What Are the Types of Epimedium?

Epimedium is a perennial medicinal plant in the Berberidaceae family (Epimedium L). It has been used as a tonic in traditional Chinese medicine for more than 2,000 years, and is one of the most widely used and time-honoured Chinese medicinal herbs. There are 43 species of Epimedium in China, which is the modern geographical center of the genus. There are about 56 species of the genus worldwide [2]. The Chinese Pharmacopoeia has a collection of five species of Epimedium [3].

It is a traditional Chinese tonic herb with the effects of tonifying the kidney yang, strengthening the muscles and bones, and dispelling rheumatism. It has significant efficacy for impotence, spermatorrhea, weak muscles and bones, numbness and cramps in the hands and feet, menopausal hypertension, cardiovascular and cerebrovascular diseases, as well as improving the body's immune system and anti-tumor effects [4], so it has great research and development prospects. In recent decades, researchers have conducted in-depth studies on the plant morphology and classification, geographical distribution, chemical composition, pharmacological effects and quality evaluation of Epimedium. The author summarizes the research progress of Epimedium in recent years.

1. The geographical distribution of Epimedium plants and the distribution of medicinal species

1.1 The geographical distribution of Epimedium plants

Epimedium plants are mainly distributed in the forest undergrowth, thickets or damp areas of the China-Japan forest plant subregion and the China-Himalaya forest plant subregion, at an altitude of 200–3700 m [5]. China is the geographical center of Epimedium plants, which are mainly distributed in Sichuan, Chongqing, Guizhou and the northeastern provinces and regions, with a small number also distributed in other southern provinces and regions.

1.2 Main medicinal Epimedium distribution

1.2.1 Epimedium

It is mainly distributed in Shaanxi, Shanxi, southern Gansu Province, eastern Henan and Gansu provinces, as well as Qinghai, Sichuan, Ningxia and other provinces. It grows in thickets at an altitude of 650 to 2100m or in relatively shady and humid areas [6].

1.2.2 Epimedium sagittatum

is one of the most widely distributed species in the genus Epimedium. It is mainly distributed in the provinces of East China and South China (except Shandong Province), while Hunan, Hubei, Sichuan, Guizhou, and Shaanxi provinces only have a small area of distribution. It grows at an altitude of 200–1300 m under sparse forests, in thickets, or along the edges of ditches.

1.2.3 Korean Epimedium

In addition to its distribution in China, it is also found in Japan and northern Korea [1]. In China, it is mainly distributed in the eastern part of Jilin Province and the eastern part of Liaoning Province. It is also found in small quantities in Heilongjiang Province in the area bordering Jilin, growing in the shade of forests or among thickets at an altitude of 200 to 900 meters [6].

1.2.4 Pilose Epimedium

It is mainly distributed in southern Shaanxi, northern to central and western Sichuan, the northwestern corner of Hubei, and the southernmost tip of Gansu, where it is also found in small quantities. It grows in the undergrowth, under the forest canopy, on mountain slopes or in shady, damp places in mountain valleys at an altitude of 300–2000 m [6].

1.2.5 Wushan Epimedium

It is distributed in two separate areas: one is in eastern Sichuan, northern Chongqing, southern Shaanxi, and a small amount is also distributed in western Hubei; the other is in southeastern Guizhou and a small amount is also distributed in northern Guangxi. The distribution area is relatively narrow. Currently, there are clear distribution records in Nanchong City and Cangxi County in Sichuan, Wanyuan County and Wushan County in Chongqing, Ankang City, Pingli County and Zhenping County in Shaanxi, Leishan County, Dushan County, Congjiang County, Sandu, Kaili County and Taijiang County in Guizhou. It grows in the grassy thickets on the slopes of mountains at an altitude of 750–1300 m [6].

1.2.6 Hairy Epimedium

is mainly distributed in the whole province of Guizhou, Chongqing City, central and southern Sichuan, northeastern Yunnan, western Hubei and northern Guangxi. Hairy Epimedium grows in the thickets, under the forest and along the ditches at an altitude of 290–2100 m [6].

2 Chemical composition research

At present, more than 130 chemical components have been isolated from plants in the Epimedium genus. The main medicinal ingredients are flavonoids and polysaccharides, in addition to alkaloids, lignans, palmitic acid, stearic acid, oleic acid, linolenic acid, phenyl glycosides, iridoids, ethanol glycosides, etc. [7]; it also contains trace elements such as Zn, Cu, Ca, Mn, Sr, and Ni [8].

2.1 Epimedium

In recent years, Li Yubo et al. [9] conducted research on the aboveground parts of the Epimedium plant and isolated and identified five compounds: hyperoside (Ⅰ), icariin (Ⅱ), epimedium B (Ⅲ), epimedium C (epimedin C, Ⅳ) and inositol (inositol, Ⅴ).

2.2 Korean epimedium

Cheng Yan et al. [10] isolated eight compounds from a Korean epimedium water extract: icariin (1), baohuoside ( 2), sagittatoside B (sag itta toside B, 3), baohuoside (baohuoside, 4), astragalin (5), etc. Some researchers have also isolated four compounds from Korean epimedium: Korean epimedium, epimedokoreanoside I, icariin and icariside II [11]. In addition, phenyl glycoside components have been discovered in Icaris from North Korea in recent years, namely icariside A7, 2-hydroxy-3,4,6,7-tetrahydroxy-9,10-dihydroxyphenanthrene [12]; a new alkaloid called icariside A has also been discovered.

2.3 Hairy Epimedium

Three flavonoids, icariin II, icariside A and icariside, were isolated from hairy epimedium [13]. Jia Xiansheng [14-15] also isolated four compounds from the root of Epimedium brevicornum: epimedoside A, 2“-rhamnosylicarioxanthin II, 2”-rhamnosylepimedoside A and epimedoside B. Four compounds were partially isolated from n-butanol: epimedoside A, epimedoside B, epimedium C, and epimedium C4.

2.4 Sagittaria sagittifolia

Isoquercetin, Icariin-3-O - α-rhamnoside, Hyperin, Sagittaria sagittifolia glycosides Sag itta toside A -C, Sagittaria sagittifolia flavonoids such as sagittaria sagittifolia flavone, 6-demethyl-7-methylchromanone, 6-demethyl-4'-methyl-8-prenylchromanone, 6-demethyl-7-prenylchromanone, and sagittaria sagittifolia flavone [16].

2.5 Wushan horny goat weed

Wushan horny goat weed is separated from the whole plant and contains wanepimedoside A, baohuoside 2-I, baohuoside 2-II, Bao-huo-side Ⅵ, 8-P reny lkaemp ferol-4′-methy lether-3- [xy-losy l (1→ 4) rhamno-side] -7- g lucoside, Rou- huoside, Rhamnosyl icariin-Ⅱ, Jian-huoside B, flavonoid components such as icariin F, icariin C, icariside II, icariside B.

2.6 thalictoside

A phenol glycoside compound was isolated from the above-ground parts of Qianling Epimedium: P -nitrophenylethyl phenol -β-D -glucopyranoside.

3 Pharmacological effects and clinical application research of Epimedium plants

3.1 Effects on the cardiovascular and hematological systems

Icaritin can significantly increase cerebral blood flow, reduce cerebral vascular resistance, and maintain relatively stable blood pressure to protect against cerebral hypoxia [18-19]. Both icariin and total flavonoids of Epimedium have a protective effect against cerebral hypoxia [20]. Researchers have found at the molecular level that icariin can promote the formation of CFU-GM colonies in the bone marrow and improve the hematopoietic function of mice. Icariin acts on bone marrow multipotent stem cells to promote the proliferation, differentiation, and maturation of blood cells, which is important for the body's hematopoietic function [21]. Epimedium polysaccharide (EPS) can increase the rate of DNA synthesis, affect the metabolism of nucleic acids, increase the proliferation rate of bone marrow cells cultured in vitro, and can partially or completely eliminate the toxic side effects caused by azidothymidine (AZT). This indicates that EPS can promote hematopoiesis in the bone marrow, suggesting that Epimedium can be used in the treatment of leukemia [22].

3.2 Effect on the immune system

Zhang Yifan et al. [23] studied the immunomodulatory effect of Icaris flavonoids and found that Icaris flavonoids can significantly increase the phagocytic function of normal mouse mononuclear macrophages and increase the level of serum hemolysin antibody production. Icariside and icariin can both improve the phagocytic function of peritoneal macrophages in mice and restore the phagocytic function of peritoneal macrophages damaged by cyclophosphamide to normal levels [24].

3.3 Antitumor effect

Studies have found that icariin plays a role in inducing apoptosis in tumor cells, enhancing the killing activity of immune effector cells, and thus exerting an anti-tumor effect [25-26]. It has also been reported that icariin II has varying degrees of inhibitory effects on tumor cells, with the highest inhibitory effect on human nasopharyngeal carcinoma KB cells, indicating that icariin II has good anti-cancer activity [18].

3.4 Anti-aging effect

Icaris flavonoids are a strong antioxidant that can reduce the formation of lipofuscin in tissues such as the heart and liver and eliminate free radicals [27]. Meng Xianli et al. [28] found that the compound of epimedium polysaccharide and total flavonoids can significantly increase the content of monoamine neurotransmitters in the hypothalamus of aging animals, improve the learning and memory behavior of aging rats and mice, inhibit the activity of cholinesterase in the brain and whole blood of aging mice, and thus delay the aging of organs and the whole body.

3.5 Effect on the reproductive system

Researchers have found that icariin can increase the weight of the seminal vesicles in mice testes, and significantly promote the basal secretion of rat interstitial cells TS, which provides a medical basis for the use of icariin to treat male infertility caused by low TS levels [29]. Icariin extract has androgen-like effects, and icariin processed products can also significantly improve sexual function, increase the weight of the accessory sex organs, and increase the plasma testosterone content.

In addition, Epimedium extract has anesthetic, anti-inflammatory, sedative, antitussive, antiasthmatic, expectorant, analgesic, hypnotic, hepatoprotective, choleretic and osteoporosis-preventive effects [30–32]. Epimedium has a wide range of clinical applications and can be used to treat psychogenic erectile dysfunction, kidney yang deficiency-type chronic aplastic anemia, infantile paralysis, neurasthenia, chronic bronchitis [33], chronic arrhythmia, sick sinus syndrome, sinus bradycardia, atrioventricular block, cerebrovascular dementia, osteoporosis, femoral head necrosis, rheumatoid arthritis [22], etc. However, its bioavailability and clinical efficacy still need to be improved.

4 Biological characteristics and physiological and ecological research on Epimedium

Epimedium is a shade-loving plant that naturally grows in low and middle mountain thickets, under sparse forests or in semi-shady forest margins. It has strict requirements for soil, and prefers neutral or slightly alkaline, loose loam or sandy loam soil rich in humus and organic matter [34]. Shi Jinyang et al. [35] showed that Epimedium has a certain degree of drought resistance, and there is a significant correlation between the flavonoid content and the early drought resistance of Epimedium.

Zhang Hao et al. [36] found that the growth, total protein content, and antioxidant capacity of Epimedium sagittatum were all affected by Nacl stress. Qin Jiamei et al. [37] found that in different habitats, the content of total flavonoids and icariin in various samples of Epimedium koreanum was highest during flowering in May, then decreased, and then increased again in late August, indicating that late August is a more reasonable time to harvest. Wu Chunmei et al. [38] showed that the maturity of Epimedium fruit is mainly affected by humidity, light and temperature. Sudden temperature changes may be one of the mechanisms that promote the ripening of Epimedium fruit. There is a very significant correlation between the number of fruits and relative light and temperature; and with changes in altitude, the ripening time of Epimedium fruit also changes accordingly. Quan Qiumei et al. [39] studied the effect of density constraints on the morphological characteristics of Epimedium sagittatum during the period of sexual reproduction. It was found that the density of clonal fragments during sexual reproduction had a significant effect on its various morphological characteristics. During sexual reproduction, Epimedium sagittatum significantly increased its leaf number, leaf width, etc., to obtain more resources for improving its reproductive capacity and survival.

5 Resource protection

Herbal medicine derived from Epimedium brevicornum mainly comes from wild resources. The result of pharmaceutical companies purchasing directly from farmers has led to the widespread destruction of wild resources. Some groups in some areas may have become extinct, and the resource structure has been severely damaged. China has not done enough research on the protection and sustainable use of wild resources of Epimedium. Some reasonable measures should be adopted to manage and utilize Epimedium resources. For example, in China, provinces such as Guizhou and Jilin have begun artificial domestication and standardized cultivation of Epimedium. Japan has made great progress in artificial cultivation and has initially commercialized Epimedium resources.

Feng et al. [40] were the first to compare the clonal phenotypes and population characteristics of Epimedium sagittatum and Epimedium pubescens in suppressive habitats, providing a theoretical basis for the introduction and cultivation of Epimedium sagittatum and the protection of its resources. In terms of micropropagation of Epimedium abroad, YAMAMOTO H et al. [41] successfully obtained callus of Epimedium diphyllum in related experiments, while SHATHA M AL-MATAR et al. [42] successfully obtained callus and seedlings in the study of micropropagation of Epimedium grandiflorum M orr. China is a country with abundant Epimedium resources, and more research should be done on the protection and sustainable use of these resources.

Epimedium is one of the medicinal plants that has been the focus of research at home and abroad in recent years, and has now shown great research prospects and development potential. At present, there have been in-depth studies on its effective chemical components and clinical applications. Epimedium saponins, epimedium total flavonoids, epimedium polysaccharides, etc. are used in many drugs, and their unique pharmacological effects cannot be replaced by other medicinal plants. However, there are still many deficiencies in the research on Epimedium sagittatum, such as: the confusion of Epimedium sagittatum medicinal herbs in the medicinal herb market, the uneven quality, the extremely complex species of Epimedium sagittatum, the overlapping distribution of different species, and the frequent mixing of multiple species in the purchased medicinal herbs, which makes the quality control of medicinal herbs more difficult.

There is still insufficient research on the conservation and sustainable use of Epimedium resources, artificial domestication and cultivation, and even less research at the molecular level. Therefore, research on the application of molecular biology methods to the isolation of functional genes, molecular fingerprinting for species identification, and monitoring of the quality of medicinal materials still needs to be further strengthened in order to lay the foundation for the breeding of superior varieties of Epimedium and the development and utilization of new drug resources. China is the center of distribution of Epimedium resources and has many endemic species. Strengthening comprehensive research on Epimedium plants in China, especially research on resource protection and sustainable use, and using more advanced techniques to study pharmacological effects will have increasingly broad application prospects.

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