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Cuscuta chinensis lam.: A systematic review on Ethnopharmacology,

phytochemistry and pharmacology of an important traditional herbal
medicine

Article  in  Journal of Ethnopharmacology · October 2014

DOI: 10.1016/j.jep.2014.09.032

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 Journal of Ethnopharmacology 157 (2014) 292–308

Contents lists available at ScienceDirect

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
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
b
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: Ethnopharmacological relevance: Cuscuta chinensis Lam. has found its use as a traditional medicine in
Received 18 April 2014 China, Korea, Pakistan, Vietnam, India and Thailand. It is commonly used as an anti-aging agent, anti-
Received in revised form inflammatory agent, pain reliever and aphrodisiac. To provide an overview of the ethnopharmacology,
18 September 2014
phytochemistry, pharmacokinetics, pharmacology and clinical applications of Cuscuta chinensis, as well
Accepted 19 September 2014
Available online 2 October 2014
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
Keywords: information was collected from journals, books, theses and electronic search (Google Scholar, PubMed,
Cuscuta chinensis Lam ScienceDirect, ESBCO, Springerlink and CNKI). Literature abstracts and full-text articles were analyzed
Tu-Si-Zi and included in the review.
Ethnopharmacology
Results: Many phytochemicals have been isolated, identified and published to date, including: at least
Phytochemistry
18 flavonoids; 13 phenolic acids; 2 steroids; 1 hydroquinone; 10 volatile oils; 22 lignans; 9 polysacchar-
Pharmacokinetics
Clinical applications
ides; 2 resin glycosides; 16 fatty acids. These phytochemicals and plant extracts exhibit a range of
pharmacological activities that include hepatoprotective, renoprotective, antiosteoporotic, antioxidant,
Chemical compounds studied in this article:
anti-aging, antimutagenic, antidepressant, improve sexual function, abortifacient effects, etc.
Quercetin (PubChem CID: 5280343)
Conclusion: This present review offers primary information for further studies of Cuscuta chinensis. The
Kaempferol (PubChem CID: 5280863)
Isorhamnetin (PubChem CID: 5281654)
in vitro studies and in vivo models have provided a bioscientific explanation for its various ethnophar-
Astragalin (PubChem CID: 5282102) macological uses and pharmacological activities (most notably antioxidant effects) especially in the
Hyperoside (PubChem CID: 5281643) prevention of hepatic disease and renal failure. It is necessary and important to do more pharmacokinetic
Rutin (PubChem CID: 5280805) and toxicological research works on human subjects in order to inform the possible active compounds in
Calycopteretin (PubChem CID: 10429470) the body and validate its safety in clinical uses.
Cinnamic acid (PubChem CID: 444539) & 2014 Elsevier Ireland Ltd. All rights reserved.
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(α)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; ERα, estrogen receptor alpha; ERβ, 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.: þ 86 22 59596163; fax: þ 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) 292–308 293

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
2. Phytochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
3. Ethnopharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
4. Pharmacokinetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
5. Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
5.1. Effect on skin protection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
5.2. Hepatoprotective activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
5.3. Anti-osteoporotic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
5.4. Immunological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
5.5. Effect on neuronal system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
5.6. Antioxidant activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
5.7. Anti-aging activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
5.8. Effects on tumor cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
5.9. Renoprotective effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
5.10. Effect on reproductive system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
5.11. Prevent abortion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
5.12. Anti-mutagenic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
5.13. Anti-diabetic activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
5.14. Cardiovascular activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
5.15. Anti-depressant activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
5.16. CNS depressant activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
5.17. Effect on melanin production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
5.18. Anthelmintic activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
5.19. Anti-nociceptive and anti-inflammatory activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
5.20. Toxicological reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6. Clinical applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6.1. Female infertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6.2. Prevent abortion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6.3. Male reproductive system disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6.4. Chyluria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6.5. Chloasma faciei . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6.6. Glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6.7. Nocturia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6.8. Treatment and prevent diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
6.9. Herpes zoster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
6.10. Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
6.11. Vitiligo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306

1. Introduction minute scales. The flowers are hermaphrodite. Inflorescence lateral,

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 defined 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, filiform, glabrous, yellowish or
pale yellowish, ca. 1 mm diam. The plant has no leaf or reduced to
compact cymose glomelurous, few to many flowered clusters or
racemes, white; bracteoles scale-like and bracts. Pedical ca. 1 mm.
Calyx lobe 4–5, capular, sepals triangular ovate ca. 1.5 mm, ridged
on outer surface, apex obtuse, partly thickened. Corolla 3–3.5 mm
long, white, urceolate, 4 or 5 lopes, lopes detoid-ovate, apex acute
or obtuse, spreading horizontally, fimbriate, reflexed, 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 2–4, broadly
ovalate, 1–2 mm long, pale brown, not smooth. Flowering in
June–October; December–March; February–May and fruits in
August–October. 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, Kyrgyz-
stan, 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) 292–308
Fig. 1. Cuscuta chinensis Lam. (A) Habitus, (B) stem and flowers, (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 find out the
chemical constituents including the pharmacological activities and
clinical applications of Cuscuta chinensis which are evidenced by an
increasing number of published scientific 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 flavonoids, poly-
saccharides, 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 flavonoids
including kaempferol, quercetin, hyperoside, astragalin and lig-
nans play an important role in the pharmacological activity
(Cornwell et al., 2004; Williamson et al., 2005). Loffler 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-O-
glucoside (29–34% of the total phenolics) among all species. The
water-soluble constituents of Cuscuta chinensis include a trypto-
phan derivative alkaloid (cuscutamine), and 2 new lignans (cus-
cutosides A and B), along with 4 known flavonoids (astragalin,
hyperoside, quercetin, quercetin-3-O-apiosyl(1-2)-galactoside),
3 known lignans (pinoresinol-4-O-glucoside, pinoresinol, epipi-
noresinol), 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 identified using atomic absorption spectrometry method
(Zhao et al., 1990). Moreover, five other compounds were isolated
from petroleum ether and chloroform fractions from the stem of
Cuscuta chinensis for the first time. Their structures were identified
as β-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 flavonoids, quercetin
3-O-β-D-galactoside-7-O-β-D-glucoside, quercetin 3-O- β-D-apio-
furanosyl-(1etin 3D-galactoside, hyperoside, quercetin and kaemp-
ferol 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 flavonoids; 13 phenolic acids; 2 steroids; 1 hydroquinone; 10
 S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292–308
Kaempferol Quercetin Isorhamnetin
Astragalin d - sesamin Chlorogenic acid
p-coumaric acid β-sitosterol daucosterol
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 flavonoids (principally hyperoside,
quercetin, rutin, isorhametin) which were selected as markers to
evaluate the quality of the plant (Shekarchi et al., 2014). Never-
theless, 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 influence 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 first 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
deficiency (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
insufficiency with lumbago, impotence, spermatorrhea, frequent urina-
tion, sterility due to cold uterus, threatened abortion or habitual
abortion, but also used in treatment of the liver insufficiency 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
295
Rutin Hyperoside
Cinnamic acid Caffeic acid
Arbutin caryophyllene
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 osteo-
porosis 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 deficiency. 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 incon-
tinence, 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 inflammations in Pakistan
(Qureshi et al., 2010). In India, the stems from this plant are used in the
treatment of sore heads, inflamed 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) 292–308

Table 1
Phytochemistry of Cuscuta chinensis.

Chemical constituents Part of plant Reference

Flavonoids
Quercetin Seed; fruit; whole plant; Ye et al., (2002, 2005); Yahara et al., (1994); Loffler et al.,
stem (1997); Kwon et al., (2000)
Pan et al., (2014)
Quercetin-3-O-glucoside Whole plant Loffler et al., (1997)
Quercetin-3-O-apiosyl(1-2)-galactoside Fruit; seed; stem Yahara et al., (1994); Ye et al., (2005)
Quercetin-3-O-β-D-galactoside-7-O-β-glucoside Seed Ye et al., (2002, 2005)
Quercetin-3-O-β-D-apiofuranosyl(1-2)-β-D-galactoside Seed Ye et al., (2002); Pan et al., (2014)
Quercetin-3-O-rhamnosylgalactoside Stem Ye et al., (2005)
Quercetin-3-O-acetylgalactoside Seed; stem Ye et al., (2005)
Kaempferol Seed; stem Ye et al., (2002, 2005); Hajimehdipoor et al., (2012);
Kwon et al., (2000); Pan et al., (2014)
Kaempferol 3,7-di-O-β-D-glucopyranoside Seed He et al., (2010)
Keampferol-3-O-galactoside Whole plant; seed; stem Loffler et al., (1997); Ye et al., (2005)
Keampferol-3-O- β-D-glucoside Seed Pan et al., (2014)
Isorhamnetin Seed; stem Hajimehdipoor et al., (2012); Ye et al., (2005)
Isorhamnetin-3-O-glucoside Seed; stem Ye et al., (2005)
Astragalin Seed;whole plant; fruit; Yang et al., (2009a, 2009b); Loffler et al., (1997);
stem Yahara et al., (1994); Ye et al., (2005)
Hyperoside Seed; Whole plant; stem Hajimehdipoor et al., (2012); Loffler et al., (1997);
Yahara et al., (1994); Pan et al., (2014);
Ye et al., (2005)
Rutin Seed Ye et al., (2001); Hajimehdipoor et al., (2012)
Calycopteretin Seed Kwon et al., (2000)
Apigenin Seed; stem Ye et al., (2005)

Phenolic acid
Chlorogenic acid Seed; stem Pan et al., (2014); Ye et al., (2005)
Caffeic acid Fruit Yahara et al., (1994)
4-Caffeoyl quinic acid Seed He et al., (2010)
5-Caffeoyl quinic acid Seed He et al., (2010)
4-Caffoyl-5-coumaroylquinic acid Seed; stem Ye et al., (2005)
Methyl 4-hydroxy-3,5-dimethoxycinnamate Seed Kwon et al., (2000)
4-Feruoyl-5-caffeoylquinic acid Stem Ye et al., (2005)
3,5-Dicaffeoylquinic acid Whole plant; seed; stem Loffler et al., (1997); Ye et al., (2005)
3,5-Dicaffeoyl-4-feruoylquinic acid or 3-feruoyl-4,5-dicaffeoylquinic acid Seed; stem Ye et al., (2005)
4,5-Dicaffeoylquinic acid Whole plant; seed; stem Loffler et al., (1997); Ye et al., (2005)
3,4,5-Tricaffeoylquinic acid Seed Ye et al., (2005)
p-Coumaric acid Fruit Yahara et al., (1994)
Cinnamic acid Seed; whole plant; fruit He et al., (2010); Loffler et al., (1997); Yahara et al., (1994)

Steroids
β-Sitosterol Seed Ye et al., (2001)
Daucosterol Seed Ye et al., (2001)

Hydroquinone
Arbutin Fruit Yahara et al., (1994)

Volatile oil
2 – Pentyl furan Seed Hou et al., (2003)
Dodecane Seed Hou et al., (2003)
3- Butene-2 –alcohol Seed Hou et al., (2003)
Furfural Seed Hou et al., (2003)
Furan-2-ylmethanol Seed Hou et al., (2003)
Heptanal Seed Hou et al., (2003)
3, 7 – Dimethyl-1, 6 – octadiene, 3 – alcohol Seed Hou et al., (2003)
Borneol Seed Hou et al., (2003)
α-Terpineol Seed Hou et al., (2003)
Caryophyllene Seed Hou et al., (2003)
α-Caryophyllene Seed Hou et al., (2003)

Lignans
20 -Hydroxyl asarinin 20 -O-β-D-apiofuranosyl-(1-2)- β –D-glucopyranoside Seed He et al., (2010); Du et al., (1998)
(Cuscutoside A)
20 -Hydroxy asarinin 20 -0-j-xylopyranosyl-(1-6)-β-glucopyranoside Seed He et al., (2010); Du et al., (1998)
(Cuscutoside B)
20 -Hydroxyl asarinin 20 -O-β-D-glucopyranoside (Cuscutoside C) Seed He et al., (2010); Du et al., (1998)
20 -Hydroxyl asarinin 20 -O-β-D-apiofuranosyl-[(1-2)- β –D-glucopyranosyl- Seed He et al., (2010); Du et al., (1998)
(1-6)-β-D-glucopyraniside (Cuscutoside D)
( þ )-Pinoresinol Fruit Yahara et al., (1994)
D-Pinoresinol Seed Ye et al., (2001)
( þ )-Epipinoresinol Fruit Yahara et al., (1994)
( þ )-Pinoresinol-4-O-glucoside Fruit Yahara et al., (1994)
d-Pinoresinol-4-O-glucoside Seed; stem Ye et al., (2005)
 S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292–308 297

Table 1 (continued )

Chemical constituents Part of plant Reference

Feruoylcaffeoyl-d-pinoresinol Seed; stem Ye et al., (2005)

Dicaffeoyl-d-piniresinol Stem Ye et al., (2005)
d-Sesamin Seed; stem Ye et al., (2005)
9(R)-Hydroxy-d-sesamin Seed Ye et al., (2001)
9α-Hydroxy-d-sesamin-9-O-glucoside Seed; stem Ye et al., (2005)
9α-Hydroxy-d-sesamin-O-glucoside Seed Ye et al., (2005)
5,50 -Dihydroxy-d-sesamin-5-O-glucoside Stem Ye et al., (2005)
4-Methyl-3-methoxy-9α-hydroxyligballinol-O-glucoside Seed; stem Ye et al., (2005)
3,4-Demethyleudesmin-4-O-glucoside Seed Ye et al., (2005)
Piperitol-4-O-glucoside Seed; stem Ye et al., (2005)
20 -Hydroxyasarinin-20 O-rhamnosylglucoside Seed Ye et al., (2005)
Lignin-O-coumaroylglucoside Stem Ye et al., (2005)
Lignin-4-O-coumaroylglucoside Stem Ye et al., (2005)

Polysaccharides
Neutral heteropolysaccharide: arabinose, rhamnose, xylose and galactose Seed Wang et al., (2001)
composition
Acidic heteropolysaccharide mainly branched: CHC-1, H3, CS-A, CS-B, CS-C Seed Wang et al., (2001)

Resin glycosides
Acylated trisaccharide: α-L-rhamnopyranosyl-(1- 3) -[2-O-(11S)-11- Seed Miyahara et al., (1996)
hydroxytetradecanoyl]-[4-O-(2R,3R) -3-hydroxy-2-methylbutyryl]-α-L-
rhamnopyranose- (1-20-[6-O-acetyl]-D-glucopyranoside
α-L-rhamnopyranosyl-(1- 3) – [2-O-(11S) -11-hydroxypamitoyl]-[4-O-(2R, Seed Miyahara et al., (1996)
3R)-3- hydroxy-2-methylbutyryl]-α-L-rhamnopyranose-(1-2-0-[6-O-
acetyl]-D-glucopyranoside

Fatty acid
Methylmyristate Seed Cheng et al., (2013)
Methyl pentadecanoate Seed Cheng et al., (2013)
Methyl hexadecanoate Seed Cheng et al., (2013)
Methyl palmitoleate Seed Cheng et al., (2013)
Methyl heptadecanoate Seed Cheng et al., (2013)
Methyl stearate Seed Cheng et al., (2013)
Methyl oleate Seed Cheng et al., (2013)
Methyl linoleate Seed Cheng et al., (2013)
Methyl linolenate Seed Cheng et al., (2013)
Methyl Arachidate Seed Cheng et al., (2013)
Methyl cis-11-eicosenoate Seed Cheng et al., (2013)
Methyl 11c,14c- eicosadienoate Seed Cheng et al., (2013)
Methyl behenate Seed Cheng et al., (2013)
Sinapic acid methylester Seed Cheng et al., (2013)
Methyl tricosanoate Seed Cheng et al., (2013)
Methyl lignocerate Seed Cheng et al., (2013)

Microelements
Calcium Seed Zhao et al., (1990)
Magnesium Seed Zhao et al., (1990)
Iron Seed Zhao et al., (1990)
Manganese Seed Zhao et al., (1990)
Copper Seed Zhao et al., (1990)

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
flavonoids(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
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 briefly 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(α)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 first application of DMBA to
298 S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292–308
Table 2
Ethnopharmacology of Cuscuta chinensis.
No. Ethnomedicinal uses
1 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
2 Treatment of chronic ulcers, wounds, painful inflammation
3 Ttreatment of sore heads and inflamed eyes
Treatment of jaundice
Removes hair dandruff
Facilitates lactation
4 Treatment of back pain and constipation
5 Improves sexual function and health
6 As an anthelminthic, and to alleviate jaundice
Table 3
Pharmacokinetic information of Cuscuta chinensis.
Species/ bio-matrix Analytes Administration route/
dosage
Rat/serum Quecrcetin Gavage 0.85g/kg of Cuscuta Kα(h-1): 5.214, α(h-1): 3.614, β(h-1): 0.568, T1/2(α) (h): 0.19, T1/2(β) (h):
chinensis 95% ethanol 1.22, T1/2(AB) (h): 0.13, Tmax (h): 0.333, Cmax (μg/ ml): 0.401
extract
Human/plasma Hyperoside Oral administration 360 g
of Cuscuta chinensis ethanol 1.55, T1/2ke(h): 3.48, Tmax(h): 3.259, Cmax(μg/ml): 3.902, AUC((μg/ml)nh):
extract
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
significantly inhibited the appearance and development of skin
papillomas and also reduced the incidence of carcinoma (Nisa
et al., 1986).
5.2. Hepatoprotective 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 significantly reduced the
evaluation of glutamate oxaloacetate transaminase, glutamate
pyruvate transaminase, and alkaline phosphatase (ALP). In addi-
tion, the ethanol extract can prevent liver histopathological
changes such as centribular hepatic necrosis, kupffer cell infiltrat-
ing lymphocytes, ballooning degradation, and APAP-induced hepa-
totoxicity 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 indi-
cate a significant 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
Parts of the plant Locality References
Seed China Teng, (2007), Li, (2009); Committee for
the Pharmacopoeia of PR China, (1995);
Ni, (2005); Li, 2013; Zhang, (2011);
Zhang, (2013)
Whole pant Pakistan Qureshi et al., (2010)
Stem India Petel and Petel, 2010
Stem Patil et al., (2012)
Stem Shubhangi and Patil, 2012
Leaf Patil et al., (2011); Patil et al., (2010)
Whole plant Vietnam Sam et al., (2008)
Seed Korea Sohn et al., (2008)
Whole plant Thailand Smittinan, (2011)
PK parameters (or important information) References
Zheng et al., (2004)
A(μg/ml): 13.45, Ke(h-1): 0.199, Ka(h-1): 0.448, Lag time(h): 0.444, T1/2ka(h): Peng, (2010)
37.423, CL/F(s)(μg/h/(μg/ml)): 0.027, V/F(c)(μg/(μg/ml): 0.134
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.
5.3. Anti-osteoporotic activity
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 significantly 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 mineraliza-
tion 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 flavonoids from Cuscuta
chinensis and found that kaempferol and hyperoside significantly
increased the ALP activity in osteoblast-like UMR-106 cells, astra-
galin promoted the proliferation of UMR-160 cells. 5 flavonoids
also promoted Hela cell, a human cervical cancer cell via estro-
genic receptor ERα and ERβ. They suggested that kaempferol and
hyperoside are the active compounds in this plant for osteogenic
 S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292–308 299

Table 4
Pharmacology of Cuscuta chinensis.

No. Activities Part of Model Formulation /dosage/ Control Result Reference

plant extract

1 Skin protective Whole Mice (in vivo) P.O. 1 g/kg body wt of Positive control: 150 μg Cuscuta chiensis inhibit both the appearance Nisa et al.,
activity plant water extract 3 times/ DMBA appy on skin for and development of skin papillomas and also (1986)
week 7 days; negative control: reduced the incidence of carcinoma
P.O. distilled water transformation.

2 Hepatoprotective Seed Rats (in vivo) P.O. 125 and 250 Positive control: P.O. 125 and 250 mg/kg ethanol extract can Yen et al.,
activity mg/kg of water and APAP 835 mg/kg single significantly inhibit liver damage caused by (2007)
ethanol extract dose; negative control: APAP-induced hepatotoxicity
I.P. normal saline
Seed Rats (in vivo) P.O. 125 and 250 Positive control: P.O. 25 and 50 mg/kg seeds ethanol extract Yen et al.,
mg/kg ethanol extract, APAP 835 mg/kg single nanoparticles formulation show significantly (2008b)
and 25 and 50 mg/kg dose; negative control: hepatoprotective effects the same as the
nanoparticles of I.P. normal saline normal 125, 250 mg/kg seeds ethanol
ethanol extract extract.

3 Musculoskeletal Seed cultured Aqueous extract Aqueous extract of Cuscuta chinensis in rat Yao et al.,
(osteoporosis neonatal rat bone cells clearly promoted the proliferation (2005)
treatment) calvarias organ and differentiation of the osteoblasts, but
(in vitro) inhibited the activities of osteoclasts
Seed MG-63 cells 100, 500 and 1000 Negative control: culture 500 and 1000 μg/ml dry seed water extract Yang et al.,
(in vitro) μg/ml aqueous extract medium mildly promoted the proliferation of MG-63 (2009a)
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 (100–1000 μg/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 significantly
induced at 500 and 1000 μg/ml
Seed (UMR-106 1, 5, 10, 50, 100 μg/ml Positive control: 0.1 μM Isolated flavonoids, show osteoporotic Yang et al.,
cells) in vitro of its organic fraction 17-β-estradiol; negative activities, keampferol and hyperoside (2011)
significantly increased the ALP activity in
and 1, 5, 10, 50 μM of control: DMSO 0.1 v/v
oteoblast-like UMR-106 cells and astragalin
its isolated flavonoids
promoted the proliferation of UMR-160 cells.

4 Immune Seed Mice (in vivo) P.O. 100, 200 or Positive control: S.C. The ethanol extract can significantly enhance Pan et al.,
regulation 400 μg of ethanol OVA 100 μg negative the mitogen- and ovalbumin (OVA)-stimulated (2005)
extract control: S.C. normal splenocyte proliferation in OVA-immunized
saline mice, and enhance a specific antibody and
cellular response against OVA in mice.
Seed Mouse bone 50 μg/ml methanol Positive control: LPS Keampferol can reduce cytokines and Lin et al.,
marrow- ectract and its organic 100 ng/ml negative chemokines produced by LPS-stimulated (2011)
derived DCs control: DMSO 0.1% v/v dendritic cells (DCS), and abrogate the ability
fraction and 20 μg/ml
(in vitro) of LPS-stimulated DCs to promote Ag-specific
kaempferol
T cell activation, both in vitro and in vivo.
Seed Mice (in vivo) P.O. 20 ml/kg of the Negative control: P.O. Cuscuta chinensis has the immune Lin et al.,
ethanol extract 200 g/l 20 mg/kg normal saline enhancement, anti-fatigue and anoxia (2003)
tolerance effects.

5 Neuroprotection Seed PC12 cells Cuscuta chinensis Positive control: 7S Cuscuta chinensis glycoside can induce Liu et al.,
activity (in vitro) glycoside up to nerve growth factor; neuronal differentiation with resulting (2003)
200 mg/l negative control: outgrowth of neutrites and increase of
distilled water acetylcholinesterase activity in rat
pheochromocytoma PC12 cells in a dose-
dependent manner
Seed Mice (in vivo) P.O. decoction of 20 g Positive control: Cuscuta chinensis with other Invigorating-Qi Liu et al.,
Cuscuta chinensis with Scopolamine drug had an evident antagonistic action to (1993)
other Invigorating-Qi I.V. 5 mg/kg; negative Scopolamine induced dysmnesia mice, and
drug control: could improve their memory.
P.O. normal saline
Seed Rats (in vivo) P.O. 50, 100 and 200 Positive control: 3 min Cuscuta chinensis with other 7 medicinal Chung et al.,
mg/day CMSD forebrain ischemia herbs (CMSD) had neuroprotective effects on (2006)
negative control: P.O. cultured primary neuron cell of neonatal rat,
vehicles with sham- and prevented ischemia-induced learning
operated disability and rescued hippocampal CA1
neurons from lethal ischemic damage in rats.
6 Antioxidant Seed SC50, IC50 The ethanol extract Positive control: They show potent antioxidant for preventing Yen et al.,
activity (in vitro) and its organic quercetin and kaemferol free radical damage to cell membranes (2008a)
fractions through scavenging of free radicals and
inhibition of the liquid peroxidation.
Seed IC50 (in vitro) Methanol extract and The ethyl acetate fraction of methanol extract Kwon et al.,
its organic fraction of Cuscuta chinensis seeds showed the (2000)
highest activity (EC50 value of 50 mg) by using
300 S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292–308

Table 4 (continued )

No. Activities Part of Model Formulation /dosage/ Control Result Reference

plant extract

the DPPH free radical scavenging method for

screening antioxidative effects
Seed MC3T3-E1 10, 20 and 40 mg/l Positive control: 0.1 mM The water extract can significantly inhibited Gao et al.,
cells (in vitro) water extract TBPH; negative control: the reactive oxygen species (ROS) generation, (2013)
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.
Seed PC 12 cells 25–250 mg/l Cuscuta Positive control: 0.3– Cuscuta chinensis flavonoids can protect PC12 Zhen et al.,
(in vitro) chinensis flavonoids 0.5 mm H2O2; negative cells against oxidative stress by its ability of (2006)
control: DMSO 0.1% v/v scavenging ROS and increasing the activity of
antioxidant enzyme.

7 Anti-aging Seed Mice (in vivo) P.O. 100, 200 and Positive control: S.C. 5% The Cuscuta chinensis polysaccharides had Cai et al.,
400 mg/kg/day of D-galactose 5 ml at the the anti-aging effects on senile mice model. (2005)
polysaccharides nape, vitamin E 200 mg/
kg/day; negative
control: S.C. distilled
water, vehicles

8 Effects on tumor Whole CCRF-CEM and 0.1–25 μg/ml water Negative control: culture Whole plant water extract has cytotoxic Zeraati
cells plant JM cells extract medium effect on human caucasian acute et al., (2010)
(in vitro) lymphoblastic leukemia (CCRF-CEM) cells.
Seed MCF-7 cells Cuscuta chinensis extract can stimulate Umehara
and T47D cells MCF-7 and T47D human breast cancer cell et al., (2004)
(in vitro) proliferation at a concentration of 10 μM
Seed Hela cells 1, 5, 10, 50, 100 μg/ml Positive control: 0.1 μM Isolated compounds from Cuscuta chinensis Yang et al.,
(in vitro) of its organic fraction 17-β-estradiol; negative seeds ethanol extract stimulated Hela cell via (2011)
and 1, 5, 10, 50 μM of control: DMSO 0.1% v/v estrogenic receptor ERα and ERβ
its isolated flavonoids

9 Renoprotective Seed Rats (in vivo) P.O. 250 mg/kg/day Positive control: renal The water extract 250 mg/kg/day oral Shin et al.,
aqueous extract arteries were clamped administration can recover rats renal (2011)
for 45 h; negative function parameters from ischemia/
control: operation reperfusion-induced ARF.
without clamping renal
arteries

10 Reproductive Seed Penile tissues 1–5 mg/ml ethanol Positive control: 1, 2, 3, 4 and 5 mg/ml of Cuscuta chinensis Sun et al.,
system (in vitro) extract 10 μmol/l phenylephrine extract has the effect on the rabbit penile (2013)
precontracted, 10 nmol/l corpus cavernosum (PCC) by relaxing PCC
sildenafil citrate; phenylephrine (10 μmol/l) induced
negative control: DMSO contraction in a dose dependent manner.
0.1%
Seed Rats (in vivo) P.O. 100 and 300 Negative control: P.O. 100 mg and 300 mg/day for 4 weeks oral Sohn et al.,
mg/kg of the herbal distilled water administration of KH-204 decresed blood (2008)
formula (KH-204) pressure and enhanced penile erection in
spontaneous hypertensive male rats.
Seed Human P.O. VPX (25 mg of Negative control: P.O. VPX can improve sexual abilities on patients Shah et al.,
(in vivo) Cuscuta chinensis placebo with erectile dysfunction. (2012)
seeds with other
herbal medicie) twice
daily
Seed Human Decoction with other Cuscuta chinensis improve sperm motility Peng et al.,
spermatozoa herbal medicine and help stabilized sperm membrane (1997)
(in vitro) function.
Seed Mice (in vivo) P.O. 33.8 mg/kg and Positive control: P.O. Seed of Cuscuta chinensis ethanol extract Yang et al.,
67.6 mg/kg of the 1.3 g/kg 33.8 mg/kg and 67.6 mg/kg can reverse the (2008)
ethanol extract metyltestoseterone or reduction of testosterone level, the androgen
6 g/kg Jinkui Shenqi receptor mRNA level and protein level
wan; negative control: P. induced by the hydrocortisone in the kidney
O. distilled water and testicle.
Seed Rats (in vivo) P.O. 5–10 mg/100 g of Negative control: P.O. Flavonoids from Cuscuta chinensis seeds (FSC) Wang et al.,
flavonoids normal saline improved the ovarian endocrine functions. (2002)

11 Prevention of Seed Pregnant rats P.O. 2.6 and 5.2 Positive control: S.C. Cuscuta chinensis total flavonoids regulate Ma et al.,
abortion (in vivo) mg/kg/day with S.C. 0.3 mg/kg/day the proliferation and apoptosis of the (2008b)
bromocriptine bromocriptine; negative deciduas and cytotrophoblasts and prevent
control: do nothing spontaneous abortion in rats.
Seed Pregnant rats P.O. 2.6 and 5.2 Positive control: S.C. Cuscuta chinensis total flavonoids can Ma et al.,
(in vivo) mg/kg/day with S.C. 0.3 mg/kg/day regulate endocrinological and immunological (2008a)
bromocriptine bromocriptine; negative network equilibrium on maternal-fetal face
control: do nothing and finally achieve prevention of fetal
abortion.
 S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292–308 301

Table 4 (continued )

No. Activities Part of Model Formulation /dosage/ Control Result Reference

plant extract

12 Antimutagenic Whole Bacteria 0.1 mg of dry plant Positive control: Trp-P-1 Cuscuta chinensis methanol extract has the Nakahara
effect plant (in vitro) methanol extract carcinogen antimutagenic effect against Trp-P-1 in Ames et al., (2002)
test, ED90 values lower than 5 μL/plate

13 Antidiabetic Seed Mice (in vivo) P.O. 150, 300 and Positive control: I.V. 300, 600 mg/kg of Cuscuta chinensis Li et al.,
activity 600 mg/kg total 50 mg/kg alloxan, P.O. polysaccharides orally significantly lower the (2008a)
flavonoids acarbose 20mg/kg; high fasting blood glucose level, raise body
negative control: P.O. weight and immune organs.
normal saline
Seed Rats (in vivo) P.O. 100, 200 and Positive control: I.V. 200, 400 mg/kg orally of Cuscuta chinensis Xu et al.,
400 mg/kg 50 mg/kg streptomycin, polysaccharides significantly improve the (2011)
polysaccharides P.O. 13 mg/kg acar bose; weight loss of diabetic rats, reduce fasting
negative control: I.V. blood glucose and glycosylated serum
sodium citrate buffer protein, CCP 400 mg/kg significantly reduce
pH 4.5 CHO level, and CCP 400, 200, 100 mg/kg
could significantly reduce TG level.

14 Cardioprotection Seed Dogs (in vivo) I.V. 0.1 g/kg Cuscuta Cuscuta chinensis decoction in dogs can Jiangsu New
activity chinensis decoction reduce their blood pressure. Medical
College,
(1997)
Seed Dogs (in vivo) I.V. 20 mg/kg and Positive control: 20 mg/kg and 1ml/kg I.V. for 1 min of Liu et al.,
1 ml/kg of 3 different P.O. 20 mg/kg 3 different methods of extraction on mature (2004)
ethanol extract Diaoxinxuekang male hybrid dogs can increase coronary
traditional chinense blood flow and reduce myocardial oxygen
formula consumption.
Seed Rats (in vivo) 2 mg/g Cuscuta Positive control: Cuscuta chinensis seeds extract slowed down Han et al.,
chinensis seeds extract coronary artery ligated heart rate of MI /RI rats, declined ST level, (2011)
negative control: sham- reduced the degree of MI and the content of
operated I.V. normal CK, CK-MB, LDH, AST in blood serum.
saline

15 Antidepressant Arial part Mice (in vivo) I.P. 50 and 100 mg/kg Positive control: Methanolic extract had antidepressant Mokhtarifar
activity methanol extract I.P. 23 mg/kg effects by significantly reduced immobility et al., (2012)
imipramine and times in TST (50 mg/kg IP) and 50 and
fluoxetine 100 mg/kg IP in FST, imipramine and
fluoxetine (both 32 mg/kg IP), as positive
controls.

16 CNS depressant Whole Mice (in vivo) P.O. 1 g/kg aqueous The extract significantly decreased the motor Akbar et al.,
plant extract activity and the tonic and clonic phases of (1985)
electrically induced seizures in mice.

17 Effects on Seed AMMC 0.1, 1, 10 and 50 mg/ml Positive control: 10  8, Cuscuta chinensis water extract promoted Li et al., (
melanogenesis (in vitro) of water extract 10  7, 10  6, 10  5 mol/l melanogenesis of AMMC in dose-dependent 2008b)
8-methoxypsoralan manner, and increased the tyrosinase
negative control: culture activities.
medium
Seed Guinea pigs Apply 0.49, 0.93 and Positive control: apply 1. 86, 0. 93 g/kg externally applied on guinea Shen et al.,
(in vivo) 1.86 g/kg of Cuscuta 5% H2O2 1 ml on skin, pig skin significantly increased the skin (2012)
chinensis in alchohol methoxsalen 1 ml; melanin generation, and tyrosinase
preparation (0.25 g/g) negative control: apply production
alcohol on skin
Seed IC50 (in vitro) 0.5–20 mg/ml of Positive control: 100 The water extract of Cuscuta chinensis show Wang et al.,
water and ethanol μg/ml arbutin; negative inhibition of tyrosinase activity in a dose (2014)
extract control: solvent of dependent manner with IC50 value of 12
sample mg/ml and decrease the synthesis of
melanin.
Seed Zebrafish P.O. 0.5–20 mg/ml of Positive control: 100 Water extract of Cuscuta chinensis seeds Wang et al.,
(in vivo) water and ethanol μg/ml arbutin; negative demonstrate depigmenting activity in (2014)
extract control: solvent of zebrafish
sample

18 Anthelminthic Seed Goldfish P.O. 1% body weight of Negative control: DMSO The EC50 of Cuscuta chinensis methanol Huang et al.,
(in vivo) 125–300 mg/l organic extract at 48 h¼ 15.9 mg/L, by using in vivo (2013)
fraction anthelminthic efficacy assay.

19 Anti-nociceptive Seed Mice (in vivo) P.O. 20–500 mg/kg 100 and 500 mg/kg of Cuscuta chinensis seeds Liao et al.,
methanol extract methanol extract significantly reduce the (2014)
writhing response, at the dose of 20–500
mg/kg it can reduce licking time

20 Anti- Seed Mice (in vivo) P.O. 20–500 mg/kg The extract can significantly reduce Liao et al.,
inflammatory methanol extract λ-carrageenan-induce edema paw in the (2014)
time of four hours after injection with
λ-carrageenan.
302 S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292–308
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
significantly enhanced the mitogen- and ovalbumin (OVA)-stimulated
splenocyte proliferation in OVA-immunized mice, and EESC could
significantly enhance a specific antibody and cellular response against
OVA in mice. Kaempferol, one of major flavonoids isolated from the
dry matured seeds of Cuscuta chinensis methanol extract can decrease
chemokines and cytokines which produced by LPS-stimulated den-
dritic 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-specific 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 inflammation (Lin
et al., 2011). Lin et al. studied about the effect of immune enhance-
ment, 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, espe-
cially 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 differ-
entiation 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 acetylcholines-
terase activity in the mice of the group that received the drug were
significantly 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-β-
induced cell death in a dose dependent manner, and the most
effective concentration was 25–50 μg/mL. CMSD was also demon-
strated to have protective effect from N-methyl-D-aspartate
receptor-mediated glutamate toxicity on primary cultured neu-
rons. In addition, CMSD oral administration in mice can also
recover the hippocampal CA1 neurons from lethal ischemic
damage and prevent learning disability because of ischemia-
induced 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 flavonoid 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 ¼50 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 osteoblas-
tic MC3T3-E1 cells against tertiary butyl hydroperoxide (TBHP)
induced injury. They found that the Cuscuta chinensis protects TBHP-
treated MC3T3-E1 cells from death in a dose-dependent manner and
it could suppress the malondialdehyde (MDA), reactive oxygen species
(ROS) productions, and significantly enhance the Glutathione S-trans-
ferase, 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 flavonoids (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, flavonoids 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 develop-
ment 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 significantly inhibited
the non-enzymatic glycosylation reaction of D-galactose-induced
rat aging model (Li et al., 2013). These findings indicate that
Cuscuta chinensis has significant 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) 292–308
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 devel-
opment 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 μg/mL, and the stronger effect was shown in the
dose up to10 μg/mL. The extract has the IC50 value of 3 μg/mL in
24 h and 2.5 μg/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 μM (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 ERα and ERβ, while quercetin,
kaempferol and isorhamnetin, and some other isolated com-
pounds showed more selectivity in ERβ (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, gastro-
esophageal 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
significantly improved and also ameliorated tubular damage in
ischemia/reperfusion induced ARF rats (Shin et al., 2011). Although
the renoprotective effect of Cuscuta chinensis against physical-
induced 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 significantly
increases sildenafil-induced PCC relaxation. The penile cavernous
tissue incubated with the Cuscuta chinensis extracts show that the
cyclic guanosine monophosphate and cyclic adenosine monopho-
sphate levels in the PCC were raised significantly. Since the Cuscuta
chinensis extract presents a relaxing effect on penile cavernous tissue
by activating the nitric oxide-cyclic guanosine monophosphate path-
way, it may improve erectile dysfunction conditions which do not
completely respond to sildenafil (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 combi-
nation with other herbal medicines called VXP can improve sexual
functions of erectile dysfunction patients, by significantly 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 flavones from Cuscuta chinensis
seeds on the kidney-yang deficiency male mouse. Total flavones 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 significantly 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 increas-
ing the LH content in anterior pituitaries and the basophilic cells,
which may be the mechanism of FSC in improving hypothalamus-
pituitary-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 Curculigi-
nis, Radix Morindae Officinalis, Radix Polgoni Multiflori, Radix Rehman-
niae 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 flavonoids of Cuscuta chinensis regulated the deciduas and
cytotrophoblasts proliferation and apoptosis, prevented sponta-
neous 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
flavonoids of Cuscuta chinensis could regulate endocrinological and
immunological network equilibration on maternal-fetal face,
finally 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 μL/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) 292–308
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 carcino-
gens, 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 significantly 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 significantly reduce fasting blood glucose, glycosylate serum
protein and increase body weight; 400 mg/kg CCP could signifi-
cantly reduce CHO levels; and 400, 200, 100 mg/kg CCP could
significantly reduce TG levels, but observed no obvious effect on
insulin levels. Moreover, Cuscuta chinensis has been used in anti-
diabetic prescriptions because it can invigorate kidney and supple-
ment 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 redu-
cing blood sugar in type-2 diabetes, but the mechanism of this
effect is still unclear. Therefore, more studies are needed to prove
clinical efficacy 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 prepara-
tion. 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
flow as well as reduce myocardial oxygen consumption. Cuscuta
chinensis seeds extract significantly 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 significantly 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 amino-
transferase (AST) in blood serum were significantly reduced when
compared to control group. However, further studies are required
to determine its specific interaction and exact mechanism of
action.
5.15. Anti-depressant 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 fluoxetine as the positive controls
significantly have the effects on both FST and TST. Administration
of 50 mg/kg I.P. significantly decreased immobility times in TST
and 50 and 100 mg/kg I.P. of Cuscuta chinensis methanolic extract
significantly reduced immobility times in FST (Mokhtarifar et al.,
2012).
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 significantly 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 significantly intensified. The amphetamine-
induced 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 pentobarbi-
tone. 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 significantly 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 mela-
noma cell and depigmenting activity in zebrafish 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 goldfish (Carassius aur-
atus). The methanol extract of Cuscuta chinensis has EC50 at
48 h ¼15.9 mg/L, by using in vivo anthelmintic efficacy 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
flukes.
5.19. Anti-nociceptive and anti-inflammatory activities
The methanol extract of Cuscuta chinensis seed was performed
to provide anti-nociceptive and anti-inflammatory activities
in vivo by using the response of acetic acid-induced writhing and
formalin-induced paw licking methods for evaluated anti-
nociceptive activities, and λ-carrageenan-induced paw edema in
mouse for evaluated anti-inflammatory activities. They found that
100, 500 mg/kg of Cuscuta chinensis seeds methanol extract sig-
nificantly reduces the writhing response. At the dose of
20–500 mg/kg, it can reduce licking time (early phase, 20 and
 S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292–308
100 mg/kg and late phases, 100 mg/kg). In formalin test assay, the
extract can significantly reduce λ-carrageenan-induced edema
paw in the time of four hours after injection with λ-carrageenan.
Moreover, it can reduce the level of IL-1β, IL-6, NF-κB, TNF-α, 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-inflammatory 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 30–40 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, respec-
tively) given by gavage for day 6–18, 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 significant 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 pharmaco-
logical 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 investiga-
tions are needed to provide more information for ethnomedicinal
uses of this plant for their anti-inflammatory, pain relieving,
anthelminthic and lactation activities.
6. Clinical applications
Currently in China, Cuscuta chinensis seeds are usually pre-
scribed by doctors or traditional Chinese medicine practitioners
with a usual dosage of 9–15 g oral administration, and the
maximum dosage of 30 g each time (Ceng and Zhang, 2000)
without obvious side effects reported for supplementing or treat-
ing various diseases, as shown below.
6.1. Female infertility
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 first day of menstruation and continue to the 18th
day (1 course of treatment). The duration of treatment is about
2–3 courses (Pan et al., 2008).
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 efficiency (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 hema-
turia which is caused by filariasis (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 multiflora dried roots 12 g each, Eclipta prostrate
dried trunks, Paeonia lactiflora 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 treat-
ment), 2–3 months, the total cure rate was 96.97% (You, 2005).
6.8. Treatment and prevent diabetes
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 officinale Rosc. roots
3 pieces, steaming and then usually drink the decoction
(Song, 2010).
306 S. Donnapee et al. / Journal of Ethnopharmacology 157 (2014) 292–308
6.9. Herpes zoster
Dried grounded seeds of Cuscuta chinensis seeds 50–100g, add
some sesame oil mix until they become an ointment, and before
using add some saline, then apply on lesion once a day for 2–5
days (Pan et al., 2008). In 98 cases, 2–5 day period of time, 100%
effective (Niu and Xia, 1994), and in another 49 cases, also found
100% effective (Sun and Fu, 2000).
6.10. Acne
Dried Cuscuta chinensis seeds 30 g in 500 ml water, apply on
the lesion, 1–2 times a day for 7 days (1 course of treatment), the
duration of treatment is about 1–2 courses, in 50 cases, 94%
effective (Yu, 1996).
6.11. Vitiligo
Cuscuta chinensis seeds 9 g, soaked in 60 ml of 95% ethanol for
2–3 day, then apply the solution on the lesion 2–3 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 efficiency 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 flavonoids, phenolic acids, steroids, hydroqui-
nones, volatile oils, lignans, alkaloids, polysaccharides, resin glyco-
sides and fatty acids. About 3.0% of the total chemical constituents
are flavonoids which have been linked to the pharmacological
activities of its extracts, especially kaempferol that shows antiox-
idant, 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 per-
formed 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 insufficient, and no major side effects have yet been discov-
ered. 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.
Acknowledgments
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.
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