Cuscuta Chinensislam. - A Systematic Review On PDF
Cuscuta Chinensislam. - A Systematic Review On PDF
Cuscuta Chinensislam. - A Systematic Review On PDF
Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jep
Review
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
Tianjin Key Laboratory of Phytochemistry and Pharmaceutical Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
art ic l e i nf o
a b s t r a c t
Article history:
Received 18 April 2014
Received in revised form
18 September 2014
Accepted 19 September 2014
Available online 2 October 2014
Ethnopharmacological relevance: Cuscuta chinensis Lam. has found its use as a traditional medicine in
China, Korea, Pakistan, Vietnam, India and Thailand. It is commonly used as an anti-aging agent, antiinammatory agent, pain reliever and aphrodisiac. To provide an overview of the ethnopharmacology,
phytochemistry, pharmacokinetics, pharmacology and clinical applications of Cuscuta chinensis, as well
as being an evidence base for further research works of the plant.
Materials and methods: The present review covers the literature available from 1985 to 2014. The
information was collected from journals, books, theses and electronic search (Google Scholar, PubMed,
ScienceDirect, ESBCO, Springerlink and CNKI). Literature abstracts and full-text articles were analyzed
and included in the review.
Results: Many phytochemicals have been isolated, identied and published to date, including: at least
18 avonoids; 13 phenolic acids; 2 steroids; 1 hydroquinone; 10 volatile oils; 22 lignans; 9 polysaccharides; 2 resin glycosides; 16 fatty acids. These phytochemicals and plant extracts exhibit a range of
pharmacological activities that include hepatoprotective, renoprotective, antiosteoporotic, antioxidant,
anti-aging, antimutagenic, antidepressant, improve sexual function, abortifacient effects, etc.
Conclusion: This present review offers primary information for further studies of Cuscuta chinensis. The
in vitro studies and in vivo models have provided a bioscientic explanation for its various ethnopharmacological uses and pharmacological activities (most notably antioxidant effects) especially in the
prevention of hepatic disease and renal failure. It is necessary and important to do more pharmacokinetic
and toxicological research works on human subjects in order to inform the possible active compounds in
the body and validate its safety in clinical uses.
& 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords:
Cuscuta chinensis Lam
Tu-Si-Zi
Ethnopharmacology
Phytochemistry
Pharmacokinetics
Clinical applications
Chemical compounds studied in this article:
Quercetin (PubChem CID: 5280343)
Kaempferol (PubChem CID: 5280863)
Isorhamnetin (PubChem CID: 5281654)
Astragalin (PubChem CID: 5282102)
Hyperoside (PubChem CID: 5281643)
Rutin (PubChem CID: 5280805)
Calycopteretin (PubChem CID: 10429470)
Cinnamic acid (PubChem CID: 444539)
Caffeic acid (PubChem CID: 689043)
p-coumaric acid (PubChem CID: 637542)
Abbreviations: ALP, alkaline phosphatase; AMMC, amelanotic elanocytes; APAP, acetaminophen; ARF, acute renal failure; AST, aspartate aminotransferase; CCP, Cuscuta
chinensis polysaccharides; CHO, cholesterol; CK, creatine kinase; CK-MB, creatine kinase muscle and brain (subunits); CMSD, Cuscuta chinensis with other 7 medicinal herbs;
CNS, central nervous system; DC, dendritic cell; DMBA, 7,12-dimethylbenz()anthracene; DPPH, 2,2-Diphenyl-1-picrylhydrazyl; EC, 50% of effective concentration; ED90, 90%
of effective concentration; EESC, ethanol extract of the dry seed of Cuscuta chinensis; ER, estrogen receptor alpha; ER, estrogen receptor beta; FSC, Flavonoids from Cuscuta
chinensis seeds; FST, force swimming test; H2O2, hydrogen peroxide; IC50, 50% of inhibition concentration; I.P., intraperitoneal; I.V., intravenous; LD50, 50% of lethal dose;
LDH, lactate dehydrogenase; LF, Lipofuscin; LH, Luteininzing hormone; LPS, lipopolysaccharides; MDA, malondialdehyde; MI/RI, myocardial ischemia /reperfusion injury;
P.O., per oral; OVA, ovalbumin; PCC, penile corpus cavernosum; PK, pharmacokinetics; ROS, reactive oxygen species; S.C., subcutaneous; SD rats, Sprague-Dawley rats; SOD,
superoxide diamutase; TBHP, tertiary butyl hydroperoxide; TG, triglyceride; TST, tail suspension test
n
Corresponding author at: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Tel.: 86 22 59596163; fax: 86 25 59596163.
E-mail address: [email protected] (Y.-x. Chang).
http://dx.doi.org/10.1016/j.jep.2014.09.032
0378-8741/& 2014 Elsevier Ireland Ltd. All rights reserved.
293
Contents
1.
2.
3.
4.
5.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phytochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ethnopharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pharmacokinetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.
Effect on skin protection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.
Hepatoprotective activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.
Anti-osteoporotic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.4.
Immunological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.5.
Effect on neuronal system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.6.
Antioxidant activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.7.
Anti-aging activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.8.
Effects on tumor cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.9.
Renoprotective effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.10. Effect on reproductive system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.11. Prevent abortion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.12. Anti-mutagenic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.13. Anti-diabetic activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.14. Cardiovascular activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.15. Anti-depressant activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.16. CNS depressant activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.17. Effect on melanin production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.18. Anthelmintic activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.19. Anti-nociceptive and anti-inammatory activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.20. Toxicological reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6. Clinical applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.1.
Female infertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.2.
Prevent abortion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.3.
Male reproductive system disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.4.
Chyluria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.5.
Chloasma faciei . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.6.
Glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.7.
Nocturia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.8.
Treatment and prevent diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.9.
Herpes zoster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.10. Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.11. Vitiligo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction
Cuscuta chinensis Lam. (Cuscuta chinensis; Convolvulaceae, (The
Plant List., 2013)) is a parasitic plant which is also known as
Chinese Dodder (Mavlonov et al., 2008), or Tu-Si-Zi in Chinese
(Flora of China, 2006). It is commonly used in traditional medicine
as a tonic and aphrodisiac in China and other Asian countries. It is
often used as a functional food by adding to alcoholic beverages or
porridge to improve sexual potency and vision and prevent
abortion (Zheng et al., 1998).
Cuscuta chinensis has two synonyms (Cuscuta. carinata R. Br. and
Cuscuta. chinensis var. carinata (R. Br.) Engelm) (The Plant List.,
2013). No articles were found after searching by using these two
names. However, it was found that Cuscuta chinensis Lam. was used
in 80 reports (both in English and Chinese articles including 35
plant-authorized articles) and was not used in 17 Chinese articles in
which the plant was just dened as Tu-Si-Zi. Cuscuta chinensis Lam.
should be used instead of Tu-Si-Zi in all publications in the future.
Cuscuta chinensis (Fig. 1) is a parasitic plant that wraps around
other plants and uses them for its nourishment. The plant grows
near seaside. Stems thin, twining, liform, glabrous, yellowish or
pale yellowish, ca. 1 mm diam. The plant has no leaf or reduced to
293
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294
Fig. 1. Cuscuta chinensis Lam. (A) Habitus, (B) stem and owers, (C) fruits, and (D) dried seeds.
Taiwan region. Its aerial parts are excavated in autumn when the
fruits are ripe and dried by natural sunlight and thrashed for
seeds. It is used in its unprocessed form or boiled after removal of
impurities. It is also pounded into cake for use after being steamed
(Liao et al., 2000; Lei, 2000; Teng, 2007 ; Costea et al., 2011) .
Although many researchers have attempted to nd out the
chemical constituents including the pharmacological activities and
clinical applications of Cuscuta chinensis which are evidenced by an
increasing number of published scientic literatures in this area, there
is no review literature available. This current review therefore aims to
provide an overview of the ethnomedicinal use, phytochemical
properties, pharmacokinetics, pharmacological activities and clinical
applications of Cuscuta chinensis, as well as being an evidence base for
further research works of this plant.
2. Phytochemistry
Cuscuta chinensis is a parasitic plant so that its phytochemical
constituents depend on the type of host (Lin et al., 2007). The
chemical constituents of Cuscuta chinensis are avonoids, polysaccharides, alkaloids, steroids, volatile oils, lignans and others
(Fig. 2) (Miyahara et al., 1996; Du et al., 1998; Wang et al., 2000,
2001; Bao et al., 2002; Hou et al., 2003). Flavonoids account for
about 3.0% of the total chemical constituents. The main avonoids
including kaempferol, quercetin, hyperoside, astragalin and lignans play an important role in the pharmacological activity
(Cornwell et al., 2004; Williamson et al., 2005). Lofer et al.
(1997) studied the plants in the genus Cuscuta and found that all
species had the same soluble phenolic compounds (Chlorogenic
acid,
3,5-dicaffeoylquinic
acid,
4,5-dicaffeoylquinic
acid,
Kaempferol
Quercetin
Isorhamnetin
Astragalin
d - sesamin
Chlorogenic acid
p-coumaric acid
-sitosterol
daucosterol
Rutin
Cinnamic acid
Arbutin
295
Hyperoside
Caffeic acid
caryophyllene
3. Ethnopharmacology
Around 2000 years ago, Cuscuta chinensis was recorded in Shen
Nong Ben Cao Jing (Shen Nong's Herbal, the ancient Chinese herbal
classic) for the rst time in Chinese history. It was listed as a top
grade drug for the kidney-tonifying and liver-strengthening functions
(Mou, 2002). The plant was used as a tonic medicine by traditional
Chinese medicine practitioners for the treatment of kidney and liver
deciency (He et al., 2010). Cuscuta chinensis has an ability to tonify
kidney and nourish liver, it can replenish essence, improve vision, stop
diarrhea and prevent abortion. It has been used not only in kidney
insufciency with lumbago, impotence, spermatorrhea, frequent urination, sterility due to cold uterus, threatened abortion or habitual
abortion, but also used in treatment of the liver insufciency with
dim and blurred vision (Teng, 2007). In the famous classic book of
Chinese materia medica, Ben Cao Gang Mu (Compendium of Materia
Medica), Cuscuta chinensis improves eyesight and prevents aging. It can
tonify the muscles, enhance the activity of bone and tendon, principally
used to treat or improve excessive cold in male and female
4. Pharmacokinetics
The studies about pharmacokinetics (PK) of Cuscuta chinensis
are very limited. There are 2 reports: the PK study of quercetin in
296
Table 1
Phytochemistry of Cuscuta chinensis.
Chemical constituents
Part of plant
Flavonoids
Quercetin
Reference
Seed; fruit; whole plant; Ye et al., (2002, 2005); Yahara et al., (1994); Lofer et al.,
stem
(1997); Kwon et al., (2000)
Pan et al., (2014)
Whole plant
Lofer et al., (1997)
Fruit; seed; stem
Yahara et al., (1994); Ye et al., (2005)
Seed
Ye et al., (2002, 2005)
Quercetin-3-O-glucoside
Quercetin-3-O-apiosyl(1-2)-galactoside
Quercetin-3-O--D-galactoside-7-O--glucoside
Quercetin-3-O--D-apiofuranosyl(1-2)--D-galactoside
Quercetin-3-O-rhamnosylgalactoside
Quercetin-3-O-acetylgalactoside
Kaempferol
Kaempferol 3,7-di-O--D-glucopyranoside
Keampferol-3-O-galactoside
Seed
Stem
Seed; stem
Seed; stem
Ye et al., (2005)
Ye et al., (2005)
Ye et al., (2002, 2005); Hajimehdipoor et al., (2012);
Kwon et al., (2000); Pan et al., (2014)
He et al., (2010)
Seed
Keampferol-3-O- -D-glucoside
Isorhamnetin
Isorhamnetin-3-O-glucoside
Astragalin
Hyperoside
Seed; stem
Seed; stem
Seed;whole plant; fruit;
stem
Seed; Whole plant; stem
Rutin
Calycopteretin
Apigenin
Seed
Seed
Seed; stem
Seed; stem
Fruit
Seed
Seed
Seed; stem
Seed
Stem
Whole plant; seed; stem
Seed; stem
Whole plant; seed; stem
Seed
Fruit
Seed; whole plant; fruit
-Sitosterol
Seed
Ye et al., (2001)
Daucosterol
Seed
Ye et al., (2001)
Hydroquinone
Arbutin
Fruit
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Hou
Hou
Hou
Hou
Hou
Hou
Hou
Hou
Hou
Seed
Seed
Seed
Seed
Seed
Seed
Fruit
Seed
Fruit
Fruit
Seed; stem
Phenolic acid
Chlorogenic acid
Caffeic acid
4-Caffeoyl quinic acid
5-Caffeoyl quinic acid
4-Caffoyl-5-coumaroylquinic acid
Methyl 4-hydroxy-3,5-dimethoxycinnamate
4-Feruoyl-5-caffeoylquinic acid
3,5-Dicaffeoylquinic acid
3,5-Dicaffeoyl-4-feruoylquinic acid or 3-feruoyl-4,5-dicaffeoylquinic acid
4,5-Dicaffeoylquinic acid
3,4,5-Tricaffeoylquinic acid
p-Coumaric acid
Cinnamic acid
Steroids
Volatile oil
2 Pentyl furan
Dodecane
3- Butene-2 alcohol
Furfural
Furan-2-ylmethanol
Heptanal
3, 7 Dimethyl-1, 6 octadiene, 3 alcohol
Borneol
-Terpineol
Caryophyllene
-Caryophyllene
et
et
et
et
et
et
et
et
et
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
(2003)
(2003)
(2003)
(2003)
(2003)
(2003)
(2003)
(2003)
(2003)
Lignans
20 -Hydroxyl asarinin 20 -O--D-apiofuranosyl-(1-2)(Cuscutoside A)
D-glucopyranoside
(1-6)--D-glucopyraniside (Cuscutoside D)
( )-Pinoresinol
D-Pinoresinol
( )-Epipinoresinol
( )-Pinoresinol-4-O-glucoside
d-Pinoresinol-4-O-glucoside
D-glucopyranosyl-
297
Table 1 (continued )
Chemical constituents
Feruoylcaffeoyl-d-pinoresinol
Dicaffeoyl-d-piniresinol
d-Sesamin
9(R)-Hydroxy-d-sesamin
9-Hydroxy-d-sesamin-9-O-glucoside
9-Hydroxy-d-sesamin-O-glucoside
5,50 -Dihydroxy-d-sesamin-5-O-glucoside
Part of plant
Reference
Seed; stem
Stem
Seed; stem
Seed
Seed; stem
Ye
Ye
Ye
Ye
Ye
et
et
et
et
et
al.,
al.,
al.,
al.,
al.,
(2005)
(2005)
(2005)
(2001)
(2005)
Seed
Ye et al., (2005)
Stem
Seed; stem
Ye et al., (2005)
Ye et al., (2005)
Seed
Seed; stem
Seed
Stem
Stem
Ye
Ye
Ye
Ye
Ye
Seed
Seed
Seed
Seed
Fatty acid
Methylmyristate
Methyl pentadecanoate
Methyl hexadecanoate
Methyl palmitoleate
Methyl heptadecanoate
Methyl stearate
Methyl oleate
Methyl linoleate
Methyl linolenate
Methyl Arachidate
Methyl cis-11-eicosenoate
Methyl 11c,14c- eicosadienoate
Methyl behenate
Sinapic acid methylester
Methyl tricosanoate
Methyl lignocerate
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Cheng
Microelements
Calcium
Magnesium
Iron
Manganese
Copper
Seed
Seed
Seed
Seed
Seed
Zhao
Zhao
Zhao
Zhao
Zhao
4-Methyl-3-methoxy-9-hydroxyligballinol-O-glucoside
3,4-Demethyleudesmin-4-O-glucoside
Piperitol-4-O-glucoside
20 -Hydroxyasarinin-20 O-rhamnosylglucoside
Lignin-O-coumaroylglucoside
Lignin-4-O-coumaroylglucoside
Polysaccharides
Neutral heteropolysaccharide: arabinose, rhamnose, xylose and galactose
composition
Acidic heteropolysaccharide mainly branched: CHC-1, H3, CS-A, CS-B, CS-C
et
et
et
et
et
al.,
al.,
al.,
al.,
al.,
(2005)
(2005)
(2005)
(2005)
(2005)
Resin glycosides
Acylated trisaccharide:
-L-rhamnopyranosyl-(1- 3) -[2-O-(11S)-11-
3R)-3- hydroxy-2-methylbutyryl]--L-rhamnopyranose-(1-2-0-[6-Oacetyl]-D-glucopyranoside
et
et
et
et
et
et
et
et
et
et
et
et
et
et
et
et
et
et
et
et
et
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
al.,
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(2013)
(1990)
(1990)
(1990)
(1990)
(1990)
5. Pharmacology
The long history of medicinal applications of Cuscuta chinensis
has inspired many pharmacological research works. The study
indicates that Cuscuta chinensis shows a broad range of biological
activities, which are briey shown in Table 4.
5.1. Effect on skin protection
Nisa et al. reported the inhibition of whole plant extract of
Cuscuta chinensis on 7,12-dimethylbenz()anthracene(DMBA)induced skin papillomas and carcinomas in mice. The water
extract 1 g/kg was orally administrated thrice a week to 22 mice
and started on the 10th day after the rst application of DMBA to
298
Table 2
Ethnopharmacology of Cuscuta chinensis.
No.
Ethnomedicinal uses
Locality
References
Seed
China
Whole pant
Stem
Stem
Stem
Leaf
Whole plant
Seed
Whole plant
Pakistan
India
2
3
4
5
6
Vietnam
Korea
Thailand
Table 3
Pharmacokinetic information of Cuscuta chinensis.
Species/ bio-matrix Analytes
Administration route/
dosage
Rat/serum
Quecrcetin
Gavage 0.85g/kg of Cuscuta K(h-1): 5.214, (h-1): 3.614, (h-1): 0.568, T1/2() (h): 0.19, T1/2() (h):
1.22, T1/2(AB) (h): 0.13, Tmax (h): 0.333, Cmax (g/ ml): 0.401
chinensis 95% ethanol
extract
Human/plasma
Hyperoside
A(g/ml): 13.45, Ke(h-1): 0.199, Ka(h-1): 0.448, Lag time(h): 0.444, T1/2ka(h): Peng, (2010)
Oral administration 360 g
of Cuscuta chinensis ethanol 1.55, T1/2ke(h): 3.48, Tmax(h): 3.259, Cmax(g/ml): 3.902, AUC((g/ml)nh):
extract
37.423, CL/F(s)(g/h/(g/ml)): 0.027, V/F(c)(g/(g/ml): 0.134
References
299
Table 4
Pharmacology of Cuscuta chinensis.
No.
Activities
Part of
plant
Model
Result
Skin protective
activity
Whole
plant
Hepatoprotective Seed
activity
Seed
Seed
Aqueous extract
cultured
neonatal rat
calvarias organ
(in vitro)
MG-63 cells
100, 500 and 1000
Negative control: culture
(in vitro)
g/ml aqueous extract medium
Musculoskeletal
(osteoporosis
treatment)
Seed
Reference
Yen et al.,
(2007)
Yen et al.,
25 and 50 mg/kg seeds ethanol extract
nanoparticles formulation show signicantly (2008b)
hepatoprotective effects the same as the
normal 125, 250 mg/kg seeds ethanol
extract.
Yao et al.,
Aqueous extract of Cuscuta chinensis in rat
bone cells clearly promoted the proliferation (2005)
and differentiation of the osteoblasts, but
inhibited the activities of osteoclasts
Yang et al.,
500 and 1000 g/ml dry seed water extract
(2009a)
mildly promoted the proliferation of MG-63
cells. Dose-dependent increases in ALP activity
and collagen synthesis, the release of BMP-2
but not osteocalcin in the MG-63 cells was
induced (1001000 g/ml). In addition, the
extract markedly increased mRNA expression
of ALP, collagen, and BMP-2 in the MG-63 cells
in a dose-dependent manner. Mineralization in
the culture of MG-63 cells was signicantly
Immune
regulation
Neuroprotection
activity
Antioxidant
activity
Seed
(UMR-106
cells) in vitro
Seed
400 g of ethanol
extract
Seed
Mouse bone
marrowderived DCs
(in vitro)
Seed
Seed
PC12 cells
(in vitro)
Cuscuta chinensis
glycoside up to
200 mg/l
Positive control: 7S
nerve growth factor;
negative control:
distilled water
Seed
P.O. decoction of 20 g
Cuscuta chinensis with
other Invigorating-Qi
drug
Seed
Positive control:
Scopolamine
I.V. 5 mg/kg; negative
control:
P.O. normal saline
Positive control: 3 min
forebrain ischemia
negative control: P.O.
vehicles with shamoperated
Seed
SC50, IC50
(in vitro)
Seed
Pan et al.,
(2005)
Liu et al.,
(2003)
Lin et al.,
(2011)
Lin et al.,
(2003)
Liu et al.,
(1993)
Chung et al.,
(2006)
Yen et al.,
(2008a)
Kwon et al.,
(2000)
300
Table 4 (continued )
No.
Activities
Anti-aging
Effects on tumor
cells
Part of
plant
Model
Seed
MC3T3-E1
cells (in vitro)
Seed
PC 12 cells
(in vitro)
Seed
Whole
plant
Seed
Seed
Result
Reference
Gao et al.,
(2013)
Zhen et al.,
(2006)
Cai et al.,
(2005)
Zeraati
et al., (2010)
D-galactose
Umehara
et al., (2004)
proliferation at a concentration of 10 M
Yang et al.,
Isolated compounds from Cuscuta chinensis
seeds ethanol extract stimulated Hela cell via (2011)
estrogenic receptor ER and ER
Renoprotective
Seed
Shin et al.,
(2011)
10
Reproductive
system
Seed
Penile tissues
(in vitro)
15 mg/ml ethanol
extract
Positive control:
Sun et al.,
(2013)
11
Prevention of
abortion
Seed
Seed
Human
(in vivo)
Seed
Seed
Human
spermatozoa
(in vitro)
Mice (in vivo)
Seed
Seed
Pregnant rats
(in vivo)
Seed
Pregnant rats
(in vivo)
10 mol/l phenylephrine
precontracted, 10 nmol/l
sildenal citrate;
negative control: DMSO
0.1%
Negative control: P.O.
distilled water
Sohn et al.,
(2008)
Peng et al.,
(1997)
Shah et al.,
(2012)
Yang et al.,
(2008)
Wang et al.,
(2002)
Ma et al.,
(2008b)
Ma et al.,
(2008a)
301
Table 4 (continued )
No.
Activities
Part of
plant
Model
12
Antimutagenic
effect
Whole
plant
Bacteria
(in vitro)
Result
Reference
Nakahara
Positive control: Trp-P-1 Cuscuta chinensis methanol extract has the
carcinogen
antimutagenic effect against Trp-P-1 in Ames et al., (2002)
test, ED90 values lower than 5 L/plate
13
14
Antidiabetic
activity
Cardioprotection
activity
Seed
Seed
Seed
Seed
Seed
Positive control:
P.O. 20 mg/kg
Diaoxinxuekang
traditional chinense
formula
2 mg/g Cuscuta
Positive control:
chinensis seeds extract coronary artery ligated
negative control: shamoperated I.V. normal
saline
Li et al.,
300, 600 mg/kg of Cuscuta chinensis
polysaccharides orally signicantly lower the (2008a)
high fasting blood glucose level, raise body
weight and immune organs.
200, 400 mg/kg orally of Cuscuta chinensis
polysaccharides signicantly improve the
weight loss of diabetic rats, reduce fasting
blood glucose and glycosylated serum
protein, CCP 400 mg/kg signicantly reduce
CHO level, and CCP 400, 200, 100 mg/kg
could signicantly reduce TG level.
Xu et al.,
(2011)
Positive control:
I.P. 23 mg/kg
imipramine and
uoxetine
Jiangsu New
Medical
College,
(1997)
Liu et al.,
20 mg/kg and 1ml/kg I.V. for 1 min of
3 different methods of extraction on mature (2004)
male hybrid dogs can increase coronary
blood ow and reduce myocardial oxygen
consumption.
Cuscuta chinensis seeds extract slowed down Han et al.,
(2011)
heart rate of MI /RI rats, declined ST level,
reduced the degree of MI and the content of
CK, CK-MB, LDH, AST in blood serum.
Methanolic extract had antidepressant
effects by signicantly reduced immobility
times in TST (50 mg/kg IP) and 50 and
100 mg/kg IP in FST, imipramine and
uoxetine (both 32 mg/kg IP), as positive
controls.
Mokhtarifar
et al., (2012)
15
Antidepressant
activity
Arial part
16
CNS depressant
Whole
plant
17
Effects on
melanogenesis
Seed
AMMC
(in vitro)
Li et al., (
Cuscuta chinensis water extract promoted
melanogenesis of AMMC in dose-dependent 2008b)
manner, and increased the tyrosinase
activities.
Seed
Guinea pigs
(in vivo)
Seed
Seed
Zebrash
(in vivo)
Wang et al.,
(2014)
Huang et al.,
(2013)
Wang et al.,
(2014)
18
Anthelminthic
Seed
Goldsh
(in vivo)
19
Anti-nociceptive
Seed
20
Antiinammatory
Seed
Liao et al.,
(2014)
302
effects (Yang et al., 2011). The results indicate that the in vitro
effect of anti-osteoporosis showed the mechanisms of this activity
by promoting bone formation and inhibiting bone absorption,
improving bone mass, balancing bone metabolism by acting as a
phytoestrogen.
5.4. Immunological effects
An ethanol extract of the dry seed of Cuscuta chinensis (EESC)
could be used as a vaccine adjuvant. Pan et al. (2005) found that EESC
signicantly enhanced the mitogen- and ovalbumin (OVA)-stimulated
splenocyte proliferation in OVA-immunized mice, and EESC could
signicantly enhance a specic antibody and cellular response against
OVA in mice. Kaempferol, one of major avonoids isolated from the
dry matured seeds of Cuscuta chinensis methanol extract can decrease
chemokines and cytokines which produced by LPS-stimulated dendritic cells (DCs), and this reduction was not because of its cytotoxicity
on DCs. Besides, kaempferol decreases the maturation of DC. An
in vitro and in vivo experiment showed that kaempferol negated
LPS-stimulated DCs ability to promote the antigen-specic T cell
activation. Therefore, the results indicate that Cuscuta chinensis seeds
have the immunosuppressive effects on DCs and that kaempferol
inhibits DC function, which suggests that kaempferol has potential in
treatment of autoimmune diseases and chronic inammation (Lin
et al., 2011). Lin et al. studied about the effect of immune enhancement, anti-fatigue and anoxia tolerance on mice of four kinds of
dodder seeds from Shandong Province. They found that Cuscuta
chinensis had better effects than the other two kinds, and that the
water extracts had better effects than the alcohol extracts in enhancing
phagocytosis of mice's macrophage, increasing the weights of thymus
and spleen of the immature mice and could prolong the survival time
of mice swimming and oxygen lacking (Lin et al., 2003). From the
studies, Cuscuta chinensis, its extracts and isolated compounds, especially kaempferol, have an impressive effect on the immune system.
The aqueous extract showed immunosuppression effects while the
ethanol extract showed immunostimulating effects. Further research
works concerning the effects of Cuscuta chinensis on other immune
organs are imperative.
5.5. Effect on neuronal system
Glycoside from Cuscuta chinensis can induce neuronal differentiation with resulting outgrowth of neutrites and improve
acetylcholinesterase activity in rat phaeochromocytoma PC12 cells
in a dose-dependent manner, and glycoside inducing the PC12
cells differentiation might be related to mitogen-activated protein
kinase-mediated signaling pathway (Liu et al., 2003). Cuscuta
chinensis, together with other invigorating-qi medicines, has an
effect on scopolamine-induced dysmnesia mice for antagonistic
action, and could improve their memory, and the acetylcholinesterase activity in the mice of the group that received the drug were
signicantly less than those in the positive control group which
received scopolamine 5 mg/kg intraperitoneally and the erroneous
times of the animal's reaction (Liu et al., 1993). Cuscuta chinensis
with other 7 medicinal herbs (CMSD) had neuroprotective effects
on cultured primary neuron cell of neonatal rat. Chung et al. found
that CMSD water extract protected the cell from Amyloid-induced cell death in a dose dependent manner, and the most
effective concentration was 2550 g/mL. CMSD was also demonstrated to have protective effect from N-methyl-D-aspartate
receptor-mediated glutamate toxicity on primary cultured neurons. In addition, CMSD oral administration in mice can also
recover the hippocampal CA1 neurons from lethal ischemic
damage and prevent learning disability because of ischemiainduced brain damage (Chung et al., 2006).
303
304
100 mg/kg and late phases, 100 mg/kg). In formalin test assay, the
extract can signicantly reduce -carrageenan-induced edema
paw in the time of four hours after injection with -carrageenan.
Moreover, it can reduce the level of IL-1, IL-6, NF-B, TNF-, and
COX-2. The mechanism of action may be due to the decrease in
MDA and NO levels by the increasing activities of SOD, glutathione
peroxidase and glutathione reductase in the liver (Liao et al.,
2014). These pharmacological studies prove the ethnomedicinal
uses of Cuscuta chinensis as an anti-inammatory agent and a pain
reliever.
6. Clinical applications
Currently in China, Cuscuta chinensis seeds are usually prescribed by doctors or traditional Chinese medicine practitioners
with a usual dosage of 915 g oral administration, and the
maximum dosage of 30 g each time (Ceng and Zhang, 2000)
without obvious side effects reported for supplementing or treating various diseases, as shown below.
305
6.7. Nocturia
Using Jisheng, one of the Cuscuta chinensis seeds formulation,
oral administration 2 times day for 1 month (1 course of treatment), 23 months, the total cure rate was 96.97% (You, 2005).
306
Acknowledgments
6.10. Acne
References
Dried Cuscuta chinensis seeds 30 g in 500 ml water, apply on
the lesion, 12 times a day for 7 days (1 course of treatment), the
duration of treatment is about 12 courses, in 50 cases, 94%
effective (Yu, 1996).
6.11. Vitiligo
Cuscuta chinensis seeds 9 g, soaked in 60 ml of 95% ethanol for
23 day, then apply the solution on the lesion 23 times a day
(PCHMPD, 2010).
Summing up, the clinical applications from Cuscuta chinensis
seeds preparation for the various diseases cited above have been
studied. Although Cuscuta chinensis alone or combined with other
traditional medicines seem to show high efciency against these
disease, the clinical studies are very limited. Therefore, further
clinical trials are necessary to provide more information before it
can be used in medical practice worldwide.
7. Conclusion
Cuscuta chinensis is commonly used in traditional medicines as
a tonic and aphrodisiac in China and some Asian countries. It is
reported to contain avonoids, phenolic acids, steroids, hydroquinones, volatile oils, lignans, alkaloids, polysaccharides, resin glycosides and fatty acids. About 3.0% of the total chemical constituents
are avonoids which have been linked to the pharmacological
activities of its extracts, especially kaempferol that shows antioxidant, estrogenic actions and impressive effect on immune
response. The in vitro studies and in vivo models have provided
evidence for various ethnomedicinal uses and pharmacological
activities which strongly indicate that Cuscuta chinensis is useful in
different diseases. Cuscuta chinensis extracts and its chemical
components show antioxidant effects, free radical scavenging
activities, and can regulate immune response, protect hepatic,
cardiovascular, renal, neurological or skin diseases, delay aging
and improve physical properties. Most of the studies were performed only based on the extract. Therefore, the chemical and
pharmacological studies should be conducted using the key
natural products reported from the species and combinations
thereof in order to clarify the pharmacological mechanism of
action and the metabolites responsible for the activities of Cuscuta
chinensis.
Research work on Cuscuta chinensis has recently become
popular, mainly focusing on its preparation, chemical constituents
analysis and pharmacological activities, but the information about
the pharmacokinetics, toxicity or side effects of Cuscuta chinensis
are insufcient, and no major side effects have yet been discovered. Further studies on the pharmacokinetics and toxicology are
needed in order to evaluate the uses of this plant, its extract and
isolated compounds in clinical practice and validate its safety in
humans. Moreover, additional research data and published clinical
trials would be necessary before it can be used in medical
practices worldwide.
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