Journal of Ethnopharmacology 134 (2011) 519–541

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Journal of Ethnopharmacology
journal homepage: [Link]/locate/jethpharm

Review

The genus Epimedium: An ethnopharmacological and phytochemical review

Huiping Ma a , Xirui He b,c , Yan Yang d , Maoxing Li a , Dingjun Hao c , Zhengping Jia a,∗
a
Department of Pharmacy, Lanzhou General Hospital of PLA, Lanzhou 730050, PR China
b
Department of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
c
Xi’an Red Cross Hospital, Xi’an 710054, PR China
d
Department of Agronomy, Gansu Agriculture University, Lanzhou 730070, PR China

a r t i c l e i n f o a b s t r a c t

Article history: Epimedium (Berberidaceae), is a genus of about 52 species in the family Berberidaceae, which also
Received 8 August 2010 known as Rowdy Lamb Herb, Xianlinpi, Barrenwort, Bishop’s Hat, Fairy Wings, Horny Goat Weed,
Received in revised form
31 December 2010
and Yangheye or Yin Yang Huo (Chinese: ). Many plants have been proven to possess effi-
Accepted 2 January 2011 cacy on sexual dysfunction and osteoporosis in traditional Chinese medicine (TCM). The paper reviews
Available online 5 January 2011 the ethnopharmacology, the biological activities and the correlated chemical compounds of Epimedium
species. More than 260 compounds have been isolated; among them prenyl-flavonoids are the major
Keywords: constituents and also important chemotaxonomic markers. Modern pharmacology studies and clinical
Epimedium practice demonstrated that Epimedium and its active compounds possess wide pharmacological actions,
Ethnopharmacology especially in strengthening yang, hormone regulation, anti-osteoporosis, immunological function mod-
Phytochemistry ulation, anti-oxidation and anti-tumor, anti-aging, anti-atherosclerosis and anti-depressant activities.
Flavonoids Currently, effective monomeric compounds or active parts have been screened for pharmacological
Biological activity activity from Epimedium in vivo and in vitro.
Strengthening yang
© 2011 Elsevier Ireland Ltd. All rights reserved.
Anti-tumor
Anti-osteoporosis

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 520
2. Botanical description and distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 520
3. Ethnopharmacological use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 522
4. Chemical constituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 522
4.1. Flavonoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 528
4.2. Lignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
4.3. Ionones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
4.4. Phenol glycosides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
4.5. Phenethyl alcohol glycosides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
4.6. Sesquiterpenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
4.7. Other compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
5. Methods of quality control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
6. Biological activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 531
6.1. Treatment of sexual dysfunction (aphrodisiac, kidney tonic) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 531
6.2. Effect on bone metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532
6.2.1. In vivo tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532
6.2.2. Effect on the multiplication and differentiation of the osteoblasts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532
6.2.3. Effect on osteoclastic cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533
6.2.4. Effect on bone marrow-derived stroma cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533
6.2.5. Effect on cartilage growth in vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533

∗ Corresponding author. Tel.: +86 931 899 4676.

E-mail address: limaox2005@[Link] (Z. Jia).

0378-8741/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/[Link].2011.01.001
520 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541

6.3.
Effect on the immune system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533
6.3.1. Effect on the thymus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
6.3.2. Effect on macrophages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
6.3.3. Effect on T and B lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
6.3.4. Effects on NK and LAK cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
6.3.5. Antibody responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
6.4. Effect on the cardiovascular system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
6.4.1. Effect on vessels, blood and heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
6.4.2. Anti-hypertensive activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
6.4.3. Anti-arrhythmia effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
6.4.4. Effect on blood system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
6.4.5. Angiogenesis effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
6.5. Anti-tumor effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
6.5.1. Induction of tumor-cell differentiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
6.5.2. Inhibition of tumor-cell proliferation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
6.5.3. Anti-tumor diffusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
6.5.4. Induction of apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
6.6. Anti-aging and anti-oxidation effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
6.7. Anti-hypoxia and anti-fatigue effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536
6.8. Anti-inflammatory, anti-virus and anti-bacterial activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536
6.9. Hepatoprotective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536
7. Clinical studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536
8. Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536
9. Side effects and acute toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536
10. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537
Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537

1. Introduction 2. Botanical description and distribution

Epimedium (Berberidaceae), also known as Rowdy Lamb Herb, Epimedium is a low-growing, deciduous, perennial plant with
Barrenwort, Bishop’s Hat, Fairy Wings, Horny Goat Weed, Xian- leathery leaves that spreads by underground stems. The scale-like
linpi, Yangheye and Yin Yang Huo (Chinese: ), is a genus leaves are alternate, long-petiolate, ternately divided twice. The
of about 52 species of herbaceous plants (Stearn, 2002). Epimedium leaflets are ovate, acuminate, cordate, and up to 2.5–13.5 cm long
is also named three branches-nine leaves grass, as there are three and 1.5–7.5 cm wide, with setose margins. The flowers of this plant
branches from the stem and three leaves in every branch. The leaves resemble a Bishop’s hat (pendant-shaped), have long spurs and vary
and stem can be used as a remedy. More than 15 species in this in color (purple, pink, rose, yellow or white) and are one to two
genus have a long history of use in traditional Chinese medicine inches wide. Flower of Epimedium has 8 piece of sepals, the outside
(TCM) and are believed to “nourishing the kidney and reinforcing 4 sepals are unequal, the inside 4 sepals are petaloid, reflexing at
the Yang”. Extracts of the aerial parts of this genus are used in a flowering time. The flower has 4 stamens and 1 ovary with several
famous botanical supplement that has been widely used as a tonic, ovules. The Epimedium species is a tough, long-lived perennial. The
aphrodisiac and antirheumatic in China, Japan and Korea for more unique, colorful flowers and leaves compose an attractive ground
than 2000 years. This supplement has shown in vivo and in vivo covers in the spring. Selected Epimedium species are shown in Fig. 1.
activity against on sexual dysfunction, osteoporosis, cardiovascu- Epimedium grows mainly on cliffs under moist forests, near
lar diseases, menstrual irregularity, asthma, chronic nephritis and streams and wet lands at altitudes ranging from 200 to 3700 m
immunoregulation (Li, 1991; Wang et al., 2004; Meng et al., 2005). (Ying and Chen, 2001). The overwhelming majority of Epimedium
In the last decades, the use of Epimedium plants in traditional species are endemic to China, although some are found in eastern,
Chinese medicine has led to a rapid increase in the informa- southern and central Asia as well as Europe (Table 1). In China, there
tion available on the active components of Epimedium, there are 43 species that are mainly distributed in the southwest and cen-
chemical compounds and the pharmacological activities of these
compounds. More than 260 compounds have been identified from
different species of Epimedium (Wu et al., 2003a). Among them,
prenyl-flavonoids are the major constituents and also impor-
tant chemotaxonomic markers. At the same time, in vivo and/or
in vitro experiments and clinical practice have demonstrated
that Epimedium and its active compounds possess wide-reaching
pharmacological actions, including strengthening yang, improv-
ing cardiovascular and cerebrovascular functions and modulating
immunological function as well as having anti-osteoporosis, anti-
oxidation, anti-tumor and anti-aging effects. In this review, we try
to present and assess recent studies about the ethnopharmacology,
phytochemistry, pharmacological activities, processing, cultivation Fig. 1. The aerial parts of Epimedium koreanum, Epimedium brevicornum, and
and propagation of the genus Epimedium. Epimedium sagittatum (Sieb. & Zucc.) Maxim.
 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541 521

Table 1
The category and distribution of Epimedium plants in the whole world.

Distribution Category

Chinese Epimedium davidii Franch; Epimedium baojingense Q.L. Chen et B.M. Yang; Epimedium dolichostemon Stearn; Epimedium koreanum Nakai;
Epimedium fargesii Franch; Epimedium elongatum Komarov; Epimedium acuminatum Franch; Epimedium simplicifolium Ying; Epimedium
brachyrrhizum Stearn; Epimedium multiflorum Ying; Epimedium enshiense B.L. Guo et Hsiao; Epimedium fangii Stearn; Epimedium reticulatum
C.Y. Wu; Epimedium sagittatum (Sieb. et Zucc.) Maxim. var. glabratum Ying; Epimedium hunanense (Hand.-Mazz.) Hand.-Mazz.; Epimedium
latisepalum Stearn; Epimedium ogisui Stearn; Epimedium chlorandrum Stearn; Epimedium platypetalum K. Meyer; Epimedium franchetii Stearn;
Epimedium truncatum H.R. Liang; Epimedium boreali-guizhouense S.Z. He et Y.K. Yang; Epimedium leptorrhizum Stearn; Epimedium
rhizomatosum Stearn; Epimedium pubescens Maxim.; Epimedium sagittatum (Sieb. et Zucc.) Maxim.; Epimedium sagittatum (Sieb. et Zucc.)
Maxim. var. sagittatum; Epimedium pauciflorum K.C. Yen; Epimedium lishihchenii Stearn; Epimedium shuichengense S.Z. He; Epimedium
sutchuenense Franch.; Epimedium myrianthum Stearn; Epimedium flavum Stearn; Epimedium wushanense Ying, Epimedium ecalcaratum G.Y.
Zhong; Epimedium glandulosopilosum H.R. Liang; Epimedium parvifolium S.Z. He et T.L. Zhang; Epimedium stellulatum Stearn; Epimedium
brevicornu Maxim; Epimedium ilicifolium Stearn; Epimedium mikinorii Stearn; Epimedium zhushanense K.F. Wu et S.X. Qian; Epimedium epsteinii
Stearn.
Japan Epimedium cremeum, Epimedium diphyllum, Epimedium grandiflorum, Epimedium grandiflorum var. thunbergianum, Epimedium grandiflorum
var. higoense, Epimedium grandiflorum var. coelestre, Epimedium kitamuranum, Epimedium macranthum, Epimedium sempervirens. Epimedium
sempervirens var. multifoliolatum, Epimedium setosum, Epimedium trifoliatobinatum.
Europe Epimedium alpinum, Epimedium pubigerum, Epimedium pinnatum, Epimedium pinnatum subsp colchium, Epimedium canrabrigensis, Epimedium
perralderianum.
North Africa Epimedium perralderianum, Epimedium pinnatum.
India Epimedium elatum.
Korea Epimedium koreanum Nakai.

tral regions (Table 2); 15 of these are circulated in the crude drug brevicornum Maxim (EB) are wildly distributed and commonly
markets for use as Yin Yang Huo. Among them, Epimedium sagitta- used.
tum (Sieb. & Zucc.) Maxim., Epimedium koreanum Nakai, Epimedium In the last 100–150 years, there is a wide array of new Chi-
pubescens Maxim., Epimedium wushanense T.S. Ying and Epimedium nese species is being cultivated in the west, many of these have

Table 2
The major medicinal plants and its specific distribution in China.

Chinese name Latin name Distribution

Dan ye yinyanghuo Epimedium simplicifolium Ying Guizhou

Xiao ye yinyanghuo Epimedium parvifolium S.Z. He et T.L. Zhang Guizhou
Shui cheng yinyanghuo Epimedium shuichengense S.Z. He Guizhou
Qian bei qinyanghuo Epimedium boreali-guizhouense S.Z. He et Y.K. Yang Guizhou
Duo hua yinyanghuo Epimedium multiflorum Ying Guizhou
Qian ling yinyanghuo Epimedium leptorrhizum Stearn Guizhou, Hunan, Hubei, Sichuan
Ni wu shan yinyanghuo Epimedium pimedium pseudowushanense B.L. Guo Guizhou
Zu shan yinyanghuo Epimedium zhushanense K.F. Wu et S.X. Qian Hubei
Pian xie yinyanghuo Epimedium truncatum H.R. Liang Hubei
En shi yinyanghuo Epimedium enshiense B.L. Guo et Hsiao Hubei
Mu yu ping yinyanghuo Epimedium franchetii Stearn Hubei, Guizhou
Zhi ju yinyanghuo Epimedium mikinorii Stearn Hubei
Xing hua yinyanghuo Epimedium stellulatum Stearn Hubei, Sichuan
Qiang jing yinyanghuo Epimedium rhizomatosum Stearn Sichuan
Si chuan yinyanghuo Epimedium sutchuenense Franch Sichuan, Guizhou, Hubei
Chuan xi yinyanghuo Epimedium elongatum Komarov Sichuan
Qing cheng shan yinyanghuo Epimedium qingchengshanense G.Y. Zhong & [Link] Sichuan
Mao wen yinyanghuo Epimedium platypetalum K. Meyer Sichuan, Shanxi
Tian quan yanyanghuo Epimedium flavum Stearn Sichuan
Duan jing yinyanghuo Epimedium brachyrrhizum Stearn Sichuan
Shao hua yinyanghuo Epimedium pauciflorum K.C. Yen Sichuan
Fang shi yinyanghuo Epimedium fangii Stearn Sichuan
Kuan’e yinyanghuo Epimedium latisepalum Stearn Sichuan
Lu shan yinyanghuo Epimedium ogisui Stearn Sichuan
Chuan e yinyanghuo Epimedium fargesii Franch Sichuan, Hubei
Bao xing yinyanghuo Epimedium davidii Franch Sichuan, Yunnan
Chang rui yinyanghuo Epimedium dolichostemon Stearn Sichuang
Lv yao yinyanghuo Epimedium chlorandrum Stearn Sichuan
Wu shan yinyanghuo Epimedium wushanense Ying Sichuan, Guizhou, Hubei, Guangxi
Ge ye yinyanghuo Epimedium reticulatum C.Y. Wu Sichuan
Cu mao yinyanghuo Epimedium acuminatum Franch Sichuan, Guizhou, Yunnan, Hubei, Guangxi
Xian mao yinyanghuo Epimedium glandulosopilosum H.R. Liang Sichuan
Wu ju yinyanghuo Epimedium ecalcaratum G.Y. Zhong Sichuan
Zi ju yinyanghuo Epimedium epsteinii Stearn Hunan
Hu nan yinyanghuo Epimedium hunanense Hand.-Mazz Hunan, Hubei, Guangxi
Jian ye yinyanghuo Epimedium sagittatum (Sieb & Zucc) Maxim Hunan, Hubei, Guangdong, Zhejiang, An’hui, Jiangxi,
Guagxi, Shanxi, Gansu, Sichuan
Tian ping shan yinyanghuo Epimedium myrianthum Stearn Hunan, Hubei
Chao xian yinyanghuo Epimedium koreanum Nakai Jilin, Liaoning, Zhejiang, An’hui
Shi zhen yinyanghuo Epimedium lishihchenii Stearn Jiangxi
Rou mao yinyanghuo Epimedium pubescens Maxim Shanxi, Gansu, Hubei, Sichuan, Henan, An’hui
Yinyanghuo Epimedium brevicornu Maxim Shanxi, Gansu, Shan, xi, Henan, Qinghai, Hubei, Sichuan
Zhen ping yinyanghuo Epimedium ilicifolium Stearn Shanxi
522 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541

Table 3
The popular traditional food therapy or medicated diet of Epimedium.

Names Prescription Uses recorded Formulation/mode of usage Ref.

Yinyanghuo wine I Epimedium, rice wine Impotence, prospermia, rheumatic Wines processing Zhao (2004)
arthralgia, spasm of limbs,
Yinyanghuo wine II Epimedium, wine Impotence, dysgenesia Wines processing Hu (2002)
Qiyang wine Testis et Penis Callorhimi, Epimedium, Azoospermia, low motility of sperm Wines processing Hu (2002)
Radix Morindae Officinalis, Ziziphus
jujuba, Semen Cuscutae, Herba
Cistanches Deserticolae, wine
Bushenzhuangyang wine Epimedium, Radix Morindae Officinalis, Impotence, prospermia, osteoporosis Wines processing Hu (2002)
Herba Cistanches Deserticolae, Radix
Codonopsis, Fructus Jujubae, Fructus
Lycii, prepared rhizome of rehmannia,
Fructus Rosae, rice wine
Yinyanghuo gourou soup Epimedium, dog meat Impotence, prospermia, spermatorrhea Decoctions Hu (2002)
Gouqi eryang soup Fructus Lycii, Epimedium, mutton Impotence, prospermia, spermatorrhea Decoctions Hu (2002)
Shuangbu soup Epimedium, Fructus Lycii, prepared Spermatorrhea, impotence, fatigue, Decoctions Zhao (2004)
Rhizome of Rehmannia, Radix prospermia, sterility, Menoxenia,
Morindae Officinalis, Colla Comus uterine bleeding
Cervi, Radix Astragali Mongolici, Radix
Codonopsis, Radix Angelicae Sinensis
Yinyanghuo Yizhi soup Epimedium, Fructus Alpiniae Diuresis Decoctions Zhao (2004)
oxyphyllae, Cortex Cinnamomi Cassiae
Yinyanghuo yangshen gruel Epimedium, Goat kidney, rice Excessive teratospermia syndrome Gruel Hu (2002)
Yinyanghuo gouqi noodles Epimedium, Fructus Lycii, longan, Azoospermia Medicated diet Hu (2002)
noodles
Custard cream of Yinyanghuo Epimedium, egg, Oleum Sesami Impotence, prospermia, emaciation, Medicated diet Zhao (2004)
osteoporosis, acratia, osteodynia, chilly
Erxian ointment Epimedium, Rhizoma Curculiginis, Essential hypertension, chronic Medicated diet Zhao (2004)
Radix Morindae Officinalis, Rhizoma nephritis, urinary infection, acratia,
Anemarrhenae, Cortex Phellodendri neurasthenia, osteoporosis, dizziness
Amurensis, Radix Angelicae Sinensis and tinnitus, magersucht

only recently been discovered, and a number have yet to be named are designated as the official sources of Herba Epimedii in the Chi-
(Wikipedia, 2000, [Link] nese Pharmacopoeia (The State Committee of Pharmacopeia, 2005).
Flora of China). Epimedium species are commonly propagated by The aerial parts of some other species, such as Epimedium myri-
rhizome division both to preserve cultivar identity and because of anthum, Epimedium acuminatum and Epimedium leptorrhizum, are
low seed viability (Mihaljević and Vršek, 2009). Epimedium prefers also used in particular localities (Xie et al., 2010). In addition to the
to be planted in acidic soil sheltered from sunshine where humid- aerial parts, the underground parts of Epimedium plants are widely
ity is relatively high. In its reproductive growth period (from early used as anti-rheumatic medicine in Chinese folk medicines (China
March to late May), it needs enough light to avoid unfavorable Herb Compilation, 1975).
influence on the rapid re-growth of roots and shoots. On hot days In China, Epimedium is held in such high regard that it is not
and in the dry season, Epimedium must be watered. Growth con- only used as a medicine to cure some diseases but also as a supple-
ditions affected the contents of the major components present in ment to prevent disease and strengthen the body. To increase its
Epimedium plants, so a proper habitat for the plant is needed (Zhang effect, Epimedium was often used with other traditional medicines,
et al., 2003). However, the information on the conservation status such as Radix Morindae Officinalis, Fructus Jujubae, Semen Cuscu-
of the species of Epimedium have not been well reported. tae, Herba Cistanches, Radix Morindae Officinalis, Herba Cistanches
Deserticolae, Radix Codonopsis, Fructus Lycii, the prepared rhizome
of rehmannia, Radix Astragali Mongolici, Radix Codonopsis and
3. Ethnopharmacological use
Radix Angelicae Sinensis and even with dog meat, mutton and testis
and penis of Callorhimi. Generally, Epimedium is macerated in wine
Certain species of Epimedium have been used in traditional Asian
or decocted with water for oral consumption. However, recently,
medicine and have proven to have remarkably therapeutic activ-
more convenient forms have been developed for consumption, such
ities (Zhang et al., 2008a,b,c,d). Many species of Epimedium have
as tablets, capsules, ointments, gruel, noodles, and cream (Table 3)
been believed to posses aphrodisiac qualities. According to legend,
(The State Committee of Pharmacopeia, 2005).
this property was discovered by a Chinese goat herder who noticed
far more active sexual activity in his goats after they ate the plants
(Ye, 2005). 400 years ago, Epimedium has been recorded in the Chi- 4. Chemical constituents
nese medical classics Shen Nong Ben Cao Jing and it was considered
as a “Middle grade” herb in the most famous Chinese medicine The genus Epimedium is rich in flavonoids and lignans.
document Ben Cao Gang Mu. In China and Japan, Epimedium sagit- Flavonoids constituted the majority of compounds isolated during
tatum (Sieb. & Zucc.) Maxim. and Epimedium grandiflorum have the 1980s and 1990s. To date, 141 flavonoids, 31 lignins, 12 ionones,
been used to treat impotence, prospermia, hyperdiuresis, osteo- 9 phenol glycosides, 6 phenylethanoid glycosides, 5 sesquiter-
porosis, menopause syndrome, rheumatic arthritis, hypertension, penes (Table 4) and a number of other compounds representing a
and chronic tracheitis. In Korea, Sam-ji-goo-yeop-cho, the herb wide spectrum of secondary metabolite classes have been isolated
Epimedium koreanum, was traditionally used for impotence, sper- and identified from the genus Epimedium. The most well-known
matorrhoea and forgetfulness (Liu and Xu, 1984). Now, the major and phytochemically characterized of these compounds are the
five Epimedium species, Epimedium brevicornum Maxim, Epimedium flavonoids, and the most prominent components are the prenylated
sagittatum (Sieb. and Zucc.) Maxim., Epimedium pubescens Maxim. flavonol glycosides. These flavonoids displayed many bioactivi-
Epimedium wushanense T.S. Ying and Epimedium koreanum Nakai ties in vivo or in vitro (see in Supplemental Table, Fig. 2). Icariin,
 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541 523

Table 4
The compounds isolated from the genus Epimedium (the parent nucleus structure of the flavonoids illustrated in Fig. 2).

No. Compounds Species References

Flavonoids
8-Prenyl-flavonoids
1 Icariin Epimedium koreanum Li et al. (1995a)
Epimedium fargesii Guo et al. (1996a)
Epimedium leptorrhizum Han et al. (2002a)
Epimedium platyetalum Zhu et al. (1993)
Epimedium wushanense Zhou et al. (2005)
Epimedium breviconu Liao et al. (1994)
Epimedium acuminatum Dong et al. (1994)
Epimedium sagittatum Mizuno et al. (1987)
Epimedium grandiflorum Tokuoka et al. (1975a)
2 Icariin I Epimedium koreanum Wang et al. (2010a,b)
Epimedium hunanense Liang et al. (1997)
3 Icariin II Epimedium koreanum Wang et al. (2010a,b)
4 Desme-O-methylicariine Epimedium sagittatum Zhao (2001)
5 Anhydroicaritin Epimedium koreanum Sun et al. (1998a)
Epimedium wanshanense Li et al. (1996a)
Epimedium brevicornum Guo et al. (1996b)
6 Anhydroicaritin 3-O-rhamnosylrhamnoside Epimedium koreanum Li et al. (1996b)
7 Anhydroicaritin-3-O-␣-l-rhamnopyranosyl-(1→2)-␣-l-rhamnopyranoside Epimedium wanshanense Li et al. (1996c)
8 Demethylanhydroicaritin Epimedium koreanum Zheng and Kong (2002)
Epimedium wanshanense Li et al. (1996a)
Epimedium wanshanense Li et al. (1996d)
9 Desmethylanhydroicaritin-3-O-␣-l-rhamnopyranosyl-(1→2)-␣-l-rhamnopyranoside Epimedium wanshanense Li et al. (1996c)
10 Icariside I Epimedium koreanum Li et al. (1995a)
Epimedium leptorrhizum Han et al. (2002a)
Epimedium wanshanense Li et al. (1996d)
Epimedium wushanense Zhou et al. (2005)
Epimedium breviconu Liao et al. (1994)
Epimedium sagittatum Mizuno et al. (1987)
11 2 -O-rhamnopyranosyl icariside I Epimedium koreanum Sun et al. (1995a)
12 Icariside II (Baohuoside I) Epimedium koreanum Sun et al. (1995a)
Li et al. (1995a)
Epimedium breviconu Liao et al. (1994)
Epimedium wanshanense Fukai and Nomura (1988)
Epimedium sempervirens Mizuno et al. (1987)
Epimedium sagittatum Zhu et al. (1993)
Epimedium platyetalum Liang et al. (1997)
Epimedium hunanense Li and Liu (1988b)
Epimedium davidii
13 2 -O-rhamnosyl icarisid II Epimedium koreanum Kang et al. (1991)
Epimedium leptorrhizum Han et al. (2002b)
Epimedium leptorrhizum Jia et al. (1999)
Epimedium wanshanense Li et al. (1996d)
Epimedium acuminatum Jia et al. (1998)
Epimedium brevicornum Guo et al. (1996c)
14 3 -Carbonyl-2 -␤-l-quinovosyl icariside II Epimedium koreanum Zhang et al. (2007)
15 Epimedin A Epimedium koreanum Oshima et al. (1987)
Epimedium sagittatum Wang and Geng (2005)
Epimedium breviconu Wang et al. (2005b)
16 Epimedin B Epimedium koreanum Oshima et al. (1987)
Epimedium fargesii Guo et al. (1996a)
Epimedium sagittatum Wang and Geng (2005)
Epimedium wanshanense Li et al. (1996a)
Epimedium breviconu Guo et al. (1996b)
Epimedium hunanense Liang et al. (1997)
17 Epimedin C Epimedium koreanum Oshima et al. (1987)
Epimedium fargesii Guo et al. (1996a)
Epimedium sagittatum Wang and Geng (2005)
Epimedium leptorrhizum Han et al. (2002a)
Epimedium wanshanense Li et al. (1996a)
Epimedium breviconu Guo et al. (1996b)
Epimedium acuminatum Jia et al. (1998)
Epimedium hunanense Liang et al. (1997)
18 Epimedin I Epimedium koreanum Sun et al. (1998b)
19 Epimedin K Epimedium koreanum Sun et al. (1996a)
20 Epimedoside Epimedium koreanum Sun et al. (1995b)
21 Epimedoside A Epimedium koreanum Sun et al. (1995a)
Epimedium fargesii Guo et al. (1996a)
Epimedium truncatum Xu and Yang (2005)
Epimedium acuminatum Dong et al. (1994)
Epimedium grandiflorum Takemoto et al. (1975)
Epimedium wushanense Takemoto et al. (1975)
524 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541

Table 4 (Continued)

No. Compounds Species References

22 Epimedoside B Epimedium koreanum Ou and Ou (1997)

Epimedium grandiflorum Tokuoka et al. (1975b)
23 Epimedoside C Epimedium koreanum Li et al. (1995b)
Epimedium truncatum Xu and Yang (2005)
Epimedium leptorrhiz um Han et al. (2002a)
Epimedium wanshanense Li et al. (1997a, b)
Epimedium grandiflorum Tokuoka et al. (1975b)
24 Epimedoside D Epimedium koreanum Ou and Ou (1997)
Epimedium grandiflorum Tokuoka et al. (1975c)
25 Epimedoside E Epimedium koreanum Ou and Ou (1997)
Epimedium grandiflorum Tokuoka et al. (1975c)
26 Epimedikoreanin A Epimedium koreanum Li et al. (1995c)
27 Epimedikoreanin B Epimedium koreanum Li et al. (1996e)
28 Epimedikoreanin C Epimedium koreanum Li et al. (1996e)
29 Epimedikoreanin D Epimedium koreanum Li et al. (1996e)
30 Epimedokoreanoside I Epimedium koreanum Pachaly et al. (1990)
31 Epimedokoreanoside II Epimedium koreanum Pachaly et al. (1990)
32 Sagittatoside A Epimedium koreanum Li et al. (1994a)
Epimedium leptorrhizum Jia et al. (1999)
Epimedium wanshanense Li et al. (1996c)
Epimedium sagittatum Mizuno et al. (1988a)
33 Sagittatoside B Epimedium koreanum Li et al. (1994a)
Epimedium wanshanense Li et al. (1996c)
Epimedium brevicornum Guo et al. (1996c)
Epimedium sagittatum Mizuno et al. (1988a)
34 Sagittatoside C Epimedium sagittatum Mizuno et al. (1988a)
35 Sagittasine A Epimedium sagittatum Mizuno et al. (1988a)
Wang et al. (2007)
36 Sagittasine B Epimedium sagittatum Mizuno et al. (1988a)
Wang et al. (2007)
37 Sagittasine C Epimedium sagittatum Mizuno et al. (1988a)
Wang et al. (2007)
38 Diphylloside A Epimedium koreanum Li et al. (1994a)
Epimedium wanshanense Li et al. (1996a)
39 Diphylloside B Epimedium diphyllum Mizuno et al. (1988b)
Epimedium wanshanense Li et al. (1996a)
Epimedium acuminatum Jia et al. (1998)
40 Diphylloside C (Ikarisosids C) Epimedium fargesii Guo et al. (1996a)
Epimedium brevicornum Guo et al. (1996c)
Epimedium acuminatum Jia et al. (1998)
Epimedium grandiflorum Fukai and Nomura (1988)
Epimedium sempervirens Mizuno et al. (1989)
Epimedium diphyllum
41 Ikarisoside A (Baohuoside II) Epimedium acuminatum Dong et al. (1994)
Epimedium leptorrhizum Han et al. (2002b)
Epimedium wanshanense Li et al. (1996d)
Epimedium grandiflorum Fukai and Nomura (1988)
Epimedium sempervirens Li et al. (1994b)
Epimedium koreanum Xu and Yang (2005)
Epimedium truncatum Guo et al. (1996c)
Epimedium brevicornum
42 2 -O-rhamnosy-likarisoside A Epimedium koreanum Kang et al. (1991)
Epimedium wanshanense Li et al. (1996d)
Epimedium acuminatum Jia et al. (1998)
43 Ikarisoside B Epimedium leptorrhizum Jia et al. (1999)
Epimedium wanshanense Li et al. (1996d)
Epimedium acuminatum Jia et al. (1998)
Epimedium grandiflorum Fukai and Nomura (1988)
44 Ikarisoside D Epimedium grandiflorum Fukai and Nomura (1988)
45 Ikarisoside E Epimedium grandiflorum Fukai and Nomura (1988)
Epimedium sempervirens
46 Ikarisoside F Epimedium koreanum Li et al. (1994a)
Epimedium brevicornum Guo et al. (1996c)
Epimedium grandiflorum Fukai and Nomura (1988)
47 Baohuosu Epimedium koreanum Li and Liu (1988b)
48 Baohuoside III Epimedium davidii Li and Liu (1988a)
Epimedium truncatum Xu and Yang (2005)
49 Baohuoside IV Epimedium koreanum Zhao (2001)
50 Baohuoside V Epimedium davidii Li and Liu (1988a)
Epimedium truncatum Xu and Yang (2005)
51 Baohuoside VI Epimedium davidii Li and Liu (1988b)
Epimedium pubescens Li (1992)
Epimedium breviconu Yan et al. (1998)
52 Baohoside VII Epimedium koreanum Li and Liu (1988b)
53 8-Isoprenylkaempferol Epimedium koreanum Sun et al. (1998b)
Sun et al. (1998a)
 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541 525

Table 4 (Continued)

No. Compounds Species References


54 8-Prenylkaempferol-4 -methylether-3- Epimedium wushanense Li and Liu (1990a)
[xylpsyl(1–4)rhamnoside]-7-glucoside
55 Breviflavone A Epimedium brevicornu Yap et al. (2005)
Shen et al. (2007)
56 Breviflavone B Epimedium brevicornu Yap et al. (2005)
Shen et al. (2007)
57 Rouhuoside Epimedium wushanense Zhou et al. (2005)
Epimedium pubescens Li and Liu (1990b)
58 Korepimedoside A Epimedium koreanum Sun et al. (1995a)
59 Korepimedoside B Epimedium koreanum Sun et al. (1996b)
60 Korepimedoside C Epimedium koreanum Sun et al. (1998a)
Sun et al. (1998c)
61 Sempervirenoside A Epimedium sempervirens Mizuno et al. (1988c)
62 Sempervirenoside B Epimedium sempervirens Mizuno et al. (1990)
63 Cuhuoside Epimedium acuminatu Liang et al. (1993)
64 Caohuoside A (Epimedin L) Epimedium koreanum Li et al. (1996f)
Wang et al. (2010a,b)
65 Caohuoside B Epimedium koreanum Li et al. (1995d)
66 Caohuoside C Epimedium koreanum Li (1995)
67 Caohuoside E Epimedium koreanum Li et al. (1995e)
68 Hexandraside E Epimedium koreanum Zheng and Kong (2002)
Epimedium breviconu Yan et al. (1998)
69 Hexandraside F Epimedium sagittatum Wang and Geng (2005)
70 Maohuosides A Epimedium platyetalum Wang et al. (2002a,b)
71 Maohuosides B Epimedium platyetalum Wang et al. (2002a,b)
72 Acuminatoside Epimedium acuminatum Hu et al. (1992a)
73 Platypetaloside A Epimedium platyetalum Zhu et al. (1993)
74 3,5,7-Trihydroxyl-4 methoxyl-8-prenylflavone-3-O-␣-l- Epimedium koreanum Li et al. (1994a)
rhamnopyranosyl-(1–2)-␣-l-rhamnopyranoside
6-Prenyl-flavonoids
75 Wushanicariin Epimedium breviconu Liang et al. (1988)
Yan et al. (1998)
8-(2,3-Substituent group)-butyl flavonoids
76 Caohuoside D Epimedium koreanum Li et al. (1995f)
77 Caohuoside F Epimedium koreanum Li and Song (2006)
78 Icaritin Epimedium koreanum Li et al. (1995a)
79 Icaritin-3-O-rhamnopyranoside Epimedium koreanum Li et al. (1994a)
80 Icaritin-3-O-rhamnoside Epimedium breviconu Wang et al. (2005b)
81 Wanepimedoside A Epimedium wanshanense Li et al. (1996d)
82 Brevicornin Epimedium brevicornum. Guo et al. (1996b)
7,8-Prenyl-lactone flavonoids(y-dimethyl-chromene flavonoids)
83 Ikarisoside Epimedium koreanum Zhao (2001)
84 Acuminatin Epimedium koreanum Sun et al. (1998d)
Epimedium acuminatum Hu et al. (1992b)
85 Acumination Epimedium acuminatum Zhao (2001)
86 Sutchuenmedin A Epimedium sutchuenense Mizuno et al. (1991)
Yu et al. (2009)
87 Sutchuenmedin B Epimedium sutchuenense Yu et al. (2009)
88 Sutchuenoside A Epimedium sutchuenense Song et al. (2009)
89 Sutchuenoside B Epimedium sutchuenense Song et al. (2009)
Biflavone
90 Ginkgetin Epimedium koreanum Sun et al. (1998b)
Sun et al. (1998a)
91 Isoginkgetin Epimedium koreanum Sun et al. (1998b)
Sun et al. (1998a)
92 Bilobetin Epimedium koreanum Sun et al. (1998b)
Sun et al. (1998a)
Other flavonoids
93 Neoicariin Epimedium sagittatum Yao et al. (2004)
94 Yinyanghuo A Epimedium sagittatum Chen et al. (1996)
95 Yinyanghuo B Epimedium sagittatum Chen et al. (1996)
96 Yinyanghuo C Epimedium sagittatum Chen et al. (1996)
97 Yinyanghuo D Epimedium sagittatum Chen et al. (1996)
98 Yinyanghuo E Epimedium sagittatum Chen et al. (1996)
99 Yinyanghuo F Epimedium sagittatum Huang et al. (1993)
100 Yinyanghuo G Epimedium sagittatum Huang et al. (1993)
101 Yinyanghuo H Epimedium sagittatum Huang et al. (1993)
102 Sutchuenoside Epimedium sutchuenense Zhao (2001)
103 Kaempferol-3-dirhamnoside Epimedium truncatum Xu and Yang (2005)
Epimedium breviconu Yang et al. (2009a)
104 Kaempferol-3-O-␤-d-gatactoside Epimedium koreanum Li et al. (1994b)
105 Kaempferol-3,7-O-␣-l-dirhamnoside Epimedium breviconu Yan et al. (1998)
106 Kaempferol-3-O-alpha-l-rhamnopyranoside Epimedium acuminatum Hu et al. (1992a)
107 Kaempferol-3-O-(2 -E-p-coumaroyl,4 -Z-p-coumaroyl)-a- Epimedium sagittatum Wang et al. (2007)
l-rhamnopyranoside
108 Kaempferol-3-O-(3 -Z-p-coumaroyl,4 -E-p-coumaroyl)-a- Epimedium sagittatum Wang et al. (2007)
l-rhamnopyranoside
526 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541

Table 4 (Continued)

No. Compounds Species References

 
109 Kaempferol-3-O-(2 ,4 -di-Ep-coumaroyl)-a-l- Epimedium sagittatum Wang et al. (2007)
rhamnopyranoside
110 Kaempferol-3-O-(2 -Z-p-coumaroyl,4 -E-p-coumaroyl)-a- Epimedium sagittatum Wang et al. (2007)
l-rhamnopyranoside
111 Kaempferol-3-O-(3 ,4 -di-E-p-coumaroyl)-a-l- Epimedium sagittatum Wang et al. (2007)
rhamnopyranoside
112 (2R,3R)-dihydrokaempferol-4 -O-b-d-glucopyranoside Epimedium sagittatum Wang et al. (2007)
113 Quercetin Epimedium koreanum Li et al. (1995a)
Epimedium wanshanense Li et al. (1996d)
114 Isoquercetin Epimedium sagittatum Wang et al. (2007)
115 Quercetin-3-O-a-l-rhamnoside Epimedium sagittatum Wang et al. (2007)
116 Quercetin-3-O-b-d-galactoside Epimedium sagittatum Wang et al. (2007)
117 Quercetin-3-O-a-l-rhamnopyranosyl(1–2)-a-l- Epimedium sagittatum Wang et al. (2007)
rhamnopyranoside
118 Hyperin Epimedium fargesii Guo et al. (1996a)
Epimedium truncatum Xu and Yang (2005)
Epimedium koreanum Sun et al. (1995a)
119 Hyperoside Epimedium koreanum Li et al. (1995a)
Epimedium brevicornu Li et al. (2005a,b)
120 Tricin Epimedium koreanum Li et al. (1995g)
Epimedium brevicornu Guo et al. (1996b)
121 Tricetin-3 ,5 -dimethyl ether Epimedium sagittatum Wang et al. (2007)
122 Tricetin-3 -methyl ether Epimedium sagittatum Wang et al. (2007)
123 5,7,4 -Trihydroxy-30-(2-hydroxy-3-methylbut-4- Epimedium sagittatum Wang et al. (2007)
enyl)flavone
124 5-Hydroxy-6,7-dimethoxy-3 ,4 -methylene-dioxyflavone Epimedium sagittatum Li et al. (1995d)
125 3,5,7,4 -Tetrahydroxyl-8-isopentene-flavonoids-3-O-␣-l- Epimedium breviconu Yang et al. (2009b)
rhamnopyranoside
126 5,7,4 -Trihydroxy-8,3 -diprenylflavone Epimedium breviconu Yang et al. (2009a)
127 Luteolin Epimedium koreanum Li et al. (1994b)
128 Astragalin Epimedium koreanum Li et al. (1994a)
129 Liquiritigenin Epimedium koreanum Li et al. (1995g)
130 Hydnocarpin Epimedium sagittatum Wang et al. (2007)
131 5 -Methoxyhydnocarpin Epimedium sagittatum Wang et al. (2007)
132 Hydnocarpin-D Epimedium sagittatum Wang et al. (2007)
133 Methoxyhydnocarpin-D Epimedium sagittatum Wang et al. (2007)
134 5 ,5 -Dimethoxyhydnocarpin-D Epimedium sagittatum Wang et al. (2007)
135 2-(␤-Hydroxyphenoxy)-5,7-dihydroxy-6-prenylchromone Epimedium koreanum Sun et al. (1998a)
136 Sagittin Epimedium sagittatum Wu et al. (1995)
137 Anthocyanin Epimedium grandiflorum Yoshitama (1984)
138 Cayratinin Epimedium grandiflorum Yoshitama (1984)
139 Eyanidin 3-p-coumaroylsophoroside Epimedium grandiflorum Yoshitama (1984)
140 Apigenin Epimedium sagittatum Wang et al. (2007)
141 Daidzein Epimedium sutchuenense Song et al. (2009)
Lignins
142 Icariside E1 Epimedium grandiflorum Miyaes et al. (1987a)
143 Icariside E2 Epimedium grandiflorum Miyaes et al. (1987a)
144 Icariside E3 Epimedium grandiflorum Miyaes et al. (1988)
145 Icariside E4 Epimedium diphyllum Miyase and Ueno (1991)
146 Icariside E5 Epimedium diphyllum Miyase and Ueno (1991)
147 Icariside E6 Epimedium sagittatum Matsushita et al. (1991)
148 Icariside E7 Epimedium sagittatum Matsushita et al. (1991)
149 Icariols A1 Epimedium sagittatum Matsushita et al. (1991)
150 Icariols A2 Epimedium sagittatum Matsushita et al. (1991)
151 Icariresinol-4 -␤-d-glucopyranoside Epimedium leptorrhizum Han et al. (2002a)
Epimedium grandiflorum Tokuoka et al. (1975d)
152 (+)Syringaresinol-O-␤-d-glucoside Epimedium grandiflorum Miyaes et al. (1987a)
153 3,5-Demethoxy-syringaresinol-glucoside Epimedium sagittatum Matsushita et al. (1991)
154 Liriodendrin Epimedium grandiflorum Miyaes et al. (1987a)
155 (−)-Olivil Epimedium sagittatum Matsushita et al. (1991)
Epimedium grandiflorum Tokuoka et al. (1975d)
156 (−)-Olivil-4 -O-␤-d-glucopyranoside Epimedium grandiflorum Miyaes et al. (1987a)
157 Dihydrodehdrodiconiferyl alcohol-4 glucoside Epimedium diphyllum Miyase and Ueno (1991)
158 (+)-Cycloolivil Epimedium diphyllum Miyase and Ueno (1991)
Epimedium koreanum Zheng and Kong (2002)
Epimedium breviconu Yang et al. (2009b)
159 (+)-Lyoniresinol-3-O-xyloside Epimedium diphyllum Miyase and Ueno (1991)
160 (−)-Lyoniresinol-3-O-xyloside Epimedium diphyllum Miyase and Ueno (1991)
161 EL1 Epimedium sagittatum Matsushita et al. (1991)
162 EL2 Epimedium sagittatum Matsushita et al. (1991)
163 EL3 Epimedium grandiflorum Miyaes et al. (1987a)
164 EL4 Epimedium grandiflorum Miyaes et al. (1987a)
165 EL5 Epimedium grandiflorum Miyaes et al. (1987a)
166 EL6 Epimedium diphyllum Miyase and Ueno (1991)
167 EL7 Epimedium grandiflorum Miyaes et al. (1987a)
168 EL8 Epimedium diphyllum Miyase and Ueno (1991)
 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541 527

Table 4 (Continued)

No. Compounds Species References

169 EL9 Epimedium sagittatum Matsushita et al. (1991)

EL1–EL6: 1-(4-hydroxy-3-methoxyphenyl-2-[4-(3-hydroxypropyl)-2-methoxyphenoxyl]-1,3-propan-ediol and its rhamnoside or glucoside
EL7–EL8: 1-(4-hydroxy-3-methoxyphenyl-2-[4-(3-rahmnopyranoxypropyl)-2-hydroxrphenoxyl]-1,3-pr-opanediol
EL9: 1-(4-hydroxy-3,5-dimethoxyphenyl-2-[4-(3-hydroxrphenoxyl)-2,6-dimethoxyphenyl]-1,3-propanediol
170 (+)-Dihydro-dehydrodiconiferyl Epimedium sagittatum Wang et al. (2007)
alcohol-4-O-␤-d-glucopyranoside
171 (7R, 8S)-4,9-dihydroxyl-3,3 -dimethyoxyl-7,8- Epimedium breviconu Yang et al. (2009b)
dihydrobenzofunan-1 -propanolneolignan-9 -O-␣-l-
rhamnopyranoside
172 (7R, 8S, 8 R)-4,4 ,8 ,9-tetrahydroxyl-3,3 -dimethyoxyl-7,9 - Epimedium breviconu Yang et al. (2009b)
monoepoxylignan
Ionones
173 Icariside B1 Epimedium grandiflorum Miyaes et al. (1987b)
Epimedium diphyllum Miyase and Ueno (1991)
174 Icariside B2 Epimedium grandiflorum Miyaes et al. (1987b)
Epimedium sagittatum Matsushita et al. (1991)
Epimedium diphyllum Miyase and Ueno (1991)
175 Icariside B3 Epimedium grandiflorum Miyaes et al. (1987a)
176 Icariside B4 Epimedium grandiflorum Miyaes et al. (1987a)
177 Icariside B5 Epimedium grandiflorum Miyaes et al. (1988)
178 Icariside B6 Epimedium grandiflorum Miyaes et al. (1988)
179 Icariside B7 Epimedium grandiflorum Miyaes et al. (1988)
180 Icariside B8 Epimedium sagittatum Matsushita et al. (1991)
Epimedium diphyllum Miyase et al. (1989)
181 Icariside B9 Epimedium sagittatum Matsushita et al. (1991)
182 Icariside B10 Epimedium grandiflorum Miyase and Ueno (1991)
183 Blumenol C glucoside Epimedium grandiflorum Miyaes et al. (1988)
184 Roseside Epimedium grandiflorum Miyaes et al. (1987a)
Phenols glycosides
185 Icariside A1 Epimedium grandiflorum Miyaes et al. (1987b)
Epimedium sagittatum Matsushita et al. (1991)
186 Icariside A2 Epimedium grandiflorum Miyaes et al. (1988)
187 Icariside A3 Epimedium grandiflorum Miyaes et al. (1988)
188 Icariside A4 Epimedium grandiflorum Miyase et al. (1989)
189 Icariside A5 Epimedium grandiflorum Miyase and Ueno (1991)
190 Icariside A6 Epimedium grandiflorum Miyase et al. (1989)
191 Icariside A7 Epimedium koreanum Sun et al. (1998b)
192 Epimedoicarisoside A Epimedium koreanum Li et al. (1995b)
193 Icarisoside A Epimedium wushanense Xie et al. (2007)
Phenylethanoid glycosides
194 Phenethyl glucoside Epimedium grandiflorum Miyaes et al. (1988)
Epimedium sagittatum Matsushita et al. (1991)
195 Ikarisoside D1 Epimedium grandiflorum Miyaes et al. (1987a)
Epimedium diphyllum Miyase and Ueno (1991)
196 Ikarisoside D2 Epimedium diphyllum Miyase and Ueno (1991)
197 Ikarisoside D3 Epimedium sagittatum Matsushita et al. (1991)
198 Salidroside Epimedium grandiflorum Miyaes et al. (1987b)
Epimedium diphyllum Miyase and Ueno (1991)
Epimedium koreanum Sun et al. (1998d)
Epimedium breviconu Yang et al. (2009a)
199 Thalictoside Epimedium grandiflorum Miyaes et al. (1987b)
Epimedium diphyllum Miyase and Ueno (1991)
Epimedium leptorrhizum Jia et al. (1999)
Epimedium hunanense Liang et al. (1997)
Sesquiterpenes
200 Icariside C1 Epimedium grandiflorurn Miyaes et al. (1987b)
Epimedium koreanum Chen and Zhang (2005)
201 Icariside C2 Epimedium grandiflorum Miyaes et al. (1987b)
202 Icariside C3 Epimedium grandiflorum Miyaes et al. (1987b)
203 Icariside C4 Epimedium grandiflorum Miyaes et al. (1987b)
204 Icariside F Epimedium koreanum Chen and Zhang (2005)
Others compounds
205 Icariside A1 Epimedium koreanum Sun et al. (1995a)
206 Ikarisoside F1 Epimedium grandiflorum Miyaes et al. (1988)
207 Ikarisoside F2 Epimedium grandiflorum Miyaes et al. (1988)
Epimedium diphyllum Miyase and Ueno (1991)
208 Ikarisoside G1 Epimedium grandiflorum Miyaes et al. (1988)
209 Icariside H1 Epimedium grandiflorum Matsushita et al. (1991)
210 6-Demethoxy-7-methylcapillarisin Epimedium sagittatum Huang et al. (1993)
211 6-Demethoxy-4 -methyl-8-isopentenylcapillarisin Epimedium sagittatum Huang et al. (1993)
212 6-Demethoxy-7-isopentenylcapillarisin Epimedium sagittatum Huang et al. (1993)
213 Syringin Epimedium diphyllum Miyase and Ueno (1991)
214 Isoliquiritigenin Epimedium koreanum Li et al. (1994b)
215 Emodin Epimedium koreanum Li et al. (1995g)
216 (Z)-3-hexenyl glucoside Epimedium grandiflorum Miyaes et al. (1988)
Epimedium diphyllum Miyase and Ueno (1991)
528 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541

Table 4 (Continued)

No. Compounds Species References

217 3,7,11-Trimethyl-2,6-dodecadien-1,10,11-trihydroxyl-10 Epimedium koreanum Chen and Zhang (2005)

(S)-O-␤-d-glucopyranoside
218 1,2-Bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol Epimedium grandiflorum Matsushita et al. (1991)
219 Maltol Epimedium koreanum Sun et al. (1995a)
Sun et al. (1998d)
220 Daucosterol Epimedium koreanum Li et al. (1995a)
221 Inositol Epimedium koreanum Zheng and Kong (2002)
Epimedium brevicornu Li et al. (2005a,b)
222 ␤-Methoxyphenol Epimedium breviconu Wang et al. (2005b)
223 1,2,3,4-Tetrahydro-3,7-dihydroxy-1-(4-hydroxy-3- Epimedium koreanum Chen et al. (2006)
methoxyphenyl)-6-methoxy-2,3-naphthalenedimethanol
224 Aseicosanol Epimedium dewuense Yang et al. (2006)
225 ␤-Sitosterol Epimedium dewuense Yang et al. (2006)
Epimedium sagittatum Wu et al. (1995)
Epimedium leptorrhizum Han et al. (2002b)
Epimedium breviconu Wang et al. (2005b)
Yang et al. (2009b)
226 ␥-Sitosterol Epimedium dewuense Yang et al. (2006)
227 Daucosterol Epimedium platyetalum Wang et al. (2002a,b)
Epimedium wanshanense Li et al. (1997a,b)
Epimedium dewuense Yang et al. (2006)
Epimedium breviconu Wang et al. (2005b)
Epimedium koreanum Li et al. (1995a)
228 6,22-Hopanediol Epimedium leptorrhizum Han et al. (2002b)
229 6-Hydroxy-11,12-dimethoxy-2,2-dimethyl-1,8-dioxo- Epimedium koreanum Liu et al. (2003)
1,3,4,8-tetrahydro-2H-7-oxa-2-azonia-benzo
[c]phenanthrene
230 Magnoflorine Epimedium koreanum Tomita and Ishii (1957a,b)
231 20-Hydroxydammar-24-en-3-one Epimedium dewuense Yang et al. (2006)
232 Artonin U Epimedium dewuense Yang et al. (2006)
233 Tritriacontane Epimedium leptorrhizum Han et al. (2002b)
234 ␤-Hydroxybenzaldehyde Epimedium breviconu Yang et al. (2009b)
235 Phydroxyphenethyl Epimedium breviconu Yang et al. (2009b)
236 Epimedokoreanone A Epimedium koreanum Li et al. (1996e)
237 1,3,5,8-Tetrahydroxy xanthone Epimedium breviconu Wang et al. (2005b)
238 1-Hydroxy-1,3,5,8-tetrahydroxy xanthone Epimedium breviconu Wang et al. (2005b)
239 5,7-Dihydroxy-2-(␤-hydroxyphenoxy)-6-prenylchromone Epimedium koreanum Sun et al. (1998b)
240 2-Phenoxychromones Epimedium sagittatum Wang et al. (2007)
241 Chlorogenic Epimedium sagittatum Wang et al. (2007)
242 ␤-Coumaric Epimedium sagittatum Wang et al. (2007)
243 ␤-Hydroxy benzoic acid Epimedium koreanum Li et al. (1994b)
244 2,4-Dihydroxy benzoic acid Epimedium koreanum Li et al. (1994b)
245 Octadecylic acid Epimedium dewuense Yang et al. (2006)
246 Oleanolic acid Epimedium truncatum Xu and Yang (2005)
247 Succinic acid Epimedium breviconu Yang et al. (2009b)
248 Behenic acid Epimedium breviconu Wang et al. (2005b)
249 Caffeoyl-hexaric acid Epimedium koreanum Wang et al. (2010a,b)
250 Cis-3-O-caffeoylquinic acid Epimedium koreanum Wang et al. (2010a,b)
251 Trans-3-O-caffeoylquinic acid Epimedium koreanum Wang et al. (2010a,b)
252 Cis-3-O-p-coumaroylquinic acid Epimedium koreanum Wang et al. (2010a,b)
253 Cis-4-O-caffeoylquinic acid Epimedium koreanum Wang et al. (2010a,b)
254 Dimer of 5-O-caffeoylquinic acid Epimedium koreanum Wang et al. (2010a,b)
255 Trans-5-O-caffeoylquinic acid Epimedium koreanum Wang et al. (2010a,b)
256 Cis-5-O-caffeoylquinic acid Epimedium koreanum Wang et al. (2010a,b)
257 Trans-4-O-p-coumaroylquinic acid Epimedium koreanum Wang et al. (2010a,b)
258 Cis-5-O-p-coumaroylquinic acid Epimedium koreanum Wang et al. (2010a,b)
259 5-O-feruloylquinic acid Epimedium koreanum Wang et al. (2010a,b)
260 1-O-␤-Glucopyransosyl-1,4-dihydroxy-2-(3 -hydroxy-3 - Epimedium breviconu Yang et al. (2009a)
methyl
butyl)benzene

icaritin, desmethylicaritin, des-methylanhydroicaritin, icariside II, including flavonol, flavone, chalcone, flavanone, and flavonol
ikarisoside A, baohuoside-1, baohuoside II, epimedokoreanin B, glycoside, have been found from 17 Epimedium species (Table 4,
breviflavone B, luteolin, hyperoside, epimedin B and epimedin Fig. 3). Of these flavonoids, 74 (1–74) were substituted with
C have been confirmed to possess yang-strengthening, estro- a pentenyl group at C-8, and the major active compounds were
genic, antitumor, antioxidant, antiradiation, anti-inflammatory, flavonol glycosides, in particular, 3-O-, 7-O- or 3,7-di-O-glycosides.
anti-microbial, anti-hepatotoxic, cardiovascular, neuroprotective, The sugar moieties of the glycosides are usually glucose, rham-
anti-aging, anti-depressant, anxiolytic and other activities. nose, xylose or their corresponding mono- or di-acetyl sugars
(Wu et al., 2003a; Zhao et al., 2008b). The best-known and most
4.1. Flavonoids thoroughly phytochemically characterized Epimedium species are
Epimedium koreanum, Epimedium sagittatum, Epimedium brevi-
Flavonoids and their derivatives are important chemical com- cornum and Epimedium grandiflorum. The chemical constituents
ponents of the genus Epimedium; more than 141 flavonoids, of Epimedium dewuense, Epimedium leptorrhizum, Epimedium
 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541 529

OH

OR 3 OH

R2 O O HO O

OR 1
OH O OH O
Name R1 R2 R3 Epimedokoreanin B
Icariin Rha Glc-Glc Me
Epimedin B Rha-Xyl Glc Me
OH
Epimedin C Rha-Rha Glc Me
Diphylloside A Rha-Glc Glc H
Desmethylicaritin Rha Glc H OCH 3
Desmethylanhydro-
H H H HO O
icaritin
Baohuoside II
H Glc Me OH
(Icariside II)
OH O
Baohuoside II
Rha H H icaritin
(Ikarisoside A)
R2
OH

HO O
R3
O CH3
OR 1
OH
HO O OH O
CH 3
Name R1 R2 R3
Luteolin Rha-Glc H OH

OH O Breviflavone B Hyperoside Glc OH H

Fig. 2. The chemical structure of some activities compounds from the genus Epimedium.

OR

O O O
O

OR OR
OR
O O
O
1 2 3

R1O O
OR2

HO O O
OH O OR3

4 O O 5

Fig. 3. The parent nucleus structure of the flavonoids.

530 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541

wanshanense, Epimedium platyetalum, Epimedium diphyllum, 4.5. Phenethyl alcohol glycosides

Epimedium hunanense, Epimedium wushanense, Epimedium sutchue-
nense, Epimedium acuminatum, Epimedium truncatum, Epimedium So far, only six phenethyl alcohol glycosides have been identi-
pubescens, Epimedium davidii and Epimedium fargesii have also fied from the genus Epimedium. Phenethyl glucoside was obtained
been determined. However, the phytochemical knowledge from Epimedium grandiflorum and Epimedium sagittatum (Sieb. &
about Epimedium myrianthum, Epimedium dewuense, Epimedium Zucc.) Maxim. (Miyaes et al., 1988; Matsushita et al., 1991), ikariso-
platyetalum, Epimedium hunanense and Epimedium davidii is far side D1 was obtained from Epimedium grandiflorum and Epimedium
from adequate, even though these species are frequently used in diphyllum, and ikarisoside D2 and ikarisoside D3 were obtained
the practice of TCM. from Epimedium diphyllum and Epimedium sagittatum (Sieb. & Zucc.)
Maxim., respectively (Miyase and Ueno, 1991; Matsushita et al.,
1991). In addition, salidroside and thalictoside were isolated from
4.2. Lignans
several Epimedium plants.

Lignans are a class of secondary metabolites, consisting 4.6. Sesquiterpenes

of two phenyl-propanoid molecules connected by 8–8 car-
bon atoms. Thirty-one lignans and their glycosides have been Sesquiterpenoids, a class of terpenes, are defined as the group
identified from the genus Epimedium. Ikarisoside E1 , ikariso- of 15-carbon compounds derived from the assembly of three iso-
side E2 , ikarisoside E3 , (+)syringaresinol-O-␤-d-glucoside, (−)- prenoid units and having the molecular formula C15 H24 . So far,
olivil-4 -O-␤-d-glucopyranoside, EL3, EL4, EL5 and EL7 were five of these compounds have been purified and characterized
obtained and identified from Epimedium grandiflorum (Miyaes from Epimedium grandiflorum, comprising ikarisoside C1 (amor-
et al., 1987a, 1988). In 1991, ikarisoside E4 , ikarisoside E5 , phous powder), ikarisoside C2 (amorphous powder), ikarisoside C3
dihydrodehydrodiconiferyl alcohol-4 glucoside, (+)-lyoniresinol- (amorphous powder) and ikarisoside C4 (amorphous powder) and
3-O-xyloside, (−)-lyoniresinol-3-O-xyloside, EL6 and EL8 were icariside F (Miyaes et al., 1987b).
isolated from Epimedium diphyllum (Miyase and Ueno, 1991).
Ikarisoside E6 , ikarisoside E7 , icariol A1 , icariol A2 , 3, 5- 4.7. Other compounds
demethoxy-syringaresinol-glucoside, (−)-olivil, EL1, EL2, EL9 and
(+)-dihydro-dehydrodiconiferyl alcohol-4-O-␤-d-glucopyranoside A range of other compounds has also been isolated from
were isolated from Epimedium sagittatum (Sieb. & Zucc.) Maxim. Epimedium plants along with the above-mentioned constituents,
(Matsushita et al., 1991; Wang et al., 2007). In addition, (+)- including acids, alkaloids, xanthones and aldehydes. In 1988,
cycloolivil was isolated from Epimedium diphyllum, Epimedium Miyaes et al. isolated three new glycosides, ikarisoside F1 , ikariso-
koreanum and Epimedium brevicornum (Miyase and Ueno, 1991; side F2 and ikarisoside G1 , together with two known glycosides,
Zheng and Kong, 2002; Yang et al., 2009b). (Z)-3-hexenyl glucoside and phenethyl glucoside, from the water
extract of Epimedium grandiflorum. Icariside H1 and 1,2-bis-(4-
4.3. Ionones hydroxy-3-methoxyphenyl)-propane-1,3 diol were also isolated
from Epimedium grandiflorum in the following year (Hiroyuki et al.,
Twelve ionones and their derivatives were isolated and iden- 1991). ␤-Hydroxy benzoic acid, 2,4-dihydroxy benzoic acid, mal-
tified from the genus Epimedium. Ikarisoside B1 , an amorphous tol, emodin, daucosterol, insistol, icariside A1 , magnoflorine
powder, was obtained from an extract of the aerial parts of and 1,2,3,4-tetrahydro-3,7-dihydroxy-1-(4-hydroxy-3-
Epimedium grandiflorum and Epimedium diphyllum and identified by methoxyphenyl)-6-methoxy-2,3-naphthalenedimethanol were
chemical and spectroscopic evidence (Miyaes et al., 1987b; Miyase obtained from Epimedium koreanum Nakai. In 2006, seven
and Ueno, 1991). Ikarisoside B2 , which forms colorless needles (mp compounds, aseicosanol, octadecylic acid, 20-hydroxydammar-
172.5–174.0 ◦ C), was isolated from aerial parts of Epimedium gran- 24-en-3-one, artonin U, ␤-sitosterol, daucosterol and ␥-sitosterol,
diflorum, Epimedium sagittatum and Epimedium diphyllum (Miyaes were isolated from Epimedium dewuense. ␤-Sitosterol was also
et al., 1987b; Matsushita et al., 1991; Miyase and Ueno, 1991); isolated from Epimedium sagittatum (Sieb. & Zucc.) Maxim.,
ikarisoside B3 (colorless needles), ikarisoside B4 (amorphous pow- Epimedium leptorrhizum and Epimedium brevicornum. (7R,
der), ikarisoside B5 (amorphous powder), ikarisoside B6 (colorless 8S)-4, 9-dihydroxyl-3,3 -dimethyoxyl-7,8-dihydrobenzofunan-
needles, mp 143–144 ◦ C), ikarisoside B7 (colorless needles, mp 1 -propanolneo-lignan-9 -O-␣-l-rhamnopyranoside, (7R,8S,8 R)4,
202–203 ◦ C), ikarisoside B10 , blumenol C glucoside and roseside 4 ,8 ,9tetrahydroxyl3,3 -dimethyoxyl7,9 -monoepoxylignan,
were obtained from aerial parts of Epimedium grandiflorum (Miyaes p-hydroxybenzaldehyde, succinic acid, p-hydroxyphenethyl,
et al., 1987a; Miyaes et al., 1988; Miyase and Ueno, 1991). Ikariso- 1,3,5,8-tetrahydroxy xanthone, 1-hydroxy-1,3,5,8-tetrahydroxy
side B8 and ikarisoside B9 were isolated from aerial parts of xanthone, ␤-methoxyphenol and behenic acid were isolated from
Epimedium sagittatum (Hiroyuki et al., 1991), and ikarisoside B8 was Epimedium brevicornum. In addition, 2-phenoxychromones, p-
also obtained from Epimedium diphyllum (Miyase and Ueno, 1991). coumaric acid and chlorogenic acid were purified and characterized
from Epimedium sagittatum (Sieb. & Zucc.) Maxim.

4.4. Phenol glycosides 5. Methods of quality control

In 1987, Miyaes et al. first isolated a phenol glycoside, ikarisoside Flavonoids are thought to be the major active components in
A1 (colorless needles, mp 220–222 ◦ C), from Epimedium grandiflo- Epimedium. The major flavonoid compounds icariin, epimedin A,
rum (Miyaes et al., 1987b). In 1988, 1989 and 1991, Miyaes et al. epimedin B, and epimedin C are frequently used as quality con-
obtained five more of these compounds, ikarisoside A2 (amor- trol markers for Epimedium and its medicinal extracts (Table 5)
phous powder), ikarisoside A3 (amorphous powder), ikarisoside (Liu et al., 2006a). In 2003, icariin and epimedin C from four
A4 , ikarisoside A5 and ikarisoside A6 , from Epimedium grandiflorum samples of Epimedium brevicornum Maxim., Epimedium sagittatum
(Miyaes et al., 1988; Miyase et al., 1989; Miyase and Ueno, 1991). In (Sieb. & Zucc.) Maxim., Epimedium pubescens Maxim and Epimedium
addition, icariside A7 and epimedoicarisoside A were isolated from koreanum Nakai were analyzed by high-performance liquid chro-
Epimedium koreanum (Sun et al., 1995b; Li et al., 1995b). matography (HPLC) to determine the differences between the
 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541 531

Table 5
Main compound content in some Chinese Epimedium species.

Plant Icariin Epimedin B Epimedin C Sagittatoside B Baohuoside I Totally

Epimedium sagittatum Trace–1.34 Trace–0.78 0.07–4.02 0.05–0.80 0.06–0.33 0.67–7.07

Epimedium brevicornu 0.63–1.18 0.17–2.01 1.09–1.19 0.09–0.11 0.08–0.09 2.76–4.58
Epimedium acuntinatum 0.44–0.86 0.32–1.16 1.65–2.34 0.19–0.93 Trace–0.24 2.89–4.77
Epimedium koreanum 1.55–3.69 0.85–1.24 0.49–0.89 0.25–0.51 0.90–1.04 4.59–7.37
Epimedium pubescens 0.41–1.40 0.74–1.28 1.14–1.76 0.06–0.68 0.12–0.65 3.47–4.77
Epimedium leptorrhizum Trace Trace–0.14 Trace Trace Trace
Epimedium wushanense 0.46–0.64 0.30–0.40 2.88–3.34 0.10–0.28 0.06–0.13 3.80–4.79

Mdideanetph (2010), [Link]

official source herbs listed in the Chinese Pharmacopoeia. In this 6. Biological activity
study, icariin and epimedin C were measured with a Hyper-
sil BDS-C18 column and gradient elution (acetonitrile and water Epimedium pharmacological actions have attracted extensive
containing 0.05% phosphoric acid) at a flow rate of 1.0 ml/min. attention. Orally, Epimedium has traditionally been used to treat
The detection wavelength was 272 nm. The icariin contents of impotence, involuntary ejaculation, sexual dysfunction, weak
Epimedium brevicornum, Epimedium sagittatum (Sieb. & Zucc.) backs and knees, osteoarthritis, postmenopausal bone loss, osteo-
Maxim., Epimedium pubescens and Epimedium koreanum were porosis, arthralgia, mental and physical fatigue, memory loss,
1.71%, 2.24%, 0.73% and 0.83%, respectively. The contents of hypertension, coronary heart disease, bronchitis, chronic hepati-
epimedin C were 1.52%, 0.58%, 0.19%, 1.36% and 2.27%, respec- tis, HIV/AIDS, polio, chronic leukopenia and viral myocarditis. It is
tively (Wang et al., 2003a). Thus, the determination of the major also used to arouse sexual desire.
flavonoids is required for the evaluation of the quality of each In clinics, Epimedium is used to treat osteoporosis, climacteric
species and the control of dosage during clinical studies. So far, period syndrome, breast lumps, hyperpiesia and coronary heart
a variety of methods, including UV spectrophotometry, thin-layer disease. Epimedium also has immunity-enhancing, anti-aging, anti-
chromatography (TLC), HPLC (Ito et al., 1986), micellar electroki- tumor and anti-AIDS pharmacological activities. Consequently,
netic chromatography (MEKC) (Liang et al., 1996), capillary zone Epimedium has enormous potential for research and exploitation.
electrophoresis (CZE) (Liu et al., 2006a), high-performance liquid The major active constituents of Herba Epimedii are flavonoids,
chromatography-diode-array detector fingerprinting (HPLC-DAD) and among them, epimedin A, B, C and icariin are considered
(Xie et al., 2010), high-performance liquid chromatography-mass major bioactive components that make up more than 52% of the
spectrometer/mass spectrometer (HPLC-MS/MS) (Ying et al., 2004), total flavonoids in Herba Epimedii (Zhang et al., 2008a,b,c,d). An
high-performance liquid chromatography-electrospray ionization- overview on the current status of modern pharmacological evalu-
mass spectrometer/mass spectrometer (HPLC-ESI-MS/MS) (Zhao ations is summarized in supplemental Table.
et al., 2008a), pressurized liquid extraction (PLE) and ultra-
performance liquid chromatography (UPLC) method (Chen et al., 6.1. Treatment of sexual dysfunction (aphrodisiac, kidney tonic)
2008), have been used to further study the flavonoids in
Epimedium. Epimedium plants are able to boost sexual activity by enhancing
The interactions of multiple chemical compounds may con- sexual arousal, increasing vitality and improving sperm counts in
tribute to the therapeutic effects of Chinese medicine. Therefore, vitro and in vivo. For a long time, this remedy has been used to cure
the analysis of multiple components is necessary to control the erectile dysfunction and other impotence conditions. The plants are
quality of medicines. In 2007, a reliable PLE and HPLC method also able to increase a man’s power and sexual desire as well.
mentioned above was developed for the simultaneous determi- Many extracts of Epimedium plants have traditionally to rein-
nation of 15 flavonoids, namely icariin, epimedin A, epimedin force the Kidney Yang, to treat “coldness” and male impotence (Li,
B, epimedin C, hexandraside E, hexandraside F, epimedoside 1991). For example, Epimedium sagittatum has been used to treat
C, baohuoside I, baohuoside II, baohuoside VII, caohuoside C, erectile dysfunction since the Han dynasty (202 bc–ad 220). Mod-
sagittatoside A, sagittatoside B, 2 -O-rhamnosyl icariside II and ern pharmacological studies have shown that phosphodiesterase-5
kaempferol-3-O-rhamnoside, in different species of Epimedium. (PDE-5) is the target protein for inhibition to treat erectile dysfunc-
The analysis was performed with a Zorbax SB-C18 analytical col- tion, and the major compounds of the herbs exhibited an inhibiting
umn (250 mm × 4.6 mm, 5 ␮m) with a gradient elution of water effect on PDE-5, based on the ligand–protein interaction observed
and acetonitrile and diode-array detection (270 nm). All of the cal- a reliable multiple linear regression model (Chen, 2009). Intracav-
ibration curves showed good linearity (r2 > 0.9997) within the test ernous administration of 300–10,000 ␮g Epimedium brevicornum
ranges (Chen et al., 2007a,b). In 2008, a rapid ultra-performance extract induced a penile erection in the rat, as measured by a signif-
liquid chromatography (UPLC) method was developed for the icant increase in the intracavernous pressure (ICP) to 99.7 ± 0.3 mm
simultaneous determination of the above 15 flavonoids in 17 Hg. Nitric oxide may be involved in this penile erection-inducing
species of Epimedium. The analysis was performed on Waters effect. No central nervous system effect of the extract appears to
Acquity UPLC system with an acquity UPLC BEH C18 column be present in the elicitation of penile erections in the rat (Chen and
(50 mm × 2.1 mm, 1.7 ␮m) and gradient elution of 50 mM acetic Chiu, 2006).
acid aqueous solution and acetonitrile within 12 min (Chen et al., Epimedium extracts possess a male-hormone-like effect. Intra-
2008). In 2010, an efficient and new method was developed to gastric administration of an Epimedium decoction to rats, at a dose
enrich and identify the prenyl flavonoid glycosides and phenolic of 2.0 mg/kg body weight (bw) for 14 days, markedly improved
acids of Epimedium using UPLC combined with quadrupole time- sexual function, increased the weight of attached genitals and
of-flight mass spectrometry (UPLC–Q-TOF-MS) and a “click oligo raised the content of testosterone in the plasma (Wang et al.,
(ethylene glycol)” (Click OEG) column. In this method, MS com- 2001). The effect of glycosides from Epimedium grandiflorum on
bined with selective enrichment provided a powerful means for the growth of guinea pigs was investigated in vivo. The glyco-
analyzing prenyl flavonoid glycosides and phenolic acids in natural sides from Epimedium grandiflorum (5 g/kg) were fed to Netherlands
products (Wang et al., 2010a,b). guinea pigs for eight weeks, and the body weight and testicular
532 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541

growth of the animals as well as the sperm density and viability The IC50 of icariin on PDE5 was 0.432 ␮mol/l and on PDE4 was
in the epididymis and vice-testis viability were observed and mea- 73.50 ␮mol/l. Epimedium also contains essential trace elements,
sured. The administration of glycosidic fraction from Epimedium such as zinc, manganese and iron. These elements are implicated in
grandiflorum, at dosage of 5 g/kg for 8 weeks strongly increased male reproductive function and the development of human genitals
the weights of the whole animal as well as those of the testicles, (Song et al., 1993).
epididymis, adenohypophysis and seminal vesicles. The adminis- Like the drugs Viagra and Cialis, Epimedium may increase libido
tration of this glycosides fraction stimulated the sensory nerves and and improve erectile function through a variety of mechanisms,
generated specific physiological signs of sexual arousal (Luo, 1998). such as increased energy and increased production of testosterone
Intragastric administration of the total flavonoids from Epimedium and sexual hormones.
brevicornum, at a dose of 150.0 mg/kg bw for 7 days, significantly
increased the weight of the anterior pituitary gland, epididymis 6.2. Effect on bone metabolism
and seminal vesicles in juvenile rats, raised the testosterone, estra-
diol and luteinizing hormone levels and promoted testosterone Epimedium has been one of the most frequently used herbs in
secretion in rat stromal cells. These results indicated that the total the prevention and treatment of osteoporosis in TCM. Experimen-
flavonoids of Epimedium brevicornum promote the male repro- tal studies have shown systematic activities of Epimedium and its
ductive system and reproductive endocrine activities (She et al., metabolites on bone metabolism, such as preventing calcium loss,
2003). The aqueous extract (250 and 500 mg/ml) of Epimedium stimulating the proliferation of osteoblasts, inhibiting bone resorp-
brevicornum improved the superoxide dismutase (SOD) vitality of tion and promoting bone formation.
sperm suspensions, reduced the malondialdehyde (MDA) content
of sperm suspensions, ameliorated the injury of sperm mem- 6.2.1. In vivo tests
branes by reactive oxygen species to some extent and protected The oral administration of total flavonoid extracts of Epimedium
the function of sperm membranes. Thus, Epimedium brevicornum (50–200 mg/kg/day, for one month) to rats with osteoporosis can
significantly protected the structure and function of sperm mem- dramatically improve the femur dry weight, femoral ash weight
branes by improving their SOD vitality and intervening in lipid and the calcium and phosphorus contents of bone, increase trabec-
peroxidation (Yang et al., 2007). Epimedium significantly improved ular bone area and the thickness of the proximal tibia as well as
the symptoms of “Yang-deficiency syndrome” induced by gluco- increase the cortical bone area percentage in the middle section
corticoid and increased testosterone levels and oestradiol levels of the tibia (Ji et al., 2000; Ma et al., 2002a). The active ingredi-
and reduced the level of luteinizing hormone. The results sug- ent of Epimedium, icariin, has been shown to activate the Na-K-ATP
gest that Epimedium facilitates the pituitary gland(s)-glandular enzyme, reduce erythrocyte aggregation and whole-blood viscos-
system (Xu, 1996). The processed product of Epimedium signifi- ity, inhibit vascular smooth-muscle extracellular Ca2+ influx and
cantly increased the level of testosterone in the plasma of mice and peripheral vascular expansion, increase blood flow and improve
promoted the proliferation and secretion of testicular tissues. This the structure and function of bone tissue.
action is similar to that of intramuscular testosterone, but no weight Intragastric administration of 10 ml/kg/day water extract of
reduction of testicular tissue was observed (Niu, 1995). However, Epimedium to rats with degenerated cervical vertebrae improved
Epimedium acuminatum, Epimedium stelluatum, Epimedium fargesii, the calcium and phosphorus contents, increased the activity of
Epimedium franchetii, Epimedium zhushanense and Epimedium leis- the serum alkaline phosphatase, inhibited the formation of osteo-
hanense exhibited higher activities than estradiol on the estrogen phytes, delayed cervical bone degeneration and prevented the
receptors ERa (mean relative efficacy: 1.58 ± 0.25) and ERb (mean degeneration of cervical bone (Zhao and Xu, 2008). Administra-
relative efficacy: 0.55 ± 0.20) (Shen et al., 2007). tion of a lyophilized aqueous extract of Epimedium at a dose of
In young mice, icariin has gonadotropin-like and male hormone- 500.0 mg/kg body weight (bw) to castrated male rats for 12 weeks
like effects; it significantly promotes the growth of the epididymis significantly increased the bone mineral density (P < 0.05), osteo-
and seminal vesicles. This finding provides a prospect for the protegerin level (P < 0.05) and decreased the microcrack percentage
treatment of male infertility caused by low testosterone levels. In per unit trabecular area. Epimedium prevented the loss of bone
addition, researchers also found that icariin increased the weight mass and improve bone structure in castrated male rats (Wang and
of the seminal vesicles in mouse testes as well as promoted basal Liu, 2008). Intragastric administration of 5 g/(kg day) Epimedium to
testosterone secretion and cAMP production in rat Leydig cells. This male rats with Kidney-Yang insufficiency induced by prednisone
result provides a medical basis for the treatment of male infertility induced bone formation and helped rebuild the injured bone by
induced by a low level of testosterone (Tian and Yang, 2004). The increasing the serum BMP-7 content and up-regulating renal and
penile erection-inducing effects of icariin (5 mg/kg) were assessed femoral BMP-7 expression (Zhou et al., 2008).
in rat arteriogenic erectile dysfunction; endothelial nitric oxide In addition, Epimedium promoted the absorption of fracture
synthase (eNOS) expression and the cGMP concentration were used hematomas, cartilage calcification, external callus bridging, callus
as the index of activity. Icariin significantly increased the expres- conversion and growth, lamellar bone emergence, marrow recanal-
sion of eNOS (Tian et al., 2004b) and the concentration of cGMP ization and bone matrix calcification (Hong and Shi, 1999).
within the corpus cavernosum smooth muscle. These two signal-
ing molecules induced the relaxation of corpus cavernosum smooth 6.2.2. Effect on the multiplication and differentiation of the
muscle and lead to the penile erection-inducing effect (Qiao et al., osteoblasts
2002). Icariin at a dose of 30–1000 ␮g/l also directly stimulated Osteoblasts originate from bone marrow stromal cells, which
the granulosa cells to secrete estradiol and, at high doses, pro- have the potential to differentiate into several different lineages,
moted the secretion of corticosterone by adrenal cortex cells to at including osteoblasts, chondroblasts, adipocytes and myoblasts.
high doses, suggesting that the reinforcing kidney and strengthen- Scleroblast is the important functioning cell type in bone formation
ing yang activities of Epimedium are related the direct stimulation and bone re-construction. Currently, alkaline phosphatase (ALP)
of the target gland to secrete hormones (Li et al., 1997a,b). The activity is considered to be the main index of osteoblast func-
inhibitory effects of icariin on PDE5 and PDE4 activities were tion and differentiation and can reflect the maturity of osteoblasts.
investigated by a two-step radioisotope procedure with [(3)H]- Higher ALP activity correlates with greater maturity. When the ALP
cGMP/[(3)H]-cAMP, and the results indicated that icariin showed activity increased, cells tended to proliferate. Type I collagen pro-
dose-dependent inhibitory effects on PDE5 and PDE4 activities. tein is another osteoblast differentiation marker and is also the
 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541 533

main component of bone organic matrix (Rodan and Noda, 1991; pathologic conditions. Parenteral administration of an Epimedium
Lynch et al., 1995; Scutt et al., 1996). solution induced osteoclast apoptosis and inhibited bone resorp-
Studies have shown that the crude extract, total flavonoids and tion in a dose-dependent manner. Further study showed that
main flavonoid constituents from Herba Epimedii stimulate the the Epimedium-treated cells showed shrinkage of cytosol, con-
proliferation of primary osteoblasts (Wang et al., 2002a,b; Han et al., densation of nuclei, breakage of nuclei, dark-stained nuclei and
2003) and osteoblast-like UMR106 cells (Meng et al., 2005; Xie et al., light-stained cytosol (Li et al., 2002b). Total flavonoids (10−4 mol/l)
2005). of Herba Epimedii decreased the numbers of the osteoclasts and
At concentrations of 1–10 mg/l, the total flavonoids of directly inhibited osteoclast resorption activity in vitro (Zhang et al.,
Epimedium pubescens significantly promoted the proliferation of 2004). Further study showed the inhibition effects of flavonoids
osteoblasts and enhanced the extent of mineralized tuberculation on the proliferation of the RAW 264.7 cell line are bidirec-
in vitro (Li et al., 2002a). Further studies have shown the flavonoids tional, depending on their concentrations and chemical structures.
of Herba Epimedii (50 ␮g/ml) promote the osteogenic differenti- Ikarisoside A is a potent inhibitor of osteoclastogenesis in NF-␬B
ation of human bone marrow-derived mesenchymal stem cells. ligand-stimulated RAW 264.7 cells as well as in bone marrow-
These compounds enhanced the mRNA expression of BMP-2, BMP- derived macrophages. Ikarisoside A (2.5–20 ␮M) decreased the
4, Runx2, ␤-catenin and cyclin D1 (Zhang et al., 2010). expression of osteoclast-specific genes, such as matrix metallopro-
Polysaccharides from Epimedium significantly increased the teinase 9, tartrate-resistant acid phosphatase, receptor activator of
rates of cell proliferation and DNA synthesis in cultured mouse NF-␬B (RANK) and cathepsin K. These data indicate that ikariso-
bone-marrow cells (Liu et al., 1991). The serum from old male side A has potential use in the treatment of diseases involving
rats that were continuously fed the water extract of Epimedium abnormal bone lysis, such as osteoporosis, rheumatoid arthritis and
(1, 2 g/ml) for one month promoted the proliferation and differen- periodontal bone erosion (Choi et al., 2010). Icariin at the concen-
tiation of newborn rat calvarial osteoblasts. These results suggest trations of 100 and 50 ␮mol/l significantly inhibited the formation
that the promotion of proliferation and differentiation by the water of osteoclast-like cells in rabbit bone-marrow cells induced by
extract of Epimedium may contribute to the generation of a rela- 1,25-(OH)2 D3 . Icariin at concentrations of 100, 50 and 10 ␮mol/l
tively large number of specific factors, such as BMP and leptin (Ma also significantly inhibited the bone-resorbing activity and greatly
et al., 2002b). In addition, Epimedium promoted gonadal secretion suppressed the number and surface area of resorption lacuna. So,
and generated a male hormone-like effect on the proliferation and icariin not only suppressed the bone-resorbing activity of mature
differentiation of osteoblasts. osteoclasts but also inhibited the formation of osteoclast-like mult-
The EtOH extract and the n-butanol fraction (1 × 10−3 mg/ml) inucleated cells, showing that it should be considered as a candidate
from the crude extract of Epimedium brevicornum were found drug for the treatment of bone loss (Zhang et al., 2007c).
to show proliferation-stimulating activity in the osteoblast-like
UMR106 cells. Furthermore, three flavonoid compounds (icariin,
epimedin B and C) isolated from this fraction by an activity-guided 6.2.4. Effect on bone marrow-derived stroma cells
assay also significantly promoted the proliferation of osteoblast- Icariin (0.1 ␮mol/l) improved the proliferation of goat bone
like UMR106 cells. These results suggested that Epimedium marrow-derived stroma cells (BMSCs) by increasing the propor-
brevicornum extracts might have activity against osteoporosis and tion of cells in the S and G2/M phases. However, 100 ␮mol/l icariin
that flavonoids such as icariin might be the active substances that depressed the proliferation of BMSCs, but icariin promoted alkaline
stimulate osteoblasts (Meng et al., 2005). In fact, further studies phosphatase activity and osteocalcin expression in goat BMSCs in
showed that various doses of icariin improved the proliferation and a dose-dependent manner (Wu et al., 2009).
activity of cultured osteoblasts. Especially at a dose of 10 ng/ml,
icariin depressed ALP activity (P < 0.05) in the early stage and 6.2.5. Effect on cartilage growth in vitro
improve ALP activity in the later stage of osteoblast proliferation A crude extract Epimedium brevicornum (0.05–10.00 mg/l)
(Wang et al., 2002a,b). Several trace elements, particularly, man- increased the weight of cartilage (P < 0.01) in a time-dependent
ganese (Mn) and zinc (Zn), are essential in bone metabolism as manner. The length as well as the wet and dry weights of femurs
cofactors for specific enzymes. It has been reported that there cultured with 1.00 mg/l total flavonoids from Epimedium brevi-
is a relationship between osteoporosis and trace-element defi- cornum for seven days was significantly improved. This finding
ciency and the efficacy of Ca, Mn and Zn supplementation on demonstrated that Epimedium brevicornum Maxim can accelerate
spinal bone mineral density in postmenopausal women. Inter- cartilage growth as well as cell proliferation (Feng et al., 2009).
esting, the mineral elements, manganese (Mn), zinc (Zn) and In conclusion of the effect on bone metabolism, the mechanism
iron (Fe), were abundant in Herba Epimedii. The combination of by which Epimedium can act in the prevention and treatment of
10 ␮mol/l Zn, Ca and Mn with icariin and total flavonoids greatly osteoporosis includes the following three points: (1) the promotion
improved cell viability and, meanwhile, dramatically enhanced of osteoblast proliferation and increase in bone formation; (2) the
alkaline phosphatase activity compared to each agent alone. An inhibition of osteoclast-raising activities and decrease in the bone
increased cell growth inhibition was also observed by combining absorption level; and (3) the promotion of collagen synthesis and
0.1 ␮mol/l, 1 ␮mol/l Zn with 10 ␮mol/l icariin and 10 ␮mol/l Mn matrix mineralization in bone stromal cells. In TCM, the kidney is
with 0.06 ␮g/ml total flavonoids. Meanwhile, decreased alkaline believed to be in charge of the bone, and Epimedium was thought to
phosphatase activity was also found with several icariin–Zn/Mn invigorate the kidney and strengthen bones and muscles; now, its
and total flavonoids–Zn/Ca/Mn combinations. These results sug- efficacy in the prevention and treatment of osteoporosis has been
gested that mineral elements greatly enhanced the efficacy of confirmed by clinical studies.
icariin and total flavonoids from Herba Epimedii on the viability
and differentiation of primary osteoblasts in certain combinations
(Zhang et al., 2008a,b,c,d). 6.3. Effect on the immune system

6.2.3. Effect on osteoclastic cells Epimedium has effects on humoral immunity, cellular immunity
Osteoclasts are bone-resorbing cells derived from multipotent and nonspecific immunity. Epimedium and its extracts or ingredi-
myeloid progenitor cells. They play a crucial homeostatic role ents had a considerable effect on the immune organs, immune cells
in skeletal modeling and remodeling and destroy bone in many and immune factors.
534 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541

6.3.1. Effect on the thymus enhanced the activity of LAK cells and acted synergistically with
The thymus, a central immune organ, plays an important role in IL-2 (Meng et al., 1996). At the same time, icariin (10–100 ug/ml)
modulating immune system function. Polysaccharides, icariin and enhanced NK-cell activity and provided a high cytotoxic activity of
related compounds from Epimedium were shown to activate the LAK cells in vitro.
thymus. A methanolic extract of roots and rhizomes of Epimedium
alpinum at low concentrations (0.1 ␮g/ml and 1 ␮g/ml) significantly 6.3.5. Antibody responses
enhanced the concanavalin A induced proliferation of splenocytes The n-butanol fraction of the aerial parts of Epimedium huna-
and thymocytes, whereas higher concentrations of the extract nense and the compound epimedin C significantly enhanced the
(50–500 ␮g/ml) showed inhibition of this process. Further data response of spleen antibody-forming cells (SAFCs) to normal lev-
showed that this effect was correlated with the up-regulation of the els in mice treated with hydrocortisone acetate. They also caused
expression of interleukin-2 receptor ␣ (IL-2R␣) and the increased a significant recovery of interleukin-2 (IL-2) production in these
production of IL-2. Epimedium polysaccharide (10–50 mg/kg) acti- mice. In conclusion, these substances are active components with
vated the thymus and decreased the intrathymic count of L3T4+ and immuno-enhancing effects (Liang et al., 1997). An aqueous extract
Lyt2 cells in mice. At the same time, it enhanced cellular immune of Epimedium koreanum at therapeutic concentrations (40 and
function by promoting the release of mature cells and increasing 120 mg/kg) enhanced the production of antibodies and cytokines
the production of IL-2 in the thymus (Ding et al., 1992). in mice, and this effect was more marked when the mice were
immunized with ovalbumin. This result suggests that the extract is
6.3.2. Effect on macrophages effective on Th-cell functions and protects the host from immune
Epimedium and its crude extract also affect the secretion of diseases (Kim et al., 2001).
macrophage cytokines and regulate immune function. Subcu-
taneous injection of 0.2 and 0.4 ml of an Epimedium-Propolis 6.4. Effect on the cardiovascular system
adjuvant (Epimedium total flavonoids and crude propolis) into 3-
day-old chicks significantly enhanced the phagocytic activities of Experiments showed that Epimedium and the non-amino-
chicken peritoneal macrophages. In mice, 0.4 ml of this prepa- acid components of its alcohol-based extract affected the
ration significantly enhanced the cytotoxic effects on peritoneal heart, blood pressure, blood rheology, and arrhythmia and
macrophages and antagonized the immune inhibition of cyclophos- that they were used to improve the subjects’ myocardial ischemia,
phamide (Hu et al., 1999). The total flavonoids of Epimedium increase coronary blood flow, decrease the heart rate, improve
(400 mg/kg) significantly strengthened the phagocytosing function myocardial ischemia tolerance and cure hypotension and arrhyth-
of the monocyte–macrophage system in normal mice, raised the mia (Mdidea, 2010, [Link]
level of serum hemolysin antibody formation, antagonized the inhi- extract/icariin/[Link]).
bition of monocyte–macrophage phagocytic capacity induced by
cyclophosphamide and reduced serum hemolysin antibody levels 6.4.1. Effect on vessels, blood and heart
as well as the intensity of delayed-type hypersensitivity (Zhang Icariin expands the coronary blood vessels, the femoral artery
and Yu, 1999). Epimedium polysaccharide, icariin and related com- and cerebral blood vessels. It has a direct effect on relaxing vascular
pounds significantly increased the phagocytosis of macrophages, smooth muscle in a non-competitive inhibition manner, signifi-
improved the lymphocyte transformation rate, and promoted the cantly reduces noradrenaline-promoting extracellular Ca2+ influx,
production of interleukin-1 and tumor necrosis factor. and reduces the contraction of the basilar artery. Studies have
shown that icariin increases the cerebral blood flow through the
6.3.3. Effect on T and B lymphocytes expansion of vascular smooth muscle and lowers cerebral vascular
In vitro, the methanolic extract of the leaf of Epimedium resistance to protect the brain from ischemic injury and improve
pubescens markedly inhibited the proliferation of mouse lympho- cerebral ischemia and cerebral hypoxia in laboratory animals (Hou
cytes induced by mitogens and the mixed lymphocyte reaction et al., 2004).
(Wang and He, 1986). In patients with vital energy deficiency, the The water extract of Epimedium sagittatum (Sieb. & Zucc.)
methanolic extract of the leaf of Epimedium sagittatum (Sieb. & Maxim. leaf had a significantly preventive effect on the ventric-
Zucc.) Maxim. significantly enhanced the leukocyte count and the ular fibrillation induced by chloroform in mice and the ventricular
lymphocyte transformation rate (Liu et al., 1985). In maintenance fibrillation induced by calcium chloride in rats. It also had obvi-
hemodialysis patients, Epimedium koreanum significantly increased ous therapeutic effect on the aconitine-induced arrhythmia in rats.
the CD4+ counts and CD4+ /CD8+ ratio (P < 0.05) and improved the An extract of herba Epimedii, at doses of 0.25 and 0.50 mg/ml
TH levels. In the delayed-type hypersensitivity mouse model, the slowed down the heart rate of isolated rat hearts and reduced
total flavonoids of Epimedium koreanum increased the CD4+ level of myocardial contraction while increasing the irrigation flow; thus,
T-lymphocyte subpopulations (Yang et al., 1998). the Epimedium extract showed a protective effect on myocardial
Studies showed that the total flavonoids of Epimedium koreanum ischemia (Guo et al., 2005). Total flavones from Herba Epimedii
reduced the T-cell apoptosis rate, down-regulated the apoptosis (24, 12, and 6 mg/kg) improved the abnormal electrocardiogram
gene FasL and the mRNA expression of TNFR1, up-regulated the J-point of the acute myocardial ischemia model and effectively pre-
apoptosis gene Bcl-2 at the level of mRNA expression and reduced vented the increase of blood viscosity. At doses of 34 and 17 mg/kg,
the abnormally high levels of caspase 8 and caspase 3 activity the total flavones lengthened the coagulation time in mice. These
in corticosterone rat T cells (Shen and Chen, 2002). Epimedium results suggest that the total flavones from Herba Epimedii have
polysaccharides (50 mg/kg) promoted the proliferation and differ- protective effects on ischemic myocardium and improve circulation
entiation of T and B mouse lymphocytes in vitro and in vivo and through the coronary artery (Wang et al., 2007d).
significantly increased the activity of these lymphocytes (Zhang
et al., 1996). 6.4.2. Anti-hypertensive activity
The aqueous extract of Epimedium grandiflorum showed
6.3.4. Effects on NK and LAK cells significant hypotensive activity in normal and spontaneously
The oral administration of the total flavones and polysaccha- hypertensive rabbits (Inokuchi et al., 1984; Inokuchi et al., 1985),
rides of Epimedium at doses of 240 mg/kg for 30 days significantly and efficacy in the treatment of hypertension-complicated coro-
enhanced the activities of NK cells in aged rats; similarly, it nary disease (Yu et al., 1992). The flavonoid glycosides of Epimedium
 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541 535

glandiflorum, at a concentration of 0.13 g/l, reduced blood pressure that icariin at a concentration of 100 ug/ml inhibited the prolifera-
by expanding the coronary blood vessels, the femoral artery and tion of HL-60, a human hepatoma cell line (H7402) and mouse bone
the cerebral vasculature as well as reducing peripheral resistance in marrow mononuclear cell leukemia cells (WEH I-3) in vitro (Zhao
isolated organs and animal models (Xu and Chen, 1994). In addition, et al., 1995).
injection of the total flavonoids of Herba Epimedii into the lateral
ventricles at a dose of 26 mg/kg promoted the secretion of an amino 6.5.3. Anti-tumor diffusion
acid neurotransmitter (r-aminobutyric acid) in the encephalocele Icariin at a concentration of 0.3 uM decreased the adhesion of
periventricular system and enhanced the affinity of GABA for the high metastatic human lung tumor cell lines (PG) to laminin and
GABAA receptors; at the same time, it strengthened the inhibition decreased the cells’ ability to invade or migrate. It reduced the
of the central sympathetic cardiovascular system and decreased expression of CD44V6, LN2R and CK18 in the highly metastatic
blood pressure (Fu et al., 2007). human lung tumor cell line. At the same time, icariin decreased the
expression of c-myc and Tiam-1 mRNA and enhanced the expres-
6.4.3. Anti-arrhythmia effect sion of Nm-3-H1 mRNA at a dose of 0.3 uM. These results suggest
A water extract of Epimedium brevicornum was found to be that icariin may play multiple anti-metastatic roles (Mao et al.,
markedly effective in preventing ventricular fibrillation induced 2001).
by chloroform in mice and ventricular fibrillation induced by
calcium chloride in rats. At the same time, intraperitoneal injec- 6.5.4. Induction of apoptosis
tion of the water extract of Epimedium brevicornum, at a dose of Icariin (0.15, 0.3 and 0.6 uM) induced apoptosis in a time- and
5.0 ml/kg bw, markedly inhibited the arrhythmia induced by aconi- dose-dependent manner in HL-60. It down-regulated the mRNA
tine in rats and obviously inhibited the action potential amplitude and protein expression of the apoptosis-associated genes bcl-2 and
of isolated sciatic nerves in toads, but it did not antagonize the c-myc (Li et al., 1999).
arrhythmia induced by adrenaline in rabbits. The results showed
that the crude extract has obviously protective effect on drug- 6.6. Anti-aging and anti-oxidation effects
induced arrhythmia, which may be related to its inhibition of Na+
or Ca2+ influx (Zeng et al., 2002). Administration of the total flavone Epimedium had obvious anti-oxidation and free radical scaveng-
glycoside of Epimedium koreanum by vena jugularis injection at ing activities; it also affects aging through different mechanisms,
the dosages of 60 mg/kg and 120 mg/kg significantly counteracted in particular by regulating the immune and endocrine systems and
barium chloride-induced arrhythmia in hamsters and adrenaline- improving metabolism and organ function.
induced arrhythmia in guinea pigs. Human embryonic lung diploid fibroblasts of the 2BS national
standard strain were used as an aging model. The effects of
6.4.4. Effect on blood system Epimedium on DNA synthesis of 2BS fusion cells were observed
Experiments on rabbits showed that the total flavonoids of by cell denucleation and cell fusion techniques. In the 0.025 (v/v)
Epimedium reduced the aggregation response of platelets and ery- Epimedium water extract-containing media, 2BS cells could be
throcytes, extending the prothrombin time, lowering whole-blood continuously cultured for 56.0 ± 2.6 passages, while in the con-
viscosity and inhibiting thrombosis (Gao, 1992a,b). Icariin pro- trol group, only 49.0 ± 2.6 passages could be achieved (P < 0.01).
moted blood-cell proliferation, differentiation and maturation and After treatment with Epimedium water extract for 2 h, the aging
plays an important role in hematopoietic function in the body. 2BS cells were denucleated and fused with young 2BS cells. The
[3H]TdR incorporation percentage in these treated cells was sig-
6.4.5. Angiogenesis effect nificantly higher than that in the untreated control cells (P < 0.01)
Studies have found that Epimedium sagittatum (Sieb. & Zucc.) (Wu et al., 2003b). With the increase in age, the mean level of
Maxim. has an angiogenic effect. Extracts of Epimedium sagittatum phosphorylation of p65, I␬B␣ and I␬B␧ in rat spleen lymphocytes
(Sieb. & Zucc.) Maxim. stems and leaves at a dose of 1 g herb D.W./ml decreased obviously, while intragastric administration (0.06 g/kg)
stimulated tiny blood vessels and showed a strong promotion of of Epimedium koreanum flavonoids activated the Rel/NF-␬B fam-
angiogenesis activity both in vitro and in vivo (Wang et al., 2004). ily and the increase the phosphorylation of p65, I␬B␣ and I␬B␧.
The results showed that Epimedium flavonoids had strongly up-
6.5. Anti-tumor effects regulated the expression of these proteins during aging (Liu et
al., 2008). In addition, intragastric administration of a mixture
6.5.1. Induction of tumor-cell differentiation of polysaccharide and total flavonoids from Epimedium to rats
Icariin (62.5,125, 250 mg/l) showed inhibitory effects on the for 60 days at doses of 30, 60, 120 mg/kg day significantly raised
human promyelocytic leukemia cell line HL-60 after a 12-h incu- the levels of the monoamine neurotransmitter NE, DA and 5-
bation. At the same time, at dosage of 100 mg/l, it increased the hydroxyindoleacetic acid in the hypothalamus of aging rats and
reduction of Nitro Blue Tetrazolium Chloride (NBT) and the mean also inhibited the activities of AchE in both brain tissues and
optical density (MOD) after a 48-h incubation. The nuclei of HL- whole blood in mice. Noradrenergic (NE), dopamine (DA) and
60 cells became rod-shaped or lobulate, and the nuclear volume 5-hydroxyindoleacetic acid promoted the ability to learn and
decreased. Further studies showed that the induction of differen- remember. The experiments showed that Epimedium delayed nat-
tiation in HL-60 cells might be related to an elevated cAMP/cGMP ural senescence in animals (Meng et al., 1996).
ratio (Zhao et al., 1996a,b; Zhao et al., 1997). Intragastric administration of fats infused by Epimedium brevi-
cornum at a dose of 0.5 g/kg/day for 8 weeks reduced mitochondrial
6.5.2. Inhibition of tumor-cell proliferation DNA deletion in heart, brain and skeletal muscles in the aged
Different alcohol extracts of Herba Epimedii had antiprolifera- rat; the same treatment increased adenosine triphosphate (ATP)
tive activities in human breast cancer cells in vitro. The 95% EtOH synthesis in the mitochondria of brain, heart and skeletal mus-
extract of Herba Epimedii significantly inhibited the proliferation of cles as well as enhanced mitochondrial respiratory chain complex
the MCF-7 human breast cancer cell line at doses of 100–800 ␮g/ml; enzyme I and II activities in skeletal muscle, brain and heart. These
the 70% alcohol extract showed a certain antiproliferative activity, results indicated that Epimedium protected mitochondrial DNA
whereas the 20% and 40% alcohol extracts showed no significant from oxidative damage in aged rats (Wang et al., 1996). The polysac-
antiproliferative activity (Cheng et al., 2007). Studies also showed charide liposomes of Epimedium wushanense at a dose of 30 mg/kg
536 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541

bw significantly increased super oxide dismutase (SOD) enzyme sorbitol dehydrogenase and resulted in a 76% protection from tox-
complex and glutathione peroxidase (GSH-Px) activity in organs icity at concentrations ranging from 1 ␮M to 20 ␮M (Lee et al.,
and blood, reduced the LPO content in the serum and liver tis- 1995).
sues of aging animals and reduced lipofuscin in the myocardium
of aging animals (Zeng et al., 1997). In an isolated culture of 7. Clinical studies
hepatic tissue, the total flavonoids from Epimedium were able
to restrain the oxygen level of liver homogenate and mitochon- The clinical effects of preparation from Epimedium for ED
dria oxidated spontaneously or inductively by VitC-Fe2+ with an (Liu, 1990), high blood pressure, coronary heart disease (Yu
IC50 of 34.87 ␮g/ml, 70.34 ␮g/ml, 198.45 ␮g/ml, and 332.65 ␮g/ml, et al., 1989) have been studied. The useful and anthoritatively
respectively. Moreover, this effect was predominant in eliminat- clinical studies were very limited and most of these preparations
ing free radicals, including DPPH, • OH and • O2− with an IC50 were made of the rude extraction from Epimedium alone or with
4.67 ␮g/ml, 598.17 ␮g/ml and 413.21 ␮g/ml, respectively. So the other herbals and most of these studies were designed very
total flavonoids from Epimedium were effective against oxidation simple. Recently, we are very interesting to see some reports
in vitro (Zhao et al., 2009). In addition, the N+ of magnoflorine in Internet. A double-blind clinical trial relating to the effect of
magnoflarine from Epimedium attracted the hydroxyl radical and Epimedium Herbal Complex Supplement on sexual satisfaction in
reduced the reactivity of • OH, so it had a protective effect on the healthy men was compared with Viagra. In the study, 25 healthy
normal function of the cell membrane (Niu et al., 2000). men and 13 men who used Viagra were assigned to initially
receive daily therapy for 45 days, and it is said daily use of this
6.7. Anti-hypoxia and anti-fatigue effects herbal complex for a minimum of 45 days resulted in a more
enhancement of sexual satisfaction than Viagra (Mdideanet,
The total flavonoids from Epimedium have shown significant 2010, [Link]
anti-hypoxia activity in normobaric hypoxia models. Intragastric [Link]).
administration of the total flavonoids from Epimedium (300, 600,
900 mg/kg) to mice prolonged the survival time of the normobaric
hypoxic mice, lessened encephaledema and pneumonedema and 8. Processing
raised the contents of hemoglobin and leukocytes (Zhang et al.,
2009). Oral administration of the total flavonoids of Epimedium, at In China, Epimedium was traditionally prepared by stir-frying
a dose of 500 mg/kg bw for 14 days, significantly prolonged the time in oil or suet. This method was claimed to produce a synergistic
of weight-bearing swimming and decreased the creatinine and urea effect on promoting sexual function (Xu et al., 1985). In Cui et al.
nitrogen levels in mice sera (Ma et al., 2009). (1996) designed a new technology to preserve the ingredients of
Epimedium and induce the synergistic effect of suet. In this method,
6.8. Anti-inflammatory, anti-virus and anti-bacterial activities 20 g suet was melted to 60 ◦ C, and then 100 g Epimedium leaf was
added and stir-fried for 10 min at 60 ◦ C. The finished product was
The total flavonoids of Epimedium significantly reduced the PGE light yellow-green, and the oil was light. The product processed by
and MDA levels, increased the vitality of erythrocyte catalase in this method had a higher icariin content and greater efficacy for
mice, inhibited the ear swelling and granulation tissue hyperblas- improving sexual desire and performance.
tosis induced by croton oil and induced the capillary permeability
induced by intraperitoneal injection of acetic acid (Palmer, 1914). 9. Side effects and acute toxicity
So we thought the anti-inflammatory properties of Epimedium
plants may contribute to their local and traditional use in rheuma- Epimedium, as a traditional Chinese herbal medicine, has been
tism. used for 2000 years as a aphrodisiac in China. Although it is listed
The total flavonoids of Epimedium significantly inhibited as a food and a medicine, investigation of its relative systematic
poliovirus and enterovirus. In addition, the flavonoids had toxicity and safety evaluations have been lacking, and no major
inhibitory effects on Micrococcus pyogenes var. albus, Staphylococcus side effects have yet been discovered. In 2006, the safety of the
aureus, Diplococcus pharyngis communis, Micrococcus catarrhalis and water extract of Herba Epimedii was evaluated in terms of its acute
Haemophilus influenzae. Clinical studies showed that the compound toxicity and cellular toxicity. Experiments including the mice bone
preparation made from Epimedium and radix Morindae officinalis marrow micro-nuclear test, the Ames test and the TK gene muta-
at the dose of 0.5 ml/kg could lower the level of viremia and tion experiment were performed. It was found that Herba Epimedii
had a positive effect on asthma in young children, especially for did not have mutagenic effects and that its LD50 was higher than
asthma caused by viral infections (Fang et al., 2003). Icariin, a major 80 g/kg. Its IC50 in Chinese hamster ovary cells and Chinese hamster
8-isoamyleneflavonol glycoside in the genus Epimedium, notably lung cells was 55.4 and 19.53 mg/ml, respectively, and all toxicity
inhibited the activities of food pollutant bacteria, with MICs of tests were negative (Sui et al., 2006). In 2007, the acute toxicity
0.23% for Aspergillus sp, 0.12% for Escherichia coli and Staphylo- of the total flavonoids of Epimedium were measured by intragas-
coccus aureus, and 0.05% for Bacillus subtilis, Penicillium sp and tric administration to NIH mice at a dose of 36 g/kg/day for 7 days.
Hansenula sp (Yan and Qiu, 2005). The anti-inflammatory, antiviral This dosage was equal to 1440 times the normal human dosage,
and antibacterial effects of this commonly used plant might be new and no mouse deaths were observed (Li et al., 2007b). The long-
hot spots for pharmacological studies in the following years. term toxicity of the total flavonoids of Epimedium was investigated
in a normal Wistar rat model by intragastric administration of the
6.9. Hepatoprotective extract, at the dosage of 410 g/kg/day for 12 weeks. No significant
differences were found in treated rats for any blood parameter ana-
The anti-hepatotoxic activity of Icariside II was evaluated by lyzed (including aspartate aminotransferase and the antioxidant
measuring the activity of glutamic pyruvic transaminase in CCl4 - enzymes glutathione peroxidase and superoxide dismutase), and
intoxicated primary cultured rat hepatocytes, and a concentration no major pathology changes were seen (Li et al., 2008).
of 200 ␮M resulted in a 78% reduction of the toxicity (Cho et al., In short, there are no known warnings or contraindications
1995). Icariin, another major flavonol glycoside in Epimedium, sig- for the use of Epimedium plants, and the ideal dosage is not
nificantly reduced the levels of glutamic pyruvic transaminase and known. Capsules or tablets are sold in various doses, ranging from
 H. Ma et al. / Journal of Ethnopharmacology 134 (2011) 519–541 537

250 to 500 mg. In very high doses, they may have a stimulatory China Herb Compilation, 1975. China Herb Compilation [M]. People’s Medical Pub-
effect and may cause sweating or feeling hot. In animal studies, lishing House, Beijing, pp. 729–730.
Cho, N.J., Sung, S.H., Lee, H.S., Jeon, M.H., Kim, Y.C., 1995. Anti-hepatotoxic activ-
prolonged use of excessive amounts of Epimedium was associated ity of Icariside II, a constituent of Epimedium koreanum. Archives of Pharmacal
with decreased thyroid activity (Mdideanetp, 2010, [Link] Research 18, 289–292.
[Link]/products/herbextract/icariin/[Link]). Regret- Choi, H.J., Eun, J.S., Park, Y.R., Kim, D.K., Li, R.H., Moon, W.S., Park, J.M., Kim, H.S.,
Cho, N.P., Cho, S.D., Soh, Y.J., 2008. Ikarisoside A inhibits inducible nitric oxide
fully, many products are standardized by their active icariin synthase in lipopolysaccharide-stimulated RAW 264.7 cells via p38 kinase and
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Cui, X.Y., Ma, Y.L., Kong, Q., Xing, Y.P., Zhang, L., 1996. Study on the processing
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In CTM, the kidney is alleged to be crucial for sexual and bone Ding, Y., Xin, S.T., Zhou, J.H., 1992. Effect of Epimedium polysaccharide on the transfer
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Dong, X.P., Xiao, C.H., Zhang, R., Li, W., 1994. Study on chemical components of
to tonify the kidneys and invigorate the yang. Modern in vitro Epimedium acuminatum. China Journal of Chinese Materia Medica 19, 614–615.
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Epimedium species. Phytochemistry 27, 259–266.
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Gao, Q.M., 1992a. Effects of total flavonoids of Epimedium on platelet in rabbits and
present in the genus, especially 8-prenylflavonoids. sedative-hypnotic and endurance capacity in mice. Northwest Pharmaceutical
Phytochemical and pharmacological studies of the compounds Journal 3, 15–17.
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mostly been performed in vitro and in vivo with animals. There- of Epimedium fargesii Franch. China Journal of Chinese Materia Medica 21,
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Guo, B.L., Li, W.K., Yu, J.G., Xiao, P.G., 1996b. Brevicornin, a flavonol from Epimedium
traditional phytotherapy. The constituents of this genus as well as brevicornum. Phytochemistry 41, 991–992.
their pharmacological and toxicity profiles should be further inves- Guo, B.L., Yu, J.G., Xiao, P.G., 1996c. Chemical constituents from the aerial part of
tigated with both in vitro and in vivo studies. In addition, taking Epimedium brevicornum Maxim. China Journal of Chinese Materia Medica 21,
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Guo, J., Li, F., Wu, Q., Gong, Q., Lu, Y., Shi, J., 2010. Protective effects of Icariin on brain
especially sexual dysfunction, osteoporosis and immunity-related
dysfunction induced by lipopolysaccharide in rats. Phytomedicine 12, 950–955.
diseases. Han, B., Shen, T., Liu, D., Yang, J.S., 2002a. Study on chemical components of
Epimedium leptorrhizum. Chinese Pharmaceutical Journal 37, 740–742.
Han, B., Shen, T., Ju, J.H., Yang, J.S., 2002b. Study on chemical components of
Appendix A. Supplementary data Epimedium leptorrhizum. Chinese Pharmaceutical Journal 37, 333–335.
Han, L.M., Liu, B., Xu, P., 2003. Influence of Herba Epimedii flavone on proliferation
of osteoblast. Shanghai Journal of Traditional Chinese Medicine 37, 55–57.
Supplementary data associated with this article can be found, in Hong, D.G., Shi, G.D., 1999. The influence of Herba Epimedii on fracture healing:
the online version, at doi:10.1016/[Link].2011.01.001. a histological and histomor phometrical study. Journal of Traditional Chinese
Orthopedics and Traumatology 11, 4–6.
Hou, J.R., Seng, J.M., Wang, X.Q., Tian, Y.X., Wu, G.J., 2004. Advances in studies on
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