Opuntia Dillenii A Forgotten Plant With Promising Pharmacological Properties

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ISSN 2093-6966 [Print], ISSN 2234-6856 [Online]

Journal of Pharmacopuncture 2019;22[1]:016-027


DOI: https://doi.org/10.3831/KPI.2019.22.002
Review article

Opuntia dillenii: A Forgotten Plant with Promising


Pharmacological Properties

Reza Shirazinia1†, Vafa Baradaran Rahimi2,3†, Ashrafali Rezaie Kehkhaie1,


Amirhossein Sahebkar4, Hassan Rakhshandeh2,3, Vahid Reza Askari2,3,4*
1
Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
2
Student Research Committee, Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3
Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
4
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

able properties of medicinal plants may be a good way


Key Words to familiarize researches with a new source of drugs
Opuntia dillenii, anti-oxidant, immuno-modulation, with lower side effects and higher efficacy.
neuro-protection, pharmacological activity, anti-tumor Opuntia dillenii, a well-known member of the Cac-
taceae family, is used as a medicinal plant in various
countries and grows in the desert, semi-desert, tropi-
List of abbreviation cal and sub-tropical areas. It shows diverse pharmaco-
ALT: Alanine transaminase logical activities such as: antioxidant, anti-inflamma-
AST: Aspartate transaminase tory, anti-tumor, neuroprotective, hepatoprotective,
DDPH: 2,2-diphenyl-1-picrylhydrazyl hypotensive etc. OD fruit also possesses valuable
GR: glucocorticoid receptor constitutes for instance: betalains, ascorbic acid, total
GSH: Glutathione phenol, protein as well as essential elements which
GSH-PX: Glutathione peroxidase suggest the significant potential of this plant as a com-
GST: Glutathione S-transferases plementary therapy against several pathological con-
Ip: intraperitoneal ditions. This review describes experimental evidence
MDA: Malondialdehyde about pharmacological and therapeutic potential of
Opuntia dillenii (OD) OD in order to give the basis of its application in the
ODT: OD tablet prevention and treatment of some chronic diseases.
RSM: Response surface methodology More studies on OD can help better understanding of
its pharmacological mechanism of action to explain its
traditional uses and to identify its potential new thera-
Abstract peutic applications.
Generative and vegetative parts of the cactuses have
had a long-lasting position in folk medicine and their 1. Introduction
effects could partly be confirmed in scientific experi-
ments. Nowadays, the cactus, fruits, and cladodes are From ancient times, in search for rescue from diseas-
the focus of many studies because of their desirable es, the people are looking for drugs in natural environ-
properties. Therefore, the summarized reports of valu- ments. The onset of the medicinal plants’ use was in-
stinctive and there was not enough information about
Received: Oct 25, 2018 Reviewed: Nov 06, 2018 Accepted: Feb 11, 2019
the reasons for the illnesses and how plants could be
utilized as a cure [1]. The genesis of iatrochemistry in

This is an Open-Access article distributed under the terms of the Creative Commons *
Corresponding Author
Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) Vahid Reza Askari. Pharmacological Research Center of Medicinal Plants, Mashhad Uni-
which permits unrestricted noncommercial use, distribution, and reproduction in any versity of Medical Sciences, Mashhad, Iran.
medium, provided the original work is properly cited. Tel: +98-513-800-2262 Fax: +98-513-882-8564
E-mail: [email protected], [email protected]
This paper meets the requirements of KS X ISO 9706, ISO 9706-1994 and ANSI/NISO
† The authors had an equal contribution as the first author.
Z39.48-1992 (Permanence of Paper).
ⓒ 2019 Korean Pharmacopuncture Institute http://www.journal.ac
Journal of Pharmacopuncture 2019;22[1]:016-027 http://www.journal.ac 017

the 16th century was the start of using plants as a source about 1 to 1.8 meters [24]. Additionally, OD has very beau-
for treatment and prophylaxis of diseases [2]. Nowadays, tiful flowers with amazing coloration due to betalain and
it is reported that about 2000 medicinal plant groups exist possess important chemicals including betanin, polysac-
throughout the world, each one has its unique clinical val- charide composition of galactose and arabinose, 3-O-me-
ue or chemical compositions [3, 4]. Plants have received thyl quercetin, kaempferide, kaempferol, isorhamnetin,
great attention in developed countries as valuable com- quercetin, beta- sitosterol, 4-ethoxy-6-hydroxymethyl-al-
pounds with acceptable efficacy and safety in treating pha-pyrone, opuntisterol, opuntisteroside, taraxerol, friede-
different diseases. It has been reported that more than 3.3 lin, methyl linoleate, 7-oxositosterol, 6-𝛽-hydroxystigmast-
billion people in the low-population countries use medici- 4-ene-3-one,daucosterol, eucomic acid, methyl eucomate
nal plant on a regular basis [5]. An estimation by the world and also with moisture, protein, brix, acidity, glucose, fruc-
health organization (WHO) showed that about 80% of Af- tose, saccharose and minerals. The species OD, Nagphana,
rican people rely on herbal medicines for the treatment is not much explored while its protective effects have so far
of many diseases [6]. Nowadays many pieces of research been reported including analgesic, anti-inflammatory [9],
have revealed side effects of chemical drugs and this made radical scavenging activity [10] and anti-spermatogenic
many people notice the medicinal plants chemical drugs. effect [11] as well as especially known as an anti-diabetic
Developed side effects even may show up at their right and anti-inflammatory agent from past decades [12, 13].
dose as well as in combination with other drugs. Drugs ad- Regarding the traditional uses, it has been suggested that
verse effects impress about 2 million patients in the Unit- the fruit of OD may be useful as a medication for gonor-
ed States annually and cause an approximately 100,000 rhea, whooping cough and constipation, as well as con-
deaths. In this regard, the exhibition of severe adverse trolling the bile secretion, spasmodic cough and expecto-
effects made US Food and Drug Administration advisory ration. Additionally, leaves of the plant have been applied
panel to ban the popular pain relievers Percocet and Vi- as a medication for the wound and inflammation as well as
codin [7, 8]. In this context, it made researches all around a treatment for ophthalmic disorders [12, 14].
the world to conduct various researches in the topics of On this basis, the aim of the present study is to summarize
medicinal plants among these researches, review studies the valid data on OD and its chemical composition and po-
expressing the value and importance of specific herbal tential pharmacologic properties to have a better insight
products play vital roles. on the position of OD among various medicinal plants and
Opuntia dillenii (OD) a plant form Cactacea growing in its further potential application (Table 1).
dry and desert environments is a great medicinal herb, a
shrub grows in desert and dry conditions with a height of

Table 1 Summarization of pharmacological properties of OD

Pharmacologic effect Model Measurements Evidence


Reduction of edema percent-
carrageenan-induced paw ede-
Anti-inflammation Percentages of edema age based on the dose- related
ma in rats
manner [9].
The most anti-inflammatory
carrageenan-induced paw ede-
Anti-inflammation Percentages of edema effect for the flower extraction at a
ma in rats
dose of 200 mg/kg [48].
arachidonic acid(AA) and 12-O- Reduction of AA and TPA
tetradecanoyl-phorbol- 13-acetate leukotriene B4 (LTB4)- reactive induced ear punch to weigh in a
(TPA) ear edema of mice- phos- oxygen species (ROS)- prostaglan- dose-dependent manner- Attenu-
Anti-inflammation pholipase A2 (PLA2)-induced din E2 (PGE2)-tumor necrosis ation of paw edema and peritoni-
mice paw edema Carrageenan and factor (TNF-α) interleukins (IL-1β tis-reduction of PGE2, LTB4, ROS
glycogen- induced peritonitis in IL- 6) and cytokine levels (TNF-α, IL-1β
rodents IL -6) [26].
Intraserous hemolysin IgM,
IgG levels- the proliferation of
OD can potentially enhance
Murine immunosuppressed by splenocytes - the proportion of T
the specific immune function of
Immunomodulatory effect intraperitoneal injection of cyclo- lymphocyte subsets in peripheral
immunosuppressed mice and the
phosphamide (Cy, ip). blood- main component purified
proliferation of lymphocytes [86].
from OD polysaccharides on the
lymphocytes in vitro
IC50 for scavenging activity on
DPPH free radical scavenging DPPH free radical was decreasing
Antioxidant DHPP assay
activity by the increment of OD extract
purity [54].
DPPH radical scavenging activi-
ties of the 3,4-dihydroxy substitut-
DPPH free radical scavenging ed flavonoids (such as quercetin)
Antioxidant DHPP assay
activity were stronger than those of the
4-hydroxyl substitutes (such as
kaempferol) [56].
2–4 month-old OD had higher
antioxidant activity than 5–10
DPPH test, hydroxyl radicals, and DPPH, hydroxyl and superoxide
Antioxidant month-old OD and a fraction
superoxide radical in vitro radicals scavenging.
isolated from OD (ODP-Ia) was
superior to 5-10 month OD [57].
018 http://www.journal.ac Journal of Pharmacopuncture 2019;22[1]:016-027

Pharmacologic effect Model Measurements Evidence


The antioxidant activity of ex-
tracts of OD fruit was based in the
On the basis of the ability to Measurement of ABTS+ free
bottom order (crude extract (CE) >
Antioxidant scavenge the ABTS+ radical in vitro radical And Folin-Ciocalteau
purified extract (PE) > red fraction
Folin-Ciocalteau reaction reduction capacity (FCRC)
(RF) > yellow fraction (YF) in con-
cordance with the (FCRC) [31].
The varieties with red-skin fruits
Measurement of the ability of
(O. streptacantha) contained the
antioxidant components in test
most ascorbic acid and the yel-
materials to inhibit the decline
Oxygen radical absorbance low-skinned fruits (Opuntia stricta
Antioxidant in R-PE fluorescence induced by
capacity (ORAC) assay var. stricta) had the most carot-
a peroxyl radical generator R-PE
enoids. Relation of antioxidant
fluorescence that is induced by a
activity to their flavonoid, ascorbic
peroxyl radical generator, AAPH.
acid and carotenoid contents [58].
Trolox equivalent antioxidant ca-
pacity (TEAC) assay as described
by Miller, Rice-Evans, Davies, Higher antioxidant capacity for
TEAC assay - Oxygen-radical
Gopinathan, and Milner [87]-Ox- betacyanin-free seeds of OD than
Antioxidant absorbance capacity assay (ORAC)
ygen- radical absorbance capacity extracts from peel and pulp with
(Clinical trial)
assay (ORAC) assay was based on betacyanins [43].
the report by Cao, Sofic, and Prior
[88] with a slight modification
Cactus polysaccharides (200 mg/
kg) significantly decreased the
neurological deficit score, reduced
Neurological deficit score- in- infarct volume, decreased neu-
farct volume- neuronal loss in the ronal loss in cerebral cortex, and
cerebral cortex- protein synthesis also reduced the protein synthesis
Brain ischemia- reperfusion inju- of inducible nitric oxide synthase- of iNOS- protection of PC12 cells
Neuro-protective ry in rats-the oxidative stress-in- cell viability- H2O2 induced apop- against hydrogen peroxide (H2O2)
duced damage in PC12 cells tosis-both intracellular and total destruction- elevation of cell via-
accumulation of reactive oxygen bility, reduction of H2O2 induced
species (ROS) production- Bax/ apoptosis decrement both intra-
Bcl-2 mRNA ratio cellular and total accumulation
of reactive oxygen species (ROS)
production, upregulation of Bax/
Bcl-2 mRNA ratio[65].
Hypoglycemic effect of this plant
Normoglycemic and alloxan-in- Plasma insulin levels blood
Anti-diabetic effect partly due to reducing intestinal
duced diabetes rabbits glucose levels
absorption of glucose [42].
Observation of symptoms- deter-
mination of FBG, PBG and 24 hrs
urinary sugar - glycosylated he-
moglobin- fasting insulin (FINS),
2 hrs post-meal insulin (PINS)
and glucagons (GC)- sensitivity of
insulin (SI)- Serum B2 micro-glob- Improve the glycometabolism of
46 type 2 diabetes mellitus (DM) ulin (SB2- MG)-urinary B2 micro- DM patients sufficiently and avoid
Anti-diabetic effect
patients (clinical trial) globulin (U-B2-MG)- serum the impairment of renal function
Tamm-Horsfall ( S-THP )- urinary in diabetic neuropathy [83].
Tamm-Horsfall (U- THP)-serum
endothelin (S-ET) and urinary
endothelin (U-ET)- micro-al-
bumin (MA)-α micro-globulin
(α-MG)- transferrin (TRF) - IgG
and plasma NO
Body weight gain%- blood glu-
cose concentration liver glycogen
Administration of OD juice to
content- lipid peroxide (MDA)
diabetic rats significantly improve
level- total cholesterol (TC),
Streptozotocin (STZ)- induced lipid profile and body weight gain
Anti-diabetic effect triacylglycerols (TAG), low-density
diabetes in rats %, it also significantly reduced
lipoprotein cholesterol (LDL-C)
MDA levels and blood glucose
and very low-density lipoprotein
[84].
cholesterol (VLDL-C) high-density
lipoprotein cholesterol (HDL-C)
The results show that OD Haw.
Streptozotocin (STZ)- induced
Anti-diabetic effect Blood glucose polysaccharides have hypoglyce-
diabetes in mice
mic activity [89].
The increment of the reaction
time of rats from the dose 100
Hotplate and writhing test in rat Number of writhing movements
Analgesic mg/kg and reduction of writhing
and mice and Reaction time
movements in a dose- dependent
manner [9].
Definite analgesic action at a dose
Analgesic Electric current test in rats Volts needed as a noxious stimuli
of 200 mg/kg of flower extract [48].
Journal of Pharmacopuncture 2019;22[1]:016-027 http://www.journal.ac 019

Pharmacologic effect Model Measurements Evidence

Prevention of SK-MES-1 cells


growth and induction of S phase
arrest. Cactus polysaccharides
cause apoptosis in SK-MES-1 cells
Cell proliferation assay- Mor-
determined by Annexin-V assay.
Lung squamous carcinoma cells phology test- Cell cycle and apop-
Anti-tumor effect cactus polysaccharides induced
(sk- mes-1) tosis analysis- Western- blotting
growth arrest and apoptosis may
analysis- Annexin-V assay
be due to the increase of P53 and
phosphatase and tensin homolog
deleted on chromosome ten
(PTEN) protein [90].

Mean Arterial Blood Pressure


(MABP)- Toxicology of extract Administration of methanolic
indicated by the change in the extract of OD and opuntioside-1
physical behavior or motor activity showed a decrease in the MABP
Sprague–Dawley rats - NMRI
Hypotensive activity of animals and appearance of of rats by three different routes
mice
the animal- Tissue Analysis and (intravenous, intraperitoneal, and
Histopathology- Serum Choles- oral) of administration is signifi-
terol, Glucose, Bilirubin, and Total cant [76].
Protein Levels

Among the various microorgan-


isms, the aqueous methanolic
extract was more active against
Micrococcus leuteum, Proteus
Determine the growth inhibition
mirabilis. In the antifungal activity
Plate hole diffusion- Agar well of bacteria- Anti-tubercular assay
of the aqueous methanolic extract
diffusion- Saubouraud dextrose using Microplate Alamar Blue As-
In-Vitro antimicrobial shows positive results for all fun-
agar medium (SDA)- cup plate say (MABA) with the suspension
gus. The antitubercular activities
method of Mycobacterium tuberculosis
were compared with standard
H37Rv strain
drug Rifampicin. The aqueous
methanolic extract was having
more percentage inhibition when
compared to other extracts [91].

antimicrobial activities of fungi


isolated from surface of OD eval-
uated against three Gram-positive Eight endophytic fungi obtained
bacteria, Bacillus subtilis (UBC from OD surface and all except
344), Staphylococcus aureus ESIMS and NMR spectroscopic. one exhibited antibacterial activi-
In-Vitro antimicrobial (ATCC 43300) and MRSA (ATCC minimum inhibitory concentra- ties against at least one of the test
33591), two Gram- negative tions (MICs) bacteria. All extracts were inactive
bacteria, E. coli (UBC 8161), P. against C. albicans. The most bio-
aeruginosa (ATCC 27853) and the active fungus was Fusarium sp. [79]
pathogenic fungus C. albicans
(ATCC 90028).

Extracts from the dried stem of


Bacillus subtilis and Staphylo-
Opuntia evaluated for antimi-
coccus aureus were susceptible
crobial activities against Bacillus
to all extracts of Opuntia dillenii.
subtilis, Staphylococcus aureus, An agar–well diffusion method
Ether and chloroform extracts of
In-Vitro antimicrobial Escherichia coli, and Salmonella was used to determinate the anti-
O.dilleniiexhibited antimicrobial
typhi by extraction in non-polar bacterial activities.
activity against Escherichia coli.
(petroleum ether and chloroform)
Salmonella typhi was resistant to
and polar solvents (methanol and
all of O.dilleniiextracts.[80]
water).

OD polysaccharides can protect


Serum ALT and AST activities,
mice against CCl4 induced hepa-
the content of liver GSH and GR,
Hepatoprotective CCl4-induced liver injury in mice totoxicity possibly due to its anti-
GST, GSH-Px activities levels,
oxidative capability of strengthen-
histopathological evaluations
ing the GSH system [75].

Alteration of hepatic- histo-


pathological changes after cadmi-
Cadmium-induced liver injury Hepato- histopathological
Hepatoprotective um treatment reveals the
in mice indicator
curative role of OD in liver injury
[74].
020 http://www.journal.ac Journal of Pharmacopuncture 2019;22[1]:016-027

prickly pear, Eltham Indian fig, erect prickly pear, pipes-


2. Material and Method
tem prickly pear, Gayndah pear, sweet prickly-pear, spiny
pest-pear, spiny pest pear, sour prickly pear, sweet prickly
This review is included available data reporting in the
pear and prickly pear [17]. It is a plant growing in deserts
literature about morphology, phytochemistry, ethnop-
and semi-desert areas, including tropical and sub-trop-
harmacological applications and pharmacology of OD
ical areas like south-eastern parts of North America and
until December 11, 2018. For collection of data, scientific
east coast of Mexico, the Bermudas, the West Indies and
databases consisting of PubMed, Science Direct, Scopus,
from the north of South America as well, the Gulf Coast
Web of Science, Scirus and Google Scholar were used. The
of Texas and the south-eastern beaches of Brazil [18-21].
search keywords were Opuntia, Opuntia dillenii (OD),
Moreover, this plant is found in around the Mediterrane-
pharmacological properties, antioxidant, anti-inflamma-
an [16], the Canary Islands, Madagascar and Mauritius,
tory, neuroprotective, hepato-protective, anti-cancer, Im-
North Yemen, India, Pakistan, the south-eastern parts of
muno-modulatory, hypotensive, anti-diabetic, chemical
Asia and Australia [9, 11, 19, 22-27].
composition and their mixture. We also explored the ther-
apeutic potential of OD in the field of ethnophytophar-
macology. Finally, about 142 articles from 1972-2018 were 2.2. Chemical composition
found that 91 cases of them were selected for our study. In
our study, the inclusion criteria were studies in English, The betalains a natural pigment with pharmacological
accessibility to full text and articles mentioned pharma- properties such as antioxidant, anti- cancer, anti-lipidem-
cological properties of OD and other genera of Opuntia. ic and antimicrobial activity are the most constitute of OD.
The articles that were not in English or the full text was not Their biosynthesis is based on the ability of plants to pro-
available, were excluded. vide betalamic acid which condenses with cyclodopa or
amino acids in non-enzymatic reactions [28-30]. The con-
sumption of OD fruits represents an important contribu-
2.1. Opuntia dillenii (OD)
tion to the intakes of fiber, ascorbic acid, Mn, Cr and total
phenolics which makes it a great antioxidant and also a
powerful complementary diet (Table 2) [31].

2.2.1. Cladode
Kalegowda P et al. showed that mucilage extracted from
cladodes of OD (Ker-Gawl) Haw in aqueous medium
yields about 6.2%. The neutral sugar composition consist-
ed of arabinose (38.80%), rhamnose (15.70%), galactose
(33.00%), xylose (5.10%) and glucose (5.10%) [32, 33]. Fur-
thermore, some investigations show the isolation of two
new α-pyrones, called opuntioside II and opuntioside III,
from the cladode and stem of OD extract with about six
known compounds together. The structures of these new
compounds were determined based on the chemical and
physicochemical researches [34].

2.2.2. Fruit
In a study conducted by Elena Díaz-Medina et al., differ-
ences in chemical compositions between the fruit of OD
and Opuntia ficus indica were evaluated. Results showed
OD had higher contents of fiber, fat, ash, acidity, ascorbic
acid, total phenolics, Na, Ca, Mg, Mn and Cr (p < 0.05) and
lower values of °Brix, proteins, pH, K, Fe, Zn and Ni [35].
These studies were not the only researches evaluating
Figure 1 OD Photograph by Sheldon Navie chemical composition of this plant. Other studies also had
revealed the chemical composition (protein, Brix, mois-
ture, acidity, saccharose, glucose, fructose and miner-
OD is a member of the Cactaceae family (Figure 1), which als), the physical properties (Linear dimensions, density,
is found in all temperature zones and has been used as an mass, shrinkage and porosity) and equilibrium properties
ornamental plant [12, 15]. The Cactaceae consists of 130 (sorption isotherms, enthalpy and entropy) of OD fruit.
genera and 1500 species, which have remained largely un- This fruit is a valuable resource for water content, min-
explored for their therapeutic potency [12, 16]. OD cactus erals, and acidity. Investigation on another plant of this
has a specific name: OD (Ker-gawl) Haw. and also called family named prickly pear has revealed a value of total
as Australian pest pear, common prickly pear, Dillen's soluble solids (12-17%), acidity (0.03-0.12%), pH (6.0-6.6),
Journal of Pharmacopuncture 2019;22[1]:016-027 http://www.journal.ac 021

Table 2 Chemical composition of O.dillenii

plant part Chemical composition


fiber, fat, ash, acidity, ascorbic acid, total phenolics, Na, Ca, Mg, Mn
and Cr, °Brix, proteins, K, Fe, Zn, and Ni. saccharose, glucose, fructose
fruit
and minerals, water content. 14C-labeled betanidin an indole carbox-
ylic acid

calcium, phosphorus, potassium, magnesium, sodium and zinc.fatty


Seed
acids such as linoleic acid, Palmitic acid.

neutral sugar composition consisted of arabinose, rhamnose, galac-


Cladode tose, xylose, and glucose, two new α-pyrones, called opuntioside II
and opuntioside III.
Opuntia dillenii

novel C29-5𝛽-sterols, opuntisterol [(24R)-24-ethyl-5𝛽-cholest- 9-ene--


𝛽,12α-diol] and opuntisteroside [(24R)-24-ethyl-6𝛽-[(𝛽- d-glucopyra-
nosyl)oxy]-5𝛽-cholest-9-ene-12α-ol], 𝛽-sitosterol, taraxerol, friedelin,
methyl linoleate, 7-oxositosterol, 6𝛽- hydroxystigmast-4-ene-3-one,
daucosterol, methyl eucomate and eucomic acid, 3-O-methyl
Stem quercetin, kaempferol, kaempferide, quercetin, isorhamnetin and
𝛽-sitosterol ,4- ethoxyl-6-hydroxymethyl-alpha-pyrone Kaempferol,
kaempferide and 3-O-methyl quercetin,methyl linoleate, 7- oxositos-
terol, 6𝛽-hydroxystigmast-4-ene-3-one and eucomic acid , opuntio-
side I, 4-ethoxyl-6-hydroxymethyl-α-pyrone, and kaempferol 7-O-𝛽-
-glucopyranosyl-(1→4)-𝛽-D- glucopyranoside.

ascorbic acid contents (20-40 mg/100 g fresh weight) nu- ferol, kaempferide and 3-O-methyl quercetin were iso-
tritional values of energy (172 kJ), vitamin C (14 mg), glu- lated for the first time from OD stems [39]. Some studies
cose (7.8 g), fibre (1.8 g), protein (0.7 g) , fats (0.5 g), potas- demonstrated that compounds like methyl linoleate,
sium (220 mg), magnesium (85 mg), calcium (56 mg) and 7-oxositosterol, 6𝛽-hydroxystigmast-4-ene-3-one and eu-
phosphorous (24 mg) for 100 g eatable portion. This plant is comic acid were isolated from the stems of OD for the first
used in dehydrated areas as an edible product too [44-46]. time [40, 41]. Furthermore, investigations obtained three
its revealed that 14C-labelled betanidin an indole carboxylic new compounds, opuntioside I, 4-ethoxy-6-hydroxyme-
acid is a compound found in the fruits of OD [36]. thyl-α-pyrone and kaempferol 7-O-𝛽-D- glucopyranosyl--
1→4)-𝛽-D-glucopyranoside, from the stem extract of OD.
2.2.3. Seed The structures of the new compounds were determined on
the basis of chemical and physicochemical evidence [10].
M. Ramdani et al. reported that the minerals of OD dry
seeds consist of: calcium at 408.28; phosphorus at 970.15; 2.3. Medicinal Uses
potassium at 201.96; magnesium at 240.30; sodium at
18.18 and zinc at 78.26 mg / 100 g dry seeds. The seed oil There is considerable evidence of using this plant as me-
of OD mainly contains fatty acids such as linoleic acid: dicinal plant in various countries throughout the world,
79.83%, Palmitic acid: 13.52% [37]. including India [11], Canary Islands [9, 42], Taiwan [43],
China [10] where this plant has drawn great attention and
some healthy drinks are provided from its extraction too
2.2.4. Stem [44-46].
The previous investigations also show two novel
C29-5𝛽-sterols, opuntisterol[(24R)-24-ethyl-5𝛽-choles- 2.4. Pharmacological properties
9-ene-6𝛽, 12α-diol] and opuntisteroside [(24R)-24-ethyl
6𝛽-[(𝛽-d-glucopyranosyl)oxy]-5𝛽-cholest-9-ene-12α-ol], 2.4.1. Immuno-modulatory, Anti-inflammatory
together with nine known compounds, 𝛽-sitosterol, tarax- activities and analgesic activities
erol, friedelin, methyl linoleate, 7-oxositosterol, 6𝛽-hydrox
ystigmast-4-ene-3-one, daucosterol, methyl eucomate and Many studies have indicated the analgesic and anti-in-
eucomic acid, were isolated from the stems of OD collect- flammatory effects of the genus Opuntia in many various
ed in Guizhou Province, China [20]. extract types like fruit extract, lyophilized cladodes or the
Qiu Yingkun et al. could isolate six compounds from OD- phytosterols from fruit and stem extracts [47]. It has been
stems called 3-O-methyl quercetin, kaempferol, kaemp- reported that this plant presents anti-inflammatory ef-
feride, quercetin, isorhamnetin and 𝛽-sitosterol on the fects. Lyophilized aqueous extract of the fruits of the plant,
basis of the chemical evidence and spectral analysis. In used in Canarian traditional medicine for gastrointestinal
another study, a new compound named 4-ethoxy-6-hy- and bronchial troubles, was evaluated for analgesic and
droxymethyl-alpha-pyrone was isolated from the 80% anti-inflammatory effects in rats and mice. The OD extract
ethanolic extract of the stems of this plant [38]. Kaemp-
022 http://www.journal.ac Journal of Pharmacopuncture 2019;22[1]:016-027

(100-400 mg/kg, i.p.) inhibited, in a dose-related way, car- and carotenoids were achieved from these extracts. The
rageenan-induced paw edema in rats. A dose-dependent varieties with red-skin fruits contained the most ascorbic
action was obtained against chemical (writhing test) and acid (815 μg/g fruits weight) and the yellow-skinned fruits
thermic (hot plate test) stimuli, respectively, with dos- (Opuntia stricta var. stricta) had the most carotenoids
es of 50 and 100 mg/kg [9]. In another study, evaluation (23.7 μg/g fw). This study also reported the fact that, the
of the anti-inflammatory and analgesic effects of the al- antioxidant capacity of cactus fruits can be related to their
coholic extracts of flowers, fruits and stems of OD using flavonoid, ascorbic acid and carotenoid contents. The
carrageenan-induced rat paw edema and electrical cur- data exhibited that cactus fruits are a precious source of
rent tests showed the most anti-inflammatory effect at natural antioxidants [58]. Chang et al. evaluated the meth-
the dose of 200 mg/kg of flower extract. Bioassay-guided anolic extract from betacyanin-free seeds of OD for anti-
fractionation of this extract by vacuum liquid chromatog- oxidant activity. The results showed in three assay systems
raphy (VLC) followed by Sephadex and paper chromatog- a higher antioxidant capacity for betacyanin-free seeds of
raphy showed three flavonoid glycosides i.e. kaempferol OD than extracts from peel and pulp with betacyanins.
3-O-α-arabinoside,isorhamnetin-3-O-glucoside and The pulp contains more ascorbic acids than peel and
isorhamnetin-3-O-rutinoside [48]. Siddiqui et al. showed seeds did not contain this valuable vitamin. The extracts
the anti-inflammatory effect of OD cladode methanol ex- obtained from the former have the greater antioxidant ca-
tracts using inhibition of arachidonic acid metabolites and pacity than the latter because of a higher amount of total
cytokines. Their report also described the anti-inflamma- phenolic compounds (133.4 versus 91.5 mg/100 g fresh
tory activity of opuntiol and opuntioside for the first time weight) [43]. Antioxidant activity of this plant in aqueous
[26]. The other members of this genus such as Opuntia fi- extractions against lipid peroxidation is also reported [59].
cus indica and Opuntia humifusa have also been reported Betanin and isobetanin are two compounds with high
to exhibit anti-inflammatory effects [49-53]. Investigation amounts of OD fruit. It was indicated that these two com-
of specific modulation of the immune system by OD poly- pounds were considered great free radical scavengers and
saccharides in a murine model immunosuppressed by in- valuable antioxidant constituted in certain pH levels [60].
traperitoneal injection of cyclophosphamide (ip) showed It is also suggested that these compounds may be consid-
that this plant can potentially enhance the specific im- ered as potentially effective bio-molecules for improving
mune function of immunosuppressed mice as well as the human health and preventing disease states [61, 62].
proliferation of lymphocytes in vitro [78].
2.4.3. Anti-tumor activity
2.4.2. Antioxidant activity
An investigation showed antitumor effects of polysaccha-
Yang Q et al. evaluated the antioxidant activity of crude rides isolated from this plant on SK- MES-1 cell lines [63].
polysaccharides from OD by DPPH assay used response Amaresh Mishra has mentioned this plant as an anti-can-
surface methodology (RSM) to optimize the extraction. cer plant [64].
Their study revealed OD crude polysaccharides had a
good antioxidant activity [54]. 𝛽-Sitosterol isolated from 2.4.4. Neuroprotective
OD as the active anti-inflammatory compound seems to
be relatively weaker compared with that of hydrocorti- Xianju Huang et al. evaluated neuroprotective and an-
sone [25, 55]. tioxidant effects of Cactus polysaccharides of OD on brain
The aqueous ethanolic extract from the fresh stems of OD ischemia-reperfusion injury in rats and on the oxidative
has potent radical scavenging activity. In this study, three stress- induced damage in PC12 cells and these com-
new compounds isolated from OD called opuntioside I, pounds isolated from OD, were considerable potency for
4-ethoxyl-6-hydroxymethyl-alpha-pyrone and kaempferol treatment of ischemia and oxidative stress-induced neuro-
7-O-beta-D-glucopyranosyl-(1→4)-beta-D-glucopyrano- degenerative disease [65]. These results may be due to OD
side, were evaluated based on the chemical and phys- valuable compounds such as flavonoids known as great an-
icochemical evidence. The radical scavenging effects of tioxidants [66-69]. Furthermore, these results are correlat-
principal compounds were examined too [56]. Li H et al., ed with the investigation of polysaccharides isolated from
evaluated the antioxidant effect of polysaccharides iso- Opuntia milpa alta on the H2O2-induced cortex and hip-
lated from OD using DPPH test, hydroxyl radicals and su- pocampal injury [70]. Other studies on the genus's Opuntia
peroxide radical in vitro. Their study showed these acidic have shown neuroprotective effects too [71-73].
polysaccharides demonstrated good antioxidant activity
[57]. A purification and fractionation of OD extract isolat-
ed several betalains and polyphenol. This process followed 2.4.5. Hepatoprotective activity
by betalainic and phenolic characterization revealed that
Published pieces of literature also represented hepa-
this plant was a valuable source of bioactive compounds,
to-protective effects of this plant. Shah et al. studied the
with a high amount of total betacyanins (16.63 mg beta-
hepatoprotective effect of fruit pulp extracts of this plant
nin/100 g fresh fruit) and betaxanthins (7.55 mg indicax-
on cadmium-induced toxicity in mice. Their results indi-
anthin/100 g fresh fruit) with elevated antioxidant activity
cated hepato-protective of OD in hepato-histopatholog-
[31]. The antioxidant activities in extracts obtained from
ical evaluations [74]. Hepatoprotective effect of polysac-
four cacti (Opuntia species) fruit varieties were investigat-
charides obtained from this plant also evaluated by Yu
ed. Quercetin, kaempferol, isorhamnetin, ascorbic acid
Journal of Pharmacopuncture 2019;22[1]:016-027 http://www.journal.ac 023

NingHua et al. in the mice model of hepatic injury induced neuropathy [83]. Investigation of the possible role of OD
by carbon tetrachloride (CCl4). Their results showed that fruit juice in the treatment of streptozotocin (STZ)-in-
OD polysaccharides could significantly reduce serum ALT duced diabetes in rats and additionally nutritive value of
and AST activities compared to CCl4 group and increase the OD fruits by Inas Z. A revealed that oral administra-
the content of liver GSH, GR, GST and GSH-Px activities tion of OD juice to diabetic rats improved lipid profile and
in liver-injured mice. OD polysaccharides also could ame- body weight gain. It also significantly reduced MDA levels
liorate the hepatic pathological changes [75]. and blood glucose as compared with the non-treated dia-
betic group [84].
2.4.6. Hypotensive activity
2.4.9. Clinical trials:
A study conducted by Saleem et al. showed that the meth
anolic extracts of OD cladodes and its pure compounds Antioxidant activity of extracts obtained from OD Haw
like α-pyrone glycoside and opuntioside-I can exert a hy- fruit (ODHF) and its active compounds on low-density
potensive effect in normotensive rats [76]. A review by Tal- lipoprotein (LDL) peroxidation by Trolox equivalent anti-
ha et al. on the herbal hypotensive compounds has report- oxidant capacity and oxygen-radical absorbance capacity
ed OD as a plant containing hypotensive properties [77]. approaches were in the order of seed > peel > pulp. Reduc-
tion of lipid peroxidation in human plasma showed that
2.4.7. In-Vitro antimicrobial synergistic and this plant possesses great antioxidant effects [43].
Zhao et al. evaluated the effect of OD tablet (ODT) in type
anti-tubercular (Tb) effects two diabetes mellitus (DM) patients in a four-week clin-
ical trial. Their results showed that ODT could improve
Investigation of the synergistic antimicrobial and anti-tu- the glycometabolism of DM patients sufficiently and also
bercular activities of OD hydro- alcoholic extract conduct- reduce the impairment of renal function in diabetic neu-
ed by Subal et al. showed the inhibitory effect upon this ropathy [83].
plant [78]. Betanin a compound with the high amount in Opuntia
At Another study done by Ratnaweera et al Endophytic species evaluated on myeloperoxidase/nitrite-induced
fungi isolated from the sterilized surface of cladodes and oxidation of human low-density lipoproteins. Their re-
flowers of OD by several nutrient media and their antimi- sults suggest that betanin scavenges the initiator radical
crobial activities were evaluated against two Gram-neg- nitrogen dioxide and can also act as a lipoperoxyl radi-
ative and three Gram-positive bacteria and Candida cal-scavenger obviously state the antioxidant effect of var-
albicans. The results showed that OD harbors several ious organs of OD [30, 85].
endophytic fungi producing various antimicrobial com-
pounds with selective antibacterial characteristics. It was
mentioned that these antimicrobial properties may be 3. Conclusion
due to secondary metabolites produced by these endo-
phytic fungi such as equisetin obtained from the endo- OD certainly should be considered as a plant with suit-
phytic Fusarium spp isolated from OD [79]. able properties against various diseases (Figure 2). Chiefly
Javeed et al evaluated the Extracts obtained from the nowadays with the great increasing rate of diseases pro-
dried stem of OD in polar and non-polar based extraction moted by the lifestyles especially including diabetes and
for antimicrobial effects, their results showed that polar cardiovascular diseases. The adaptation with various envi-
extraction of OD exhibits potent antimicrobial effects [80]. ronments and great productivity of this plant make it suita-
ble for medicinal researches in order to purify and isolation
new pharmacologically valuable compounds with more
2.4.8. Anti-diabetic effect efficacies in the prevention and treatment of various dis-
eases. In addition to other studies on the genus Opuntia,
Perfumi and Tacconi investigated the anti-hyperglyce- the pharmacologic properties such as anti-hyperlipidem-
mic effect of OD in normoglycemic and alloxan-induced ia, anti-atherosclerotic, anti-inflammatory, anti-diabetic,
diabetic rabbits and reported a hypoglycemic effect of this antiviral, antioxidant and anti-ulcerogenic properties were
plant. Furthermore, they indicated that this effect is due revealed. Vitamins B1, B2, C, 𝛽 - carotene, E and D3 were
to reducing intestinal absorption of glucose; however, this observed. The great effectiveness and fewer side effects in
may not be the only hyperglycemic action of this plant. comparison to other drugs may be complementary to men-
For example, this plant may contain some insulin-like tion the value of botanic industries and researches reveal-
compound leading to this effect. This fact should be men- ing the importance of using herbal plants instead of chem-
tioned that in an oral toxicity study of OD extract, rats giv- ical drugs. Unfortunately, this plant is neglected in the sites
en doses of up to 50 ml/kg exhibited no symptoms of tox- of origin and found attention at the other regions of the
icity [42, 81]. Ripe fresh fruit of OD in the Canary Islands world. At the end we can announce Opuntia genus and es-
is included in folk medicine as an antidiabetic crude drug pecially OD as great genus and plant in the Cactaceae fam-
[82]. zhao et al. evaluated the efficacy of OD tablet (ODT) ily needing more investigations to obtain valuable botanic
in type two diabetes mellitus (DM) patients in a four- compounds in order to promotion of botanic industries as
week clinical trial. Their results showed that ODT could the future of pharmapuncture.
improve the glycometabolism of DM patients sufficiently
and reduce the impairment of renal function in diabetic
024 http://www.journal.ac Journal of Pharmacopuncture 2019;22[1]:016-027

Figure 2 Summarization of OD pharmacologic properties


Journal of Pharmacopuncture 2019;22[1]:016-027 http://www.journal.ac 025

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