Taxonomic, genetic, chemical and estrogenic characteristics of Epimedium species

To understand the factors contributing to estrogenic properties of extracts from the genus Epimedium L. (Berberidaceae), we performed taxonomic, genetic and chemical characterization on 37 specimens from 18 species and related these to estrogen receptor (ERalpha and ERbeta) bioactivity, as measured by reporter genes in stable human cells. Boot strap values derived from amplified fragment length polymorphisms indicated that specimens of E. koreanum, E. brevicornum, E. myrianthum, E. leishanense, and E. membranaceum were genetically distinct and this was supported by their very similar ERalpha activities. In contrast, specimens from E. pubescens and E. sagittatum were diverse both genetically, chemically and in terms of ERalpha and ERbeta bioactivities. Strikingly, a genetic cluster comprising six rare Epimedium species exhibited strongest ERalpha and ERbeta activity, and this bioactivity was positively correlated with content of trace flavonoid aglycones (kaempferol, apigenin, quercetin, luteolin and breviflavone B). In contrast, there was no association between estrogenic activity and the major flavonol glycoside constituents (icariin and epimedin A-C). Although they exhibited equally strong ERalpha and ERbeta activity, E. koreanum can be clearly differentiated from E. pubescens and E. brevicornum by genetic distance and its significantly lower content of epimedin C. Our morphologic, genetic, chemical and bioactivity profiling provide the basis for the production of extracts with reproducible estrogenic properties. Such reproducibility will be critical for the standardization of Epimedium-based products.