacerbated when an antibiotic is compared to the other drugs (Ernst, et al., 1997).
pronounced ineffective or with absenteeism. Additionally,
many traditional antibiotics have adverse side effects. One
Contraindications
Toxicology
The suggested dose, taken orally, should not exceed 10g of the
dried leaf with 0.03% phenol per day. Ensuring not to exceed
this dose will most likely prevent toxicity, however, each
individual will metabolize and respond to the compounds in
thyme differently (see subsection Contraindications). Thyme
oil, the essential oil and most active compound in thyme, is
highly toxic. Symptoms of toxicity implicating exposure or
over-exposure include nausea, tachypnea and hypotension
(Basch, et al., 2004). The lethal dose (LD) of the essential oil is
roughly 2.84g/kg of body weight (this is measured for rats),
and in mice, oral doses of concentrated thyme extract
equivalent to 4.3-26 g/kg of thyme decreased locomotor
activity and respiratory activity (Basch, et al., 2004).
Typically, if one has a known allergy or sensitivity to members
of the Lamiaceae (Mint) family or any aspect of thyme, the
plant should be avoided. Many contact allergies have been
reported, in cases recorded as long ago as the 1940s. Cases
usually detail contact dermatitis, allergic alveolitis, and
pruritic contact dermatitis provoked by the thyme plant and Figure 6. Listerine with thymol (Johnson & Johnson
thymol. If one is allergic to other plants such as birch pollen, Healthcare Products, 2012).
celery, or species in the mint family like oregano there is a
chance for cross-reactions (Basch, et al., 2004).
applications (Basch, et al., 2004). In regards to the neurologic
and CNS, one may experience headache or dizziness with the
Adverse Effects ingestion of thyme, and in some cases the essential oil has
caused seizure or coma. There have been reports of
Traditional and historical use of the thyme flower and leaves conjunctivitis in exposure to thyme dust as well as contact
appears to generally be safe, especially when used in culinary dermatologic reactions. Occupational asthma, as well as
pursuits. However, caution is advised when attempting to use allergic alveolitis and rhinitis due to exposure to the dust has
the product for its medicinal properties. As mentioned in the also been reported. Most side effects are related to an
toxicology subsection, thyme oil or thymol when concentrated individual having some sort of established sensitivity to the
is highly toxic and should be diluted if used for topical plant and its constituents, however, a relative of Thymus
effectiveness as a broad-spectrum antibiotic against species
like Streptococcus mutans, herpes simplex virus, and influenza
A. It is also effective in the treatment of supragingival plaque
and gingivitis (Basch, et al., 2004). Many parents also
continually seek after Bronchipret as a natural remedy for
their children with bronchitis. A typical CAM remedy for
cough, the dried leaves can be used to make a tea; with one
teaspoon of dried thyme per cup of water and consumed three
times daily. The addition of honey, interestingly enough,
increases the effectiveness of the tea (Thymes, 1998). These
same proportions (1 teaspoon of dried thyme per cup of
Figure 7. Typical herbal medicine preparations (Source: boiling water) can be used as a gargle to treat sore throat
(Ltd)). (Dworkin, 1998). Thyme can also be used to unplug clogged
sinuses through steam inhalation. The preparation of such a
vulgaris, Thymus serpyllum has been shown to have more steam bath includes pouring three cups of boiling water over
severe reactions such as those that interrupt TSH and two tablespoons of crushed thyme leaves in a medium bowl
prolactin in rats (Basch, et al., 2004). and placing one’s face 10-12 inches above the fragrant water
with a towel over the head to concentrate the vapors (Shinn,
2011).
Interactions In the herbal supplement market, products based on thyme
Some drug interactions include anti-thyrotrophic effects, and its extracts are typically those containing the essential oil,
estradiol and progesterone receptor-binding, and thymol. Most products display that the constituents come
percutaneous absorption of topical thymol. Herbal from Thyme and usually tote the fact that they contain the
supplements with estrogen or progesterone may interact with pure extract. (Figure 7) However, as mentioned, earlier, the
thyme’s interaction with these receptors (Basch, et al., 2004). use of the concentrated extract is quite dangerous and if it is
to be used for topical application, it is highly recommended
that the oil be diluted first.
Current use in Allopathic and CAM Therapies
A common drug or household item is mouthwash. Listerine
Discussion
(Figure 6) is the brand name of such oral cleansers, however,
many use them without any idea of the true nature of their Upon first inspection, Thyme is a very mundane and common
efficacy. Listerine is an antiseptic and contains a combination plant. However, upon further investigation one discovers the
of essential oils like eucalyptol, menthol, thymol (found in T. multifaceted and immense amount of applications that the
vulgaris) and methyl salicylate. Studies have shown Listerine’s plant can boast of. Centuries ago, the use of thyme developed a
homology between cultures, which lead to its popularity as a Thyme (Thymus vulgaris L.) Grown in Castilla - La Mancha
medicinal agent and has maintained its use in traditional (Central Spain). Journal of Essential Oil Research, 21(4), 360-
medicine, allopathic and homeopathic medicine today. Thyme 362.
was commonly prescribed for respiratory ailments like Babaei, M., Abarghoei, M. E., Ansari, R., Vafaei, A. A., Taherian, A. A.,
bronchitis and whooping cough or for skin infections and Akhavan, M. M., . . . Mousavi, S. (2008). Antispasmodic effect
inflammations. The continued use of thyme throughout of hydroalcoholic extract of Thymus vulgaris on the guinea-
history for these ailments and many others implicates a level pig ileum. Natural product research, 22(13), 1143-1150. doi:
of chemical activity that is biologically important. This turns Doi 10.1080/14786410601130257
out to be the case because thyme’s chemical composition Basch, E., Ulbricht, C., Hammerness, P., Bevins, A., & Sollars, D.
confirms its antimicrobial and antibiotic properties (as well as (2004). Thyme (Thymus vulgaris L.), thymol. [Review].
others). T. vulgaris undoubtedly offers new avenues of drug Journal of herbal pharmacotherapy, 4(1), 49-67.
discovery, especially in this age of over use of antibiotics; Carvalho, A. F. U., Melo, V. n. M. M., Craveiro, A. n. A. o., Machado, M.
exploring its inherent compounds (like thymol and carvacrol) I. L., Bantim, M. r. B., & Rabelo, E. F. (2003). Larvicidal
as well as possible synthetic derivatives may allow for the activity of the essential oil from Lippia sidoides cham.
expansion of the applications for which it is currently used. against Aedes aegypti linn. Mem√≥rias do Instituto Oswaldo
However, any uses that are investigated and potentially Cruz, 98, 569-571.
proposed for thyme and its derivatives should be carefully Culpeper, N. (1955). Complete herbal: consisting of a comprehensive
studied so as to ensure that its biological activity and description of nearly all herbs with their medicinal properties
application is taken advantage of in a way to prevent its and directions for compounding the medicines extracted from
decline into the same category of over-use as many antibiotics them. London, New York,: Foulsham.
have today. It would be a shame to waste such a magnificent Darlington, W. (1847). Agricultural botany. Philadelphia: J. W.
plant. Moore;.
Dworkin, N. (1998). Sore throat relief. [Article]. Vegetarian
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10.1016/J.Foodchem.2004.05.056
Uncaria tomentosa (Willd. ex Roem. & Schult.) DC., Rubiaceae
Taryn DeGrazia
Introduction
The plant Uncaria tomentosa is part of the Rubiaceae family
and the Cinchonoideae subfamily. It is commonly known as
Cat’s Claw or Una de Gato because of the penduncles (curved
thorns) that sprout from the side shoots and resemble the
nails of a cat (Figure 1). There are currently 34 species in the
Uncaria genus, only two of which grow in tropical America,
the other being Uncaria guinensis (Heitzman et al. 2004;
Keplinger et al. 1998). U. tomentosa has been used for over
2,000 years by Peruvian tribes for medicinal and religious
purposes but has recently grown in popularity in Europe and
the Americas (Pilarski et al. 2006). Throughout the past 20
years, U. tomentosa has become a plant of interest because it is Figure 1. A photograph of Uncaria tomentosa highlighting
rich in secondary plant metabolites such as alkaloids, the claw-like thorns (Image source: Taylor 2000).
terpenes, quinovic acid glycosides, flavonoids and courmarins.
The compounds are commonly used as treatments for
orange (Figure 2). Furthermore, the penduncles on U.
wounds, ulcers, fevers, headaches, gastrointestinal illnesses,
guinensis are more curved than the penduncles of U.
and bacterial/fungal infections. Typically U. tomentosa is
tomentosa which tend to be straight or mildly sickle-shaped
applied topically or ingested as a decoction or tea (Heitzman
(Taylor 2004; Keplinger et al. 1998). Thorns on U. tomentosa
et al. 2004).
are painfully sharp and the leaves have no covering but rather
display a waxy appearance (Figure 3). Reaching a diameter of
Botanical Description over 20 cm, the main vines dangle from the rainforest canopy
and can form impenetrable thickets when growing in a
Uncaria tomentosa, a “woody climber,” is a vine indigenous to secondary forest or on the edges of the rainforest (Keplinger
Central and South American rainforests that can grow up to 30 et al. 1998; Figure 4).
m tall (Heitzman et al. 2004; Taylor 2004). U. tomentosa may
be confused with Uncaria guinensis, another member of the
genus Uncaria that grows in the tropical Americas. The two Traditional Uses
can be distinguished by their flowers: U. tomentosa has small,
Uncaria tomentosa has traditionally been used in Peru and is
yellow-white flowers while U. guinensis’ flowers are red-
still currently used by the 60,000 Ashaninka Indians who live
Figure 3. Uncaria tomentosa leaves. (Image source:
http://www.macapunch.com/ingles/catsclaw.html)
Figure 2. The Uncaria tomentosa flower. (Image source: communication between the physical and spiritual worlds,
http://thehealthyhavenblog.com/2011/06/08/cats-claw-for- restoring balance and health. It is believed the plant contains
osteoarthritis-and-rheumatoid-arthritis-support/) magical healing powers, therefore Cat’s Claw is used
exclusively by priests, highlighting its significance in
between the Pichis-Palcazu, Ucayali and Perene-Tambo rivers Ashaninka culture (Heitzman et al. 2004; Keplinger et al.
(Keplinger et al. 1998). The Aguaruna, Cashibo, Conibo, and 1998).
Shipibo tribes in Peru have historically used Cat’s Claw as The bark and roots of the vine are typically the parts of the
well, however the Ashaninka have reportedly been using it the plant used to make Cat’s Claw decoctions and teas because
longest (Taylor 2004). Humans in Ashininka culture are they contain the oxindole alkaloids which are essential for
believed to be composed of three elements: ivátsa, a physical healing. When a Peruvian man was observed in his traditional
being, isancáne, a spiritual being and ineatátsiri, a being who preparation of U. tomentosa, the process involved boiling
mediates between the physical and spiritual. When all three approximately 20 g of sliced root bark in a liter of water
beings are in harmony, a person is considered to be healthy, (Figure 5). After forty five minutes of boiling, the remaining
however when one element becomes unbalanced, illness liquid was poured off and more water was added to the liquid
arises. The Ashaninka priests use U. tomentosa to facilitate the
in order to replace the water losses due to evaporation. The
decoction was then ready to be used as a medicinal treatment.
U. tomentosa can also be applied topically if an external illness
is being treated (Keplinger at al.1998).
Cat’s Claw has traditionally been used throughout the
Americas to treat asthma, cancer, cirrhosis, fever, gastritis,
diabetes, rheumatism, dysentery, inflammation of the urinary
tract and many other illnesses (Keplinger et al 1998; Table 1).
Women commonly use U. tomentosa after child birth, to
correct menstrual irregularity or as a birth control measure.
For birth control use, a decoction is made and one cup is
consumed daily for three consecutive months. This method is
believed to promote sterility for three to four years. In
Figure 4. Central Vine. (Image source:
http://www.lianaecologyproject.com/photos) WORLDWIDE ETHNOMEDICAL USES
Colombia for dysentery, gonorrhea
French for dysentery

Guiana
Peru for abscesses, AIDS, arthritis, asthma, blood cleansing,
bone pains, cancer, cirrhosis, diabetes, diarrhea, disease
prevention, dysentery, fevers, gastric ulcers, gastritis,
gonorrhea, hemorrhages, herpes, immune disorders,
inflammations, intestinal affections, menstrual
irregularity, kidney cleansing, prostatitis, rheumatism,
shingles, skin disorders, stomach disorders, ulcers
problems, urinary tract disorders, tumors, wounds
Suriname for dysentery, intestinal disorders, wounds

Figure 5. Sliced root bark that can be used to make teas
Table 1. The most common uses of Uncaria tomentosa in
and decoctions. (Image source:
Colombia, French Guiana, Peru and Suriname (modeled after
http://www.sanat.tv/en/plants/uncaria-tomentosa.html)
Taylor, 2004).
general, U. tomentosa is regarded as a means of “normalizing
the body” (Taylor 2004).

Uncaria tomentosa is particularly sought after because of the
alkaloids and triterpenes found within the plant. An initial
report analyzing the leaves and stems identified
rhynchophylline and isorhynchophylline as the major
alkaloids in addition to the minor alkaloids, mitraphylline,
isomitraphylline, dihydrocorynantheine, hirsutine and
hirsuteine (Figure 6). Two other minor alkaloids,
rotundifoline and isorotundifoline, were later identified in the
leaves and stem as well. In the bark, the stereoisomeric
alkaloids pteropodine, isopteropodine, speciophylline,
uncarine F and isomitraphylline were found. The roots
revealed six pentacyclic oxindole alkaloids and, in a few cases,
two tetracyclic oxindole alkaloids (Table 2). The oxindole
alkaloids from Uncaria tomentosa’s roots reportedly have
immune-stimulant and antileukemic properties and are
widely sought after when preparing remedies. The root’s bark
has been shown to contain eight types of quinovic acid
glycosides, four types of polyhydroxylated triterpenes, the
precursor alkaloid 5α-carboxystrictosidine, oleanolic acid and
ursolic acid. The quinovic acid is thought to be responsible for
the anti-inflammatory and antiviral effects of the plant.
(Keplinger et al. 1998; Taylor 2004). Compounds found
elsewhere in the plant include flavonoids, glucosinolates,
sterols, polyunsaturated fatty acids and carbolines. The anti-
inflammatory response to U. tomentosa is also thought to be
due to the antioxidant chemicals and plant sterols that it
Figure 6. Structures of Uncaria tomentosa constituents contains (Rinner et al. 2009; Taylor 2004). A more complete
(Image source: Heitzman et al. 2004). list of U. tomentosa constituents can found in Table 3.
Oxindole Pentacyclic Alkaloids Tetracyclic Alkaloids
Alkaloids Other identified Uncaria tomentosa Constituents
Pteropodine Rhynchophylline
ajmalicine mitraphylline
Isopteropodine Isorhynchophylline
akuammigine oleanolic acid
Speciophylline Corynoxeine
Uncarine F Isocorynoxeine campesterol palmitoleic acid
Mitraphylline catechin procyanidins

Isomitraphylline
carboxyl alkyl esters pteropodine
Indole Akuammigine Hirsutine chlorogenic acid quinovic acid glycosides

Alkaloids
cinchonain rhynchophylline
Tetrahydroalstonine Dihydrocorynantheine
corynantheine rutin
Isoajmalicine Hirsuteine
corynoxeine sitosterols
Corynantheine
Table 2. Chart showing the alkaloids present in Uncaria daucosterol speciophylline
tomentosa and organized by whether the compound is a
epicatechin stigmasterol
pentacyclic alkaloid or a tetracyclic alkaloid and an
oxindole alkaloid or an indole alkaloid (Modeled after harman strictosidines
Keplinger et al., 1998).
hirsuteine uncarine A thru F
A revolutionary discovery made regarding Uncaria tomentosa hirsutine vaccenic acid

was that the plant has two different chemotypes: One
chemotype containing pentacyclic indole and oxindole iso-pteropodine
alkaloids and the other chemotype containing tetracyclic
loganic acid
indole and oxindole alkaloids. While studies have found U.
tomentosa to possess many health benefits, some antagonistic lyaloside
health effects have been associated with the chemotype
Table 3. Additional compounds found in Uncaria
containing the tetracyclic alkaloids. The difference is thought
tomentosa (Taylor, 2004).
to lie in the different types of alkaloids with pentacyclic
alkaloids being the “good” alkaloids and tetracyclic alkaloids
being the “bad” alkaloids (Keplinger et al. 1998). It is widely
accepted that the oxindole alkaloids from U. tomentosa are presence of each extract. The constituents reduced adverse
mainly responsible for the desired medicinal effects effects of chemotherapy by producing reactive oxygen species,
associated with the plant, therefore it is important the proper releasing cytochrome C and activating caspases in human
alkaloids are being used when preparing remedies. leukemia cells. However, the finding of most significance to
this study was the induction of apoptosis in HL60 cells,
making U. tomentosa a key ingredient to consider when
Biological Activity developing chemopreventative medicines (Cheng et al. 2007).
Anticancer In addition, the impact of aqueous Uncaria tomentosa extracts
on the growth activity of human leukemia cell lines K562 and
One study involved incubating leukemic cell lines HL60 and U- HL60 and a human EBV-transformed B lymphoma cell line
937 with different concentrations of alkaloids extracted from was analyzed. The U. tomentosa extracts were found to
U. tomentosa for 7 days. To measure the antiproliferative significantly inhibit growth of HL60 cells, however growth of
effect of the extracts, colorimetric and clonogenic assays were K562 cells was only moderately inhibited. The study found
used. Results showed growth of HL60 and U-937 leukemic that the U. tomentosa extracts induced apoptosis, the
cells to be inhibited by the pentacyclic oxindole alkaloids (IC50 mechanism of action by which the plant is believed to be able
values were in the range 10−5 to 10−4 mol/l). Uncarine F to treat cancer (Heitzman et al. 2004). Finally, a study
demonstrated the most significant effect on inhibiting cell performed on human medullary thyroid carcinoma cells
growth. Furthermore, uncarine F appeared to selectivity exhibited a significant pro-apoptotic effect as well when
inhibit cell growth of cancerous cells and normal cells treated with the alkoloids isopterpodine and pteropodine
(Keplinger et al. 1998). (Rinner et al. 2009).
In another study, Uncaria tomentosa was observed to have a
positive effect on myeloid progenitor cells (cells that can
develop into other types of blood cells) when tested in vivo Anti-inflammatory
using mice. The mice were given 5 and 15 mg of U. tomentosa A recent experiment on rats deduced that quinovic acid-3-β-O-
orally for four days along with Filgrastim. One of the worst (β-d-quinovopyranosyl)-(27→1)-β-d-glucopyranosyl ester
side effects of chemotherapy is the loss of healthy white blood decreased the inflammatory response by 33% at a dosage of
cells, therefore this study is significant because it implies that 20 mg/kg p.o (Keplinger et al. 1998). However, no individual
U. tomentosa may have the potential to be used alongside compound can be accredited for the anti-inflammatory
chemotherapy treatments as a means of enhancing the activity. There appears to be a synergistic effect due to the
proliferation of healthy cells (Farias et al. 2011). combination of different compounds found in Uncaria
Yet another study was conducted supporting the use of U. tomentosa. When mitraphylline was isolated from U.
tomentosa as a complementary treatment to chemotherapy. tomentosa bark and given orally to mice, it displayed activity
Four types of extracts where made by dissolving Cat’s Claw in against cytokines, which are responsible for the inflammation
various solvents, then cell growth was observed in the process, indicating mitraphylline is one potential anti-
inflammatory compound. Overall, the study concluded that the lines in addition to stimulating the immune system (Heitzman
compound mitraphylline did cause a decrease in inflammation et al. 2004; Keplinger et al. 1998).
(Rojas-Duran et al. 2012).
The effects of aqueous extracts on the immune system were
also studied in vivo by conducting a mouse feeding study. It
Antiviral was determined that immune cells such as B, T and NK cells,
granulocytes and memory lymphocytes increased in number.
When applied to HeLa cells, the six quinovic acid glycosides This effect extended the cell lifetime but did not seem to
extracted from Uncaria tomentosa bark showed reduced increase the rate of cell growth. The antioxidants in U.
activity of the rhinovirus type 1B infection (Heitzman et al. tomentosa, such as the proanthocyanidins and cinchonains,
2004). The glycosides also showed antiviral activity against have demonstrated protection against oxidative stress and
two types of RNA viral infections (Keplinger et al. 1998). NF-jB activation which may counteract apoptosis and increase
These studies provide strong support for the use of U. DNA repair (Heitzman et el. 2004). In another in vivo study
tomentosa against viral infections. on mice, an aqueous-ethanol extract of U. tomentosa was
found to reduce glycemic levels and prevent the progression
of immune-mediated diabetes. The compounds extracted
Immunostimulant from the Cat’s Claw appeared to interfere with distinct
Uncaria tomentosa has shown high amounts of pathways that fuel diabetes (Dominguez et al. 2011).
immunostimulant activity during in vitro and in vivo studies of
phagocytosis. For example, in the late 1900s research was
published claiming that U. tomentosa increased immune Antimutagenic
function by 50% (Taylor 2004). The phagocytosis of human In vitro studies on S. typhimurium using the Salmonella
granulocytes and macrophages may increase due to the microsome test (Ames test) led to the conclusion that Uncaria
pentacyclic oxindole alkaloids found in U. tomentosa. A tomentosa extracts and fractions are effective in protecting
granulocyte-smear test, chemoluminescence model and a against photomutagenesis (Heitzman et al. 2004). U.
carbon-clearance test were performed with U. tomentosa tomentosa does not appear to cause mutations but, based on
extracts and pure alkaloids isolated from the plant. the findings, can in fact protect against mutagenic agents.
Pteropodine, isomitraphylline and isorhynchophylline
enhanced phagocytosis but the isopteropodine was found to
have the strongest effect on immune stimulation. Contraception
Mitraphylline and rhynchophylline did not produce any
Testing done on 29 rats with experimental endometriosis
stimulating effects on the immune system. A catechin, or
demonstrated the contraceptive effect of Uncaria tomentosa.
antioxidant, had to be added to the inactive alkaloids in order
The test group of rats received 32 mg/ml of U. tomentosa
to see any effect in the carbon-clearance test. These
extract daily for fourteen days and then the ovaries were
constituents may also inhibit the proliferation of myeloid cell
removed and analyzed. By analyzing the cells it was
determined that the extracts displayed a significant receiving the FAC (Fluorouracil, Doxorubicin,
contraceptive effect (Nogueira et al. 2011). Further studies Cyclophosphamide) treatment were administered U.
performed on rats treated with U. tomentosa showed a tormentosa along with their regular dosage. Results showed
decrease in uterine cell growth. These findings supported the that U. tormentosa reduced neutropenia, or low white blood
use of U. tomentosa as an alternative treatment for cell count, and restored cellular DNA damage caused by the
endometriosis (Nogueira et al. 2011). chemotherapy. Thus, it was concluded that U. tomentosa was
successful in reducing the adverse effects of chemotherapy
and was an effective adjuvant breast cancer treatment (Santos
Rejuvenation Araújo Mdo et al. 2012).
Quinic acid, one of Uncaria tomentosa’s active compounds, One study compared two 35 year old men, one who was a
could have a rejuvenating effect on neurons and lead to future habitual smoker and the other who had never smoked. A
Alzheimer’s treatments. When tested on Caenorhabditis decoction was made of Uncaria tomentosa in accordance with
elegans under deleterious conditions (heat stress and traditional practices and both participants consumed the
oxidative stress) the experiment yielded promising results; decoction for 15 consecutive days. Results found that
quinic acid enhanced DNA repair and was able to generate mutagenicity of the smoker’s urine significantly decreased.
protective effects in the neurons (Zhang et al. 2012). This demonstrates the anitmutagenic properties of Cat’s Claw
and the benefits that can be attained by consuming it (Rizzi
1993).
Clinical Studies
Because of its anti-inflammatory properties, Uncaria
tomentosa is believed to be a good remedy for rheumatoid Contraindications
arthritis. In a clinical trial, the occurrence of painful joints was Toxicity of Uncaria tomentosa was tested by examining the
reduced by 53.2% in the group treated with U. tomentosa. effects of an aqueous extract on Chinese hamster cells. The
This was compared to the control group which did not receive Neutral red assay, total protein content, and tetrazolium assay
the botanical treatment and had a 24.1% reduction in painful supported the claim that the herb is not toxic and was indeed
joints (Heitzman et al. 2004). U. tomentosa could prove to be a found to be non-toxic in vitro at the concentrations tested. In
viable source of pain relief for those suffering of rheumatoid another study of cytotoxicity, uncarines C, D and E were
arthritis. However, these controlled studies were small and specifically isolated from the inner bark. After being assayed
the results are inconclusive due to an insufficient amount of against SK- MEL, KB, BT-549, SK-OV-3 and VERO cell lines, it
clinical data (Rinner et al. 2009). was determined that uncarine D was the most cytotoxic. IC50
Another clinical trial examined the effects of U. tomentosa ranged from 30 to 40 lg/ml in all cell lines (Heitzman et al.
treatments in conjunction with chemotherapy which was 2004).
being administered to breast cancer patients. Randomized
patients with Invasive Ductal Carcinoma-Stage II who were
Acute toxicity was measured in a study with mice where products, indicating the presence of both species. In one such
lethargy and piloerection (“goose bumps”) were observed not product, up to 80% of the total alkaloids were found to be
long after the administration of high doses of Uncaria tetracyclic alkaloids, the “bad” alkaloids (Keplinger et al.
tomentosa. Other symptoms included hemorrhaging of the 1998).
stomach and intestines, pallor of the liver and spleen and
Thus far, scientific findings have been not been extensive
death. The mice that survived, however, completed their
enough to conclusively determine whether or not U.
recovery within five days of being exposed to the U. tomentosa
tomentosa can be used as an effective treatment for any health
extract. In another study where 1000 mg/kg of aqueous
condition. Because U. tomentosa has been traditionally used a
extract was administered daily to mice for 28 days, minor but
method of birth control, women who are pregnant or trying to
statistically significant results were collected. The mice
become pregnant should not take U. tomentosa supplements.
showed an increase in the percentage of lymphocytes
Also, due to findings that some plant properties may enhance
expressed and a decrease in the percentage of neutrophil
the immune system, it is still unknown what effect U.
granulocytes. In both male and female mice an increase in the
tomentosa may have on people with conditions affecting the
relative weight of the kidneys occured, however there were no
immune system such as HIV/AIDS. Slight toxicity was
deaths during the experiment (Keplinger et al. 1998).
observed in rats, however this was only at the highest
It is suspected that U. tomentosa may potentially interact with concentrations of U. tomentosa (Heitzman et al. 2004).
protease inhibitors or non-nucleoside reverse transcriptase
inhibitors present in other drugs. If taking Cat’s Claw
simultaneously with other treatments, users should be aware Current Uses in Allpathic and CAM Therapies
of the likelihood this reaction may occur. The possibility that Commercial interest was taken in Uncaria tomentosa at least a
U. tomentosa could induce pharmacokinetic interactions with quarter of a century ago when rumors of its miraculous
other drugs first came to light during in vitro study reports healing powers began circulating. Klaus Keplinger was the
(Muller et al. 2011). U. tomentosa may however protect first to truly investigate its medicinal potential and his
against the gastrointestinal damage that accompanies NSAIDs research eventually led to the production of U. tomentosa in
(Taylor 2004). Germany, Austria and the United States (Taylor 2004). Since
Most manufacturers of U. tomentosa are unaware of the two the production of Cat’s Claw, the commercial use of U.
types of Uncaria plants that come from Peru and have never tomentosa has taken off and there are over 50 dietary
bothered to consult a Peruvian authority. Thus, companies are supplement manufacturers in the United States who produce
unknowingly packaging supplements that contain the wrong products containing the plant or its extracts (Keplinger et al.
type of Uncaria. This adulteration could pose negative health 1998). Capsule and tablets containing U. tomentosa extracts
effects instead of the desired positive ones. One study can be found in most health food stores and are typically used
analyzed approximately fifty Cat’s Claw products sold in the as a general tonic, for inflammation reduction, or as a
United States, Peru and Central America and found varying treatment of bowel problems (Figure 7). For those suffering
amounts of pentacyclic and tetracyclic alkaloids in the
relationship between the spititual and physical worlds and
restore health. U. tomentosa may be a viable treatment for
osteoarthritis and rheumatoid arthritis, though it has only
been tested in small-scale human trials. Cat’s Claw also has the
potential to stimulate the immune system based on laboratory
evidence. Unfortunately, these results have not been
translated to humans and the results are inconclusive. Clinical
trials on U. tomentosa as a chemotherapy supplement appear
promising and commercially available Cat’s Claw extracts are
popularly used as adjunct cancer treatments even though no
concrete conclusions have been formed. Alas, further studies
on larger groups of patients are required to validate these
claims as well. Minor studies have also been conducted to
evalute U. tomentosa’s effects on inflammation, mutagenicity,
contraception and viral infections, highlighting the plant’s
broad spectrum of applications.
Cat’s Claw is an herbal remedy that has grown in popularity
among the public and the scientific world, however, much
more research must be conducted on the plant for it to be
regarded as a viable treatment for any illnesses. As of yet, the
abilities of Uncaria tomentosa have barely been uncovered
Figure 7. An example of how Uncaria tomentosa is and the room for growth is endless. Promising areas for future
marketed (Image source: iherb.com). research include Alzheimers and diabetes, two fields with very
few, if any, available treatments. Natural remedies, such as U.
tomentosa, tend to be overlooked but their chemistry is unlike
from the side effects of chemotherapy, Cat’s Claw has been a
anything that can be generated in the lab. It is evident from
popular herbal supplement due to promising but inconclusive
the culmination of many findings that the Ashaninkas belief
studies (Taylor 2004). As with any natural supplement, the
Cat’s Claw is a powerful plant with many medical applications
best source is always the unmanufactured herb itself.
is actually rooted in the plant’s phytochemistry.
Discussion
References Cited
Uncaria tomentosa has traditionally been a way for Peruvian
Cheng AC, Jian CB, Huang YT, Lai CS, Hsu PC, Pan MH. 2007.
tribal priests, such as the Ashaninka priests, to facilitate the Induction of apoptosis by Uncaria tomentosa through
reactive oxygen species production, cytochrome c release, Nogueira Neto, J., Cavalcante, F. L., Carvalho, R. A., Rodrigues, T. G.,
and caspases activation in human leukemia cells. Food and Xavier, M. S., Furtado, P. G., & Schor, E. 2011.
Chemical Toxicology, 45(11), 2206-2218. Contraceptive effect of Uncaria tomentosa (cat's claw) in rats
with experimental endometriosis. Acta Cir Bras, 26 Suppl
Domingues A, Sartori A, Golim MA, Valente LM, da Rosa LC, Ishikawa
2, 15-19.
LL, Siani AC, Viero RM. 2011. Prevention of
experimental diabetes by Uncaria tomentosa extract: Th2 Nogueira Neto, J., Coelho, T. M., Aguiar, G. C., Carvalho, L. R., de
polarization, regulatory T cell preservation or both? Journal Araujo, A. G., Girao, M. J., & Schor, E. 2011. Experimental
of Ethnopharmacology, 137(1), 635-642. endometriosis reduction in rats treated with Uncaria
tomentosa (cat's claw) extract. European Journal of
Farias, I., do Carmo Araujo, M., Zimmermann, E. S., Dalmora, S. L.,
Obstetrics and Gynecological ReproductiveBiology, 154(2),
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205-208. doi: 10.1016.
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137(1), 856-863. doi: 10.1016/ activity of ethanolic and aqueous extracts of Uncaria
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Urtica dioica L., Urticaceae
Sarah Henkel
Introduction
Urtica dioica L., of the Urticaceae family, is commonly known
as a stinging nettle (Lewis and Elvin-Lewis, 2003). Other
common names include burn weed and burn nettle (Olsen,
1921). This plant is used as a treatment in a wide variety of
ailments, both in traditional and modern medicine, such as
bladder and kidney disorders, diabetes, various allergies,
anemia, internal bleeding, osteoarthritis, and musculoskeletal
aches. In some places, the plant is even eaten as food. Recent
medical research has narrowed the use of the plant, making it
more medicinally effective. The basic components of U. dioica
are vitamin C, carotene, polysaccharides, beta-sitosterol,
quercetin, rutin, and kaempferol (Rodriguez-Fragoso et al.,
2008).
Description
Urtica dioica plants grow in a wide variety of areas and are
spread throughout Europe, Asia, Denmark, America, and
North Africa, in areas where moist soil is available. This Figure 1. The leaves, flowers, and stem of Urtica dioica.
green, leafy plant grows to be in between three and seven feet (Source:http:// www.fitoterapia.net)
tall, with leaves reaching between one and six inches in length.
These leaves are arranged on opposite sides of the wiry stalk
and continue up the whole length of the plant. capable of branching. The stings of this plant cause multiple,
painful blisters. The stinging nettle is often found in areas of
Although the plant bears green leaves and numerous brown or dense growth and is capable of cohabitating with other plants,
green flowers, its extensive root system and rhizomes are a due to its strong root system (Olsen, 1921). The plants are
bright yellow color. The leaves and stems have visible hairs, pollinated by a variety of different insects. In Figure 1, the
which contain the chemicals responsible for the plant’s green flowers and leaves of the plant can be seen. Figure 2
characteristic sting. These hairs provide the plant protection shows the stinging hairs on the plant, while Figure 3 shows
and can grow to be more than one meter long. They are also the results of a sting on human skin.
Figure 3. A rash resulting from contact with stinging
Figure 2. The stinging hairs on the nettle stalk. (Source:
http://www.acupuncturebrooklyn.com/altern ative-health/nettles) nettles’ hairs. (Source: http://creationwiki.org/File:
Nettle_sting.jpg)
Traditional Uses U. dioica was also used by the ancient Greeks and Romans
Medical Uses back in BCE times. Theophrastus, a student of Aristotle,
describes the medical warming uses of the stinging nettle
Traditional medical uses of the stinging nettle are thought to plant in his book De historia et causis plantarum. Pliny the
have originated in Europe, especially in Germany. Urtica Elder also recorded the medicinal uses of the stinging nettle in
dioica is one of the plants mentioned in the 10th century book his The Natural History of Pliny. According to him, the plant
“Nine Herbs Charm.” Many forms of traditional medicine used should be eaten in order to prevent disease during the winter
U. dioica in a variety of ways to treat GI ailments, kidney (Kavalali, 2003).
disorders, musculoskeletal aches, osteoarthritis, and
rheumatoid arthritis. However, recent studies have provided
scientific evidence to support the use of stinging nettle in only Food Uses
a few of these ailments which will be discussed later in this
Records show that many cultures utilizing U. dioica for
paper (Rodriguez-Fragoso et al., 2008).
medical purposes also utilized the plant as a source of food,
The use of U. dioica has been recorded in Egypt over 2,000 including the Native Americans. The leaves of the plant were
years ago for the treatment of arthritis and lumbago pains. It first boiled in water to remove the stinging chemicals and then
was also one component used in a mixture of Passover herbs. eaten as cooked greens. In some cultures, the water was
The plant can still be found there today (Kavalali, 2003). saved and used for medical purposes, while in others it was
simply discarded (Rodriguez-Fragoso et al., 2008). Nettles
have also been used to make nettle soup, nettle tea, and nettle
ale (Kavalali, 2003).

There are approximately fifty active chemical compounds in
the Urtica dioica plant including sterines, coumarins, simple
phenols, triterpenic acids, lignans, hydroxyl fatty acids, and a.
b.
ceramides (Kavalali, 2003). However, most of the medicinal
uses of U. dioica come from chemicals located in the stinging
hairs of the plant. Here, there is thought to be three significant
chemicals responsible for the plant’s smooth muscle c.
stimulation: acetylcholine, histamine, and 5-
hydroxytryptamine. The presence of 5-hydroxytryptamine Figure 4. The chemical structures of three compounds
was just recently accepted and is based on the result of six present in the stinging nettle’s hairs. (a) Acetylcholine, (b)
properties: the constriction of blood vessels in a rabbit’s ear, 5-hydroxytryptamine, (c) Histamine.
the lowering of a rabbit’s blood pressure, complete solubility
in ether, simulation of a guinea-pig’s and rabbit’s small
and natural antioxidants. In this experiment, U. dioica’s
intestine and instability in the boiling of an alkaline solution
antioxidant activity was measured by reducing power,
(Collier and Chesher, 1956). The chemical structures of these
superoxide anion scavenging activity, and metal chelating
three smooth muscle stimulators can be seen in Figure 4.
activity. These measurements showed that the higher the
concentration of WEN, the higher its antioxidant properties.
Biological Activity Also, the power of the stinging nettle's antioxidants was
Urtica dioica has many different biological activities. In an shown to be higher than that of the common ALPHA
experiment by Gulcin et al (2003), scientists used water tocopherol. No in vivo experiments were done in this study.
extract of nettle (WEN) to test the nettle's antioxidant, In order to test the antimicrobial activity of U. dioica, agar with
antimicrobial, and antiulcer biological activity. WEN was infected by ten different microbial agents:
Gulcin et al (2004) first tested the plant’s antioxidant Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis,
activity. The reason scientists are so interested in its Citrobacter koseri, Enterobacter aerogenes, Staphylococcus
antioxidant activity is because many common antioxidants aureus, Streptococcus pneumoniae, Micrococcus luteus,
have recently been shown to cause liver damage and cancer in Staphylococcus epidermidis, and Candida albicans. Then results
some lab animals. Researchers are looking for more effective were recorded by measuring zones of growth inhibition on the
agar plate. Each microbial agent was inhibited at least slightly, Contraindications
with the most significant inhibition being with Staphylococcus
So far, no negative interactions with other drugs have been
epidermis and Miccrococcus luteus. No in vivo experiments
recorded. However, it is recommended that pregnant women
were done in this study.
and breast-feeding women do not use any form of Urtica
Forty albino male rats were used for an in vivo study of the dioica. The plant and its drug derivatives are known to cause
antiulcer activities of Urtica dioica in this study also. Using the gastrointestinal issues, skin irritation, and sometimes diarrhea
ethanol-induced ulcer model, researchers injected the rats (Anderson, 2003). Also, one molecular contraindication is
with 10 mg/kg WEN and then thirty minutes later with that the extract of the plant’s leaf can reduce the amount of
ethanol. One hour after the injection of ethanol the rats were TNF-alpha and IL-1 beta in humans (Oberteis, 1996).
killed and their stomachs examined. The larger amounts of
WEN the rats, received, the fewer ulcers they had.
Current Use in Allopathic & CAM Therapies
Urtica dioica can be found in several drug therapies today.
Clinical Studies
One drug marketed containing stinging nettle is known as
Numerous clinical studies on Urtica dioica have been Bazoton, which is taken in 300 milligram capsules, twice daily,
conducted in the past and are still being conducted today. In for up to sixth months. One CAM therapy used today, for the
this monograph, a focus is placed on three different conditions treatment of allergic rhinitis, calls for the patient to take 600
for which U. dioica has been tested as a treatment. First, U. milligrams of freeze dried nettles as soon as symptoms
dioica has been proven to treat lower urinary tract infections appear. Many nettle supplements exist, in which patients can
in several clinical trials (Lopatkin 2007, Lopatkin 2006, buy a bottle of nettle capsules over the counter in pharmacies
Safarinejad 2005). Sometimes U. dioica was used in and online (“Nettle,” 2010).
combination with other chemicals or drugs, but in each of
these three studies the administered drugs proved effective.
Another ailment for which U. dioica has been used to treat is Discussion
that of benign prostatic hyperplasia or benign prostatic The Urtica dioica plant has been utilized for both medical and
syndrome. In several clinical trials, U. dioica has been proven food purposes throughout history. Today, modern science has
to relieve irritative symptoms (Popa 2005, Schneider 2004). found many of the key elements in the stinging nettle that
Other clinical trials studied the effect of U. dioica on gingivitis, make it useful as a medicine. For thousands of years, humans
but the plant did not offer any effective treatment (Van der have utilized this plant and as science continues to narrow
Weijden, 1998). down the useful chemicals and possible dangers of the plant,
its popularity as a drug is likely to grow.
References Cited extract for lower urinary tract symptoms--a placebo-
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activities of nettle (Urtica dioica L.).” Journal of Sabal-urtica preparation in the symptomatic treatment of
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S, Avdeĭchuk IuI, Golubev GV, Mel'nik KP, Elenberger Safarinejad MR. “Urtica dioica for treatment of benign prostatic
NA, Engelman U. “Efficacy and safety of a combination of hyperplasia: a prospective, randomized, double-blind,
Sabal and Urtica extract in lower urinary tract symptoms-- placebo-controlled, crossover study.” J Herb Pharmacother.
long-term follow-up of a placebo-controlled, double-blind, 2005; 5 (4):1-11.
multicenter trial.” Int Urol Nephrol. 2007; 39(4):1137-46.
Schneider T, Rübben H. “Stinging nettle root extract (Bazoton-uno)
Lopatkin NA, Sivkov AV, Medvedev AA, Walter K, Schlefke in long term treatment of benign prostatic syndrome (BPS).
S, Avdeĭchuk IuI, Golubev GV, Mel'nik KP, Elenberger Results of a randomized, double-blind, placebo controlled
NA, Engelman U. “Combined extract of Sabal palm and nettle multicenter study after 12 months.” Urologe A. 2004;
in the treatment of patients with lower urinary tract 43(3):302-6.
symptoms in double blind, placebo-controlled trial.”
Urologiia. 2006; 2:12, 14-19. Sökeland J. “Combined sabal and urtica extract compared with
finasteride in men with benign prostatic hyperplasia:
Lopatkin N, Sivkov A, Walther C, Schläfke S, Medvedev A, Avdeichuk analysis of prostate volume and therapeutic outcome.” BJU
J, Golubev G, Melnik K, Elenberger N, Engelmann U. “Long- Int. 2000; 86(4);439-42.
term efficacy and safety of a combination of sabal and urtica
Vaccinium macrocarpon Aiton, Ericaceae
Sarah McMullin
Introduction
Vaccinium macrocarpon Aiton, or American Cranberry, is a
member of the Ericaceae family. Sometimes the plant is placed
in a genus its own, called, Oxycoceus (TWC staff, 2007). It is
one of only three species of fruit native to North America, the
other two being the blueberry and the bilberry, which are part
of the same genus, Vaccinium (Lynch, 2004). ). It grew wild
until 1816 when it was cultivated with difficulty by Henry Hall
(History, 2011). Now US farmers grow over 40,000 acres of
cranberries every year, primarily in Wisconsin,
Massachusetts, and New Jersey (Wisconsin produces over
50% of the national total) (Keough, 2011). Cranberries are
usually commercially harvested by flooding the bog where
they grow, beating the berries off the bushes and then
collecting the berries that float on top of the water (CCCGA,
2011) (See Figure 1). In 2011 growers in the United States Figure 1. Workers harvesting cranberries from bog. (Photo
courtesy of Wisconsin Farm Bureau Federation. < http://www.history.org
are projected to produce 7.5 million barrels of cranberries, /foundation/journal/holiday06/cran.cfm>)
and they received on average $46.50 a barrel for their
harvested cranberries in 2010 (Keough, 2011). production in the United States is projected to be up 10%
Cranberries were used as a food source and as part of from 2010 production this year (Keough, 2011).
traditional medicine by Native Americans before Europeans While V. macrocarpon juice has been used under anecdotal
arrived in North America. It is even thought that cranberry evidence since before colonization as a prophylactic
sauce sweetened with maple sugar was part of the first prevention for urinary tract infections, recently clinical trials
Thanksgiving feast between the Native Americans and the have been adding hard scientific evidence its efficacy for this
Pilgrims. Cranberries continue to be very important in food, use (The Natural Standard Research Collaboration, 2011). The
especially around the holiday season. They are seen on scientific community’s interest in V. macrocarpon has even
shelves in virtually all grocery stores near Thanksgiving and in extended beyond this common treatment to explore other
the freezer aisle and as juice, all year-round. Cranberry possible medicinal properties it might have, including possible
compounds that treat heart disease and cancer.
Figure 3. V. macrocarpon in bloom. (Photo courtesy of Tom
Harville. http://www.ncwildflower.org/index.php/plants/details/
Vaccinium-macrocarpon/)
of the Vaccinium genus (Figure 2). The plants spread by

rhizomes (TWC Staff, 2007), horizontal stems that grow new
Figure 2. Vaccinium macrocarpon sketch. (Source: Britton, N.L., stems up to the surface from nodes. This allows the plants to
and A. Brown. http://plants.usda.gov/java/profile?symbol=VAMA spread very quickly but can make them difficult to transplant
&photoID=oxma6_001_avd.tif) (Beaulieu, 2011). The leaves are very small, ¼ inch to ½ inch
(0.64cm to 1.28cm) long, leathery and oval shaped. They are
shed in late summer every two years. The flowers have four
petals and are white to pink in color. They hang inverted and
Cranberry plants are low growing perennial evergreen shrubs, flower for two to four weeks in late June to early July (Reiger,
less than 12 inches (30cm) high, that grow in moist bog-like 1990). As the flower ages its petals curve back (Figure 3).
acidic soil (pH 4.0 to 6.1) in partial shade. They are native to Early settlers called the berries “craneberries”, because the
cool temperate boreal forests in the Northeastern United early flowers’ (before they expanded) shape resembled a
States and Southeastern Canada (TWC Staff, 2007). They are crane. The flower discourages self-pollination because the five
close relatives of the blueberry plant, which is also a member
Figure 4. Reproductive parts of V. macrocarpon flower. Figure 5. Ripe V. macrocarpon on bush. (Source: <http://www.
(Photo courtesy of K.S. Delaplane & D.F. Mayer http://ag.udel.edu/enwc justbio.ca/products/vacciniummacrocarpon>)
/faculty/dmcaron/Pollination/cranberry.html)
kidney problems (Block, 2011). They were also used for
to eight stamens are exposed first, releasing their pollen stomach problems, wounds, blood poisoning and appetite loss.
before the single stigma is exposed. The pollen is heavy and Cranberries were used as a poultice to spread on the skin for
not easily transported by wind, so insects, especially bees, are wound healing and treating inflammation, and mixed with
very important for pollination (Delaplane, 2011) (Figure 4). cornmeal to cure blood poisoning. An infusion of branches
The flower takes on more of a pink color if it is not pollinated. was made to treat pleurisy, chest pain caused by inflammation
The flowers produce some nectar, which is what attracts in the lining of the lungs and chest (Speck, 1917) (Dugdale,
pollinators. The fruit is a small “false” berry (epigynous), 2011). An infusion of the fruit could be made to treat nausea.
which starts out green then changes to white and then bright (Smith, 1932). A decoction of the fruit could also be made to
to dark red as it matures. The berry matures in 60-120 days treat diarrhea (Lantis, 1959).
after fertilization, and is very tart to taste (Rieger, 1990)
(Figure 5). V. macrocarpon is high in vitamin C and therefore was very
valuable to early explorers in preventing scurvy, a debilitating
and often deadly disease caused by lack of vitamin C in the
Traditional uses diet. The fruit could be sun or fire dried and kept over winter
as a food source which was easily portable and could be taken
Native Americans and Canadians called cranberries on hunting expeditions (Waugh, 1916). Cranberries have also
sassamanash and used them most often to treat bladder and been used to treat type 2 diabetes (NIH, 2011), and have also
been used for infections, especially urinary tract infections, for
hundreds of years, especially before the discovery of
antibiotics (Lynch, 2004).
Native Americans made a sauce with the berries that was
sweetened with maple syrup, and it is thought that this was
likely part of the first Thanksgiving celebration. The berries
were eaten either raw or cooked (Densmore, 1928), and were
also used to make a special very high-energy food called
pemmican which consists of dried meat or fish and berries
pounded into a pulp, shaped into a cake and dried. It could
then easily be stored and transported. It was taken along on
canoe trips and became very important to the Métis people
(Native people who intermarried with early French settlers in
Canada). They often sold it as food to European traders along
the French Fur Trade Route. (Block, 2011)
Traditional non-medical uses for cranberries include use of
the juice for dying fabrics, such as blankets and rugs (Caruso,
2000), and the making of jewelry from firm ripe berries strung
together (Leighton, 1985).
Figure 6. Compounds found in cranberry. (Courtesy of
Catherine C. Netto. <http://jn.nutrition.org/content/137/1/186S/F1.
Chemistry and Pharmacology expansion.html>)
The major active constituents of Vaccinium macrocarpon are
members of the flavonoid group of compounds. Flavonoids are protoanthocyanidins), are usually bound to a sugar, making a
water-soluble polyphenols made by plants. They consist of flavonoid glycoside (Higdon, 2005). The bioavailability of
two benzene rings connected by another three-carbon ring these compounds is strongly dependent on the structure of
that often contains oxygen (Figure 6). These compounds are the bound sugar. These flavonols are strong free radical
responsible for plant color (Top Cultures, 2011). Vaccinium neutralizers. Free radicals are very dangerous and can kill
macrocarpon has one of the highest phenolic contents in fruit. cells, and damage DNA and proteins, which can cause cancer
These include: phenolic acids, anthocyanins, flavonols, and (University of Maryland, 2011). The stability of these flavonols
flavan-3-ols, procyanidins and proanthocyanidins caused by their aromaticity allows them to absorb the reactive
(Vvedenskaya, 2003). The most prevalent flavonol is extra electron into their rings, thereby stopping its ability to
quercetin. Most flavonoids, except flavanols (catechins and react with parts of the cell.
Biological Activity and is associated with increased risk for cardiovascular events
including heart attack. The mechanism that caused the
Flavonoids are the main active chemical constituents of
decreased stiffness is still unknown, but future studies hope to
Vaccinium macrocarpon. They have been shown to have many
discover this information.
positive effects against disease. Studies have shown that
flavonoids are able to induce apoptosis, programmed cell A huge problem associated with bacterial infection is the
death, in tumor cells. MacLean et al. (2011) showed that whole colonization of many bacteria into biofilms. Pseudomonas
cranberry extract induced apoptosis in human prostate aeruginosa is a type of bacteria that normally lives in soil,
adenocarcinoma through caspase-8 activation. They found water or plants and causes many opportunist infections in
that it was the proanocyanidin and flavonol-enriched fractions humans with compromised immune systems (Todar, 2011). It
of the extract that increased caspase-8 and 9 activities, uses flagellum-mediated swimming to move towards surfaces
suggesting that it is these compounds that are involved in to attach itself and to swarm with other bacteria. They also
apoptosis activation. Caspase-8 cleaves the Bid protein, which use quorum sensing to move together as a group. O’May and
causes release of cytocrome-c from the mitochondria. Tukenjkji showed that proanthocyanidins from V.
(MacLean et. al., 2011) Cytocrome C initiates a cascade of macrocarpon inhibit this swarming ability. This means that
events that destroy the cell from the inside out and package it the bacteria were unable to form a colony on a surface.
into vesicles for disposal by macrophages (apoptosis). This is Cranberry extracts as low as 20 micrograms per milliliter
a very important mechanism in which cancer cells often have almost completely blocked swarming. However, there was no
a defect. Normally if a cell senses a defect it will intrinsically effect on the growth rate of bacteria. These particular bacteria
initiate this apoptosis pathway. Cancer cells often over produce a biosurfactant, similar to a soap, to reduce surface
express BCL-2, which has been suggested to block tension so the bacteria can move across a liquid’s surface.
cytochrome-c release (Yang, 1997). Kuida et al. also showed When surfactant, rhamnolipid, was added after cranberry
that mice lacking caspase 9 die early because of lack of treatment the bacteria regained some of its swarming ability.
apoptosis. (Kuida, 1998) Ferguson et al. showed that a fraction This suggests that the V. marcrocarpon proanthocyanidins
taken from cranberry presscake, the wet hulls left after juice is somehow interferes with the biosurfactant production. It is
squeezed out, containing flavonoids was active against breast also possible that a compound in cranberries interferes with
and prostate cancer. This fraction slowed proliferation and bacteria quorum sensing ability (O’May, 2011).
induced cell-cycle arrest and apoptosis in mouse tumors In 1991 Ofek et. al. presented their findings in the New
(Ferguson, 2004). England Journal of Medicine in which they stated that
Another amazing property cranberries possess was shown in cranberry, and other members of the Vaccinium genus,
a 2011 study by Dohadwala et al. Extra-strength cranberry blocked the colonizing ability of E. coli bacteria in the urinary
juice, provided by Ocean Spray, was given to patients with tract. They showed that an isolate from cranberry juice
coronary artery disease, and was shown to provide an acute inhibited adhesion of bacteria to the mucosal cells of mouse
decrease in carotid femoral pulse wave velocity, which is bladders, which prevented urinary tract infection. The isolate
directly related to arterial stiffness (Dohadwala et. al., 2011), seemed to act on the adhesins on the pili which extend off the
surface of Escherichia coli cells (Ofek, 1991). Twenty years Another earlier clinical trial by Kontiokari et al. also showed
later Gupta et al. showed that it was the proanthocyanidin the effectiveness of cranberry juice in preventing recurrent
component of V. macrocarpon that produces this adhesion UTIs. It compared women who drank 50mL of cranberry-
inhibition. An isolation that contained 10-50 micrograms per lingdonberry concentrate daily for six months to those who
milliliter of proanthocyanidin inhibited 70% of adhesion in received no intervention. The recurrent rate in the cranberry
both sensitive and multidrug resistant E. coli. It is theorized group was 16% compared to 36% in the control group. This is
that this inhibition is associated with the A-type linkages of statistically significant and shows that drinking cranberry
proanthocyanidin, but the specific mechanism in not certain juice has some effect on the likelihood of a urinary tract
(Gupta, 2011). infection returning. (Kontiokari et. al., 2001)
Another study using female children was also promising.
Children who had suffered more than one urinary tract
Clinical Studies
infection in the previous year were given either daily
Many clinical trials have been undertaken to examine whether cranberry juice or one of two controls (Lactobacillus or no
Vaccinium macrocarpon can reduce the number of recurrent treatment). Only 18.5% of the children in the cranberry group
urinary tract infections in patients, and most have proved suffered an infection during the trial, compared to 42.3% and
inconclusive. One study looked at women over the age of 45 48.1% in the controls. There were no negative reactions
who suffered from recurrent urinary tract infections. The except for a few children who did not like the taste of
most common treatment for people with recurrent UTIs is cranberry juice. (Ferrara et. al., 2009)
low-dose, long-term, antibiotic prophylaxis. Many clinical
Despite these studies showing promising results, a more
trials have shown this to be very effective, but there are
recent study of 319 women between 18 and 40 years of age by
significant side effects including fungal infections and a high
Barbosa-Cesnik et al. was less positive. The participants in this
risk for the development of antibiotic resistance. The study by
study drank either 8oz of a low calorie 27% cranberry juice
McMurdo et al. compared the use of this prophylactic
cocktail, or an 8oz of a placebo twice a day for six months. The
antibiotic treatment to daily treatment with 500mg of
placebo group had a recurrence rate of 16% while the
cranberry extract. The median time for UTI recurrence in the
cranberry group had a recurrence rate of 19%, indicating that
antibiotic group was 91 days, compared to 84.5 days in the
cranberry juice gave no protection against recurrent UTIs
cranberry group. The difference was not statistically
(Barbosa-Cesnik et. al., 2011). It is possible however, that the
significant and the women taking cranberry extract had fewer
low concentration (27%) of cranberry juice in the cocktail did
and less severe side effects and did not develop antibiotic
not contain enough of the active V. macrocarpon flavonoids to
resistant bacteria. It was concluded that women should talk to
obtain good results. Most studies showing positive results
their doctors about possibly taking Vaccinium macrocarpon
used extra-strength cranberry juice, which has a higher
instead of antibiotics to prevent infection, because it is
percentage of active compounds, or cranberry extract pills,
natural, much cheaper, has fewer side effects and works
which are equivalent to several glasses of juice.
almost as well (McMurdo et. al., 2008).
Contraindications slightly more than cranberry extract, but more importantly it
puts patients at risk for many side effects, including antibiotic
Vaccinium macrocarpon is generally regarded as safe and no
resistance. The National Institute of Health rates cranberry
significant drug interactions have been reported, but there is a
juice and supplements as “possibly effective” for preventing
lack of solid long-term safety information (Lynch, 2004).
urinary tract infections, and it is often recommended first by
There is a possibility that cranberry may increase the amount
physicians for prevention of, or to complement antibiotic
of time Warfarin, a drug prescribed to slow blood clotting,
treatment of, UTIs (NIH, 2011). The American Institute for
remains in the body. This could lead to bruising or bleeding
Cancer Research also suggests eating cranberries to lower the
(NIH, 2011). Some very small studies have shown the
risk of certain cancers, and there have been many news stories
possibility that cranberry juice can increase oxalate levels in
over the past few years promoting this (American Institute for
the urine, which is the main cause of kidney stones. Large
Cancer Research, 2011). Since cranberry juice and cranberry
doses of cranberry can also lead to diarrhea (Burak, 2010).
extract pills do not require a prescription, it can be assumed
Diabetics should also be careful when they consume large
that many people may take cranberry juice as a preventative
quantities because its high sugar content could result in high
measure for cancer and UTIs without consulting a doctor.
blood sugar.
Discussion
Vaccinium macrocarpon has played an important role for
Many cranberry supplements can be purchased in pharmacies.
centuries in food and complementary and alternative
Most are in pill form and are advertised for improved urinary
medicine, among Native Americans and then European
tract health and antioxidant benefits (Enzymatic Therapy,
settlers. It had been used under circumstantial evidence for
2011). Urinary tract infections account for approximately 8
treatment of urinary tract infections for years, especially
million outpatient and emergency room visits per year, and
before Alexander Flemming discovered antibiotics in 1928
combined direct and indirect cost associated with UTIs in
(Bellis, 2011). While antibiotics are affective against the
America is $1.6 billion (Bowen, 2007). The recommended
bacteria causing UTI’s, the infection often recurs, which is
dosage of unsweetened cranberry juice for UTI prevention is
where V. macrocarpon becomes important yet again. Studies
8oz, three times per day, or one 300-400mg tablet of
have shown V. macrocarpon to be effective at significantly
concentrated cranberry extract (Lynch, 2004). One 64oz
reducing the recurrence rate of these infections, while
bottle of Ocean Spray Pure Cranberry Juice Costs
producing virtually no side effects. These promising studies
approximately $6 (Ocean Spray, 2011), and a thirty day supply
of extract tablets costs between $10-$15 (Lynch, 2004). A 60 have encouraged researchers to explore cranberries for many
other disease fighting properties in the past few years,
day supply of the most common antibiotic prescribed for
including the treatment and prevention of cancer and heart
prophylaxis, Trimethoprim (Regional Drug and Therapeutics
disease. Many papers have also been published this year
Center, 2004), costs approximately $33 at
exploring more unorthodox possible uses for this remarkable
healthwarehouse.com (Health Warehouse, 2011); this is
berry such as, antifungal, wound healing, osteoclast inhibition 23, 2011).
in people with periodontitis, and blood pressure reduction Bellis, Â Mary. "History of Penicillin - Alexander Fleming - John
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Inc. - Vitamins, supplements, and all natural medicines..
Vaccinium myrtillus L., Ericaceae
Tiffany Baerwaldt
Introduction
Vaccinium myrtillus L., commonly known as bilberry, is a
member of the Ericaceae family. It is also known as
whortleberry, European blueberry, huckleberry, black
whortles, trackleberry, and bleaberry. The name Bilberry is
derived from the Danish “bollebar,” meaning dark berry
(Grieve, 1959). It belongs to a large genus (Vaccinium) of
plants that also contains blueberry (Vaccinium corymbosum)
and cranberry (Vaccinium macrocarpon). Bilberry is
sometimes referred to as “blueberry” because both share
many of the same characteristics and features, but the true
blueberry is native to the United States (Benzie and Wachtel-
Galor, 2011).
Bilberry is a perennial shrub whose fruit is purple or bluish
black in color and is sweet tasting. It is native to northern
Europe but can also be found in the mountainous regions of
the northern hemisphere. Bilberry was used traditionally as
food and also as medicine for ulcers, diarrhea, dysentery,
diabetes, urinary infections, and vision, and its extracts were
also used for bilberry’s anti-inflammatory properties.
Dioscorides highly regarded the bilberry plant and its fruit,
and bilberry fruit was also noted in Ayurvedic medicine as .
having use for oral infections and teeth cleaning. The leaves of Figure 1. Line drawing of Vaccinium myrtillus L. (Source:
the bilberry plant contain many active constituents including Flora of China Illustrations vol. 14, fig. 688, 1 http://tropicos
tannins, polyphenolics acids, flavanoids, arbutin, and .org/Image/73875)
quercetin. Its berries contain anthocyanoside flavanoids, as
well as polyphenols and anthocyanins, which contribute to properties, as demonstrated in many recent experiments.
much of its pharmacological activities. Bilberry has Bilberry also has a long history of use as for various eye
antioxidant, vaso-protective, antimicrobial, and lipid-lowering conditions. It has corneal renewing effects, and is believed to
the form of an extract, as a vitamin supplement for vision
improvement, vascular problems, diabetes, and as a tea for
vision health as well as antioxidant support for the whole
body.
Vaccinium myrtillus is a colony-forming, perennial,
rhizomatous shrub ranging from 5-120 cm high. Its twigs and
leaves are sharp-edged and green. It has alternating leaves
that are broadly elliptical and approximately 19-27 by 7-11
mm in size. The leaves lack in rigor and firmness and are
glandular beneath (Figure 1). The calyx is green and has a
smooth surface without hairs or projections. The corolla, or
part of the flower that consists of the petals, is thin, globose,
and pink, cream, or greenish white in color (Vander Kloet and
Dickinson, 1999, 242). The fruit of the bilberry plant are
berries that are purple black or bluish black in color, and 7-9
mm in diameter. The berries grow in small clusters (Figure
2). The meat of the fruit is purple, unlike the American
blueberry, which is usually cream or white (Thorne Research
Inc, 2001, 500). The bilberry seedling takes approximately 6-
10 weeks to develop its first leaves and shoot, and at 3 months
the juvenile plant begins to show the features indicative of the
adult plant (Ritchie, 1956, 297) (Figure 3).
V. myrtillus is native to northern Europe and is also abundant
Figure 2. Photograph of Vaccinium myrtillus L. (Source: in the mountains and forests of the northern hemisphere,
http://www.zufglobus.com/xzcv/Page/index/135). including northern and central Asia and in northern North
America (Ritchie, 1956). Bilberry has been shown to have its
improve human night vision and has promise for the highest vegetative and reproductive performance in
treatment of cataracts and prevention of glaucoma. Bilberry is woodlands, but it may also occur in mountainous heath soils,
most commonly used for improvement of night vision and upland heaths, boggy communities, degraded meadows, open
general eye health. Bilberry is generally considered as safe coniferous forests, pine forests, parklands, disturbed or open
when used properly, and is currently used as an antioxidant in birchwoods, hummocky seepage slopes, podsols and
examined where severe cutting back of the young green
shoots was evident. Observation suggests that this has the
effect of stimulating further growth and branching producing
a densely busy habit.” It was also established that bilberry is
pollinated by insects, birds, and through self-pollination by
gravity.
Traditional Uses
Due to its rich, sweet and enjoyable flavor, as well as its
nutritive value, bilberry has been used as food and as
medicine for centuries. In addition to its use in tarts, pies, and
Figure 3. Diagrams of bilberry seedlings to illustrate the
preserves, bilberry was traditionally used in juices, jams, and
early stages of development. (Source: Ritchie, 1956)
wine as a colorant, and was also used to dye wool due to the
moraines. Bilberry can flourish at altitudes from sea level to presence of tannins in the fruit. In addition, according to “A
2600 meters above sea level. The abundance of the bilberry Modern Herbal” written by Grieve in 1959, bilberry was used
plant as well as its size, shape, and color is determined by soil widely in the ancient world, and was highly regarded by
conditions such as the drainage factor and amount of organic Dioscorides. It was also noted that a decoction of the leaves or
matter in the soil. Climate conditions such as the presence of bark of the root was used as a local application to ulcers, and
strong winds may also impact the morphological features of could also be applied to ulceration of the mouth and throat.
bilberry. One study determined that the tallest bilberry plants The fruit’s astringent properties were used for diarrhea and
with the greatest density are usually found in mountain dysentery in the form of syrup (Grieve, 1959). The fruit was
habitats, while populations in lowland forests are generally also used for scurvy, tuberculosis, and urinary complaints
lower in height and grow in more erratic patches (Rolson et al. (Grieve, 1959), and a tea made from the leaves was used as
2011, 238). However, results from previous studies remedy for the treatment of diabetes (Cignarella et al. 1996,
demonstrated that the height of bilberry decreases with 311-312). Bilberry fruit was also used traditionally in Europe
altitude, which could be the result of other environmental for discharges, as a lactation inhibitor (Grieve, 1959), in anti-
factors influencing the morphological features of the plant inflammatory mixtures, and is commonly used as medicine for
(Woodward, 1986). improving vision (Song et al. 2010, 520). Traditional herbal
preparations are still used to enhance circulation and improve
Bilberry also interacts with various biotic factors that enhance eye conditions, and dried berries are sold for the traditional
its distribution and pollination. According to Ritchie (1956, treatment of mild diarrhea and inflammation of the mouth and
294), “When other more palatable plants are unavailable, throat (Grieve, 1959).
sheep will graze bilberry, and areas in Derbyshire have been
Bilberry fruit was also included in Ayurvedic medical
practices. Deformities of the oral cavity, plaques, and
infections were managed in ancient India, and it was noted
that bilberry fruit and hawthorn berry stabilize collagen,
strengthening the gum tissue (Singh and Purohit, 2011, 66).

Bilberry leaves contain several active constituents including Figure 4. Chemical composition of bilberry fruit extract:
tannins, polyphenolic acids, flavanoids, arbutin, cathechins, Anthocyanins. (Source: National Toxicology Program, 1999. Bilberry
iridoids, and quercetin (Rolson et al. 2010, 238). In addition, Fruit Extract 84082-34-8 http://ntp.niehs.nih.gov/ntp/htdocs/Chem
_Background/ExSumPdf/Bilberry.pdf)
bilberry berries contain anthocyanoside flavonoids, or
anthocyanins, vitamins, sugars, and pectins (Thorne Research
(Rolson et al. 2010, 241). Polyphenols account for
Inc, 2001, 500). Polyphenols and anthocyanins are the main
approximately 50-80% of the total polyphenol content in
components in bilberry, and many of the pharmacological
bilberries (Karlsen et al. 2009, 346). A concentration of
activities of bilberry can be attributed to anthocyanins (Song
30mg/g of quercetin in bilberries has been reported (Erlund
et al. 2010, 520). Bilberry is one of the richest natural sources
et al. 2003, 37). Another study determined and summarized
of anthocyanins (Benzie and Wachtel-Galor, 2011, 55).
the content of the major polyphenol classes found in bilberry,
Anthocyanins are water soluble, glycosylated, nonacetylated
which include polyphenolic acids, tannins, arbutin, flavanoids,
polyphenolic compounds responsible for the red, blue, and
and anthocyanins (Karlsen et al. 2009, 352) The main
purple pigments of fruits. These pigments are absorbed by the
anthocyanins in bilberry and their relative concentrations
gastrointestinal tract after consumption, and have been shown
include delphinidins, cyanidins, petunidins, malvidins, and
to have tumor suppressive, anti-inflammatory, anti-viral, and
peonidins (Benzie and Wachtel-Galor, 2011, 57). The chemical
anti-diabetic properties. Anthocyanins are also potent
composition of 25% bilberry extract, which is considered the
antioxidant and reactive oxygen species scavengers, and the
standardized amount of anthocyanins in bilberry extract,
anthocyanin concentration of fruit is highly correlated with
contains a natural mixture of glycosides of aglycone
the oxygen radical absorbance capacity (Bell and Gochenaur,
anthocyanins, cyanidin, delphindin, and malydin (National
2006, 1164).
Toxicology Program, 1999) (Figure 4).
In a study conducted to evaluate the morphological and
chemical variability of wild populations of bilberry in Poland,
the content of phenols in bilberry leaves and fruits were Biological Activity
determined. It was found that the content of tannins in The anthocyanins present in bilberry are safe and proven
bilberry leaves can reach 7.5-12%, and the content of antioxidants and chemoprotective agents. A variety of in vitro,
anthocyanins in bilberry fruit can amount from 0.5 to 0.399%
in vivo, and human studies have demonstrated that and conducted an in vitro analysis of the direct vasoactive or
anthocyanins have antioxidant effects, promote healthy vision, vasoprotective properties of berry pigment extracts using
urinary tract health, and skin health. Anthocyanins also coronary artery rings from mature female pigs. Their results
exhibit cardiovascular, neuroprotective, anticarcinogenic suggest that such extracts could have significant beneficial
potential, and antidiabetic properties and health benefits effects in the treatment of vascular disease.
(Zafra-Stone et al. 2007).
Huttunen et al. (2011) found that the antimicrobial activity of
A study that aimed at examining whether bilberry extract juice fractions including bilberries was notable against
alleviates pruritus, or the sensation that causes the reflex to Streptococcus pneumonia binding to human bronchial cells,
scratch, in mice with chronic allergic contact dermatitis and that pneumococcal growth was completely inhibited at a
concluded that anthocyanins from bilberry extract may be concentration of ~86 mg/g. In summary, the results indicate
beneficial in the treatment of chronic pruritus. Chronic that bilberry is a novel source for both antiadhesive and
pruritus occurs in patients with anti-inflammatory skin antimicrobial agents against pneumococci.
diseases such as atopic dermatitis, which is the most common
An in vitro study on the protective effect of bilberry extracts
chronic inflammatory skin disorder and always induces
on cultured human limbal epithelial cells found that bilberry
pruritus. The daily intake of bilberry may provide a useful
extract may be beneficial for the physiological renewal and
treatment and source of relief for pruritus in these patients
homeostasis of corneal epithelial cells (Song et al. 2010, 520).
(Yamaura et al. 2011).
Another study was conducted that generated a mouse model
In an in vivo study using type 2 diabetic mice, the effect of of endotoxin-induced uvetis that showed retinal inflammation
dietary bilberry extract on hyperglycemia and insulin and swelling of the middle layer of the eye. Mice that were
sensitivity was examined. It was found that dietary bilberry pretreated with an anthocyanin-rich bilberry extract were
extract significantly reduced the blood glucose concentration analyzed, and the effect on the retina was documented. The
and enhanced insulin sensitivity. The upregulation of glucose anthocyanin-rich bilberry extract prevented the impairment
transporter in white adipose tissue, skeletal muscle, and the of photoreceptor cell function, endotoxin-induced uvetis
liver of diabetic mice fed with bilberry extract was also shown. decreased, and the shortening of outer segments in
Acetyl-CoA carboxylase was also inactivated and PPARα, acyl- photoreceptor cells were suppressed at the cellular level. The
CoA oxidase, and carnitine palmitoyltransferase-1A were extract induced inflammation-related rhodopsin decrease, and
upregulated in the liver. The result of these changes was the extract ameliorated the intracellular elevation of reactive
improvement in hyperglycemia and insulin sensitivity in type oxygen in the inflamed retina. It was determined that
2 diabetes, which provides a biochemical basis for the use of anthocyanin-rich bilberry extract has a protective effect on
bilberry fruits and implications for the prevention and visual function when the retina is inflamed (Miyake et al.
treatment of type 2 diabetes (Takikawa et al. 2010). 2011).
Bell and Gochenaur (2006) recognized that plant pigment Cignarella et al. (1996) discovered that bilberry leaves have
anthocyanins are especially potent oxygen radical scavengers, lipid-lowering properties by administering bilberry leaf
extract to streptozotocin-diabetic rats. Plasma glucose levels period. The results of this study recommend the increased
consistently dropped about 26% at two different stages of intake of berries due to their bioavailable quercetin content in
diabetes. The findings indicated that the active constituents of addition to the presence of other beneficial compounds.
bilberry leaves, which include anthocyanins, might prove
The flavanoid anthocyanosides found in bilberry are potent
useful for the treatment of dyslipidaemia, or an abnormal
antioxidants and have effects on the eye and vascular tissues.
amount of lipids in the blood.
In a study of 50 patients with senile cataracts, a combination
of bilberry extract with 25% anthocyanosides and vitamin E
Clinical Studies was given for four months. Taken twice daily, the extract
stopped the progression of cataracts in 96% of the patients
Human data with respect to anthocyanins from bilberry are treated compared to 76% in the control group (Head, 2001).
lacking, however dietary polyphenols present in bilberry fruit Consumption of bilberry extract may also have potential for
have been associated with the prevention and treatment of protection against the development of glaucoma, or damage of
chronic inflammatory diseases, including cardiovascular the optic nerve. Eight patients with glaucoma were given a
disease (CVD). CVD has many risk factors including obesity, dose of 200mg Vaccinium myrtillus anthocyanosides and
diabetes, hypertension, elevated lipid levels, and demonstrated improvement due to bilberry’s collagen-
inflammation, and a novel treatment is therefore necessary. A enhancing and antioxidant properties (Thorne Research Inc,
clinical study on the effect of polyphenols in bilberry juice 2001).
determined that a supplementation with bilberry juice
resulted in significant decreases in plasma concentrations of
C-reactive protein, interleukin, and monokine. Increases in Contraindications
plasma quercetin and p-coumaric acid were also observed in
Bilberry is classified as a Class 1 herb by the American Herbal
the bilberry group. These findings suggest that the
Products Association, and is therefore considered safe when
supplementation with bilberry polyphenols may modulate the
consumed appropriately. It has no reported mutagenic activity
inflammation process (Karlsen et al. 2010, 345).
and there are no cited contraindications to its use (Benzie and
Quercetin, a polyphenolic flavanoid found in bilberry, exhibits Wachtel-Galor, 2011, 56). Dosages as high as 400 mg/kg body
antioxidative, anticarcinogenic, and enzyme-inhibiting weight have been administered to rats without toxicity. Long-
activities. A study by Erlund et al. (2003) aimed to determine term oral administration in humans of doses equivalent to 180
the impact of daily consumption of 100g of berries (black mg/kg anthocyanosides per day for six months produced no
currants, lingonberries, and bilberries) on serum quercetin toxic effects (Thorne Research Inc, 2001).
concentrations in healthy, middle-aged men, and found that in
According to the University of Maryland Medical Center
the berry group, the mean calculated intake of quercetin was
(UMMC), bilberry fruit and extract are generally considered as
significantly higher at the end of the 8 week study compared
safe, and have no known side effects. However, as with any
to the baseline group. Concentrations of quercetin were 32-
substance, bilberry leaf and extract should not be taken in
51% higher in the berry group during the berry consumption
large excessive quantities for extended periods of time, twice daily, preferably with a meal. Bilberry tea, prepared
especially because bilberries contain tannins, which may similarly to most packaged tea bags, is also available and
cause severe weight loss, muscle spasms, and possible death. promoted for vision health and support. Skin Actives
The UMMC also notes that taking bilberry extract may change Scientific, a skin care manufacturer, also markets bilberry for
the way other remedies, medicines, and vitamins work and use as a face and body cream. Standardized for anthocyanins,
operate with one another. Using these products together may which give this extract its color, the extract is said to have
cause harmful effects and lead to dangerous consequences. vasoprotective, anti-inflammatory, antioxidant and healing
The UMMC also acknowledges that the anticoagulant activity.
properties of anthocyanosides in bilberry may increase the
risk of bleeding if taken with blood-thinning medication. The
UMMC also proclaims that because bilberry may lower blood Discussion
sugar, it could have synergistic effects with diabetes Vaccinium myrtillus L. has been used for centuries in northern
medication (UMMC, 2011). Europe as a functional food product as well as in jams,
preserves, and baked goods such as pies and tarts. The use of
bilberry across the northern hemisphere provides strong
evidence for its efficacious medicinal properties. Bilberry is
Currently, bilberry is used in products such as OptiBerry, a one of the richest natural sources of anthocyanins, which are
multiple-berry extract formulated for whole body antioxidant responsible for bilberry’s high antioxidant content, anti-
support. Its suggested uses include enhanced antioxidant inflammatory, antimicrobial, and lipid-lowering effects, and
protection, cardiovascular support, skin support, healthy for the promotion of vision health and improvement.
cellular function, and healthy cognitive function. The Therefore, bilberry has high potential in the treatment and
recommended dose for the 50 mg capsules is 1-2 capsules per prevention of conditions associated with diabetes,
day, taken with a meal (Pure Encapsulations, 2011). OptiBerry hyperglycemia, cardiovascular disease, inflammation, cancer,
has been demonstrated as being safer and more potent and eye conditions. However, human data with respect to
compared to the extracts of the individual berries used in the anthocyanins from bilberry are lacking. The antioxidant
OptiBerry blend. OptiBerry also demonstrated superior effects of the anthocyanins present in bilberries give incentive
bioavailability, antioxidative, antiangiogenic, antibacterial, for further clinical studies that aim to explore the additional
anti-inflammatory, and antiatherosclerotic properties (Zafra- health benefits from bilberry’s antioxidant properties. The
Stone et al. 2007, 675). vasodilatory and anti-inflammatory effects of bilberry may
Bilberry leaf and berry is also sold as a liquid extract and as also provide further therapies for age-related degenerative
vitamin supplement for its antioxidant and vision-improving diseases. Due to its many biological activities, bilberry should
effects. Among many other supplement producers, Puritan’s be regarded as a functional food whose constituents hold the
Pride sells bilberry as a supplement claiming to contain 1,000 potential to provide therapies for a number of conditions
mg bilberry extract. They suggest taking one soft gel once or whose current treatments are limited. More research on
bilberry and its constituents is necessary in order to fully pneumoniae Binding to Human Bronchial Cells.”
recognize and benefit from the medicinal properties of the Phytotherapy Research 25:122-127. doi: 10.1002/ptr.3240.
bilberry plant. Karlsen, Anette, Ingvlid Paur, Siv K. Bohn, Amrit K. Sakhi, George I.
Borge, Mauro Serafini, Iris Erlund, Petter Laake, Serena
Tonstad, and Rune Blomhoff. 2010. “Bilberry juice
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Zingiber officinale Roscoe, Zingiberaceae
Sarah Mosby
Introduction
Zingiber officinale Roscoe, of the Zingiberaceae family, has
played an integral part in human history, culture, and
medicine, and it remains the most widely cultivated spice
(Ravindran 2005, 7). The knotted rhizome (Zingiberis
rhizoma) of the plant is commonly as ginger or ginger “root,
though the latter is a misnomer. Ginger has been used in
traditional healing remedies believed to affect nearly every
human body system, and many of its medicinal uses have been
verified as effective by in vitro, in vivo, and clinical studies. The
use of ginger in complementary and alternative medicine
(CAM) is growing and today includes use as a carminative,
anti-emetic, anti-inflammation agent, and analgesic. It shows
promise in biomedicine in treatments of arthritis, nausea and
vomiting, and cancer.
Zingiber officinale belongs to the tropical/sub-tropical family
Zingiberaceae and the order Zingiberales. The specific origin Figure 1. The oblong flower of Z. officinale.
of Z. officinale species is unknown, but it is most likely to have (Source: http://www.types-of-flowers.org/pictures/ginger_flower.jpeg)
origins in tropical or sub-tropical India. Variants of the species
are dependent on the environment and Z. officinale var. from the stem are smooth, pale green, lanceolate leaves that
cholmondeleyi F. M. Bailey, Z. officinale var. macrorhizonum can grow to 5-30 cm long, 8-20 cm wide, and up to 2 cm thick.
Makino, Z. officinale var. rubens Makino, Z. officinale var. A few shorter stems bear an ovate-oblong spiked flower: a
rubrum Theilade, and Z. officinale var. sichuanense Z. Y. Zhu et purple anterior petaloid divided into three rounded lobes
al. (Tropicos 2011). surrounds a tufted stigma and a fruit capsule with small
arillate seeds (Figure 1). These branches extend horizontally
Z. officinale is a perennial herb, making it useful as an aesthetic
from the stem of the plant, which projects vertically from the
plant, and can attain a stem length of 1.5 m. Branching out
rhizome (WHO 2011).
Production Production
Country Country
(tons) (tons)
India 380100 Mauritius 616
China 331393 Dominican Republic 600
Indonesia 192500 Jamaica 459
Nepal 174268 Guyana 424
Thailand 170125 Kenya 245
Nigeria 152106 Dominica 169
Bangladesh 72608 Trinidad and Tobago 145
Japan 52000 Uganda 144
Philippines 27415 Reunion 107
Cameroon 12000 Puerto Rico 100
Malaysia 11200 Pakistan 94
Sri Lanka 10780 Ghana 81
Cote d'Ivoire 7680 Madagascar 29
Ethiopia 6834 Saint Lucia 14
United Republic of
Bhutan 3766 Tanzania 10
Fiji 3041 Africa 179852
Figure 2. The knotted rhizome known as ginger is used in Republic of Korea 3000 Americas 3832
food and medicine around the world. (Source: precision Costa Rica 1105 Asia 1429249
nutrition.com) USA 816 World 1615974
The dried rhizome of Z. officinale is scientifically referred to as Table 1. World production of ginger. India remains the
Zingiberis rhizoma (Figure 2). The subterranean rhizomes earliest and largest producer of ginger (Source: FAO Statistics
are thickly lobed and tuberous with a yellowish-brown to pale Division 2011.)
buff external surface with few scales. When the skin is peeled,
the aromatic rhizomes show fine longitudinal striations in the The rhizomes are harvested in stages dependent on their
pale yellow to white-colored flesh (Pakrashi 2003, 16-18). intended use. “Green ginger” is harvested before five months
have passes since sowing, and “dry ginger” is harvested
The optimal conditions for cultivation of ginger include an between 7-8 months after planting. Green ginger is used more
elevation of 300-900m and at least 1.98 meter of rainfall per often as a preservative, whereas dry ginger is more common
year (Pakrashi 2003, 6). Today, ginger is cultivated in Asia, in food preparation; both are commercially distributed
Africa, the Americas and Oceania. Propagated by planting of (Pakrashi 2003, 8-10).
rootstalk cutting, cultivation of ginger ideally begins in April.
Though native to Asia, ginger is commercially grown and and Romans considered it a favorite spice, second to black
harvested in 34 countries spanning four continents. The pepper (Pakrashi 2003, 2).
majority of production and world trade still occurs in the
Ginger is mentioned in the Koran, although not in the
Asian countries of India, China, Indonesia, Nepal, and
Christian Bible, and has long been incorporated into folklore,
Thailand, but Nigeria and Cameroon maintain significant
indicating its historical culinary and medicinal importance.
levels of production as well. Table 1 shows the most recent
Westerners are most likely familiar with the story of the
statistics of world production. India was the earliest producer
Gingerbread man, a common child’s folktale. Gingerbread
of ginger and remains the largest producer today contributing
became popular in Europe under Henry VIII’s
to 30-40% of the world’s production. India exports both dried
recommendation to consume ginger in preventive measures
rhizomes and extracted ginger oil, but only 10-15% of ginger
against the plague. In eastern Africa, ginger is associated with
produced in India is exported. China is the largest consumer of
auspiciousness and is essential to the Savaras tribe for
ginger, and contributes significantly to world ginger
religious and marital ceremonies (Pakrashi 2003, 2;
production (Ravindran 2005, 9-10). Like other species of the
Ravindran 2005, 4). Another interesting example of ginger in
Zingiberaceae family–turmeric and cardamom–, ginger has a
culture is the Chinese Red Egg and Ginger party. It is
long history of consumption as a spice and food additive as
traditional for parents or grandparents to welcome a newborn
well as a medicinal role.
into the world with a celebration, and these celebrations often
include “announcement packages” of red-dyed hard-boiled
Traditional Uses eggs and ginger root. This tradition is carried out today often
with banquets or, in America, buffet-style lunches, when the
Ginger has been used by humans since antiquity, and it baby is around one-hundred days old (Gong 2005, 164).
remains the world’s most widely cultivated spice. In its
country of origin, ginger’s use is prehistoric. It was renowned
as mahabheshaj, mahaoushadi, meaning “the great cure, the Culinary
great medicine,” and was one of the most essential
The use of ginger as a cooking spice or condiment dates back
components of household folk medicines. Ginger’s use in
4,400 years to Asia, and it remains an integral part of Asian
China dates back to at least 500 BC, as recorded by Confucius.
culinary use today. It has a distinctive, hot, pungent aroma and
The trade of ginger began with maritime circulation
flavor that is essential to many modern and traditional Asian
throughout India, China and Indochina, and by the 8th century
cuisines such as curry and chutney. The spice and flavor of
AD, ginger was commonly traded throughout the
ginger can be elicited from fresh or dried ginger root; the
Mediterranean. In second century Rome, ginger was one of the
fleshy rhizome is first washed and peeled, then sliced, grated,
few items on which was imposed an import levy at Alexandria,
or cooked whole. Ginger pickled in sweet vinegar is a common
evidence of its extensive trade (Ravindran 2005, 2-5). It was
palette-cleanser in Asia, accompanying meals such as sushi,
well known in Europe by the 11th century, where the Greeks
while crystallized or preserved ginger is consumed as a
confection. Ground ginger is a convenient kitchen spice that is hypothermia (Gogte 2000). Ginger’s balancing action against
available in most commercial grocery markets. “cold” is appropriate for its characteristically “hot” aroma and
Ginger was one of the first spices of the orient to arrive in the flavor; and it is advised not to use ginger in the summer and
West through trade. In Western food and culture, ginger is autumn seasons.
well-known as the spice of gingerbread, ginger beer, and Internally, ginger is believed to act upon the nervous system
ginger ale. The origins of gingerbread may date back to the as a nerve-stimulant to improve impulse transmission and
ancient Greeks, who wrapped ginger in bread and consumed it relieve pain. Prepared with castor oil, ginger powder is useful
after meals as a digestive aid (O’Hara 1998, 530). The spice is against rheumatoid arthritis. The stimulating and anti-
also incorporated into biscuits, cakes, puddings, soups, and inflammatory action extends to the heart and circulatory
pickles (Ravindran 2005, 12). system, where it also acts as a blood-purifier. Consumption of
ginger prepared with honey is an Ayurvedic remedy for
asthmatic bronchitis, hiccups, coughs, and respiratory colds.
Medicinal In the reproductive system, ginger acts as an aphrodisiac and
Many Zingiberaceous plants play a role in traditional sex stimulant. Most importantly, however, are ginger’s uses in
medicine, especially in Asian medical systems such as the digestive system. Ginger improves appetite and digestion
Ayurvedic and Traditional Chinese Medicine. Across medical and is antiflatulent, antihaemorrhoidal, and antispasmodic. It
systems, ginger has been used medically as a carminative and is also used to treat anorexia, nausea, vomiting, abdominal
a stimulant in the digestive tract (Tuntiwachwuttikul 1986, pain, jaundice, and piles (Gogte 2000).
191). The medicinal use of ginger dates back 2,500 years to
ancient Chinese and Indian civilizations for treatments of
many ailments including nausea, rheumatism, and headaches. Traditional Chinese Medicine (TCM)
The use of ginger in TCM is comparable to that of Ayurveda.
Ginger has traditionally been thought of as ‘hot’ and ‘spicy,’
Ayurveda both of which can treat coldness and weakness by mobilizing
In Ayurvedic medicine, Zingiber officinale is referred to by the body’s reserves of qi. The Chinese distinguish between
many Sanskrit names, most notably by Ardrak. Ardrak relieves fresh, roasted, and dried ginger, attributing each with different
the three dosha (energies of health), vatakapha and pitta, and healing properties. Fresh ginger is regarded as “mildly warm”,
thus can help maintain balance of dosha in multiple systems of dried ginger “warm,” and roasted ginger “hot.” All forms of
the body (Garodia et al. 2007, 2). Uses of Ardrak in Ayurvedic ginger, however, have an “opening up” or “loosening” effect,
medicine are numerous and include external application as enhancing the body’s ability to integrate external stimuli. This
well as ingestion. Externally, ginger can be prepared as a paste assimilating property pertains to effects of certain foods and
with milk or water to reduce infantile cold and swelling. The relates to ginger’s perceived power in the digestive system
ginger powder and oil are also used in massage therapy to (Pokert and Ullmann 1988, 218). Ginger is generally included
alleviate chills, cold and stiffness, excessive swelling and in prescriptions for digestive ailments, appetite disorders, and
queasiness, and is useful in TCM because many of the The most medicinally active chemicals present in ginger
remedies involve absorption through the GI tract. In addition, rhizomes are components of the volatile oil and non-volatile
Chinese meals are extremely rich and are eaten late in the pungent principles (gingerols and shogaols). Other
evening, thus the incorporation of ginger may be important in components include fats, waxes, carbohydrates, vitamins such
aiding digestion. as Nicacin and Vitamin A, minerals, and zingibain, a
proteolytic enzyme (Shukla and Singh 2006, 684; Murray
2004, 134).
Western Medicine
Like ancient Asian peoples, Europeans took notice of ginger’s
activity on the digestive system (Alcock 2006). The laxative Volatile Oil
properties are described by the first century physician scholar There are over 50 components of ginger’s volatile essential oil,
Dioscorides, writer of De Materia Medica (Alcock 2006). which is present in amounts of 1-3% and is responsible for the
Ginger is also described by author Charles Lamb to “make aroma of fresh ginger (Dewick 2009, 168). Most of the
[millet] go down the more glibly” in his 18th-century works components are monoterpenoids [β-phellandrene, (+)-
(Lamb 1994, 351). Henry VIII recommended the use of ginger camphene, cineole, geraniol, curcumene, citral, terpineol,
in curing or preventing the plague, as by 1416, preserved borneol] and sesquiterpenoids [α-zingiberene (30–70%), β-
ginger was a common import from China (Ravindran 2005, sesquiphellandrene (15–20%), β-bisabolene (10–15%), (E-E)-
279). α-farnesene, ar-curcumene, zingiberol] (Ali et al. 2008, 410).
Chemistry and Pharmacology Pungent Compounds

The wealth and variety of chemicals present in rhizomes of The non-volatile pungent principles are responsible for the
Zingiber officinale are responsible for ginger’s taste, aroma, hot taste sensation of ginger. These include the biologically
and healing properties. Specific constituents of ginger extracts active chemicals gingerols, shogaols, paradols, gingerdiols,
are dependent upon the origin of the variant and the condition and gingerones as well as derivatives.
of the rhizomes (fresh or dried). According to a phytochemical
review of ginger, 63 compounds have been identified in fresh
ginger compared to 115 compounds identified in dry ginger, Gingerols
and 45 of these compounds are shared by fresh and dry The pungent taste of fresh ginger rhizomes is mainly due to
ginger. The compounds responsible for the pungency of fresh the presence of homologous, phenolic ketones called gingerols
ginger, gingerols, become the dehydrated shogaols (Figure 3). The gingerols are differentiated by the number of
responsible for the pungency of dried ginger (Ali et al. 2008, carbons in their C-5 side chains (Jolad et al. 2004). The
410). compound [6]-gingerol is the most abundant at portions of 28-
34%, followed by [10]-gingerol and [8]-gingerol. Gingerols
Figure 3. [6]-gingerol is the main pungent principle of Figure 4. [6]-shogaol is the main pungent principle of
fresh ginger. (Source: http://www.dalton.com/images/prod/23513- dried ginger, it is the product of dehydration of [6]-
14-6.jpg) gingerol. (Source: http://upload.wikimedia.org/wikipedia/commons
/thumb/0/05/Shogaol.png/300px-Shogaol.png)
degrade into shogaols or paradols under pH-specific
conditions (for shogaols: when pH is between 2.5 and 7.2) powders and extracts, another source of conflicting results
upon the addition of heat. Studies on isolations of [6]-gingerol could lie in the doses administered, the treatment duration,
have suggested antipyretic, antioxidant, and anti- and the quality of the ginger products. As a result,
inflammatory effects (Young et al. 2005, 207). standardization of ginger products is essential in researching
its medicinal effects (Schwertner et al. 2006).
Shogaols
Shogaols (Figure 4) are the products of dehydration of Anti-inflammatory and anti-pyretic
gingerols and are thus found in the dried rhizomes of Zingiber Anti-inflammatory action has been demonstrated in vitro and
officinale and in non-fresh ginger powder. These compounds in vivo since the 1980s. Anti-inflammatory and soothing action
are analogous to gingerols and contribute to the pungency of from gingerols and shogaols may be the result of dual
dried ginger. The structural difference from gingerols is ta inhibition of both cyclooxygenase and lipooxygenase
double bond between C-4/C-5 and the absence of the pathways that are involved in inflammatory processes (Yip
hydroxide on the C-5 carbon (Jolad et al. 2004). and Tam 2008, 137; Jolad et al. 2004, 1937). Specific
constituents such as gingerdiones and shogaols have
properties mimicking dual-acting non-steroidal anti-
Biological Activity inflammatory drugs in vitro, and the principle pungent
Results of in vitro and in vivo studies on ginger root extract ketones [6]-gingerol, [6]-pearadol, and zerumbone have been
are often contradictory. One possible reason for discrepancies shown to have strong anti-inflammatory activity (Shukla and
is the variability in chemical composition of the studied Singh 2007, 687). In vivo, anti-inflammatory and analgesic
ginger, as it is dependent on whether the rhizome is fresh or activity of [6]-gingerol was shown by significantly reduced
dried. Besides the differences in composition of the ginger writing of animals (Young 2005, 208, Chrubasik 2005, 691).
Other demonstrations of anti-inflammatory action include Anti-fungal
ginger’s action against cytokines secreted at inflammation
Of three plant extracts (ginger, onion, and garlic), an ethanolic
sites, ginger’s modulation of some pathways activated in
extraction of ginger was found to be the most effective in
chronic inflammation, and ginger extract’s suppression of pro-
inhibiting fungal growth (Tagoe et al. 2011, 286). The isolated
inflammatory cytokines and chemokine expression (Ali et al.
compound gingerenone A exhibited complete inhibition of
2008, 413-414).
hyphae invation of Pyricularia oryzae and moderate inhibition
Ginger plant extract has also been found to reduce swelling in of Eimeria tenella at concentrations of 10 ppm (Endo et al
a nearly identical fashion to aspirin. In a study of rats, dosages 1989, 798). Ginger oil and oleoresin show moderate to good
of 50 mg/kg of ginger extract reduced swelling in rats’ paws inhibition of fungal growth in both food poison and inverted
by 22%, while an equal dose of acetylsalicylic acid reduced petri plate methods (Singh et al 2008, 3301). An antifungal
swelling by 23% (Mascolo et al. 1989). This study also protein was also identified from ginger extract, showing
demonstrated that anti-pyretic effects of ginger extract are strong antifungal activity similar to the potency of Asparagus
similar to the effects of equal dosages of acetylsalicylic acid. officinalis seeds (Wang et al. 2005, 103).
Anti-emetic Anti-bacterial
Both in vivo and in vitro studies suggest that ginger is an Ginger extract has been shown to inhibit both Gram-positive
effective treatment for nausea and vomiting. The mechanism and Gram-negative bacteria growth (Mascolo et al. 1989; Gao
of action for the carminative and anti-emetic effects has not et al. 2010, 43). Essential oil and oleoresins of ginger exhibit
been identified. However, it has been suggested that [6]- inhibitory effects towards bacterial growth comparable to
gingerol may enhance gastrointestinal transport; that other streptomycin and chloramphenicol. Oleoresins were shown to
ginger compounds have anti-hydroxytryptamine activity in be less effective than the essential oil. This activity is most
vivo; that galanolactone, a constituent of ginger, is a likely due to the phenolic compounds of the oil and oleoresin,
competitive antagonist at ileal 5-HT3 receptors; or that ginger and it is likely that the efficacy is synergistic of many of these
affects emesis through the central nervous system (Ernst and phenolic constituents of ginger (eugenol, shogaols, zingerone,
Pittler 2000, 368). Current antiemetics act as ilieal 5-HT3 gingerdiols, gingerols) (Singh et al. 2008, 3300).
receptor antagonists. In vivo, ginger juice inhibited cisplatin
In one recent study, freeze-dried ginger was observed to have
(an anticancer drug) -induced emesis in rats and in dogs
a significant effect on the relative radiation sensitivity of pork
(Sharma 1998, 54; Sharma 1997, 95).
inoculated with Escherichia coli, providing supportive
evidence of antibacterial properties of ginger (Yun et al.
Hypoglycaemic 2011). In a comparison of onion juice and ginger juice,
however, ginger juice was found not to be effective against
Mascolo et al. found ginger extract to exhibit potential multi-drug resistant bacteria (Adeshina et al. 2011, 293).
hypoglycaemic activity in vivo (Mascolo et al. 1989).
Antioxidant that 1 g of ginger powder daily alleviated clinical nausea of
The antioxidant activity of ginger has been demonstrated in diverse causes such as pregnancy-induced nausea, drug-
many in vitro and in vivo studies, and this activity may explain induced nausea, and motion sickness (Ernst and Pittler 2000,
the protective actions of ginger against toxicity and radiation 368). Ginger has been shown to be more effective in reducing
(Ali et al. 2008, 416). Bioactive components of ginger extract severity of nausea in pregnant women than vitamin B6 or
such as [6]-gingerol, zingerone, and dehydrozingerone have placebo (Ensiyeh 2009; Ozgoli et al. 2009, 245).
been shown to have potent antioxidant and tyrosinase
inhibition activities, and zingerone may act as a scavenger of
Rheumatism
superoxide anions (Chrubasik 2005, 689; Shukla and Singh
2006, 686). Relief from rheumatism from ginger was shown to be
comparable to that from ibuprofen (Haghighi et al. 2005). In
osteoarthritis patients, reduction in knee pain on standing was
Cancer preventative effects superior for those taking ginger extract than placebo (Altman
Cancer preventative effects of ginger have been found in and Marcussen 2001).
studies relating to skin, gastrointestinal, colon, and breast
cancer. Alcoholic extracts of ginger have been found to be
Contraindications
cytotoxic to certain tumor cells in vitro. Both [6]-gingerol and
[6]-paradol showed suppressive effects on proliferation of Ginger root extract is generally recognized as safe (GRAS) by
human cancer cells through the induction of apoptosis. the FDA, but pregnant women are discouraged from use due
Another chemical constituent, zerumbone, inhibits activation to lack of relevant research. Some adverse effects have been
of NK-κB-regulated gene expression that is induced by reported by a study of pregnant rats including elevated birth
carcinogens. In vivo, ginger and specifically [6]-gingerol were rate of the fetal rat (Ali et al. 2004). However, the overall low
shown to suppress promotion of skin carcinogenesis in toxicity of ginger and its chemical constituents have been
laboratory mice. Animals treated with ginger extract also confirmed by multiple studies (Weidner et al. 2000, Chang et
showed significantly lower tumor body burdens compared to al. 1995, Ali et al. 2004). Minor adverse effects observed in
controls (Shukla and Singh 2006, 686-688). The essential oil research include heartburn, mild diarrhea, and IGE-mediated
of ginger also showed antitumor activity (Chrubasik 2005, allergy (Ali et al. 2004). Dangerously toxic effects have only
689). been observed in extremely or unnaturally high dosages.
The potential interaction of ginger root extract with warfarin
has been studied due to conflicting evidence of blood-thinning
Clinical Studies
properties of gingerols, but no evidence suggests a significant
Nausea and Vomiting effect of ginger on warfarin. Ginger root extract does have a
In a review of the antiemetic effects of ginger, it was reported synergistic interaction similar to aspirin with nifedipine on
anti-platelet aggregation (Ali et al. 2008).
Current Use in Allopathic and CAM Therapies Discussion
Ginger extracts are commercially available around the world The use of ginger for multiple millennia serves as support to
from multiple distributors in the form of capsules. However, its efficacy and pertinence in human health. Because of
the standardization of ginger root extract remains an unsolved ginger’s low cost and low toxicity, there are few, if any,
problem. In a study of ten ginger dietary supplements, only deterrents to pursuing research on the chemical components
five manufacturers listed a dosage recommendation. Of the of ginger and their roles in both biomedicine and CAM.
recommendations, the serving size varied widely. Listing of Because ginger is not found growing wild, as long as
expiration dates, ingredients, or methods of standardizations cultivation promotes biological variation, there is little danger
were not consistently present from all manufacturers. Finally, in continuing the large-scale cultivation and harvesting of
the composition of the ginger supplements was varied ginger. The variability of the chemical makeup of ginger so
significantly (Schwertner et al. 2006). These results expose a dependent on its preparation is a prime example of a research
problem characteristic not only to ginger supplements but area for ethnobotanists. Ethnobotanical approaches could
also to much of the natural product market. The verification of potentially expose different methods of preparing and storing
the chemical constituents of ginger extracts is especially the rhizome and their applications to different treatments.
important due to the variability of chemical composition
Especially of clinical interest is the role of ginger extract in
based on preparation methods.
cancer treatments. Because of the anti-emetic properties,
Ginger is also used medicinally as a tea, where the fresh or ginger would be useful in relieving nausea induced by
dried rhizome is chopped and steeped in water. Ginger tea and chemotherapy. Simultaneously, the antioxidant activity of
ginger capsules are the most used natural product by ginger extract undoubtedly plays a role in reducing the
pregnant women suffering from nausea, vomiting, and oxidative stress that may accelerate tumor growth. Further
“morning sickness” symptoms (Hollyer 2002). Most women in research is necessary in this field as some studies have found
this study who did not use CAM to alleviate nausea and conflicting evidence into carcinogenic properties of ginger’s
vomiting reasoned that they wished to know more about the chemical constituents. Ginger also shows promising results in
safety of ginger extract and other natural products. The safety clinical studies with osteoarthritis, and there is substantial
of medicinal use of ginger in pregnant women has yet to be support for ginger’s effectiveness as an antiemetic for diverse
intensively studied. causes.
Massage therapists and aromatherapists take advantage of the Until ginger rhizome extracts are standardized for maximum
healing properties of ginger essential oil. Few of the ginger effectiveness, the biomedical future of ginger extract seems to
remedies using used in these manners have been clinically be more promising than ginger’s use as a natural product. For
evaluated for safety in efficacy, though their uses are one, the healing properties of gingerols are not found in ginger
extensive. In one study, however, both ginger essential oil and powder unless it is a fresh ginger preparation, therefore the
ginger powder were shown to relieve pain when used in use of dried ginger or ground ginger in the kitchen is not likely
massage therapy (Yip and Tam 2008, 137). to provide benefits in consumption. As ethnobotany becomes
more closely tied to biomedical and pharmacological research, Chaiyakunapruk, N., Nantawarn Kitikannakorn, Surakit Nathisuwan,
Zingiber officinale will remain a prime investigational target. Kittiboon Leeprakobboon, and Chutchai Leelasettagool
(2006). "The efficacy of ginger for the prevention of
postoperative nausea and vomiting: A meta-analysis."
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Edited

by: Cassandra L. Quave, Ph.D.

Preface Echinacea purpurea (L.) Moench, Asteraceae

Anderson, Sam Hampton, Aerhealle Morris, Alisha

Absinthe Elderberry Ojé

EXPLANATION OF MONOGRAPH SECTIONS Traditional Uses

Discussion Srinivasan, D., S. Nathan, T. Suresh, and P.L. Permalsamy. 2001.

English Herbarium (950 AD), Bald’s Leechbook (900-1000 AD),

Current Use in Allopathic and CAM Therapies

Figure 4. Structure of bromelain. This illustrates the Biological Activity

Biological Activity Hepatoprotective effect

Protection against lead poisoning

Stalks and stems

Traditional Uses Figure 2. A. uva-ursi fruits. (Source: http://calphotos.berkeley.edu

Current Use in Allopathic and CAM therapies

Figure 1. Structure of allyl isothiocyanate (top) and Biological Activity

branches while the false leaves, termed cladolia, are actually

In vitro 3 (25R/S)-furostane-3β,22,26-triol-3-O-[α-L- 25.5

3-O-[a-L-rhamnopyranosyl (1- Antitumor Activity

Current Use in Allopathic and CAM Therapies

typically grows and matures rapidly during the spring and

(Dobkin de Rios, 1971; Flores & Lewis, 1978; Kjellgren et al.,

rather she perceived but mild pseudohalucinations. Finally,

wrongdoing. The natives also mentioned that, while under the

Current Uses in Allopathic and CAM Therapies

Botanical Description Traditional Uses

Portugal As an alternative to saffron, C.officinalis is occasionally used in

Inflammation was also induced by LPS after 5 days of

Immortalized, non-cancerous human breast epithelial

Figure 6. CBD is a major cannabinoid found in the plant.

promote health by preventing and mitigating damage caused

Chemistry and Pharmacology

Current Use in Allopathic and CAM Therapies

Figure 1. The Cinnamomum verum tree.

7.5-20 cm wide and have more shine on the top than

Chemistry and Pharmacology

Caffeine and Asthma

C. nitida can be found in hot and humid climates located in

marriage proposal (returning a white kola means yes while a

Elastase Reduction Activity

Antimicrobial Ocular Activity

Cardiovascular and CNS Activity Clinical Studies

Current Use in Allopathic and CAM Therapies

Biological Activity writhes (completely rescued by naxolone and morphine) and

Introduction antioxidant (Gupta, 2008). Some common names of this

2003). The sap is also used to treat tuberculosis and bone

Chemistry and Pharmacology respectively. And Korberins A and B at administered amounts

Leaf O-Coumaric Acid, Protocatechuic Acid, Syringic Acid, Vanillic Acid

Table 2. The amount of dose recommended for adults

Figure 2. Digitalis purpurea (Purple foxglove). Traditional Uses

traditional foxglove teas were made by boiling D. purpurea

order to bear fruit. Only female trees with solitary, flowers

Introduction Photograph by Rhonda Stewart. http://www.fs.fed.us/wildflowers

Plant Part Active Constituents

Current Use in Allopathic & CAM Therapies

Figure 2. The structure of ephedrine. (Source:

(by untrained eyes) with species Ficus crassiuscula Warb. One

Current Use in Allopathic and CAM Therapies

References Cited Malthouse P, Brocklehurst K. (1976) “Preparation of fully active

Carboxylic acids Phenolic and non-phenolc 13