ArticlePDF AvailableLiterature Review

Saussurea involucrata: A review of the botany, phytochemistry and ethnopharmacology of a rare traditional herbal medicine

Authors:
  • Guangxi Botanical Garden of Medicinal Plant

Abstract and Figures

Ethnopharmacological relevance: Saussurea involucrata Matsum. & Koidz. is an endangered species of the Asteraceae family, growing in the high mountains of central Asia. It has been, and is, widely used in traditional Uyghur, Mongolian and Kazakhstan medicine as well as in Traditional Chinese Medicine as Tianshan Snow Lotus (Chinese: ). In traditional medical theory, S. involucrata can promote blood circulation, thereby alleviating all symptoms associated with poor circulation. It also reputedly eliminates cold and dampness from the body, diminishes inflammation, invigorates, and strengthens Yin and Yang. It has long been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in Uyghur and Chinese medicine. Aim of the review: To comprehensively summarize the miscellaneous research that has been done regarding the botany, ethnopharmacology, phytochemistry, biological activity, and toxicology of S. involucrata. Method: An extensive review of the literature was carried out. Apart from different electronic databases including SciFinder, Chinese National Knowledge Infrastructure (CNKI), ScienceDirect that were sourced for information, abstracts, full-text articles and books written in English and Chinese, including those traditional records tracing back to the Qing Dynasty. Pharmacopoeia of China and other local herbal records in Uighur, Mongolian and Kazakhstan ethnomedicines were investigated and compared for pertinent information. Results: The phytochemistry of S. involucrata has been comprehensively investigated. More than 70 compounds have been isolated and identified; they include phenylpropanoids, flavonoids, coumarins, lignans, sesquiterpenes, steroids, ceramides, polysaccharides. Scientific studies on the biological activity of S. involucrata are equally numerous. The herb has been shown to have anti-neoplastic, anti-inflammatory, analgesic, anti-oxidative, anti-fatigue, anti-aging, anti-hypoxic, neuroprotective and immunomodulating effects. Many have shown correlations to the traditional clinical applications in Traditional Chinese Medicine and medicines. The possible mechanisms of S. involucrata in treating various cancers are revealed in the article, these include inhibition of cancer cells by affecting their growth, adhesion, migration, aggregation and invasion, inhibition of epidermal growth factor receptor signaling in cancer cells, hindrance of cancer cell proliferation, causing cytotoxicity to cancer cells and promoting expression of tumor suppressor genes. Dosage efficacy is found to be generally concentration- and time-dependent. However, studies on the correlation between particular chemical constituents and specific bioactivities are limited. Conclusion: In this review, we have documented the existing traditional uses of S. involucrata and summarized recent research into the phytochemistry and pharmacology of S. involucrata. Many of the traditional uses have been validated by phytochemical and modern pharmacological studies but there are still some areas where the current knowledge could be improved. Although studies have confirmed that S. involucrata has a broad range of bioactivities, further in-depth studies on the exact bioactive molecules and the mechanism of action are expected. Whether we should use this herb independently or in combination deserves to be clarified. The exact quality control as well as the toxicology studies is necessary to guarantee the stability and safety of the clinic use. The sustainable use of this endangered resource was also addressed. In conclusion, this review was anticipated to highlight the importance of S. involucrata and provides some directions for the future development of this plant.
Content may be subject to copyright.
Saussurea involucrata: A review of the botany, phytochemistry and
ethnopharmacology of a rare traditional herbal medicine
Wai-I Chik
a,1
, Lin Zhu
a,1
, Lan-Lan Fan
b,1
, Tao Yi
a,
n
, Guo-Yuan Zhu
c
, Xiao-Jun Gou
d
,
Yi-Na Tang
a
, Jun Xu
a
, Wing-Ping Yeung
a
, Zhong-Zhen Zhao
a
, Zhi-Ling Yu
a
,
Hu-Biao Chen
a,
nn
a
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, China
b
Guangxi Botanical Garden of Medicinal Plant, Nanning, Guangxi 530023, China
c
The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
d
Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610051, China
article info
Article history:
Received 4 March 2015
Received in revised form
16 June 2015
Accepted 18 June 2015
Available online 23 June 2015
Keywords:
Saussurea involucrata
Traditional Chinese Medicine
Uyghur local medicine
Phytochemistry
Ethnopharmacology
Rheumatoid arthritis
abstract
Ethnopharmacological relevance: Saussurea involucrata Matsum. & Koidz. is an endangered species of the
Asteraceae family, growing in the high mountains of central Asia. It has been, and is, widely used in
traditional Uyghur, Mongolian and Kazakhstan medicine as well as in Traditional Chinese Medicine as
Tianshan Snow Lotus (Chinese: ). In traditional medical theory, S. involucrata can promote blood
circulation, thereby alleviating all symptoms associated with poor circulation. It also reputedly eliminates
cold and dampness from the body, diminishes inammation, invigorates, and strengthens Yin and Yang.It
has long been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and
altitude sickness in Uyghur and Chinese medicine.
Aim of the review: To comprehensively summarize the miscellaneous research that has been done re-
garding the botany, ethnopharmacology, phytochemistry, biological activity, and toxicology of S. in-
volucrata.
Method: An extensive review of the literature was carried out. Apart from different electronic databases
including SciFinder, Chinese National Knowledge Infrastructure (CNKI), ScienceDirect that were sourced
for information, abstracts, full-text articles and books written in English and Chinese, including those
traditional records tracing back to the Qing Dynasty. Pharmacopoeia of China and other local herbal
records in Uighur, Mongolian and Kazakhstan ethnomedicines were investigated and compared for
pertinent information.
Results: The phytochemistry of S. involucrata has been comprehensively investigated. More than 70
compounds have been isolated and identied; they include phenylpropanoids, avonoids, coumarins,
lignans, sesquiterpenes, steroids, ceramides, polysaccharides. Scientic studies on the biological activity
of S. involucrata are equally numerous. The herb has been shown to have anti-neoplastic, anti-in-
ammatory, analgesic, anti-oxidative, anti-fatigue, anti-aging, anti-hypoxic, neuroprotective and im-
munomodulating effects. Many have shown correlations to the traditional clinical applications in Tra-
ditional Chinese Medicine and medicines. The possible mechanisms of S. involucrata in treating various
cancers are revealed in the article, these include inhibition of cancer cells by affecting their growth,
adhesion, migration, aggregation and invasion, inhibition of epidermal growth factor receptor signaling
in cancer cells, hindrance of cancer cell proliferation, causing cytotoxicity to cancer cells and promoting
expression of tumor suppressor genes. Dosage efcacy is found to be generally concentration- and time-
dependent. However, studies on the correlation between particular chemical constituents and specic
bioactivities are limited.
Conclusion: In this review, we have documented the existing traditional uses of S. involucrata and
summarized recent research into the phytochemistry and pharmacology of S. involucrata. Many of the
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/jep
Journal of Ethnopharmacology
http://dx.doi.org/10.1016/j.jep.2015.06.033
0378-8741/&2015 Elsevier Ireland Ltd. All rights reserved.
Abbreviations: DSE, dark-septate endophytic; SEM, scanning electron microscope; RA, rheumatoid arthritis; NO, nitric oxide; PGE
2
, prostaglandin E
2
; ROS, reactive oxygen
species; DPPH, 2, 2-diphenyl-1-picrylhydrazyl; ABTS, 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); HIF-1, hypoxia-inducible factor-1; ATP, adenosine triphosphate;
LAC, laccase; LD, lactate dehydrogenase; SOD, superoxide dismutase; MDA, malondialdehyde; GPx, glutathione peroxidase; PBMC, peripheral blood mononuclear cell
n
Corresponding author. Fax: þ852 3411 5571.
nn
Corresponding author. Fax: þ852 3411 2461.
E-mail addresses: yitao@hkbu.edu.hk (T. Yi), hbchen@hkbu.edu.hk (H.-B. Chen).
1
These authors contributed equally to this work.
Journal of Ethnopharmacology 172 (2015) 4460
traditional uses have been validated by phytochemical and modern pharmacological studies but there are
still some areas where the current knowledge could be improved. Although studies have conrmed that
S. involucrata has a broad range of bioactivities, further in-depth studies on the exact bioactive molecules
and the mechanism of action are expected. Whether we should use this herb independently or in
combination deserves to be claried. The exact quality control as well as the toxicology studies is ne-
cessary to guarantee the stability and safety of the clinic use. The sustainable use of this endangered
resource was also addressed. In conclusion, this review was anticipated to highlight the importance of S.
involucrata and provides some directions for the future development of this plant.
&2015 Elsevier Ireland Ltd. All rights reserved.
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
2. Ethnopharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
3. Botany ........................ ....................................... ....................................... ....... 46
3.1. Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
3.2. Plant occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
3.3. Botanical description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
3.4. Conservation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
4. Quality control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.1. Species authentication. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.2. Limits of indicator compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5. Phytochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.1. Phenylpropanoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.2. Flavonoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.3. Coumarins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.4. Lignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
5.5. Sesquiterpenes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
5.6. Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
5.7. Ceramides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
5.8. Polysaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
6. Bioactivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
6.1. Anti-neoplastic. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
6.2. Anti-arthritic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
6.3. Anti-oxidative and anti-aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
6.4. Anti-fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
6.5. Neuro-protective and anti-hypoxic. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
6.6. Immunomodulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
6.7. Other pharmacological activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
7. Toxicological studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
8. Modern clinical application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
8.1. Anti-arthritic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
8.2. Counteracting infertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
8.3. Others application of S. involucrata-containing compound prescription. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
9. Conclusion and prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Reference...............................................................................................................58
1. Introduction
In central Asia, Saussurea involucrata Matsum. & Koidz. (Fig. 1.)
has long been used under the herbal names Tianshan Snow Lo-
tus,Xinjiang Xuelian,Xuelian Huaand Xuehe Hua(Flora of
China Editorial Committee, 1999).S. involucrata has been an im-
portant medicinal herb in various ethnomedical systems which are
namely Traditional Chinese Medicine, Uyghur medicine, Mon-
golian medicine and Kazakhstan medicine, among which simila-
rities in pattern of usage has been manifested. These include
treatment of rheumatoid arthritis and regulation of menstrual
cycle. It is recorded in Pharmacopoeia of People's Republic of
China since 2005 and earlier in local herbal records of the above
mentioned ethnomedicines (Chinese Pharmacopoeia Commission,
2010;National Institutes for Food and Drug Control, 1984).
According to the Guangdong Provincial Traditional Chinese
Medicine Hospital, which is the top Traditional Chinese Medicine
hospital in China, S. involucrata has a broad-spectrum of clinical
applications, including anti-inammatory and analgesic, anti-oxi-
dative, anti-hypoxia, anti-fatigue, anti-aging and hormonal-related
gynecological disorders, infertility as well as immunomodulation.
These are closely correlated with those traditional uses. In recent
years, the effectiveness in anti-cancer therapy has further put S.
involucrata under the spotlight.
Along with its growing reputation, chemical constituents of S.
involucrata have been extensively studied. Phenylpropanoids, a-
vonoids, coumarins, lignans, sesquiterpenes, steroids, ceramides
and polysaccharides as main compositions were isolated and
identied. Among them, rutin and chlorogenic acid have been
proven with pharmacological evidence and active compounds in
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 4460 45
abundance of S. involucrata (Yi et al., 2009b) and they are the
chemical markers for its quality control in the current version of
Chinese Pharmacopoeia (Chinese Pharmacopoeia Commission,
2010).
In this review, advances in ethnopharmacology in different
ethnomedical systems, phytochemistry, biological and pharmaco-
logical activities, toxicology and clinical application of S. in-
volucrata are revealed.
2. Ethnopharmacology
The dried aerial parts of S. involucrata have long been used as
an herbal medicine in different parts of China and Kazakhstan. The
use of S. involucrata in local medicines in Central Asia has a long
history (Table 1). However, the earliest scientic record can only
be traced back to the Qing Dynasty (from 1636 A.D. to 1912 A.D.).
The earliest literature on S. involucrata was in Bencao Gangmu
Shiyi, in English Supplement to Compendium of Materia Medica
(Zhao, 1963), in which S. involucrata can be used to nourish Yin and
Yang, which is considered the origin of life and materials to
maintain balance in body in Traditional Chinese Medicine theory,
treat diseases related to internal coldness (Fig. 2). It can also
promote fertility in aged people and enhance recovery from
measles (Xie, 1968;Zhao, 1963). Impotence in men can also be
improved by using the decoction of 6 g of Herba Saussureae In-
volucratae together with 3 g of Radix Angelicae Sinensis and
Fructus Lycii each (Committee for National Revolution of Xinjiang
Uyghur Autonomous Region Health Bureau, 1976).
The extensive use of S. involucrata has been demonstrated in
different ethnomedical systems including Uyghur medicine,
Mongolian medicine, Kazakhstan medicine and Traditional Chi-
nese Medicine (Table 1). Amazingly, similarities in clinical appli-
cations among different local medicines were observed in treat-
ment of gynecological disorders, reliving respiratory symptoms
and pain-killing. It was worth to point out that unlike other herbs
in Traditional Chinese Medicines, in traditional herbal records, S.
involucrata is usually used independently instead of in herbal
formulas having prescription theories as monarch, minister,
assistant and guide(Chinese Medicinal Materials Corporation,
1994).
3. Botany
3.1. Nomenclature
According to The Plant List,S. involucrata Matsum. & Koidz is
the only accepted name for the herb, with a synonym S. in-
volucrata (Kar. & Kir.) Sch. Bip.(The Plant List, Version 1.1, 2013).
However, being the more widely accepted name in China, S. in-
volucrata Kar. & Kir.has been used as the ofcial name instead for
the herb in Pharmacopoeia of People's Republic of China and Flora
of China (Chinese Pharmacopoeia Commission, 2010;Flora of
China Editorial Committee, 1999).
A recent review has indicated the importance of accurate sci-
entic nomenclature for plants so as to minimize ambiguity of
species (Rivera et al., 2014) and therefore, the confusion con-
cerning S. involucrata mentioned above is expected to be resolved.
3.2. Plant occurrence
The habitats of S. involucrata include mountain slopes, moun-
tain valleys, meadows and rock ssures at elevations of 2400
4100 m. Due to the incredibly high altitudes at which it grows; S.
involucrata is named Tianshan Snow Lotuswhich means the
Snow Lotus that grows on sky-high mountains. The species is
mainly distributed in Xinjiang of China, but it also occurs in Ka-
zakhstan, Kyrgyzstan and Mongolia (Chen et al., 1999).
Unfortunately, due to over-exploitation, the wild population of
S. involucrata is dwindling rapidly (Kang et al., 2010). According to
the People's Daily, S. involucrata has decreased from being found
over 50,000,000 acres in the 1960s and 1970s to a few hundred
acres at present. At this rate, in less than 10 years, this rare species
could become extinct. It has thus been listed as a second grade
national protected wild plant in China (Fu and Jin, 1991).
Fig. 1. Photos of Saussurea involucrata plant and its medicinal material.
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 446046
Table 1
The traditional uses of Saussurea involucrata in different ethnomedical systems.
Traditional Chi-
nese Medicine
Uyghur medicine Mongolian medicine Kazakhstan medicine References
Herbal name Tianshan Xuelian
(Chinese: )
Tage Leylishi(Uyghur: )Banzhi Dawa(Mongolian:
)
Huojia Quepu(Kazakhstan: )Chinese Pharmacopoeia Commission (2010),Jia et al.
(2005a)
Part(s) of herb used Aerial parts Whole part Aerial parts Not mentioned
Dosage 36g
Indications on pregnancy Prohibited Prohibited Not mentioned Not mentioned
Independent use
Drug form Clinical application Traditional Chi-
nese Medicine
Uyghur
medicine
Mongolian
medicine
Kazakhstan medicine References
Decoction/
Tincture
Rheumatoid arthritis √√ Chinese Pharmacopoeia Commission (2010),Committee for National Revolution of Xinjiang
Uyghur Autonomous Region Health Bureau (1976),Jia et al. (2005b),Liu and Shawuti (1985),
Commission of Chinese Materia Medica (1999),Xie (1975),National Institutes for Food and
Drug Control (1984)
Menstrual pain √√ √ Chinese Medicinal Materials Corporation (1994),Chinese Pharmacopoeia Commission (2010),
Jia et al. (2005a),Liu and Shawuti (1985),Commission of Chinese Materia Medica (1999),
National Institutes for Food and Drug Control (1984)
Irregular menstruation
cycle
√√ √ Chinese Medicinal Materials Corporation (1994),Chinese Pharmacopoeia Commission (2010),
Jia et al. (2005a),Liu and Shawuti (1985),Commission of Chinese Materia Medica (1999),Xie
(1975),National Institutes for Food and Drug Control (1984)
Infertility Chinese Pharmacopoeia Commission (2010),Xie (1975),Zhao (1963)
Labor-inducing agent Jia et al. (2005a),Xie (1975)
Cough √√ Jia et al. (2005a),Commission of Chinese Materia Medica (1999),Xie (1975)
Decoction Other pain √√ √ Jia et al. (2005a),Liu and Shawuti (1985),National Institutes for Food and Drug Control
(1984)
Tuberculosis Jia et al. (2005a)
Measles √√ Chen (1963),Commission of Chinese Materia Medica (1999),Zhao (1963)
Strain Jia et al. (2005a)
Snow lotus
injection (i.
m.)
Rheumatoid arthritis;
Inammation
√√ Commission of Chinese Materia Medica (2005)
Classic formula
Formula name Ingredients Clinical application Traditional
Chinese
Medicine
Uyghur medicine Mongolian
medicine
Kazakhstan
medicine
References
Xuelian tincture Herba Saussureae Involucratae,
Radix Angelicae Sinensis, Fructus
Lycii
Menstrual pain, irregular
menstruation cycle, infertility
√√ Committee for National Revolution of
Xinjiang Uyghur Autonomous Region
Health Bureau (1976),Commission of Chi-
nese Materia Medica (1999)
Xuelian honghua
tincture
Herba Saussureae Involucratae,
Flos Carthami, Fructus Mori,
Fructus Lycii
Immunodeciency, poor
blood circulation
Commission of Chinese Materia Medica
(2005)
Xuelian lingzhi
tincture
Herba Saussureae Involucratae,
Ganoderma
Infertility, immunodeciency √√Commission of Chinese Materia Medica
(2005)
Xuelian patches
(protected
formula)
Herba Saussureae Involucratae Anti-neoplastic agent √√ Commission of Chinese Materia Medica
(2005)
Other commonly used formula
Formula name Ingredients Clinical application Traditional Chinese Medicine Uyghur medicine Mongolian
medicine
Kazakhstan
medicine
References
Xuelian tincture Herba Saussureae Involucratae ,
Flos Carthami, Radix Gentianae
Macrophyllae, Radix Angelicae
Arthritis, pain √√ Orally
transmitted
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 4460 47
3.3. Botanical description
S. involucrata is a perennial herb 1550 cm tall. It has an un-
branched, stout caudex which is densely covered with brous
remains of petioles. Its stem is solitary with its rosette and stem
leaves petiolated. The leaf blades are narrowly ovate, elliptic, or
obovate, with both surfaces being green and glandular hairy. The
uppermost stem leaves are sessile, ovate to elliptic, being mem-
branous with both surfaces pale yellow; and stellately surround
the synorescence. The synorescence is hemispheric to broadly
campanulate with 1020 capitula. Its phyllaries are in 3 or 4 rows,
dark or light brown with dark margins and sparsely pubescent.
The achenes are straw-colored with blackish spots, cylindrical, and
each has a dirty-white pappus. Plants ower from July to August
and bear fruit from August to October (Flora of China Editorial
Committee, 1999).
3.4. Conservation
S. involucrata is a valuable medicinal herb and it has also been
an important source of a wide range of bioactive compounds;
syringin, chlorogenic acid, and 1, 5-dicaffeoylquinic acid are the
chemicals most commonly extracted from it (Chen et al., 2014b).
Wild populations of S. involucrata are dwindling rapidly. To reduce
the demand for the wild S. involucrata, researches have been done
to increase yield of chemicals by modied cultivation method,
developing tissue culture systems for its rapid propagation and
nding substitutes.
According to a study, the increasing duration of growth in the
cultivation of S. involucrata can increase the amount of some of its
bioactive compounds (Chen et al., 2013d). Besides, a dark-septate
endophytic (DSE) fungus EF-37 isolated from the roots of S. in-
volucrata has also demonstrated a signicant positive effect on
plant growth and its rutin content (Wu and Guo, 2008;Wu et al.,
2010), though with withheld mechanism. Optimization in condi-
tions of micropropagation systems for maximization of chemicals
having desirable biocativities have been investigated, such as the
reduction of atmospheric pressure which has resulted in variation
of morphogenic potential and anti-oxidative enzymatic activities
(Guo et al., 2011,2007). According to one study, hairy root culture
system of S. involucrata through agrobacterium-mediated trans-
formation was established and the amount of syringin and hispi-
dulin, two of the active components, was found to be even higher
than in the wild species (Fu et al., 2006;Qiu et al., 2010). These
suggest the feasibility of using tissue culture of S. involucrata to
replace its wild plant source.
Closely-related plant species often share similar secondary
metabolites and bioactivities (Mpala et al., 2012). With reference
to a recent review on the genus, the Saussurea shows resemblance
in phytochemical constituents as well as bioactivities. Dehy-
drocostus lactone (Li and Jia, 1989;Madhavi et al., 2012), 3a,8a-
dihydroxy- 11bH-11,13-dihydrodehydrocostus lactone (Li and Jia,
1989), 35,36, 3a,8a- dihydroxy-11bH-11,13-dihydrodehydrocostus
lactone 8-O-β-D-glucopyranoside (Fan et al., 2006;Li and Jia,
1989), 8a-hydroxy-11bH-11,13-dihydrodehydrocostus lactone (Fan
et al., 2006;Li and Jia, 1989) are phytochemicals present in S. in-
volucrata, but are also found in other close species including S.
lappa, or other easily confused species of S. involucrata like S.
medusa or S. laniceps (Wang et al., 2010). Besides, S. ussuriensis,S.
petrovii,S. costus and S. medusa have similar pharmacological
function in anti-rheumatic arthritis (Wang et al., 2010). These can
serve as evidence for the possible substitution of herbal resources
by their closely-related species. Cock has pointed out, which
would provide insight into new direction of research as in prin-
cipal active compound identication, common phytochemicals are
good targets for bioactivity testing when one or more species
Table 1 (continued )
Traditional Chi-
nese Medicine
Uyghur medicine Mongolian medicine Kazakhstan medicine References
Pubescentis, Fructus Lycii
Xuelian fengshiling mixture Herba Saussureae Involucratae,
Processed Radix Aconiti, Radix An-
gelicae Pubescentis
Rheumatoid arthritis, arthritis-related
pain, inammation
Orally
transmitted
Xuelian guiqi decoction Herba Saussureae Involucratae, Ra-
dix Angelicae Sinensis, Radix
Astragali
Forgetfulness, insomnia, dizziness,
exhaustion
Orally
transmitted
Xuelian chongcao mixture Herba Saussureae Involucratae,
Cordyceps
Polyuria, exhaustion Orally
transmitted
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 446048
within a genus are known to possess similar therapeutic proper-
ties (Mpala et al., 2012).
4. Quality control
4.1. Species authentication
Snow Lotus prepared by herbs of different species or different
places of origin contains different amount of chemical constituents
and thus give rise to different medical value. Therefore, quality
control is crucial, for both drug efcacy and safety. There are
confusions in the species of herbs contributing to the Chinese
Materia Medica Snow Lotus. Three representative easily-con-
fused species include S. involucrata,Saussurea laniceps. and Saus-
surea medusa (Chen et al., 2014a). According to the Pharmacopoeia
of China, S. involucrata is the only species being accepted (Chinese
Pharmacopoeia Commission, 2010). Therefore, traditional and
contemporary authentication methods are required to ensure the
use of the ofcial species. As demonstrated by a study, the con-
fused species can be differentiated using macroscopic identica-
tion of the crude drug, microscopic identication of the powered
crude drug and a combination of microscopic identication
methods of its pollen grains including ordinary light microscopy,
polarized light microscopy and SEM (Chen et al., 2014a).
4.2. Limits of indicator compounds
In the view of its chemical content, chlorogenic acid (not less
than 0.15% of dried sample) and rutin (not less than 0.15% of dried
sample), being the major chemical constituents of S. involucrata,
are used as the indicator compound to characterize the quality of
this herb (Chinese Pharmacopoeia Commission, 2010). The abun-
dance of chemical constituents differs in herbs obtained from
different origins. It is believed that the quality of Snow Lotus
sourced from Tianshan of Xinjiang in China (Yi et al., 2009b) is the
best of all.
5. Phytochemistry
More than 70 compounds have so far been isolated and iden-
tied from S. involucrata. As aerial parts of S. involucrata have been
used as in Traditional Chinese Medicine, other folk medicine sys-
tems and remain the only medicinal part till now, chemical con-
stituent analysis mainly focused on its above-ground portion.
HPLC-MS has been the most common analytical means for quali-
tative analysis of chemicals present in S. involucrata; a diversity of
compounds were identied including phenylpropanoids,
avonoids, coumarins, lignans, sesquiterpenes, steroids, ceramides
and polysaccharides. In quantitative analysis of the chemicals,
which is not as comprehensive as qualitative analysis, HPLC was
mainly used. The contents of chlorogenic acid and rutin, which
have been set for quality control for S. involucrata in the Chinese
Pharmacopoeia 2010 edition, ranged from 1.19 to 14.43 mg/g and
0.14 to 16.02 mg/g respectively. Total phenolic content was found
to be ranging from 23.58 to 41.56 mg/g while the content for total
avonoid is 9.08 and 15.84 mg/g. Other bioactive compounds were
qualitatively determined as well, including syringin (0.20
0.58 mg/g), arctiin (0.051.62 mg/g), apigenin (0.0050.015 mg/g)
and hispidulin (0.050.16 mg/g) (Chen et al., 2013a;Li and Zhong,
2013;Qiu et al., 2010;Xu et al., 2009;Yi et al., 2009b).
5.1. Phenylpropanoids
Syringin (1), 3-caffeoylquinic acid (2) 5-caffeoylquinic acid (3),
4-caffeoylquinic acid (4), 1,3-dicaffeoylquinic acid (5), 1,4-di-
caffeoylquinic acid (6), 1,5- dicaffeoylquinic acid (7), 4,5-di-
caffeoylquinic acid (8), 1,5-dicaffeoyl-3- succinoylquinic acid (9),
1,5-dicaffeoyl-4-succinoylquinic acid (10), 1,5-dicaffeoyl- 3,4-dis-
uccinoylquinic acid (11) have been found in S. involucrata (Chen
et al., 2013a;Chen et al., 2013b;Qiu et al., 2010). One study also
found tangshenoside III (12)(Chen et al., 2010)(Fig. 3).
5.2. Flavonoids
Many studies have reported nding a variety of avonoids in S.
involucrata. These different avonoids can be categorized into four
sub-groups, namely avone aglycones, avone glycosides, avonol
aglycones and avonol glycosides.
The avone aglycones include hispidulin (13), jaceosidin (14),
luteolin (15), nepetin (16 ), apigenin (17) and 5,6-dihydroxy-7,8-
dimethoxyavone (18). The avone glycosides include apigenin 7-
O-glycoside (19), hispidulin 7-O-glucoside (20), luteolin7-O-glu-
coside (21), nepetin 7-O-glucoside (22), apeginin 7-O-glucuronide
(23), chrysoeriol 7-O-glucuronide (24), chrysoeriol 7-O-glycoside
(25) and chrysoeriol 7-O-rhamnoside (26)(Iwashina et al., 2010;
Jing et al., 2013;Qiu et al., 2010).
Two avonol aglycones have been found, quercetin (27) and
kaempferol (28). The avonol glycosides found include quercetin
3-O-rhamnoside (29), quercetin 3-O-rutinoside (rutin) (30), quer-
cetin 3-O-glucoside (31), isorhamnetin 3-O-rutinoside (32) and
kaempferol 7-O-glucopyranoside (33)(Iwashina et al., 2010)(
Figs. 47).
5.3. Coumarins
Eight coumarins have been isolated from S. involucrata.
Fig. 2. The earliest literature on Saussurea involucrata (in Bencao Gangmu Shiyi book).
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 4460 49
These include one simple coumarin, osthol (34), and seven pyr-
anocoumarins. The latter are isopimpinellin (35), bergapten (36),
xanthotoxol (37), alloisoimperatorin (38), oroselol (39), edultin
(40) and vaginidiol diacetate (41)(Yang et al., 2006)(Fig. 8).
5.4. Lignans
Several lignans including arctigenin-4-O-(6-O-acetyl-β-
D
-glu-
coside) (42), arctigenin-4-O-(2-O-acetyl-β-
D
-glucoside) (43), arc-
tigenin-4-O-(3-O-acetyl-β-D- glucoside) (44), arctiin (45) and
arctigenin (46) have been identied (Li et al., 2012;Liu and Aisa,
2010)(Fig. 9).
5.5. Sesquiterpenes
Sesquiterpenes are bitter substances. They often contain as a
major structural feature an α,β-unsaturated-γ-lactone which, in
recent studies, has been shown to be associated with anti-tumor,
cytotoxic, anti-microbial and phytotoxic activities (Picman and
Towers, 1983). Bioassay-directed separation of the ethyl acetate
extract of the aerial parts of S. involucrata has led to the isolation of
sausinlactone A-(1S, 3S, 5S, 6S, 7S, 11S)-3-hydroxyl-11, 13-dihy-
drodehydrocostuslactone (47), sausinlactone B-(1S, 3S, 5S, 6S, 7S,
11R)-3-hydroxyl-11, 13-dihydrodehydrocostuslactone (48), sau-
sinlactone C-(1S, 3S, 5S, 6S, 7S, 8S, 11S)-3-hydroxyl-11,13-dihy-
drodehydrocostuslactone (49), 3α,8α-dihydroxyl-11βH-11, 13- di-
hydrodehydrocostuslactone (50)8α-hydroxyl- 11βH-11,13-
dihydrodehydrocostuslactone (51), 11β,13-dihydrodehy-
drocostuslactone- 8-O-β-D-glucoside (52), 11β,13-dihydrodehy-
drocostuslactone-8-O-[6-O-acetyl-β-D- glucoside] (53), 11α,13
-dihydroglucozaluzanin C (54)3α-hydroxyl-11β,13- dihydrodehy-
drocostuslactone-8-O-β-D-glucoside (55) and japonicolactone (56)
(Li et al., 2007;Wang et al., 2007). 10β,14-Dihydroxy-11βH-guai-4-
(15)-ene-12,6α-olide 14-O-β-D-glucoside (57) and involucratin
(58), and 11βH-2α-hydroxy-eudesman- 4(15)-en-12,8β-olide,
which is a eudesmanolide (59), were also isolated (Chen et al.,
2010)(Fig. 10).
5.6. Steroids
Seven steroids have been isolated from S. involucrata. These
are: bufotalin (60), telocinobufagin (61), gamabufotalin (62),
daucosterol (63), β-sitosterol (64), 3-O-(6-O-palmitoyl-β-D-glu-
cosyl)-β-sitosterol (65) and 3-O-(6-O-linoleoyl-β-D-glucosyl)- β-
sitosterol (66)(Chen et al., 2010;Wu et al., 2009)(Fig. 11).
5.7. Ceramides
Rel-(3R,4S,5S)-3-[(2R)-2-hydro-
xynonadecanoylpentacosanoylamino]-4-hydroxy-5-[(4E)-hep-
tadecane-4-ene]-2, 3, 4, 5-tetrahydrofuran (67a67g) were the
identied ceramides from S. involucrata (Wu et al., 2009)(Fig.12).
1
OH
O
O
O
O
HO
HO
HO
OH
O
O
HCO
HCO
CH=CH-CH-OH
CHCH=CH
OCH
O
OCH
HOHC
HO
HOOH
O
CHOH
OH
OH
HO
12
HOOC OR
1
OR
2
OR
3
RO
OH
OH
O
OH
O
O
succinoyl
OH
O
O
maloyl
OH
caffeoyl
2R
1
=HR
2
=caffeoylR
3
=HR
4
=H
3R
1
=HR
2
=HR
3
=HR
4
=caffeoyl
4R
1
=HR
2
=HR
3
=caffeoylR
4
=H
5R
1
=caffeoylR
2
=caffeoylR
3
=HR
4
=H
6R
1
=caffeoylR
2
=HR
3
=caffeoylR
4
=H
7R
1
=caffeoylR
2
=HR
3
=HR
4
=caffeoyl
8R
1
=HR
2
=HR
3
=caffeoylR
4
=caffeoyl
9R
1
=caffeoylR
2
=succinoylR
3
=HR
4
=caffeoyl
10R
1
=caffeoylR
2
=HR
3
=succinoylR
4
=caffeoyl
11 R
1
=caffeoylR
2
=succinoylR
3
=succinoylR
4
=caffeoyl
Fig. 3. Structures of phenylpropanoids in Saussurea involucrata.
O
R
2
OHO
R
4
OH
R
1
13R
1
=OCH
3
R
2
=HR
3
=HR
4
=H
14 R
1
=OCH
3
R
2
=HR
3
=HR
4
=OCH
3
15R
1
=HR
2
=OHR
3
=HR
4
=OH
16R
1
=OCH
3
R
2
=HR
3
=HR
4
=OH
17R
1
=HR
2
=HR
3
=HR
4
=H
18R
1
=OHR
2
=OCH
3
R
3
=OCH
3
R
4
=H
R
3
Fig. 4. Structures of avone aglycones in Saussurea involucrata.
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 446050
5.8. Polysaccharides
Total polysaccharides with high purities have been separated
from S. involucrata through adsorption using macroporous resin
and precipitation using ethanol (Wang et al., 2012a). Poly-
saccharides from cultivated S. involucrata (CSIP) were puried; two
major fractions (CSIP1-2 and CSIP2-3) were investigated for their
molecular weights, monosaccharide compositions and in vitro
antioxidant activities. According to the results, the molecular
weights of CSIP1-2 and CSIP2-3 were approximately 163.5 kDa and
88.6 kDa, respectively. CSIP1-2 was composed of glucose, ga-
lactose, xylose, rhamnose, arabinose and galacturonic acid with a
molar ratio of 1.65:0.39: 0.06:8.33:1.76:40.43. CSIP2-3 was com-
posed of glucose, galactose, xylose, rhamnose, arabinose and ga-
lacturonic acid with a molar ratio of 0.76:0.66:0.11:5.59:0.32:44.66
(Yao et al., 2012).
6. Bioactivity
S. involucrata is traditionally used to treat a wide spectrum of
disorders; its pharmacological evidence is grounded by long his-
tory of usage and promising experimental results. Traditional
clinical applications were considered guide for bioactivity eva-
luations, and many correlations were found between the phar-
macological action in traditional records of the herb and bioac-
tivities conrmed in modern studies (Table 2). Researches have
revealed more bioactivities and its therapeutic spectrum of S. in-
volucrata is still broadening, with scientic evidence.
6.1. Anti-neoplastic
It has been an emerging clinical application for S. involucrata to
be used as an anti-neoplastic agent in the recent decade. S. in-
volucrata has gained widespread global praise owing to its effec-
tiveness in anti-cancer therapy. Experiments have veried the
anti-cancer bioactivity of S. involucrata through different me-
chanism of action, including its interference on the cell growth
process (Byambaragchaa et al., 2013), mainly by causing cell
apoptosis (Chen et al., 2012;Way et al., 2010) and cytotoxicity (Wu
et al., 2009;Xiao et al., 2011b;Zhang et al., 2011b); affecting cell
adhesion, migration and aggregation; while in gene level, it also
has certain impact on transcription activity (Byambaragchaa et al.,
2013). Human cancer cell lines were mainly targets in the anti-
cancer bioactivities assessments and different assays were used to
monitor the level of certain protein expression in the tumor cells
(Byambaragchaa et al., 2013;Chen et al., 2012;Way et al., 2010;
Wu et al., 2009;Zhang et al., 2011b) while in vivo experiments
involved the xenograft model (Chen et al., 2012;Way et al., 2010).
The principal active compound has not yet been conrmed so far
but experiments have suggested high possibility for it to be lying
within the ethanol extract (7595%) or the ethyl acetate fraction.
O
OH
R
3
OH
R
2
O
O
R
1
19R
1
=HR
2
=glcR
3
=H
20R
1
=OCH
3
R
2
=glcR
3
=H
21 R
1
=HR
2
=glcR
3
=OCH
3
22 R
1
=HR
2
=glcR
3
=OH
O
OH
O
OH
HO
HO
23R
1
=HR
2
=R
3
=H
24 R
1
=OHR
2
=R
3
=OCH
3
25R
1
=HR
2
=glcR
3
=OCH
3
26R
1
=OHR
2
=rhaR
3
=OCH
3
O
OH
O
OH
HO
HO
Fig. 5. Structures of avone glycosides in Saussurea involucrata.
O
OH
R
OH
HO
O
OH
27R=OH
28R=H
Fig. 6. Structures of avonol aglycones in Saussurea involucrata.
O
OR
1
OOH
R
2
O
R
3
OH
29R
1
=rhaR
2
=HR
3
=OH
30 R
1
=glc-glcR
2
=HR
3
=OH
31R
1
=glcR
2
=HR
3
=OH
32R
1
=glc-glcR
2
=HR
3
=OCH
3
33 R
1
=HR
2
=glcR
3
=H
Fig. 7. Structures of avonol glycosides in Saussurea involucrata.
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 4460 51
The effective dose ranged from microgram level in vitro to milli-
gram level in vivo; dose- and time-dependent manner has been
demonstrated in some studies (Byambaragchaa et al., 2013;Chen
et al., 2012;Way et al., 2010;Wu et al., 2009;Zhang et al., 2011b).
6.2. Anti-arthritic
Rheumatoid arthritis (RA) is a chronic, inammatory, systemic
autoimmune disorder of withheld etiology for which there is no
cure. (Doan and Massarotti, 2005) It is characterized by synovial
inammation and destruction of cartilage and bone (Klareskog
et al., 2014). Currently, the aim of treatment is to mitigate the
symptoms and prevent disability (Doan and Massarotti, 2005). S.
involucrata, which is used for the treatment of rheumatoid arthritis
in folk medicines, has demonstrable anti-inammatory and an-
algesic effects (Zhai et al., 2010).
The anti-inammatory activity of S. involucrata extract has been
observed in mice and rats, with xylene or carrageenan-induced
paw edema and ear edema (Jia et al., 2011;Wang et al., 2011;Yi
et al., 2010;Zhai et al., 2010). Acetic acid-induced excessive ab-
dominal capillary permeability (Jia et al., 2011;Zhai et al., 2010),
primary and secondary adjuvant arthritis were the other models
used in anti-inammatory evaluation (Tao et al., 2007;Wang et al.,
2011). RAW 264.7 macrophage were monitored for examination of
the inhibitory effect of S. involucrata in nitric oxide (NO) and
prostaglandin E
2
(PGE
2
) production in LPS-activated macrophage
(Xiao et al., 2011a). NO is considered as a pro-inammatory
mediator that induces inammation due to over production in
abnormal situations (Sharma et al., 2007). PGE
2
is one of the most
abundant PGs produced in the body. During inammation, PGE
2
is
of particular interest because it is involved in all processes leading
to the classic signs of inammation: redness, swelling and pain
(Ricciotti and FitzGerald, 2011;Funk, 2001). Therefore, their re-
lative abundance in the animal models can act as indicators for the
degree of inammation.
Investigations on the analgesic effects included acetic acid-in-
duced writhing (Jia et al., 2011;Wang et al., 2011;Zhai et al., 2010),
hot-plate test (Zhai et al., 2010) in mice. Central analgesic effect
was also demonstrated by (Almeida et al., 2001).
Ethanol extracts of S. involucrata were given to mice and rats
via intragastric route (i.g.) with dose ranging from 15400 mg/kg
and not more than 42 mg/kg in rats depending on the area of
edema for no longer than 7 days (Jia et al., 2011;Wang et al., 2011;
Yi et al., 2010); while a much lower dose of 0.36 mg/kg was given
to mice by injection form (Tao et al., 2007). According to the report
in the rat paw edema model (Yi et al., 2010), the peak inhibitory
effects of S. involucrata (42.2%) were recorded with a dose of
400 mg/kg at 3h post-carrageenan injection; while oral adminis-
tration of S. involucrata extract (400 mg/kg) resulted in a sig-
nicant 33.3% inhibition of ear edema in mice. Flavonoids, found to
be present in plasma after administration of the extracts, are be-
lieved to be the basis of the observed pharmacological effects (Yi
O O
H
3
CO
CH
2
CH=C(CH
3
)
2
34
O O
O
R
1
R
2
35R
1
=OCH
3
R
2
=OCH
3
36 R
1
=OCH
3
R
2
=H
37R
1
=HR
2
=OH
38R
1
=OHR
2
=CH
2
-CH=C(CH
3
)
2
OO
O
C
Me
OH
Me
39
O O
O
R
Me
Me
AcO
40R=OCOC(CH
3
)=CH(CH
3
)
41 R=OAc
Fig. 8. Structures of coumarins in Saussurea involucrata.
H
3
CO
RO
O
O
OCH
3
OCH
3
O
HO
HO
H
3
CO=CO
OH
42 R=
O
HO
HO
HO
OC=OCH
3
43R=
O
HO
H
3
CO=CO
HO
OH
44 R=
O
HO
HO
HO
OH
45R=
46R=H
Fig. 9. Structures of lignans in Saussurea involucrata.
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 446052
et al., 2010).
In addition, the tissue culture of S. involucrata was found to
exhibit anti-inammatory and analgesic activities, suggesting that
cultured tissue of S. involucrata could substitute for wild-grown
plant material in the pharmaceutical industry (Jia et al., 2011).
However, the resemblance of animal models of arthritis to the
patients developing symptoms and therefore the predictive power
of these researches is in doubt. Animal models of arthritis are
widely used to de-convolute disease pathways and to identify
novel drug targets and therapeutic approaches. However, the high
attrition rates of drugs in phase II/III rates means that a relatively
small number of drugs reach the market, despite showing efcacy
in pre-clinical models (McNamee et al., 2015). Other assays for
better prediction of pharmacological evidence of herbs in treating
arthritis are anticipated (McNamee et al., 2015).
6.3. Anti-oxidative and anti-aging
According to the free radical theory of aging, aging results from
the accumulation of deleterious effects caused by free radicals, and
the ability of an organism to cope with cellular damage induced by
reactive oxygen species (ROS) plays an important role in de-
termining organismal lifespan (Harman, 1956). Experimentally,
increased ROS production is frequently detected in aged tissues
(Maynard et al., 2009;Sawada et al., 1992;Sohal and Sohal, 1991)
and many studies have found that increased oxidative damage in
cells is associated with aging (Chakravarti and Chakravarti, 2007;
Fraga et al., 1990;Hamilton et al., 2001;Oliver et al., 1987).
With reference to traditional records (Zhao, 1963), S. involucrata
has been used to postpone aging by invigorating Yin and Yang in
body, which in some sense means promoting the activity of dif-
ferent organs in body. Multiple phytochemicals from S. involcurata
were found to possess anti-oxidative pharmacological function.
Polysaccharides of S. involucrata have demonstrated anti-oxidative
effect by scavenging superoxide anions in nitroblue tetraazolium
colorimetric method, DPPH, hydroxyl and ABTS radical scavenging
assay and by inhibiting the formation of thiobarbituric acid re-
actant in mouse liver homogenate (Yao et al., 2012;Zheng et al.,
1993). Research has also revealed a positive correlation between
antioxidant activity and the amount of phenolic and avonoid
compounds in S. involucrata extracts, suggesting they could be the
active constituents accounting for the antioxidant activity (Qiu
et al., 2010;Wang et al., 2012b). Further in vitro bioactive in-
vestigations have demonstrated that 3, 5-dicaffeoyl-1-O-(2-O-
caffeoyl-4-maloyl)-quinic acid has signicant anti-oxidative effect
in DPPH and ABTS radical scavenging assays (Zou et al., 2014).
The oxidation-inhibitory effects were found to be in a con-
centration-dependent manner by comparison with the effects of
the same doses of vitamin C that the scavenging effect of S. in-
volucrata on free radicals increased with quantity (Lee et al., 2011).
6.4. Anti-fatigue
Physiological fatigue, an incapacitating or disabling illness,
means a reduction in the force output and energy generating ca-
pacity of a body after chronic exposure to work or usual activities
at the same intensity (Shevchuk, 2007). Studies focused on the
character of reactive oxygen species in conrmation of anti-fatigue
bioactivity. Extensive evidence has accumulated demonstrating
the benecial effects of antioxidants in chronic fatigue. S. in-
volucrataseffectivenesss in coping with the ROS has been dis-
cussed in Section 6.3. Besides, the ability of S. involucrata to reduce
fatigue has also been tested in experiments with mice. Decreased
oxygen consumption and prolonged swimming time were ob-
served after administration of polysaccharides of S. involucrata.
This provides clear evidence of its anti-fatigue effect and supports
the traditional belief that the Snow Lotus herb can strengthen and
invigorate the body (Zheng et al., 1993).
6.5. Neuro-protective and anti-hypoxic
Petrolleum ether extract, ethyl acetate extract and ethanol ex-
tract of S. involucrata were found to possess neuro-protective effect
and can reverse damage of brain cells under hypoxia state (Ma
et al., 2014a,2014b;Yang et al., 2011).
In hypoxic state, hypoxia-inducible factor-1 (HIF-1), which is a
Fig. 10. Structures of sesquiterpenes in Saussurea involucrata.
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 4460 53
transcription factor and also a heterodimer composed of HIF-1α
and HIF-1βprotein subunits. It is essential for the activation of
hypoxia-inducible genes like erythropoietin, some glucose trans-
porters, the glycolytic enzymes, and vascular endothelial growth
factor. As HIF-1 activation may promote cell survival in hypoxic
tissues, studies focused on the effect of hypoxic preconditioning on
HIF-1 expression in hypoxia models of mice or rats (Bergeron
et al., 2000;Ma et al., 2014b;Yang et al., 2011) by Western Blot
assay (Ma et al., 2014b). Metabolism parameters, including ATP,
ATPase, LAC, LDH, LD (Ma et al., 2011;Yang et al., 2011) and levels
of oxidative stress indicators like SOD and MDA levels (Ma et al.,
2014a;Yang et al., 2011) in pretreated hypoxic mice models were
also determined in some studies. Besides, in other experiments,
prolonged survival time of mice in conditions of acute anoxia and
drop in mortality under acute decompression conditions were
shown (Ma et al., 2011;Yang et al., 2011). Extracts had to be ad-
ministered via intraperitoneal injection route (Ma et al., 2014a,
Fig. 11. Structures of steroids in Saussurea involucrata.
O
OH
(CH
2
)
10
CH
3
HN (CH
2
)
n
CH
3
O
OH
67an=13
67bn=14
67cn=15
67dn=16
67en=17
67fn=18
67gn=19
Fig. 12. Structures of ceramides in Saussurea involucrata.
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 446054
Table 2
Bioactivities of Saussurea involucrata as demonstrated in experiments.
Activity Experimental protocol Target animal(s)/ cell(s) Result
(þ/)
Dose Chemical(s) /extract(s) Reference(s)
Anti-neoplastic
Cell growth CCK-8 cell proliferation assay kit SK-Hp1 human HCC cell line þ200400 mg/mL 95% ethanol extract Byambaragchaa et al. (2013)
4Cell cycle arrest P21 and p27, cyclin D1, CDK4 biomarker Human PC-3 cells þ12.5200 mg/mL Ethyl acetate fraction of SI
(incl. hispidulin, rutin)
Chen et al. (2012),Way et al.
(2010)
4Apoptosis Bax expression, cytochrome C release, cas-
pase-3 and caspase -9 activation, Bcl-2
expression
Human PC-3 cells þ12.5200 mg/mL Ethyl acetate fraction of SI
(incl. hispidulin, rutin)
Chen et al. (2012),Way et al.
(2010)
EGFR overexpression, Akt, STAT3 PC-3 xenograft model þdose-dependent; 10 and
30 mg/kg; i.g.; 3 times/
week
Ethyl acetate fraction of SI
(incl. hispidulin, rutin)
Chen et al. (2012),Way et al.
(2010)
4Cytotixicity Cytotoxicity MTT assay GepG2, MCF-7 cell lines þIC
50
0.050.5 mM Bufotalin, telocinobufagin,
gamabufotalin
Zhang et al. (2011b)
HL-60, A375-S2, HeLa cell lines þ- Ceramides (75% ethanol
extract)
Wu et al. (2009)
A549 cells þIC
50
0.01 mM (A) IC
50
2.89 mM (B)
Susquiterpene lactones sau-
sinlactones A, B
Xiao et al. (2011)
Cell adhesion Cell adhesion assay SK-Hp1 human HCC cell line þ200400 mg/mL 95% Ethanol extract Byambaragchaa et al. (2013)
Cell migration Wound closure assay SK-Hp1 human HCC cell line þ200 mg/mL 95% Ethanol extract Byambaragchaa et al. (2013)
Cell aggregation Cell aggregation assay SK-Hp1 human HCC cell line þ400 mg/mL 95% Ethanol extract Byambaragchaa et al. (2013)
Gene transcriptional level
and activity
mRNA analysis, reverse transciption-PCR,
quantitative real time assays
SK-Hp1 human HCC cell line þdose-dependent 95% Ethanol extract Byambaragchaa et al. (2013)
Anti-arthritis related disorders
Anti-inammatory Xylene induced-ear edema Mice þ3050% Ethanol extract Zhai et al. (2010)
Mice þ1560 mg/kg XL-12 Wang et al. (2011)
Mice þ95% Ethanol extract Jia et al. (2011)
Xylene-induced paw edema Mice þ400 mg/kg; i.g. 50% Ethanol extract Yi et al. (2010)
Carrageenan-induced paw edema Rats þ400 mg/kg; i.g. 50% Ethanol extract Yi et al. (2010)
Carrageenan induced-hind paw edema Rats þ75300 mg/kg; i.g.; 7 d 95% Ethanol extract Jia et al. (2011)
Acetic acid-induced excessive abdominal ca-
pillary permeability
Mice þ3050% Ethanol extract Zhai et al. (2010)
Mice þ75300 mg/kg; i.g.; 7 d 95% Ethanol extract Jia et al. (2011)
Adjuvant arthritis induced by injection of
Freud's complete adjuvant (primary)
Mice þ0.36 mg/kg; inj. Tao et al. (2007)
Rats þ10.542 mg/kg XL-12 Wang et al. (2011)
Adjuvant arthritis induced by injection of
Freund's complete adjuvant (secondary)
Rats þ10.542 mg/kg XL-12 Wang et al. (2011)
RAW 264.7 macrophage proliferation, NO
production
RAW 264.7 macrophage þ25200 mmol/L 95% Ethanol extract Xiao et al. (2011a)
Analgesic Acetic acid induced-writhing test Mice þ3050% Ethanol extract Zhai et al. (2010)
Mice þ75300 mg/kg; i.g.; 7 d 95% Ethanol extract Jia et al. (2011)
Mice þ1560 mg/kg XL-12 Wang et al. (2011)
Hot plate test Mice þ3050% ethanol extract Zhai et al. (2010)
Central analgesic Mice þ20 mg/kg NA Almeida et al. (2001)
Immunomodulation [þStimulatory; Inhibitory]
Carbon clearance rate(non-specic
immunity)
Mice 150 mg/kg; i.g.; 7 d Ethanol extract Jia and Wu (2007)
Serum hemolysis formation Mice þ300 mg/kg; i.g.; 7 d Ethanol extract Jia and Wu (2007)
Peripheral blood mononuclear cells (PBMC)
specic cytotoxicity to Human K562, Raji cell
lines
PBMC þ0.6 mg/mL Total avone Ma et al. (1998)
PHA induced-lymphocyte transformation
percentage
Mice þ4080 mg/kg Total avone Fan et al. (1996)
Serum hemagglutination antibody against
SRBC
Mice þ4080 mg/kg Total avone Fan et al. (1996)
Hemolytic antibody Mice þ4080 mg/kg Total avone Fan et al. (1996)
DNCB induced-delated hypersensitivity (non- Mice 300 mg/kg; i.g.; 7 d Ethanol extract Jia and Wu (2007)
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 4460 55
Table 2 (continued )
Activity Experimental protocol Target animal(s)/ cell(s) Result
(þ/)
Dose Chemical(s) /extract(s) Reference(s)
specic immunity)
T cell and B lymphocyte proliferation Rats 0.130.14 mg/mL XL-12 Wang et al. (2011)
Neuro-protective and anti-hypoxic
Metabolism parameters (ATP, ATPase, LAC,
LDH)
Mice þ51 mg/kg Petroleum ether extract Ma et al. (2011)
Metabolism parameters (LD, LDH, ATP,
ATPase)
Normobaric, decompression, and
chemistry poisoning hypoxia in
mice
þ250500 mg/kg Ethanol extract Yang et al. (2011)
Brain tissues of hypoxia in rats þ125500 mg/kg; i.p. Petroleum ether extract Ma et al. (2014a)
Oxidative stress indicators (SOD and MDA
levels)
Normobaric, decompression, and
chemistry poisoning hypoxia in
mice
þ250500 mg/kg Ethanol extract Yang et al. (2011)
Brain tissues of hypoxia rats
(hypoxia)
þ125500 mg/kg; i.p. Petroleum ether extract Ma et al. (2014a)
D-galactose induced-brain injury in
mice
þ30 mg/kg/d; 6 weeks Ethyl acetate extract; rutin Chen et al. (2013c),Yang et al.
(2012)
Blood sugar, muscle glycogen and hepatic
glycogen under chronic decompression
conditions
Mice þ52 mg/kg Petroleum ether extract Ma et al. (2011)
Survival time under hypoxia conditions Normobaric, decompression, and
chemistry poisoning hypoxia in
mice
þ250500 mg/kg Ethanol extract Yang et al. (2011)
Mortality under acute decompression
conditions
Mice þ50 mg/kg Petrolleum ether extract Ma et al. (2011)
Western Blot assay (HIF-1alpha gene
expression)
Brain tissues of hypoxia in rats þ125500 mg/kg; i.p. Petrolleum ether extract Ma et al. (2014b)
Gene expression assay (EPO, HO-1 mRNA
expression)
Brain tissues of hypoxia in rats þ125500 mg/kg; i.p. Petrolleum ether extract Ma et al. (2014b)
Anti-oxidative and anti-aging
Superoxide radical assay þPolysaccharides Yao et al. (2012)
þApigenin Fan and Yue, (2003),Li et al.
(2006),Matkowski, (2008)
þ10
6
M Quercetin, rutin, morin Chen et al., (1990)
DPPH radical scavenging assay þPolysaccharides Yao et al. (2012)
þ16 mg/mL Methanol extract Wang et al. (2012a)
þ0.741.05 mmol/L Phenolic acids Zou et al. (2014)
Hydroxyl radical scavenging assay þPolysaccharides Yao et al. (2012)
ABTS radical scavenging assay þ0.94 mg/mL Methanol extract Wang et al. (2012a)
þ54.75 mmol/g PCA, CGA, rutin, cynarine,
hispidulin
Qiu et al. (2010),Qiu et al. (2013)
þ0.550.99 mmol/L Phenolic acids Zou et al. (2014)
Ferric reducing/antioxidant power (FRAP)
assay
þ82.62 mmol/g PCA, CGA, rutin, cynarine,
hispidulin
Qiu et al. (2010)
Qiu et al. (2013)
Anti-aging
D
-galactose induced-brain injury in
mice
þ30 mg/kg/d; 6 weeks Ethyl acetate extract; rutin Yang et al. (2012)
Lipid peroxidation
Anti-fatigue
Reduction in serum urea nitrogen Mice þ1 g/kg; p.o.; 15 d 95% Ethanol extract Jia and Wu (2008)
Oxygen consumption and swimming time Mice þPolysaccharides Zheng et al. (1993)
Mice þ1 g/kg; p.o.; 15 d 95% Ethanol extract Jia and Wu (2008)
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 446056
2014b) in order to be blood-brain-barrier crossing.
The neuroprotective activity of S. involucrata has been de-
monstrated by the ability of its ethyl acetate fraction to inhibit
MDA expression level, increase GPx activity, and decrease the
expressions of COX-2, PARP and caspase-3, via downregulation of
NF-kappaB. This biochemical cascade ultimately protects neural
tissue (Chen et al., 2013c).
6.6. Immunomodulation
Both whole extracts (Jia and Wu, 2007) and specic compo-
nents of S. involucrata including avones (Fan et al., 1996;Ma et al.,
1998), XL-12 fraction of extraction (Wang et al., 2011) have been
shown to have modulatory effects on immunity. Non-specic de-
fense mechanisms and delayed hypersensitivity in mice has been
inhibited by S. involucrata, but humoral immunity activity has
been stimulated upon administration of higher doses of S. in-
volucrata (Jia and Wu, 2007). Another experiment also reveals that
S. involucrata extract has an anti-allergic effect (Wang et al., 2011).
Enhanced activity of mononuclear phagocytic system was re-
ected by increased colloidal carbon clearance index rate de-
monstrated in an in vivo mice study (150 mg/kg; once a day; in-
tragastrically adminstrated for a consectutive 7 days) (Fuller, 1992;
Jia and Wu, 2007). S. involucrata has also induced cytotoxicity of
PBMC against K562 myelocytic leukemia cells and Raji Burkitt
lymphoma cells and enhanced suboptimal concentration of rhIL-2-
induced cytotoxicity but exhibited no effect on the large dose rhIL-
2-induced cytotoxicity (Ma et al., 1998). Besides, signicant en-
hancement of murine immunological function was observed, as
reected in increased percentage of lymphocyte transformation
induced by PHA, the titer of serum hemagglutinin antibody against
SRBC and hemolysin antibody (Fan et al., 1996). Apart from that,
proliferation of T lymphocytes was promoted while B lymphocyte
proliferation was hindered by S. involucrata injection of the same
concentration (Tao et al., 2007) and this serves as a ultimate proof
of S. involucrata's peformance in two way adjustment function.
These research nding is consistent with Traditional Chinese
Medicine usage as S. involucrata has been described possessing
invigorating power of both Yin and Yang, which include a meaning
of maintaining balance in body.
6.7. Other pharmacological activities
It has been listed in Supplement to Compendium of Materia
Medica (Zhao, 1963) since Qing Dynasty, which is a few hundred
years ago, that S. involucrata can be used to treat infertility due to
aging (Zhao, 1963). Besides, S. involucrata has been listed in
modern Pharmacopoeia of China and local Pharmacopoeia re-
garding its menstrual cycle regulation effect (Chinese Pharmaco-
poeia Commission, 2010;Liu and Shawuti, 1985). Researches have
consistently demonstrated its effect in prevention of premature
ovarian failure of mice, which has correlations to estrogen reg-
ulation, caused by continuous light upon intra-gastri administra-
tion of 0.5 mL extract of S. involucrata together with 0.9% of NaCl
(Zhang et al., 2013).
Other bioactivities of S. involucrata include anti-microbial and
anti-fungal (Lv et al., 2010), anti-hypertensive (Yu and Chen,
2009), and anti-radiation (Gao et al., 2003;Jia et al., 20 05a). It
appears that its water-soluble constituents, avonoids and poly-
saccharides are responsible for these effects. (Chinese Pharmaco-
poeia Commission, 2010) Furthermore, S. involucrata also has the
ability to increase replication of bone mesenchymal stem cells
(Zhang et al., 2011a)
7. Toxicological studies
The use of S. involucrata in pregnant women is prohibited in the
Pharmacopoeia of China (Chinese Pharmacopoeia Commission,
2010). Similarly, it is proven to be abortion inducing in rats in
early, mid-trimester and late pregnancy with different abortion
rate. The highest rate has found to be as high as 100% in mid-
trimester and late pregnancy for 0.3 mL administered in-
travenously once per day for consecutive two days. Early preg-
nancy is also sensitive to S. involucrata injection. Apart from having
toxicity to fetus, it is also accused for causing arrhythmia, hypo-
tension, paralysis, nausea and other nervous and cardiovascular
disorders as its adverse effects in overdose condition (Commission
of Chinese Materia Medica, 1999).
However, contradictorily, S. involucrata injection has been
proven to be safe, with no evidence of any distinct toxicity or side
effects in some researches. In one long-term toxicology test, rats
were injected with S. involucrata for 45 days; blood routine ex-
amination and pathologic histology examination showed no da-
maging effects (Sun et al., 2005). Another experimental study of
the toxicity of long-term S. involucrata injection was carried out. In
this study, rats were given intraperitoneal injection for 90 days
and were observed for 14 days subsequently. No abnormal changes
of appearance or organ function, as indicated by blood and liver
and kidney function evaluation, and pathological examination of
13 kinds of visceral tissue, were discovered. These studies, as well
as the centuries of traditional use, conrm the safety of S. in-
volucrata in clinical use (Lian et al., 1996). Therefore, more quali-
ed toxicological studies are expected for prediction of the ther-
apeutic index so as to ensure safe use S. involucrata.
8. Modern clinical application
8.1. Anti-arthritic
The uses of S. involucrata are extensive (Xiao et al., 2011a);
however, in modern actual practice, it is seldom used in-
dependently, but typically in association with other herbs
nowadays.
Xuelian injection, which is the only pharmaceutical product
that involved only extract of S. involucrata,isofcially used in
hospitals in China for treatment of rheumatoid arthritis. Clinical
trials were performed in order to evaluate its pharmacological
evidence since 2006. One study involved 48 individuals who had
developed rheumatoid arthritis with similar stage and 12 of them
were randomly the positive control group which was injected with
an efcacy-proven drug called Compound arthritis injection.
Xuelian injection of 4 mL was intramuscularly injected into the 36
individuals in experimental group once per day consecutively for
20 days. Total effective rate was found to be increased by 22.2%
compared to the positive control group (Bao et al., 2006). Besides,
another study has investigated the deviation in pharmacological
evidence if the Xuelian injection was injected in more specic
sites, i.e. acupuncture points according to the theory of Traditional
Chinese Medicine. The rate of effectiveness was found to be in-
creased to 100% in 60 tested individuals, with 4 mL of Xuelian
injection dissolved in 23 mL of 0.9% NaCl injection once a day for
15 days. Reoccurrence was developed in only 25% of the in-
dividuals after one year of treatment (Gu et al., 2009).
8.2. Counteracting infertility
Recently, the pharmacological evidence of Xuelian injection has
been tested on treating erectile dysfunction. Seventy individuals
were involved and among them, thirty were randomly selected to
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 4460 57
be the positive control group with injection of Vitamin B with
same dose as the experimental group while the remaining 40 in-
dividuals were injected, in specic acupuncture points, 0.5 mL of
Xuelian injection. The result was promising, compared to the po-
sitive control group, an increase of 20.83% of effective rate, dened
by successful vaginal penetration for not less than 1 min before
ejaculation has been shown (Liu and Zhang, 2013).
8.3. Others application of S. involucrata-containing compound
prescription
As mentioned, compound prescription of herbs is one of the
key characteristics of Traditional Chinese Medicine. The under-
lying principal is herbal interaction effects including synergistic
and antagonistic effect. The chemical prole of an herb can be very
sophisticated and interactions of herbs, to be more specic, of
different chemical constituents in herbs, can further complicate
the case. Hundreds of years of clinical practices in China have
demonstrated that best pharmacological evidence is reached only
when herbs are used together. Therefore, there are vast amount of
pharmaceutical products containing, but not merely, S. involucrata
as the active components and they are used to treat a wide variety
of disorders; these include neoplasm (Liang, 2013), cardiovascular
diseases (Baima, 1997), allergies and asthma (Hu, 1996), derma-
tological disorders and injury (Wang et al., 2012b).
This indicated the potential of S. involucrata in treating a wide
spectrum of diseases. Identication of principal active compound,
however, would be of utmost importance for further studies on
maximizing of pharmacological evidence while minimizing of
toxicity.
9. Conclusion and prospects
S. involucrata is a rare alpine herb that is frequently prescribed
in various ethnomedical systems especially central Asia. This re-
view summarized the existing botany, phytochemistry, pharma-
cological properties and application researches on S. involucrata.
The amount of modern experimental data manifested the multiple
disease ameliorating properties of S. involucrata and evidenced the
traditional medical uses. Among them, the most widespread tra-
ditional use of this alpine herb has been for the treatment of in-
ammation. As inammation has long been considered to be as-
sociated with the development of cancer, in recent decade, the
emerging pharmacological evidence in treating cancer has further
put S. involucrata under the spotlight.
However, although increasing interest has prompted more
studies on S. involucrata, it is still noteworthy that several gaps in
our understanding of its application exist. The rst gap is that the
intrinsically active compositions and the mechanism of action of S.
involucrata were ambiguous. For example, although S. involucrata
has gained widespread global praise owing to its effectiveness in
anti-cancer therapy, the possible mechanism is still not conclusive
and the responsible active components has not yet been conrmed
only attributed to the ethanol extract or the ethyl acetate fraction.
Therefore, further more studies should undoubtedly have the
priority to identify the individual bioactive component and to
more clearly dissect the molecular mechanism of the pharmaco-
logical effects of S. involucrata.
Secondly, interestingly we have observed that the traditional
use of S. involucrata is seldom coupled with other herbs, while in
modern clinical practice, S. involucrata is usually used in associa-
tions with other herbs. Since compound prescription is one of the
key characteristics of Traditional Chinese Medicine, therefore it is
important to verify this contradictory phenomenon whether we
should use this herb independently or in combination with other
herbs by both traditional theory and modern pharmacological
evidences.
Thirdly, the contents of chlorogenic acid and rutin, which have
been set for the quality control of S. involucrata in the Chinese
Pharmacopoeia 2010 edition, varied from 1.19 to 14.43 mg/g and
0.14 to 16.02 mg/g respectively in the herbs obtained from differ-
ent habitat and/or harvest's time. This may contribute to differ-
ences in the quality of various batches of S. involucrata. Thus, how
to exclusively and accurately monitor and evaluate quality of
samples, to ensure and maintain their clinical and pharmaceutical
stability, should be further studied. In addition, since it is proven
to be abortion inducing in rats in early, mid-trimester and late
pregnancy and also accused for causing arrhythmia, hypotension,
paralysis, nausea and other nervous and cardiovascular disorders
in overdose condition, further research into its toxic effects is
necessary for prediction of the therapeutic index so as to ensure
the safe use of S. involucrata.
Lastly, S. involucrata, under stress habitats in rocky and alpine
environments, has limited distributions and grows very slowly. In
recent years, the wild sources of S. involucrata are dwindling
dramatically due to the exhaustive exploitation. In order to cope
with the problem of over-exploitation and its endangered species
status, the use of S. involucrata must be restricted to sustainable
levels, and alternatives to the wild material must be developed.
The use of the cultivated and/or tissue-cultured species as an al-
ternative to the wild S. involucrata should be encouraged, as stu-
dies have provided proof of their equivalent effectiveness. Another
possibility is to explore other species of the genus Saussurea as
potential substitutes for S. involucrata. Other species are in fact
currently being used, together with S. involucrata, and recent re-
search has demonstrated common biological activities and simi-
larities in chemotaxonomy (Yi et al., 2009a;2009b;2010,2012,
2014).
In a word, S. involucrata is a valuable herb that is worth addi-
tional attention because of its wide uses, extensive biological ac-
tivities, and reliable clinical efcacy. Deep phytochemical and
pharmacological investigation of S. involucrata, especially its me-
chanism of action, to illustrate its ethno-medicinal use will un-
doubtedly be the focus of future research.
Acknowledgments
This work was supported by the Faculty Research Grant of
Hong Kong Baptist University (FRG2/14-15/061), the Natural Sci-
ence Foundation of Guangdong Province (2014A030313766) and
Science and Technology Fund of Sichuan Province for Young
Scholar (2012JQ0044).
Reference
Almeida, R.N., Navarro, D.S., Barbosa-Filho, J.M., 2001. Plants with central analgesic
activity. Phytomedicine 8, 310322.
Baima, J.C., 1997. Tibetan preparatory medicine and preparation method thereof.
Chinese Patent CN 1161849A.
Bao, L., Zhuo, Y., Chen, Z.C., Xu, X.Y., Li, X.M., 2006. Clinical trial of Xuelian injection
in treatment of rheumatoid arthritis. Chin. J. Inf. Tradit. Chin. Med. 13, 6970.
Bergeron, M., Gidday, J.M., Yu, A.Y., Semenza, G.L., Ferriero, D.M., Sharp, F.R., 2000.
Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in
neonatal rat brain. Ann. Neurol. 48, 285296.
Byambaragchaa, M., de la Cruz, J., Yang, S.H., Hwang, S.G., 2013. Anti-metastatic
potential of ethanol extract of Saussurea involucrata against hepatic cancer in
vitro. Asian Pac. J. Cancer Prev. 14, 53975402.
Chakravarti, B., Chakravarti, D.N., 2007. Oxidative modication of proteins: age-
related changes. Gerontology 53, 128139.
Chen, F.J., Yang, Y.G., Zhao, D.X., Gui, Y.L., Guo, Z.C., 1999. Advances in studies of
species, habitats distribution and chemical composition of Snow Lotuses
(Saussurea) in China. Chin. Bull. Bot. 16, 561566.
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 446058
Chen, Q.L., Yi, T., Tang, Y.N., Wong, L.L., Huang, X.X., Zhao, Z.Z., Chen, H.B., 2014a.
Comparative authentication of three Snow Lotusherbs by macroscopic and
microscopic features. Microsc. Res. Tech. 77, 631641.
Chen, R.D., Liu, X., Zou, J.H., Yang, L., Dai, J.G., 2014b. Regulation of syringin,
chlorogenic acid and 1, 5-dicaffeoylquinic acid biosynthesis in cell suspension
cultures of Saussurea involucrata. China J. Chin. Mater. Med. 39,22752280.
Chen, R.D., Zou, J.H., Jia, J.M., Dai, J.G., 2010. Chemical constituents from the cell
cultures of Saussurea involucrata. J. Asian Nat. Prod. Res. 12, 119123.
Chen, R., Liu, X., Zou, J., Yang, L., Dai, J., 2013a. Qualitative and quantitative analysis
of phenylpropanoids in cell culture, regenerated plantlets and herbs of Saus-
surea involucrata. J. Pharm. Biomed. Anal. 74, 3946.
Chen, X.J., Liu, Q.H., Yu, P., Zhang, J., 2013b. HPLC determination of chlorogenic acid
and rutin in Saussurea involucrata (Kar. et Kir.) seed. Xinjiang Med. J 9, 139142.
Chen, Y., Hsiao, P., Lin, F., Wu, G., Tsai, C., 2012. Evidence-based anticancer com-
plementary and alternative medicine. In: Cho, C.S. William (Ed.), Materia
Medica for Various Cancers. Springer, Netherlands, Dordrecht, pp. 110111.
Chen, Y.L., Tsay, H.S., Way, T.D., Lee, P.L., Yu, C.Y., Chen, C.H., 2013c. Saussurea in-
volucrata extract, pharmaceutical composition and use for anti-fatigue and
anti-aging. United States Patent US 20130177661 A1.
Chen, Y.R., 1963. Medical dictionary of China. Jianwen Publisher, Hong Kong, p.
1263.
Chen, Y.R., Wang, X.J., Aidarhan, N., Zhao, B., Yuan, X.F., Li, Y., 2013d. Effects of
mowing strength on the chemical composition content in Saussurea involucrata
Kar. Et Kir. Adv. Mater. Res. 610613, 34323436.
Chen, Y.T., Zheng, R.L., Jia, Z.J., Ju, Y., 1990. Flavonoids as superoxide scavengers and
antioxidants. Free Radic. Biol. Med. 9, 1921.
Chinese Medicinal Materials Corporation, 1994. Zhongguo Minjian Dan Yanfang.
China Social Sciences Publishing House, Beijing, p. 804.
Chinese Pharmacopoeia Commission, 2010. Pharmacopeia of the People's Republic
of China, vol. 1. Chemical Industry Press, Beijing, pp. 5051 .
Commission of Chinese Materia Medica, 1999. Materia Medica of China, vol. 7.
Shanghai Scientic and Technical Publishers, Shanghai, pp. 927929.
Commission of Chinese Materia Medica, 2005. Materia Medica of China (Uyghur
Medicine). vol. 33. Shanghai Scientic and Technical Publishers, Shanghai, pp.
338339.
Committee for National Revolution of Xinjiang Uyghur Autonomous Region Health
Bureau, 1976. Xinjiang Zhongcaoyao. Xinjiang People's Publishing House, Xin-
jiang, pp. 342343.
Doan, T., Massarotti, E., 2005. Rheumatoid arthritis: an overview of new and
emerging therapies. J. Clin. Pharmacol. 45, 751762.
Fan, C.Q., Yue, J.M., 2003. Biologically active phenols from Saussurea medusa. Bioorg.
Med. Chem. 11, 703708.
Fan, C.Q., Zhu, X.Z., Zhan, Z.J., Ji, X.Q., Li, H., Yue, J.M., 2006. Lignans from Saussurea
conica and their NO production suppressing activity. Planta Med. 72, 590595.
Fan, G.X., Ren, H.X., Yuan, Y.K., Liu, H.F., 1996. Effect of Saussurea involucrata Kar Et
Kir Ex maxim avone on murine immunology function. J. XiAn Med. Univ. 17,
452454.
Flora of China Editorial Committee, 1999. Flora of China. vol. 78. Science Press,
Beijing, China, pp. 3537.
Fraga, C.G., Shigenaga, M.K., Park, J.W., Degan, P., Ames, B.N., 1990. Oxidative da-
mage to DNA during aging: 8-hydroxy-2-deoxyguanosine in rat organ DNA and
urine. Proc. Natl. Acad. Sci. U. S. A. 87, 45334537.
Fu, C.X., Xu, Y.J., Zhao, D.X., Ma, F.S., 2006. A comparison between hairy root cul-
tures and wild plants of Saussurea involucrata in phenylpropanoids production.
Plant Cell Rep. 24, 750754.
Fu, L.G., Jin, J.M., 1991. China Plant Red Data Book: Rare and Endangered Plants. vol.
1. Science Press, Shanghai, China, pp. 234235.
Fuller, R., 1992. Probiotics: The scientic basis. Springer, Netherlands, Dordrecht.
Funk, C.D., 2001. Prostaglandins and leukotrienes : advances in eicosanoid biology.
Science 294, 18711875.
Gao, B., Liang, Z.Q., Gu, Z.L., 2003. Protective effect of extract of Saussurea in-
volucrata on radiation injured mice. Chin. Tradit. Herb. Drugs 34, 443445.
Gu, Y., Xie, J.P., Yang, Y., 2009. Xuelian injection in acupuncture points in treating
rheumatoid arthritis: 60 cases. Shanxi J. Tradit. Chin. Med. 25, 30.
Guo, B., Abbasi, B.H., Wei, Y.H., 2011. Effects of hypobaric growth conditions on
morphogenic potential and antioxidative enzyme activities in Saussurea in-
volucrata. Biol. Plant 55, 783787.
Guo, B., Gao, M., Liu, C.Z., 2007. In vitro propagation of an endangered medicinal
plant Saussurea involucrata Kar. et Kir. Plant Cell Rep. 26, 261265.
Hamilton, M.L., Van Remmen, H., Drake, J.A., Yang, H., Guo, Z.M., Kewitt, K., Walter,
C.A., Richardson, A., 2001. Does oxidative damage to DNA increase with age?
Proc. Natl. Acad. Sci. U. S. A. 98, 1046910474.
Harman, D., 1956. Aging: a theory based on free radical and radiation chemistry. J.
Gerontol. 11, 298300.
Hu, C.G., 1996. Chinese medicinal composition for treatment of trachitis and gas-
tritis. Chinese Patent CN 1129134A.
Iwashina, T., Smirnov, S.V., Damdinsuren, O., Kondo, K., 2010. Saussurea species
from the Altai Mountains and adjacent area, and their avonoid diversity. Bull.
Natl. Mus. Nat. Sci., Ser. B 36,141154.
Jia, J.M., Wu, C.F., 2007. Effect of Saussurea involucrata culture on mouse immune
function. China J. Tradit. Chin. Med. Pharm. 4, 238240.
Jia, J.M., Wu, C.F., 2008. Antifatigue activity of tissue culture extracts of Saussurea
involucrata. Pharm. Biol. 46, 433436.
Jia, J.M., Wu, C.F., Liu, W., Yu, H., Hao, Y., Zheng, J.H., Ji, Y.R., 2011. Antiinammatory
and analgesic activities of the tissue culture of Saussurea involucrata. Biol.
Pharm. Bull. 28, 16121614 .
Jia, J.M., Wu, C.F., Yu, H., Hu, G.S., 2005a. Anti-radiation activity of the tissue culture
of Saussurea involucrata Kar. et Kir. J. Shenyang Pharm. Univ. 444448 (6), 462.
Jia, M.R., Li, X.W., Zhang, H., Yan, Z.Y., Liao, X.R., 2005b. Ethnomedicines in China
(Zhongguo Minzuyao Zhiyao). China Medical Science Press, Beijing, pp.
544545.
Jing, L.L., Fan, X.F., Fan, P.C., He, L., Jia, Z.P., 2013. 5,6-Dihy-droxy-7,8-di-meth-oxy-
avone. Acta Crystallogr. Sect. E. Struct. Rep. Online 69, o1096.
Kang, X.L., Wang, X.J., Li, T.N., Yuan, Y.X., 2010. Study on seed germination char-
acteristics of the endangered & medicinal plant Saussurea involucrata Kar.et Kir.
Seed 5, 8183.
Klareskog, L., Amara, K., Malmström, V., 2014. Adaptive immunity in rheumatoid
arthritis: anticitrulline and other antibodies in the pathogenesis of rheumatoid
arthritis. Curr. Opin. Rheumatol. 26, 7279.
Lee, J.C., Kao, J.Y., Kuo, D.H., Liao, C.F., Huang, C.H., Fan, L.L., Way, T.D., 2011. Anti-
fatigue and antioxidant activity of alcoholic extract from Saussurea involucrata.
J. Tradit. Complement. Med. 1, 6468.
Li, F.X., Jin, Z.P., Zhao, D.X., Cheng, L.Q., Fu, C.X., Ma, F.S., 2006. Overexpression of the
Saussurea medusa chalcone isomerase gene in S. involucrata hairy root cultures
enhances their biosynthesis of apigenin. Phytochemistry 67, 553560.
Li, J.R., Liu, L., Liu, Y.Q., Sa, A.J., 2012. Determination of arctiin in seeds of Saussurea
involucrata by HPLC. Lishizheng Med. Mater. Med. Res. 23, 21192120.
Li, Y., Jia, Z.J., 1989. Guaianolides from Saussurea involucrata. Phytochemistry 28,
33953397.
Li, Y., Wang, C.L., Guo, S.X., Yang, J.S., Xiao, P.G., 2007. Three guaianolides from
Saussurea involucrata and their contents determination by HPLC. J. Pharm.
Biomed. Anal. 44, 288292.
Li, Y.M., Zhong, H., 2013. Simultaneous determination of ve avonoids in Saussurea
involucrata by capillary electrophoresis. J. Chem. Soc. Pak. 35, 12881292.
Lian, J., Xiong, Y.J., Zhu, H.H., Lu, X.M., 1996. Experimental study on long-term
toxicity of Xuelian injection. Mod. J. Integr. Tradit. Chin. West. Med. 16,
458460.
Liang, S.J., 2013. Traditional Chinese medicine powder prepared from three owers,
ve seeds and six whites for treating lung cancer. Chinese Patent CN
103432401A.
Liu, L.J., Zhang, J.J., 2013. Xuelian injection in treating erectile dysfunction. Tradit.
Chin. Med. Res. 26, 5152.
Liu, Y.D., Aisa, H.A., 2010. Three new lignans from the seeds of Saussurea involucrata.
J. Asian Nat. Prod. Res. 12, 828833.
Liu, Y.M., Shawuti, Y., 1985. Pharmacography of Uighur. Part 1. Xinjiang People's
Publishing House, Urumqi, China, pp. 385389.
Lv, Y.L., Zhang, F.S., Chen, J., Cui, J.L., Xing, Y.M., Li, X.D., Guo, S.X., 2010. Diversityand
antimicrobial activity of endophytic fungi associated with the alpine plant
Saussurea involucrata. Biol. Pharm. Bull. 33, 13001306.
Madhavi, M., Mallika, G., Lokanath, N., Vishnu, M.N., Madhusudhana Chetty, C.,
Mohamed Saleem, T.S., 2012. A review on phytochemical and pharmacological
aspects of Saussurea lappa. Int. J. Life Sci. Med. Res. 2, 2431.
Ma, H.J., Fan, G.X., Ren, H.X., Yuan, Y.K., 1998. Effect of Saussurea involucrata Kar Et
Kir Ex Maxim avone on human peripheral blood mononuclear cells. J. XiAn
Med. Univ. 19 (168169), 200.
Ma, H.P., Fan, P.C., Jing, L.L., Yao, J., He, X.R., Yang, Y., Chen, K.M., Jia, Z.P., 2011. Anti-
hypoxic activity at simulated high altitude was isolated in petroleum ether
extract of Saussurea involucrata. J. Ethnopharmacol. 137, 15101515.
Ma, H.P., Jiao, Y., Gao, R.M., Yang, Y., Fan, P.C., Jing, L.L., Jia, Z.P., 2014a. Effect of
ethanol extract from Saussurea involucrata on biochemical indicators of sti-
mulated high-altitude hypoxia induced mice. J. Chin. Med. Mater. 37, 99103 .
Ma, H.P., Yao, J., Wu, J.H., Gao, R.M., Fan, P.C., Jing, L.L., 2014b. Protective effect and
action mechanism of petroleum ether extracts from Saussurea involucrata on
brain tissues of hypoxia rats. China J. Chin. Mater. Med. 39, 27102715.
Matkowski, A., 2008. Plant in vitro culture for the production of antioxidantsa
review. Biotechnol. Adv. 26, 548560.
Maynard, S., Schurman, S.H., Harboe, C., de Souza-Pinto, N.C., Bohr, V.A., 2009. Base
excision repair of oxidative DNA damage and association with cancer and aging.
Carcinogenesis 30, 210.
McNamee, K., Williams, R., Seed, M., 2015. Animal models of rheumatoid arthritis:
How informative are they? Eur. J. Pharmacol. 759, 278286.
Mpala, L., Cock, I.E., Chikowe, G., 2010. No evidence of antiseptic properties and low
toxicity of selected Aloe species. J. Pharm. Negat. Results 1, 1016.
National Institutes for Food and Drug Control, 1984. Zhongguo Minzu Yaozhi.
People's Medical Publishing House, Beijing, pp. 448449.
Oliver, C.N., Ahn, B.W., Moerman, E.J., Goldstein, S., Stadtman, E.R., 1987. Age-re-
lated changes in oxidized proteins. J. Biol. Chem. 262, 54885491.
Picman, A.K., Towers, G.H.N., 1983. Antibacterial activity of sesquiterpene lactones.
Biochem. Syst. Ecol. 11, 321327.
Qiu, J., Gao, F., Shen, G., Li, C., Han, X., Zhao, Q., Zhao, D., Hua, X., Pang, Y., 2013.
Metabolic engineering of the phenylpropanoid pathway enhances the anti-
oxidant capacity of Saussurea involucrata. PLoS One. 8, e70665.
Qiu, J., Xue, X., Chen, F., Li, C., Bolat, N., Wang, X., Baima, Y., Zhao, Q., Zhao, D., Ma, F.,
2010. Quality evaluation of snow lotus (Saussurea): quantitative chemical
analysis and antioxidant activity assessment. Plant Cell Rep. 29, 13251337.
Ricciotti, E., FitzGerald, G.A., 2011. Prostaglandins and inammation. Arterioscler.
Thromb. Vasc. Biol. 31, 986100 0.
Rivera, D., Allkin, R., Obón, C., Alcaraz, F., Verpoorte, R., Heinrich, M., 2014. What is
in a name? The need for accurate scientic nomenclature for plants. J. Ethno-
pharmacol. 152, 393402.
Sawada, M., Sester, U., Carlson, J.C., 1992. Superoxide radical formation and asso-
ciated biochemical alterations in the plasma membrane of brain, heart, and
Wai-I Chik et al. / Journal of Ethnopharmacology 172 (2015) 4460 59
liver during the lifetime of the rat. J. Cell Biochem. 48, 296304.
Sharma, J.N., Al-Omran, A., Parvathy, S.S., 2007. Role of nitric oxide in inammatory
diseases. Inammopharmacology 15, 252259.
Shevchuk, N.A., 2007. Possible use of repeated cold stress for reducing fatigue in
chronic fatigue syndrome: a hypothesis. Behav. Brain Funct. 3, 55.
Sohal, R.S., Sohal, B.H., 1991. Hydrogen peroxide release by mitochondria increases
during aging. Mech. Ageing Dev. 57, 187202.
Sun, Y.H., Hamrati, Zhang, Y.C., Yang, L.L., Li, T., Liu, F., 2005. Long-term toxicology
study on Saussurea involucrata injection. Lishizhen Med. Mater. Med. Res. 2,
7071.
Tao, H.Y., Huang, H., Hou, G.P., Liu, F., 2007. Effect of Saussurea involucrata injection
on counteracting adjuvant-induced arthritis and its immonuregulation func-
tion. Tradit. Chin. Drug Res. Clin. Pharmacol. 18, 269273.
The Plant List, Version 1.1, 2013. URL http://www.theplantlist.org.
Wang, L.L., Wang, X., Liu, Y., Hua, Y., Yang, Q.L., Xu, F., Huang, H., 2011. Main
pharmacodynamics of Saussurea involucrata extract XL-12. Chin. Tradit. Pat.
Med. 33, 18681874.
Wang, Q., Liu, L., Aisa, H.A., 2012a. Chemical composition and antioxidant activity of
Saussurea involucrata seed. Chem. Nat. Compd. 48, 663665.
Wang, X.L., Gesang, S.L., Jiao, W., Liao, X., Ding, L.S., 2007. Two new sesquiterpenoid
glucosides from the aerial parts of Saussurea involucrata. J. Integr. Plant Biol. 49,
609614.
Wang, Y.F., Ni, Z.Y., Dong, M., Cong, B., Shi, Q.W., Gu, Y.C., Kiyota, H., 2010. Secondary
metabolites of plants from the genus Saussurea: chemistry and biological ac-
tivity. Chem. Biodivers. 7, 26232659.
Wang, Y.F., Wang, X.C., Xue, G.P., Xing, J.G., Ma, J.H., Ma, X.L., 2012b. Preparation
method of transdermal composition containing rutin and chlorogenic acid
extracted from Chinese medicine Saussurea involucrata. Chinese Patent CN
102349938A.
Way, T.D., Lee, J.C., Kuo, D.H., Fan, L.L., Huang, C.H., Lin, H.Y., Shieh, P.C., Kuo, P.T.,
Liao, C.F., Liu, H.S., Kao, J.Y., 2010. Inhibition of epidermal growth factor receptor
signaling by Saussurea involucrata, a rare traditional Chinese medicinal herb, in
human hormone-resistant prostate cancer PC-3 cells. J. Agric. Food Chem. 58,
33563365.
Wu, L., Guo, S., 2008. Interaction between an isolate of dark-septate fungi and its
host plant Saussurea involucrata. Mycorrhiza 18, 7985.
Wu, L.Q., Lv, Y.L., Meng, Z.X., Chen, J., Guo, S.X., 2010. The promoting role of an
isolate of dark-septate fungus on its host plant Saussurea involucrata Kar. et Kir.
Mycorrhiza 20, 127135.
Wu, W., Qu, Y., Gao, H.Y., Yang, J.Y., Xu, J.G., Wu, L.J., 2009. Novel ceramides from
aerial parts of Saussurea involucrata Kar. et. Kir. Arch. Pharm. Res. 32,
12211225.
Xiao, W., Li, N., Bolati, M., Wang, X.J., Jia, X.G., Zhao, Y.Q., 2011a. Advances in studies
on chemical components and pharmacological activities of Saussurea In-
volucratae Herba. Drugs Clin. 26, 344348.
Xiao, W., Li, X., Li, N., Bolati, M., Wang, X.J., Jia, X.G., Zhao, Y.Q., 2011b. Sesquiterpene
lactones from Saussurea involucrata. Fitoterapia 82, 983987.
Xie, J.S., 1968. Xibei Yuji. Yee Wen Publishing Company, Taibei.
Xie, Z.W., 1975. National Herbal Compendium. People's Medical Publishing House,
Beijing, pp. 863864.
Xu, Y.J., Zhao, D.X., Fu, C.X., Cheng, L.Q., Wang, N.F., Han, L.J., Ma, F.S., 2009. De-
termination of avonoid compounds from Saussurea involucrata by liquid
chromatography electrospray ionization mass spectrometry. Nat. Prod. Res. 23,
168 91698.
Yang, J.S., Xie, F.Z., Liu, Q.H., Wu, X., 2006. Studies on coumarins of Saussurea in-
volucrata Kar. et Kir. Chinese Pharm. J. 41, 1774177 6.
Yang, Y., Ma, H.P., Chen, Y., Zhang, R.X., He, X.R., Yao, J., Fan, P.C., Jia, Z.P., 2011. Anti-
hypoxia effects of ethanol extract from Saussurea involucrata. Chin. J. Exp.
Tradit. Med. Formulae 17, 145148 .
Yang, Y.C., Lin, H.Y., Su, K.Y., Chen, C.H., Yu, Y.L., Lin, C.C., Yu, S.L., Yan, H.Y., Su, K.J.,
Chen, Y.L.S., 2012. Rutin, a avonoid that is a main component of Saussurea
involucrata, attenuates the senescence effect in
D
-galactose aging mouse model.
Evid. Based. Complement. Alternat. Med. 2012, 980276.
Yao, L., Zhao, Q., Xiao, J., Sun, J., Yuan, X., Zhao, B., Su, H., Niu, S., 2012. Composition
and antioxidant activity of the polysaccharides from cultivated Saussurea in-
volucrata. Int. J. Biol. Macromol. 50, 849853.
Yi, T., Chen, H.B., Zhao, Z.Z., Jiang, Z.H., Cai, S.Q., Wang, T.M., 2009a. Comparative
analysis of the major constituents in the traditional Tibetan medicinal plants
Saussurea laniceps and S. medusa by LCDADMS. Chromatographia 70,
957962.
Yi, T., Chen, H.B., Zhao, Z.Z., Jiang, Z.H., Cai, S.Q., Wang, T.M., 2009b. Identication
and determination of the major constituents in the traditional Uighur medic-
inal plant Saussurea involucrata by LC-DAD-MS. Chromatographia 69, 537542.
Yi, T., Lo, H.W., Zhao, Z.Z., Yu, Z.L., Yang, Z.J., Chen, H.B., 2012. Comparison of the
chemical composition and pharmacological effects of the aqueous and etha-
nolic extracts from a Tibetan Snow Lotus(Saussurea laniceps) herb. Molecules
17, 7 183 7194.
Yi, T., Zhao, Z.Z., Yu, Z.L., Chen, H.B., 2010. Comparison of the anti-inammatory and
anti-nociceptive effects of three medicinal plants known as Snow Lotusherb
in traditional Uighur and Tibetan medicines. J. Ethnopharmacol. 128, 405411.
Yi, T., Zhu, L., Tang, Y.N., Zhang, J.Y., Liang, Z.T., Xu, J., Zhao, Z.Z., Yu, Z.L., Bian, Z.X.,
Yang, Z.J., Chen, H.B., 2014. An integrated strategy based on UPLC-DAD-QTOF-
MS for metabolism and pharmacokinetic studies of herbal medicines: Tibetan
Snow Lotusherb (Saussurea laniceps), a case study. J. Ethnopharmacol. 153,
701713.
Yu, X.D., Chen, H., 2009. Effect of four species of characteristic vegetable drugs in
Xinjiang on cardiovascular system. Lishizhen Med. Mater. Med. Res. 20,
1357 1358.
Zhai, K.F., Duan, H., Xing, J.G., Huang, H., 2010. Study on the anti-inammatory and
analgesic effects of various puried parts from Saussurea involucrata. Chin. J.
Hosp. Pharm. 5, 374377.
Zhang, A.G., Cai, J.P., Xu, B.M., Tan, X.L., 2011a. Effect of four traditional Chinese
medicine decoctions and ethanolic extract from Saussurea involucrata on bone
marrow mesenchymal stem cell proliferation activity in vitro. J. Clin. Rehabil.
Tissue Eng. Res. 15, 42874290.
Zhang, J., Zhang, M.M., Wang, J., Zhang, B.B., Yang, H., Zhuang, S.Z., Zhang, X.H.,
2013. Preliminary study on the Saussurea involucrata extraction in preventing
premature ovariall failure of mice. J. Anhui Agric. Sci. 41 (