Estrogenic properties of six compounds derived from Eucommia ulmoides Oliv. and their differing biological activity through estrogen receptors α and β

Eucommia ulmoides Oliv. (Du-zhong), a well known Chinese herbal medicine, has been increasingly used as a nutraceutical supplement. The aim of this study was to identify and characterise novel estrogenic compounds in E. ulmoides. We report that six compounds, namely pinoresinol 4′-O-β-d-glucopyranoside, pinoresinol di-O-β-d-glucopyranoside, aucubin, wogonin, baicalein, and α-O-β-d-glucopyranosyl-4,2′,4′-trihydroxydihydrochalcone, activated estrogen receptor (ER)-dependent transcription of both transfected and endogenous target genes. Strikingly, these compounds exhibited significant difference in ER subtype (α vs. β) selectivity. Cell proliferation and ER subcellular localisation analyses also demonstrated that they mediated the estrogenic effects by the genomic action of ERα. This study suggests that E. ulmoides is a rich source of new selective estrogen receptor modulators and evaluations of its health benefit and safety as a food additive should take into account the diverse phytoestrogen activities of the individual components.