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Journal of Ethnopharmacology 157 (2014) 292308

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Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jep

Review

Cuscuta chinensis Lam.: A systematic review on ethnopharmacology,


phytochemistry and pharmacology of an important traditional
herbal medicine
Sineeporn Donnapee a,b, Jin Li a, Xi Yang a,b, Ai-hua Ge a,b, Paul Owusu Donkor a,
Xiu-mei Gao a,b, Yan-xu Chang a,b,n
a
b

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: Tcmcyx@126.com (Y.-x. Chang).
http://dx.doi.org/10.1016/j.jep.2014.09.032
0378-8741/& 2014 Elsevier Ireland Ltd. All rights reserved.

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

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

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minute scales. The owers are hermaphrodite. Inorescence lateral,


compact cymose glomelurous, few to many owered clusters or
racemes, white; bracteoles scale-like and bracts. Pedical ca. 1 mm.
Calyx lobe 45, capular, sepals triangular ovate ca. 1.5 mm, ridged
on outer surface, apex obtuse, partly thickened. Corolla 33.5 mm
long, white, urceolate, 4 or 5 lopes, lopes detoid-ovate, apex acute
or obtuse, spreading horizontally, mbriate, reexed, infrastaminal
scales shorter than tube. Stamens anthers ovoid, exserted. Ovary
subglobose, locues 2, ovules 4, styles 2, slender. Stigmas globose,
capitates. Capsules globose, ca. 3 mm wide, enclosed by persistent
corolla; pericarp thin, circumscissile. The seeds 24, broadly
ovalate, 12 mm long, pale brown, not smooth. Flowering in
JuneOctober; DecemberMarch; FebruaryMay and fruits in
AugustOctober. It can grow in semi-shade (light woodland) or
no shade and requires moist soil. It is often on the plants of
Fabaceae, Asteraceae, and Zygophyllaceae. Cuscuta chinensis is
distributed in Africa: Ethiopia; Middle Asia: Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan; Mongolia; Russia;
China; Western Asia: Iran, Iraq, Afghanistan; Tropical Asia: India,
Sri Lanka; Indonesia; Eastern Asia: Korea, Japan, Taiwan, Thailand;
Australasia. It is distributed in most parts of China mainly in
Henan, Jiangsu, Shandong, Hebei, Jilin, Liaoning provinces and

294

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

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,

hyperoside, quercetin, astragalin, kaempferol-3-O-galactoside


and quercetin-3-O-glucoside) with various quantities, and Cuscuta
chinensis having extremely high content of kaempferol-3-Oglucoside (2934% of the total phenolics) among all species. The
water-soluble constituents of Cuscuta chinensis include a tryptophan derivative alkaloid (cuscutamine), and 2 new lignans (cuscutosides A and B), along with 4 known avonoids (astragalin,
hyperoside, quercetin, quercetin-3-O-apiosyl(1-2)-galactoside),
3 known lignans (pinoresinol-4-O-glucoside, pinoresinol, epipinoresinol), p-coumaric acid, caffeic acid, chlorogenic acid, and
arbutin (Yahara et al., 1994). The microelements of this plant such
as calcium, magnesium, iron, manganes, and copper have so far
been identied using atomic absorption spectrometry method
(Zhao et al., 1990). Moreover, ve other compounds were isolated
from petroleum ether and chloroform fractions from the stem of
Cuscuta chinensis for the rst time. Their structures were identied
as -sitosterol, d-sesamin, 9(R)-hydroxy-d-sesamin, D-pinoresinol
and daucosterol by chemical and spectroscopical methods (Ye
et al., 2001). They also isolated 5 principal avonoids, quercetin
3-O--D-galactoside-7-O--D-glucoside, quercetin 3-O- -D-apiofuranosyl-(1etin 3D-galactoside, hyperoside, quercetin and kaempferol by RP-HPLC (Ye et al., 2002). Furthermore, other 2 new lignan
glycosides (cuscutoside C and D) have been isolated in 2010 (He
et al., 2010). In addition, Cheng et al. (2013) studied about the
content of fatty acid in the Cuscuta chinensis seed oil n-hexane
extract by using capillary gas chromatography and they found 16
kinds of fatty acid, primarily including palmitic acid, linoleic acid,
oleic acid, and linolenic acid.
Cuscuta chinensis is an important traditional medicine, which
has many isolated phytochemical compounds including at least
18 avonoids; 13 phenolic acids; 2 steroids; 1 hydroquinone; 10

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

Kaempferol

Quercetin

Isorhamnetin

Astragalin

d - sesamin

Chlorogenic acid

p-coumaric acid

-sitosterol

daucosterol

Rutin

Cinnamic acid

Arbutin

295

Hyperoside

Caffeic acid

caryophyllene

Fig. 2. Structure of some chemical constituents isolated from Cuscuta chinenesis.

volatile oils; 22 lignans; 9 polysaccharides; 2 resin glycosides and


16 fatty acids (more details about the occurrence, the chemical
group and pure compounds isolated from Cuscuta chinensis are
summarized in Table 1). The main chemical constituents of
Cuscuta chinensis seed are avonoids (principally hyperoside,
quercetin, rutin, isorhametin) which were selected as markers to
evaluate the quality of the plant (Shekarchi et al., 2014). Nevertheless, the studies on phytochemistry of the plant are mainly
targeting on the seed while the studies on other parts of the plant
are minority. Therefore, more phytochemistry studies on other
parts of the plant are needed. Meanwhile, the inuence of
different hosts on the contents of phytochemical constituents also
needed to clarify in the future.

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

reproductive organs, spermatorrhea, frequent urination, thirst, mouth's


bitter taste feeling or aggregation of the blood due to cold (Li, 2009).
Moreover, it has been listed in the Pharmacopoeia of the People's
Republic of China (Committee for the Pharmacopoeia of PR China,
1995) since 1995, some of its prescriptions have been used to improve
sexual function, prevent and treat cardiovascular diseases, treat osteoporosis and prevent senescence in clinic. Among them, Gu Jing Bu Shen
pills have been employed for the treatment of premature ejaculation
and spleen and kidney deciency. In addition, many classical medicine
books in China, like Ben Cao Hui Yan, Ben Cao Yuan Shi, Ben Jing Feng
Yuan and Ben Cao Zheng Yi, have recorded that the plant and its
famous prescriptions are used to treat various diseases such as
impotence, infertility, wet dreams, urinary retention, urinary incontinence, lower abdominal and back pain etc. (Ni, 2005; Li, 2013; Zhang,
2011; Zhang, 2013).
Furthermore, the paste of the plant is applied on chronic ulcers and
wounds. Poultice is applied on painful inammations in Pakistan
(Qureshi et al., 2010). In India, the stems from this plant are used in the
treatment of sore heads, inamed eyes (Petel and Petel, 2010),
jaundice (Patil and Patil, 2012) and for removing hair dandruff
(Shubhangi and Patil, 2012). The leaves and the stems of this plant
are used to increase lactation (Patil and Birada, 2011 and Patil et al.,
2010). In Vietnam, the whole plant of Cuscuta chinensis is used for back
pain and constipation (Sam et al., 2008). In Korea, the seeds with other
herbal medicines are used to improve sexual function and health
(Sohn et al., 2008). In Thailand, the whole plant is boiled in water and
used as an anthelminthic and as a body wash for treatment of jaundice
(Smittinan, 2011; Cruz-Garcia and Price, 2011) as shown in Table 2.

4. Pharmacokinetics
The studies about pharmacokinetics (PK) of Cuscuta chinensis
are very limited. There are 2 reports: the PK study of quercetin in

296

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

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

Ye et al., (2002); Pan et al., (2014)

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

Whole plant; seed; stem Lofer et al., (1997); Ye et al., (2005)


Seed
Pan et al., (2014)

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

Hajimehdipoor et al., (2012); Ye et al., (2005)


Ye et al., (2005)
Yang et al., (2009a, 2009b); Lofer et al., (1997);
Yahara et al., (1994); Ye et al., (2005)
Hajimehdipoor et al., (2012); Lofer et al., (1997);
Yahara et al., (1994); Pan et al., (2014);
Ye et al., (2005)
Ye et al., (2001); Hajimehdipoor et al., (2012)
Kwon et al., (2000)
Ye et al., (2005)

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

Pan et al., (2014); Ye et al., (2005)


Yahara et al., (1994)
He et al., (2010)
He et al., (2010)
Ye et al., (2005)
Kwon et al., (2000)
Ye et al., (2005)
Lofer et al., (1997); Ye et al., (2005)
Ye et al., (2005)
Lofer et al., (1997); Ye et al., (2005)
Ye et al., (2005)
Yahara et al., (1994)
He et al., (2010); Lofer et al., (1997); Yahara et al., (1994)

-Sitosterol

Seed

Ye et al., (2001)

Daucosterol

Seed

Ye et al., (2001)

Hydroquinone
Arbutin

Fruit

Yahara et al., (1994)

Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed
Seed

Hou
Hou
Hou
Hou
Hou
Hou
Hou
Hou
Hou

Seed
Seed

Hou et al., (2003)


Hou et al., (2003)

Seed

He et al., (2010); Du et al., (1998)

20 -Hydroxy asarinin 20 -0-j-xylopyranosyl-(1-6)--glucopyranoside


(Cuscutoside B)

Seed

He et al., (2010); Du et al., (1998)

20 -Hydroxyl asarinin 20 -O--D-glucopyranoside (Cuscutoside C)

Seed

He et al., (2010); Du et al., (1998)

Seed

He et al., (2010); Du et al., (1998)

Fruit
Seed
Fruit
Fruit
Seed; stem

Yahara et al., (1994)


Ye et al., (2001)
Yahara et al., (1994)
Yahara et al., (1994)
Ye et al., (2005)

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

20 -Hydroxyl asarinin 20 -O--D-apiofuranosyl-[(1-2)-

(1-6)--D-glucopyraniside (Cuscutoside D)
( )-Pinoresinol
D-Pinoresinol
( )-Epipinoresinol
( )-Pinoresinol-4-O-glucoside
d-Pinoresinol-4-O-glucoside

D-glucopyranosyl-

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

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

Wang et al., (2001)

Seed

Wang et al., (2001)

Seed

Miyahara et al., (1996)

Seed

Miyahara et al., (1996)

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-

hydroxytetradecanoyl]-[4-O-(2R,3R) -3-hydroxy-2-methylbutyryl]--Lrhamnopyranose- (1-20-[6-O-acetyl]-D-glucopyranoside

-L-rhamnopyranosyl-(1- 3) [2-O-(11S) -11-hydroxypamitoyl]-[4-O-(2R,

3R)-3- hydroxy-2-methylbutyryl]--L-rhamnopyranose-(1-2-0-[6-Oacetyl]-D-glucopyranoside

rat and hyperoside in human after oral administration of Cuscuta


chinensis. Zheng et al. studied about the PK of Cuscuta chinensis in
rat's serum by using HPLC-UV to determine the concentrations of
quercetin in rats plasma. The rats were given 0.85 g/kg 95%
ethanol extract of the Cuscuta chinensis seeds by gavage. They
found that the highest concentration of quercetin was 0.401 ng/mL
after 0.333 h (Zheng et al., 2004). The PK of hyperoside was
studied after oral administration of Cuscuta chinensis ethanol
extract in 5 healthy female volunteers by HPLC-UV. At 3.259 h,
the highest concentration of hyperoside was 3.902 ng/mL (Peng,
2010). All the parameters of PK are shown in Table 3. This
information showed that the main phytochemical constituents
that were found in the body after oral administration were
avonoids(quercetin and hyperoside). Moreover, there is a report that
quercetin can inhibit CYP450 enzymes (Gaudineau et al., 2004). Due to
the limited information about the PK of Cuscuta chinensis, further
research works such as the study of the PK of Cuscuta chinensis and the
individual chemical constituents, the bioavailability, the relationship of

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)

PK and pharmacodynamics especially in human subjects should be


conducted.

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

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

Table 2
Ethnopharmacology of Cuscuta chinensis.
No.

Ethnomedicinal uses

Parts of the plant

Locality

References

Treatment of male infertility, importance, spermatorrhea


Treatment of female infertility due to cold uterus
Treatment of frequent urination
Treatment of diarrhea
Prevent abortion
Improve vision
Prevent aging
Improve activity of bone and tendon
Treatment of thirsty, bitter taste feeling or dry mouth
Treatment of blood aggregation due to the cold
Treatment of urinary retention
Treatment of urinary incontinence
Treatment of lower abdominal and back pain
Treatment of chronic ulcers, wounds, painful inammation
Ttreatment of sore heads and inamed eyes
Treatment of jaundice
Removes hair dandruff
Facilitates lactation
Treatment of back pain and constipation
Improves sexual function and health
As an anthelminthic, and to alleviate jaundice

Seed

China

Teng, (2007), Li, (2009); Committee for


the Pharmacopoeia of PR China, (1995);
Ni, (2005); Li, 2013; Zhang, (2011);
Zhang, (2013)

Whole pant
Stem
Stem
Stem
Leaf
Whole plant
Seed
Whole plant

Pakistan
India

Qureshi et al., (2010)


Petel and Petel, 2010
Patil et al., (2012)
Shubhangi and Patil, 2012
Patil et al., (2011); Patil et al., (2010)
Sam et al., (2008)
Sohn et al., (2008)
Smittinan, (2011)

2
3

4
5
6

Vietnam
Korea
Thailand

Table 3
Pharmacokinetic information of Cuscuta chinensis.
Species/ bio-matrix Analytes

Administration route/
dosage

PK parameters (or important information)

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

the 252nd day. They observed the decreases in the number of


papillomas per mouse in 190th day and the volume of papillomas
per mouse on 206th day. The results show that Cuscuta chinensis
signicantly inhibited the appearance and development of skin
papillomas and also reduced the incidence of carcinoma (Nisa
et al., 1986).

References

Zheng et al., (2004)

enzymes may be the major mechanism of Cuscuta chinensis


ethanol extract to prevent the development of liver damage
induced by APAP (Yen et al., 2007). Moreover, it will be more
effective when the seed of Cuscuta chinensis is prepared in
nanoparticles (Yen et al., 2008b). These two studies indicate that
Cuscuta chinensis seeds have an exact effect on prevention of
hepatotoxicity.

5.2. Hepatoprotective activity


5.3. Anti-osteoporotic activity
There are two ethnomedicinal references for the use of Cuscuta
chinensis in liver disease. The study of hepatoprotective activity
was performed to prove the claims that Cuscuta chinensis has
hepatoprotective effect. Yen et al. studied about hepatoprotective
effect of the aqueous and ethanol extracts of Cuscuta chinensis
against acetaminophen (APAP)-induced hepatotoxicity in rats.
They found that the seed of Cuscuta chinensis ethanol extract at
oral dose of both 125 and 250 mg/kg signicantly reduced the
evaluation of glutamate oxaloacetate transaminase, glutamate
pyruvate transaminase, and alkaline phosphatase (ALP). In addition, the ethanol extract can prevent liver histopathological
changes such as centribular hepatic necrosis, kupffer cell inltrating lymphocytes, ballooning degradation, and APAP-induced hepatotoxicity in rats. They also found that high doses of APAP could
lead to decreased levels of antioxidant enzymes (glutathione
peroxidase superoxide diamutase (SOD), and catalase) and indicate a signicant level of hepatotoxcity, and the ethanol extract of
Cuscuta chinensis could raise the levels of SOD, catalase and
glutathione peroxidase. In contrast, the aqueous extract did not
show any effect. However, the enhanced levels of antioxidant

Cuscuta chinensis has been used for treatment of osteoporosis in


China and in some Asian countries. Yao et al. (2005) demonstrated
that addition of an aqueous extract of Cuscuta chinensis in rat bone
cells signicantly promoted the differentiation and proliferation of
osteoblasts, but the activities of osteoclasts were inhibited. The
water extract of dry Cuscuta chinensis seed can promote
osteoblast-like MG-63 cells differentiation in a dose-dependent
manner. The extract enhances ALP activity, collagen synthesis,
bone morphogenetic protein (BMP-2) expression, and mineralization in MG-63 cells (Yang et al., 2009a). These observations
indicate that Cuscuta chinensis has osteogenic effects. Moreover,
Yang et al. studied about antiosteoporotic compounds from seeds
of Cuscuta chinensis. They isolated 5 avonoids from Cuscuta
chinensis and found that kaempferol and hyperoside signicantly
increased the ALP activity in osteoblast-like UMR-106 cells, astragalin promoted the proliferation of UMR-160 cells. 5 avonoids
also promoted Hela cell, a human cervical cancer cell via estrogenic receptor ER and ER. They suggested that kaempferol and
hyperoside are the active compounds in this plant for osteogenic

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

299

Table 4
Pharmacology of Cuscuta chinensis.
No.

Activities

Part of
plant

Model

Formulation /dosage/ Control


extract

Result

Skin protective
activity

Whole
plant

Mice (in vivo)

P.O. 1 g/kg body wt of Positive control: 150 g


water extract 3 times/ DMBA appy on skin for
week
7 days; negative control:
P.O. distilled water

Cuscuta chiensis inhibit both the appearance Nisa et al.,


and development of skin papillomas and also (1986)
reduced the incidence of carcinoma
transformation.

Hepatoprotective Seed
activity

Rats (in vivo)

P.O. 125 and 250


mg/kg of water and
ethanol extract

125 and 250 mg/kg ethanol extract can


signicantly inhibit liver damage caused by
APAP-induced hepatotoxicity

Seed

Rats (in vivo)

Positive control: P.O.


APAP 835 mg/kg single
dose; negative control:
I.P. normal saline
Positive control: P.O.
P.O. 125 and 250
mg/kg ethanol extract, APAP 835 mg/kg single
and 25 and 50 mg/kg dose; negative control:
I.P. normal saline
nanoparticles of
ethanol extract

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

1, 5, 10, 50, 100 g/ml Positive control: 0.1 M


of its organic fraction 17--estradiol; negative
and 1, 5, 10, 50 M of control: DMSO 0.1 v/v
its isolated avonoids

Seed

Mice (in vivo)

P.O. 100, 200 or

Positive control: S.C.

400 g of ethanol
extract

OVA 100 g negative


control: S.C. normal
saline

Seed

Mouse bone
marrowderived DCs
(in vitro)

Positive control: LPS


50 g/ml methanol
ectract and its organic 100 ng/ml negative
control: DMSO 0.1% v/v
fraction and 20 g/ml
kaempferol

Seed

Mice (in vivo)

P.O. 20 ml/kg of the


Negative control: P.O.
ethanol extract 200 g/l 20 mg/kg normal saline

Seed

PC12 cells
(in vitro)

Cuscuta chinensis
glycoside up to
200 mg/l

Positive control: 7S
nerve growth factor;
negative control:
distilled water

Seed

Mice (in vivo)

P.O. decoction of 20 g
Cuscuta chinensis with
other Invigorating-Qi
drug

Seed

Rats (in vivo)

P.O. 50, 100 and 200


mg/day CMSD

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)

The ethanol extract


and its organic
fractions

Seed

IC50 (in vitro)

Methanol extract and


its organic fraction

induced at 500 and 1000 g/ml


Yang et al.,
Isolated avonoids, show osteoporotic
(2011)
activities, keampferol and hyperoside
signicantly increased the ALP activity in
oteoblast-like UMR-106 cells and astragalin
promoted the proliferation of UMR-160 cells.
The ethanol extract can signicantly enhance
the mitogen- and ovalbumin (OVA)-stimulated
splenocyte proliferation in OVA-immunized
mice, and enhance a specic antibody and
cellular response against OVA in mice.
Keampferol can reduce cytokines and
chemokines produced by LPS-stimulated
dendritic cells (DCS), and abrogate the ability
of LPS-stimulated DCs to promote Ag-specic
T cell activation, both in vitro and in vivo.
Cuscuta chinensis has the immune
enhancement, anti-fatigue and anoxia
tolerance effects.

Pan et al.,
(2005)

Cuscuta chinensis glycoside can induce


neuronal differentiation with resulting
outgrowth of neutrites and increase of
acetylcholinesterase activity in rat
pheochromocytoma PC12 cells in a dosedependent manner
Cuscuta chinensis with other Invigorating-Qi
drug had an evident antagonistic action to
Scopolamine induced dysmnesia mice, and
could improve their memory.

Liu et al.,
(2003)

Cuscuta chinensis with other 7 medicinal


herbs (CMSD) had neuroprotective effects on
cultured primary neuron cell of neonatal rat,
and prevented ischemia-induced learning
disability and rescued hippocampal CA1
neurons from lethal ischemic damage in rats.
Positive control:
They show potent antioxidant for preventing
quercetin and kaemferol free radical damage to cell membranes
through scavenging of free radicals and
inhibition of the liquid peroxidation.
The ethyl acetate fraction of methanol extract
of Cuscuta chinensis seeds showed the
highest activity (EC50 value of 50 mg) by using

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

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

Table 4 (continued )
No.

Activities

Anti-aging

Effects on tumor
cells

Part of
plant

Model

Formulation /dosage/ Control


extract

Seed

MC3T3-E1
cells (in vitro)

10, 20 and 40 mg/l


water extract

Seed

PC 12 cells
(in vitro)

25250 mg/l Cuscuta


chinensis avonoids

Seed

Mice (in vivo)

P.O. 100, 200 and


400 mg/kg/day of
polysaccharides

Whole
plant
Seed

Seed

CCRF-CEM and 0.125 g/ml water


JM cells
extract
(in vitro)
MCF-7 cells
and T47D cells
(in vitro)
Hela cells
(in vitro)

Result

the DPPH free radical scavenging method for


screening antioxidative effects
Positive control: 0.1 mM The water extract can signicantly inhibited
TBPH; negative control: the reactive oxygen species (ROS) generation,
DMSO 0.1% v/v
malondialdehyde (MDA) production, and
increased the activity of superoxide
dismutase (SOD), GR, GST, and G6PD in
murine osteoblastic MC3T3-E1 cells tertiary
butyl hydroperoxide (TBHP) induced injury.
Cuscuta chinensis avonoids can protect PC12
Positive control: 0.3
0.5 mm H2O2; negative cells against oxidative stress by its ability of
control: DMSO 0.1% v/v scavenging ROS and increasing the activity of
antioxidant enzyme.

Reference

Gao et al.,
(2013)

Zhen et al.,
(2006)

Positive control: S.C. 5% The Cuscuta chinensis polysaccharides had


the anti-aging effects on senile mice model.
5 ml at the
nape, vitamin E 200 mg/
kg/day; negative
control: S.C. distilled
water, vehicles

Cai et al.,
(2005)

Negative control: culture Whole plant water extract has cytotoxic


medium
effect on human caucasian acute
lymphoblastic leukemia (CCRF-CEM) cells.
Cuscuta chinensis extract can stimulate
MCF-7 and T47D human breast cancer cell

Zeraati
et al., (2010)

D-galactose

1, 5, 10, 50, 100 g/ml Positive control: 0.1 M


of its organic fraction 17--estradiol; negative
and 1, 5, 10, 50 M of control: DMSO 0.1% v/v
its isolated avonoids

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

Rats (in vivo)

P.O. 250 mg/kg/day


aqueous extract

Positive control: renal


arteries were clamped
for 45 h; negative
control: operation
without clamping renal
arteries

The water extract 250 mg/kg/day oral


administration can recover rats renal
function parameters from ischemia/
reperfusion-induced ARF.

Shin et al.,
(2011)

10

Reproductive
system

Seed

Penile tissues
(in vitro)

15 mg/ml ethanol
extract

Positive control:

1, 2, 3, 4 and 5 mg/ml of Cuscuta chinensis


extract has the effect on the rabbit penile
corpus cavernosum (PCC) by relaxing PCC

Sun et al.,
(2013)

11

Prevention of
abortion

Seed

Rats (in vivo)

P.O. 100 and 300


mg/kg of the herbal
formula (KH-204)

Seed

Human
(in vivo)

Seed

Seed

Human
spermatozoa
(in vitro)
Mice (in vivo)

P.O. VPX (25 mg of


Cuscuta chinensis
seeds with other
herbal medicie) twice
daily
Decoction with other
herbal medicine

Seed

Rats (in vivo)

P.O. 510 mg/100 g of


avonoids

Seed

Pregnant rats
(in vivo)

P.O. 2.6 and 5.2


mg/kg/day with S.C.
bromocriptine

Seed

Pregnant rats
(in vivo)

P.O. 2.6 and 5.2


mg/kg/day with S.C.
bromocriptine

P.O. 33.8 mg/kg and


67.6 mg/kg of the
ethanol extract

10 mol/l phenylephrine
precontracted, 10 nmol/l
sildenal citrate;
negative control: DMSO
0.1%
Negative control: P.O.
distilled water

phenylephrine (10 mol/l) induced


contraction in a dose dependent manner.
100 mg and 300 mg/day for 4 weeks oral
administration of KH-204 decresed blood
pressure and enhanced penile erection in
spontaneous hypertensive male rats.
VPX can improve sexual abilities on patients
with erectile dysfunction.

Sohn et al.,
(2008)

Cuscuta chinensis improve sperm motility


and help stabilized sperm membrane
function.
Seed of Cuscuta chinensis ethanol extract
Positive control: P.O.
33.8 mg/kg and 67.6 mg/kg can reverse the
1.3 g/kg
reduction of testosterone level, the androgen
metyltestoseterone or
receptor mRNA level and protein level
6 g/kg Jinkui Shenqi
wan; negative control: P. induced by the hydrocortisone in the kidney
and testicle.
O. distilled water
Negative control: P.O.
Flavonoids from Cuscuta chinensis seeds (FSC)
normal saline
improved the ovarian endocrine functions.

Peng et al.,
(1997)

Negative control: P.O.


placebo

Positive control: S.C.


0.3 mg/kg/day
bromocriptine; negative
control: do nothing
Positive control: S.C.
0.3 mg/kg/day
bromocriptine; negative
control: do nothing

Cuscuta chinensis total avonoids regulate


the proliferation and apoptosis of the
deciduas and cytotrophoblasts and prevent
spontaneous abortion in rats.
Cuscuta chinensis total avonoids can
regulate endocrinological and immunological
network equilibrium on maternal-fetal face
and nally achieve prevention of fetal
abortion.

Shah et al.,
(2012)

Yang et al.,
(2008)

Wang et al.,
(2002)
Ma et al.,
(2008b)

Ma et al.,
(2008a)

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

301

Table 4 (continued )
No.

Activities

Part of
plant

Model

Formulation /dosage/ Control


extract

12

Antimutagenic
effect

Whole
plant

Bacteria
(in vitro)

0.1 mg of dry plant


methanol extract

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

Positive control: I.V.


50 mg/kg alloxan, P.O.
acarbose 20mg/kg;
negative control: P.O.
normal saline
Positive control: I.V.
50 mg/kg streptomycin,
P.O. 13 mg/kg acar bose;
negative control: I.V.
sodium citrate buffer
pH 4.5

Seed

Mice (in vivo)

P.O. 150, 300 and


600 mg/kg total
avonoids

Seed

Rats (in vivo)

P.O. 100, 200 and


400 mg/kg
polysaccharides

Seed

Dogs (in vivo)

I.V. 0.1 g/kg Cuscuta


chinensis decoction

Seed

Dogs (in vivo)

Seed

Rats (in vivo)

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)

Cuscuta chinensis decoction in dogs can


reduce their blood pressure.

I.V. 20 mg/kg and


1 ml/kg of 3 different
ethanol extract

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

Mice (in vivo)

I.P. 50 and 100 mg/kg


methanol extract

16

CNS depressant

Whole
plant

Mice (in vivo)

P.O. 1 g/kg aqueous


extract

The extract signicantly decreased the motor Akbar et al.,


(1985)
activity and the tonic and clonic phases of
electrically induced seizures in mice.

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

IC50 (in vitro)

0.1, 1, 10 and 50 mg/ml Positive control: 10  8,


of water extract
10  7, 10  6, 10  5 mol/l
8-methoxypsoralan
negative control: culture
medium
Positive control: apply
Apply 0.49, 0.93 and
5% H2O2 1 ml on skin,
1.86 g/kg of Cuscuta
methoxsalen 1 ml;
chinensis in alchohol
preparation (0.25 g/g) negative control: apply
alcohol on skin
Positive control: 100
0.520 mg/ml of
water and ethanol
g/ml arbutin; negative
extract
control: solvent of
sample

Seed

Zebrash
(in vivo)

P.O. 0.520 mg/ml of


water and ethanol
extract

Positive control: 100


g/ml arbutin; negative
control: solvent of
sample

1. 86, 0. 93 g/kg externally applied on guinea Shen et al.,


(2012)
pig skin signicantly increased the skin
melanin generation, and tyrosinase
production
The water extract of Cuscuta chinensis show
inhibition of tyrosinase activity in a dose
dependent manner with IC50 value of 12
mg/ml and decrease the synthesis of
melanin.
Water extract of Cuscuta chinensis seeds
demonstrate depigmenting activity in
zebrash

Wang et al.,
(2014)

Huang et al.,
(2013)

Wang et al.,
(2014)

18

Anthelminthic

Seed

Goldsh
(in vivo)

P.O. 1% body weight of Negative control: DMSO


125300 mg/l organic
fraction

The EC50 of Cuscuta chinensis methanol


extract at 48 h 15.9 mg/L, by using in vivo
anthelminthic efcacy assay.

19

Anti-nociceptive

Seed

Mice (in vivo)

P.O. 20500 mg/kg


methanol extract

100 and 500 mg/kg of Cuscuta chinensis seeds Liao et al.,


(2014)
methanol extract signicantly reduce the
writhing response, at the dose of 20500
mg/kg it can reduce licking time

20

Antiinammatory

Seed

Mice (in vivo)

P.O. 20500 mg/kg


methanol extract

The extract can signicantly reduce


-carrageenan-induce edema paw in the
time of four hours after injection with
-carrageenan.

Liao et al.,
(2014)

302

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

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).

5.6. Antioxidant activities


The ethyl acetate organic fraction from ethanol extract of the seeds
of Cuscuta chinensis was observed to possess strongest antioxidant
effects with highest content of the avonoid compounds kaempferol
and quercetin. Ethanol extract of Cuscuta chinensis seeds is an effective
antioxidant for free radical damage on cell membranes prevention
through scavenging of free radicals and by inhibiting the liquid
peroxidation process (Yen et al., 2008a). The ethyl acetate fraction of
Cuscuta chinensis seeds methanol extract showed the highest activity
(EC50 50 mg) by using the DPPH free radical scavenging method for
screening anti-oxidative effects, and there are 5 compounds isolated
from this fraction; methyl 4-hydroxy-3,5-dimethoxycinnamate, caffeic
acid, quercetin, kaempferol and calycopteretin (EC50 values of 0.6, 8,
19, 17 and 12 mg, respectively) (Kwon et al., 2000). Gao et al. studied
about Cuscuta chinensis water extraction protecting murine osteoblastic MC3T3-E1 cells against tertiary butyl hydroperoxide (TBHP)
induced injury. They found that the Cuscuta chinensis protects TBHPtreated MC3T3-E1 cells from death in a dose-dependent manner and
it could suppress the malondialdehyde (MDA), reactive oxygen species
(ROS) productions, and signicantly enhance the Glutathione S-transferase, superoxide dismutase (SOD), glutathione reductase, and
Glucose-6-phosphate dehydrogenase activities. In mitochondria, the
release of the caspase 3 and Bax expression and cyto c were decreased,
but the expression of antiapoptotic IDH2, Sirt3, and Bcl-2 was
increased in the cells incubated with Cuscuta chinensis. Therefore they
suggested that the treatment of Cuscuta chinensis with the TBHP
regulated the oxidative stress-induced apoptosis in MC3T3-E1 cells
because of its antioxidant abilities and functioning against
mitochondria-dependent pathways (Gao et al., 2013). Pretreatment
of Cuscuta chinensis avonoids (CF) with different concentrations for
0.5 h enhances the survival rate of PC12 cells, inhibits H2O2-induced
apoptosis and CF had the DPPH-generated scavenging free radicals
activity in a dose-dependent manner. These results suggest that CF can
protect PC12 cells against oxidative stress by its scavenging ROS ability
and increasing the antioxidant enzymes activity (Zhen et al., 2006).
The in vitro antioxidant activities considered to be due to phenolic
compounds, avonoids and phenolic acids found in Cuscuta chinensis
which can act as free radical scavengers. The antioxidant activity could
be useful in preventing oxidative stress implicated with the development of many diseases such as cardiovascular or neurological diseases.
5.7. Anti-aging activities
Cai et al. studied the effect of a polysaccharide from Cuscuta
chinensis (PCCL) in senile mice model. The results showed that
polysaccharides from Cuscuta chinensis with oral administration of
100, 200, 400 mg/kg/d (for 7 weeks) can raise Lipofuscin (LF),
spleen index, thymus index, glutathione peroxidase and SOD in
the liver and kidney. In the brain, LF and MDA contents were
dropping which in senile mice model the results were found the
opposite way, indicating that the PCCL can scavenge free radicals,
has anti-lipid peroxidation and anti-aging activities (Cai et al.,
2005). Ethanol extract of Cuscuta chinensis showed anti-aging
effects in the D-galactose-induced rat aging model. The D-galactose
aging Wistar rat model was performed by subcutaneous injection
of 48 mg/kg D-galactose in the cervico-dorsal region once daily for
45 days. While Cuscuta chinensis was given by gavage, the results
showed that on day 30, Cuscuta chinensis signicantly inhibited
the non-enzymatic glycosylation reaction of D-galactose-induced
rat aging model (Li et al., 2013). These ndings indicate that
Cuscuta chinensis has signicant anti-aging effects in animals.
Moreover, Cuscuta chinensis is indicated in Tai Ping Sheng Hui
Fang which are recorded anti-aging prescriptions. The research
showed that Cuscuta chinensis could regulate immune function,
prolong cell cycle, improve body metabolism and the function of

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

internal organs and stress ability, which express as anti-aging


effects (Yang and Huang, 1998). From these results, it has obvious
effects on anti-aging and can prove the claim of the anti-aging
uses in ancient times. However, further research work and development should be performed to provide more information about
the adverse effects or toxicities.
5.8. Effects on tumor cells
Zeraati et al. (2010) studied about cytotoxic effect of Cuscuta
chinensis whole plant water extract on human Caucasian acute
lymphoblastic leukemia (CCRF-CEM) and a human lymphocyte,
Jurkat (JM) cells. The minimum effective concentration of the plant
extract was 1 g/mL, and the stronger effect was shown in the
dose up to10 g/mL. The extract has the IC50 value of 3 g/mL in
24 h and 2.5 g/mL in 48 h, respectively. But in these doses the
extract did not have cytotoxic activity on JM cells. Seeds of Cuscuta
chinensis extract can stimulate MCF-7 and T47D human breast
cancer cell proliferation at a concentration of 10 M (Umehara
et al., 2004), and the Cuscuta chinensis seeds absolute ethanol
extract show no cytotoxicity against T47D cells (Ahmed et al.,
2014). Compounds isolated from the ethanol extract of Cuscuta
chinensis seeds promoted Hela cells (a human cervical cancer cell
line) through estrogenic receptor ER and ER, while quercetin,
kaempferol and isorhamnetin, and some other isolated compounds showed more selectivity in ER (Yang et al., 2011). The
cytotoxic effects of Cuscuta chinensis on human cancer cell line
may also have the potential in anticancer application and might
support the use of this plant in prostate, bladder, gastroesophageal and brain cancers (Alaoui-Jamali, 2010), except in the
human cell line that requires estrogen to grow because Cuscuta
chinensis and some of its extracts can act as a phytoestrogen so can
be counter-productive in such cell lines.
5.9. Renoprotective effects
Cuscuta chinensis seed water extract has a recovery effect in
ischemia/reperfusion-induced acute renal failure (ARF) rats on the
renal function parameters. In oral administration of 250 mg/kg/
day of the extract in male SD rats for four days, the results
indicated that the parameters of renal function including urinary
excretion rate, osmolality, potassium, sodium and chloride ions,
creatinine clearance and solute-free water reabsorption were
signicantly improved and also ameliorated tubular damage in
ischemia/reperfusion induced ARF rats (Shin et al., 2011). Although
the renoprotective effect of Cuscuta chinensis against physicalinduced kidney damage in rats was investigated and showed
satisfactory results, the mechanism and the chemical constituents
responsible for these activities are still unclear, therefore further
research work should be conducted.
5.10. Effect on reproductive system
The ethanol extract of Cuscuta chinensis has effects on the rabbit
penile corpus cavernosum (PCC) by relaxing PCC phenylephrine
induced contraction in a dose dependent manner and signicantly
increases sildenal-induced PCC relaxation. The penile cavernous
tissue incubated with the Cuscuta chinensis extracts show that the
cyclic guanosine monophosphate and cyclic adenosine monophosphate levels in the PCC were raised signicantly. Since the Cuscuta
chinensis extract presents a relaxing effect on penile cavernous tissue
by activating the nitric oxide-cyclic guanosine monophosphate pathway, it may improve erectile dysfunction conditions which do not
completely respond to sildenal (Sun et al., 2013). Sohn et al. also
investigated the effects of the formulation of Cuscuta chinensis with
other herbal medicines called KH-204 on the penile erection and

303

corpus cavernosum of spontaneous hypertensive male rats. They


found that the KH-204 herbal formulation enhances intracavernous
pressure and nitric oxide-cyclic guanosine monophosphate activity in
penile tissues of spontaneous hypertensive male rats (Sohn et al.,
2008). Moreover, 12 weeks treatment of Cuscuta chinensis in combination with other herbal medicines called VXP can improve sexual
functions of erectile dysfunction patients, by signicantly improving
IIEF-Erectile Function scores including orgasmic function, sexual
desire, intercourse satisfaction, and overall satisfaction, while there
was no difference in incidence of side effects and subject's rating for
tolerability against placebo group (Shah et al., 2012). Yang et al.
discovered the effect of the total avones from Cuscuta chinensis
seeds on the kidney-yang deciency male mouse. Total avones from
Cuscuta chinensis seeds can reverse the reduction of testosterone
level, androgen receptor mRNA level and protein level induced by the
hydrocortisone in the kidney and testicle (Yang et al., 2008). Peng
et al. studied about the effects of Cuscuta chinensis on human sperm
motility in vitro and cytomembrane function. The results showed that
the motility of sperm signicantly improved and after incubation the
function of sperm membrane became more stable (Peng et al., 1997).
Flavonoids from Cuscuta chinensis seeds (FSC) enhanced the ovarian
endocrine functions in female rats exposed to psychological stress by
reducing the beta-endorphin content in hypothalamus and increasing the LH content in anterior pituitaries and the basophilic cells,
which may be the mechanism of FSC in improving hypothalamuspituitary-ovary axis (Wang et al., 2002). In order to investigate the
effects of herbal medicines on small uterus (infantile uterus), 46
cases of patients with infantile uteruses were treated with a
compound formula containing Cuscuta chinensis, Rhizoma Curculiginis, Radix Morindae Ofcinalis, Radix Polgoni Multiori, Radix Rehmanniae Praeparata, Cervus elaphus and Herba Epimedii. This drug formula
was taken together with diethylstilbestrol 1 mg dosage by starting on
the 5th day of the menstrual cycle, only once a day for 20 days.
Following treatment, 37 cases exhibited complete recovery while
9 cases showed improvement (Yin et al., 1992). The in vitro and
in vivo studies about the reproductive system of Cuscuta chinensis, its
extracts and isolations showed potential improved effects in both
male and female reproductive system including improved fertility.
5.11. Prevent abortion
Total avonoids of Cuscuta chinensis regulated the deciduas and
cytotrophoblasts proliferation and apoptosis, prevented spontaneous abortions by enhancing expression of proliferating cell
nuclear antigen on trophoblast and deciduas, heparin blinding
epidermal growth factor on trophoblast, progesterone receptor on
deciduas, and decreased expression of heparin blinding epidermal
growth factor on deciduas in pregnant rats (Ma et al., 2008b). Total
avonoids of Cuscuta chinensis could regulate endocrinological and
immunological network equilibration on maternal-fetal face,
nally achieving the prevention of abortion (Ma et al., 2008a).
Moreover, Cuscuta chinensis with Radix Codonopsis Pilosulae, Colla
Corii Asini, Rhizoma Atractylodis Macrocephalae and Radix Dipsaci
were used in treatment of 110 threatened abortion cases. Oral
administration of the medicine once daily in the patients for 10
days, and the total effective rate was found to be 96.36% (Zhu et al.,
1987).
5.12. Anti-mutagenic activity
The methanol extract of Cuscuta chinensis has antimutagenic
effect against Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]
indole) in Ames test, which has ED90 (suppressed 90% of the
mutagenesis) values lower than 5 L/plate of 0.1 mg dry plant
material equivalent (Nakahara et al., 2002). From the results, we
also know that Cuscuta chinensis methanol extract may not cause

304

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

cancer (the mutagenic chemical may act as a carcinogen) and has


an ability to prevent mutation but the Ames test is only one of the
initial screens for potential drugs to weed out possible carcinogens, so further investigation should continue.

5.13. Anti-diabetic activities


Li et al. studied about Cuscuta chinensis polysaccharides (CCP)
effects on diabetic mice induced by alloxan. Oral administration of
300, 600 mg/kg CCP signicantly decreases the high fasting blood
glucose level, increases weight of body and immune organs
(Li et al., 2008a,). Moreover, Xu et al. (2011) studied CCP effects
in diabetic rat model. They found that after 15 days of treatment
with oral administration of 200 and 400 mg/kg CCP in diabetic rats
could signicantly reduce fasting blood glucose, glycosylate serum
protein and increase body weight; 400 mg/kg CCP could signicantly reduce CHO levels; and 400, 200, 100 mg/kg CCP could
signicantly reduce TG levels, but observed no obvious effect on
insulin levels. Moreover, Cuscuta chinensis has been used in antidiabetic prescriptions because it can invigorate kidney and supplement essence (Li et al., 2004; Chauhan et al., 2010). These
mentioned above results of preclinical investigations show that
Cuscuta chinensis polysaccharides show potential effect on reducing blood sugar in type-2 diabetes, but the mechanism of this
effect is still unclear. Therefore, more studies are needed to prove
clinical efcacy and reveal the exact mechanism of action.

5.14. Cardiovascular activities


Cuscuta chinensis seeds in the preparation of tincture and
decoction exhibit a contractile effect on toad heart model
in vitro. The heart rate was shown to rise with the decoction
preparation but was shown to decrease with the tincture preparation. Administration of 0.1 g/kg bodyweight of Cuscuta chinensis
seeds decoction given to anaesthetized dogs by intravenous (I.V.)
injection produced a reduction in their blood pressure (Jiangsu
New Medical College, 1997). Liu et al. (2004) administered IV
injection of Cuscuta chinensis seeds extract to mature male hybrid
dogs and found that the extract could increase coronary blood
ow as well as reduce myocardial oxygen consumption. Cuscuta
chinensis seeds extract signicantly has a protective effect on
myocardial ischemia/reperfusion injury (MI/RI) rats (Han et al.,
2011). The results show that the extract can slow down heart rate.
The level of ST signicantly declined when blood is reperfused for
60, 90, 120 min. The degree of myocardial infarction was obviously
decreased and the content (U/L) of creatine kinase (CK), creatine
kinase (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) in blood serum were signicantly reduced when
compared to control group. However, further studies are required
to determine its specic interaction and exact mechanism of
action.

5.16. CNS depressant activities


The aqueous extract of the whole plant of Cuscuta chinensis was
studied for its CNS-depressant activity. Administer of 1 g/kg body
weight per os of the extract in mice signicantly reduced the
motor activity and the tonic/clonic phases of electrically-induced
seizures. The narcosis and survival time under hypoxia in mice of
pentobarbitone were signicantly intensied. The amphetamineinduced excitation was antagonized and the extract also exhibited
marked analgesic activity. However, the extract did not affect the
reserpine-induced hypothermia and normal body temperature in
rats (Akbar et al., 1985). The results indicate that Cuscuta chinensis
has CNS depressant activity due to its potential effect against
seizure and synergistic effect when combined with pentobarbitone. Further research should be considered to evaluate the effects
in human subjects.
5.17. Effect on melanin production
Li et al. studied about the Cuscuta chinensis aqueous extract on
the differentiation of amelanotic melanocytes (AMMC) of outer
root sheath from human hair follicles. The results showed that the
extract promoted melanogenesis of AMMC and increased the
tyrosinase activities in a dose-dependent manner, but the effect
was weaker than 8-methoxypsoralan (Li et al., 2008b). The doses
of 1.86, 0.93 g/kg Cuscuta chinensis preparation externally applied
on guinea pig skin which signicantly increased the skin melanin
generation and tyrosinase production, and high doses of Cuscuta
chinensis increased the activity of cholinesterase and reduced the
activity of monoamine oxidase. It also showed good effects on
vitiligo treatment in guinea pigs (Shen et al., 2012). Furthermore,
there is another study on melanogenesis effect of Cuscuta chinensis
seeds water extract and ethanol extract in vitro and in vivo.
Tyrosinase activity assay in mushroom and mouse B16F10 melanoma cell and depigmenting activity in zebrash were performed.
The water extract showed the inhibition of tyrosinase activity in a
dose-dependent manner with IC50 value of 12 mg/mL (after
2 weeks of preparation extract) while the ethanol extract showed
the opposite effect in tyrosinase activity, and the water extract
decreased the synthesis of melanin. They conclude that the
contrast effect on melanin production is due to the different
extraction methods (Wang et al., 2014).
5.18. Anthelmintic activities
Cuscuta chinensis can be used as an anthelmintic drug against
Dactylogyrus intermedius (Monogenea) in goldsh (Carassius auratus). The methanol extract of Cuscuta chinensis has EC50 at
48 h 15.9 mg/L, by using in vivo anthelmintic efcacy assay
(Huang et al., 2013). The work on anthelminthic activity is very
little with only one monogean parasite being studied. Therefore,
the studies on other models of animal and human subjects should
be considered for its effects against tapeworms, roundworms or
ukes.

5.15. Anti-depressant activities

5.19. Anti-nociceptive and anti-inammatory activities

Mokhtarifar et al. studied the antidepressant effects of Cuscuta


chinensis methanol extract in mice by using force swimming test
(FST) and tail suspension test (TST). The results showed that
32 mg/kg I.P. of imipramine and uoxetine as the positive controls
signicantly have the effects on both FST and TST. Administration
of 50 mg/kg I.P. signicantly decreased immobility times in TST
and 50 and 100 mg/kg I.P. of Cuscuta chinensis methanolic extract
signicantly reduced immobility times in FST (Mokhtarifar et al.,
2012).

The methanol extract of Cuscuta chinensis seed was performed


to provide anti-nociceptive and anti-inammatory activities
in vivo by using the response of acetic acid-induced writhing and
formalin-induced paw licking methods for evaluated antinociceptive activities, and -carrageenan-induced paw edema in
mouse for evaluated anti-inammatory activities. They found that
100, 500 mg/kg of Cuscuta chinensis seeds methanol extract signicantly reduces the writhing response. At the dose of
20500 mg/kg, it can reduce licking time (early phase, 20 and

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

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.

5.20. Toxicological reports


Toxicity of Cuscuta chinensis is very low, as the LD50 of Cuscuta
chinensis seeds ethanol extract intradermal injection into mice was
found to be 2.465 g/kg. Gavage 3040 g/kg of Cuscuta chinensis
seeds water extract in rats did not demonstrate any intoxicating
symptoms. Furthermore, when rats were gavaged with 4.15 g/kg of
Cuscuta chinensis seeds water extract or tincture once daily for 70
days, no development in pathological change or abnormality was
found (Jiangsu New Medical College, 1997). The acute toxicity study
revealed the drug to be non-toxic up to an oral dose of 5 g/kg body
weight of whole plant aqueous extract in mice (Akbar et al., 1985).
The toxicity of this plant against rat embryo was studied because of
its ability to prevent abortion. A total of 60 SD pregnant rats were
divided into 6 groups for high, medium and low dose of Cuscuta
chinensis water extract (40 g/kg/d, 20 g/kg/d and 10 g/kg/d, respectively) given by gavage for day 618, using normal saline 100 mL as
a negative control and cyclophosphamide injection 12.5 mg/kg on
day 13 as a positive control group. No signicant difference was
found in low, medium and high dose on embryo development of
appearance, body length, tail length, body weight, dry weight,
placenta weight, skeletal development when compared to negative
control. The maximum tolerance dose of water extract of Cuscuta
chinensis in SD rats is 80 g/kg, which belongs to non-toxic drugs
(Xia, 2012). Up to date, there are no reports on human toxicity or
side effects of Cuscuta chinensis. It can be noticed that pharmacological and toxicological studies have been conducted on only the
seeds of Cuscuta chinensis. Studies on the fruit or whole plant which
contains some phytochemical constituents are very little, especially
the fruits which show no pharmacological studies at all. Studies on
the leaf and stem also indicate that the ethnomedicinal uses of
these parts are still unknown. We suggest that further investigations are needed to provide more information for ethnomedicinal
uses of this plant for their anti-inammatory, pain relieving,
anthelminthic and lactation activities.

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

6.2. Prevent abortion


Cuscuta chinensis dried seeds 30 g, Semen soojiae Atricolor fruits
50 g, and Semen oryzae Glutinosae fruits 100 g are mixed together
till they become porridge, and are usually taken (PCHMPD, 2010).
6.3. Male reproductive system disease
Cuscuta chinensis dried seeds 30 g, with some other traditional
Chinese medicine decocted with water. Oral administration for 20
days to 4 months can treat male infertility, chronic prostatitis,
erectile dysfunction (Wang, 2000). In 19 cases of male infertility,
oral administration of Cuscuta chinensis dried seeds 9 g and fructus
lycii dried mature fruits 30 g, decocted with water, divided into
3 times a day every day for 2 months (1 course of treatment),
which found 89.5% of total efciency (Wang, 2001).
6.4. Chyluria
Fried Cuscuta chinensis dried seeds, Cervus Nippon Temminck
horn, Codonopsis pilosula dried roots 12 g each, Tenodera sinensis
Saussure dried ootheca, Smilax corbularia dried rhizome, Angelica
sinensis dried roots 9 g each, Chinemys reevesii carapace 21 g,
Astragalus membranaceus dried roots, Meretrix meterrix Linnaeus
shell podwder 30 g each, Poria cocos dried scerotium 18 g, Citrus
reticulate dried fruits peel 6 g. If combined with hematuria, add
Eclipta prostrate dried trunks 15 g, decocted with water for oral
administration, and this preparation can treat chyluria or hematuria which is caused by lariasis (Pan et al., 2008).
6.5. Chloasma faciei
Cuscuta chinensis dried seeds, fresh and cooked Rehmannia
glutinosa dried roots 15 g each, Ligustri lucidium dried mature
fruits, Polygonum multiora dried roots 12 g each, Eclipta prostrate
dried trunks, Paeonia lactiora Pall dried roots, Angelica sinensis
dried roots 10 g each, Equus asinus skin, Lycium barbarum L. dried
mature fruits 9 g each. If combined with anemia, add Codonopsis
pilosula dried roots, Astragalus membranaceus dried roots 15 g
each, Spatholobus subersctus Dunn dried trunks 30 g, Psoralea
corylifolia Linn. dried mature fruits 9 g, decocted with water for
oral administration (Pan et al., 2008).
6.6. Glomerulonephritis
Dried Cuscuta chinensis seeds 30 g, decocted with water 300 ml,
oral administration 2 times a day for 3 months. In a 13 case study,
12 cases were found to be effective (92.31%) (Xia, 2000).

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).

6.1. Female infertility

6.8. Treatment and prevent diabetes

Cuscuta chinensis dried seeds 25 g and Angelica sinensis dried


roots 10 g, decocted with water for oral administration 3 times a
day. Start on the rst day of menstruation and continue to the 18th
day (1 course of treatment). The duration of treatment is about
23 courses (Pan et al., 2008).

Dried Cuscuta chinensis seeds, Lycium barbarum dried mature


fruits, cooked Rehmannia glutinosa dried roots 10 g each, Ilex
pubescens dried roots 30 g, freas Zingiber ofcinale Rosc. roots
3 pieces, steaming and then usually drink the decoction
(Song, 2010).

306

S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292308

6.9. Herpes zoster

Acknowledgments

Dried grounded seeds of Cuscuta chinensis seeds 50100g, add


some sesame oil mix until they become an ointment, and before
using add some saline, then apply on lesion once a day for 25
days (Pan et al., 2008). In 98 cases, 25 day period of time, 100%
effective (Niu and Xia, 1994), and in another 49 cases, also found
100% effective (Sun and Fu, 2000).

This research was supported by the National Natural Science


Foundation of China (81374050) and (NSFC81125024), Program for
Innovative Research Team in Universities of Tianjin (TD12-5033)
and Tianjin Research Program of Application Foundation and
Advanced Technology (12JCQNJC08800) and we are thankful to
Prof. Michael Heinrich and the other three anonymous reviewers
for their useful comments and suggestions on the manuscript.

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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