Some plant compounds or herb mixtures are popular alternatives to conventional therapies and contain organic compounds that bind to some nuclear receptors, such as the estrogen receptor (ER), to exert various biological effects. We studied the effect of various herbal extracts on ERα and ERβ isoforms. One herbal extract, Rhei rhizoma (rhubarb), acts as an agonist to both ERα and ERβ. The phytochemical lindleyin, a major component of rhubarb, might contribute to this estrogenic activity through ERα and ERβ. 4-Hydroxytamoxifen, an ER antagonist, completely reversed the estrogenic activity of lindleyin.

Lindleyin binds to ERα in vitro, as demonstrated using a fluorescent polarization assay. The in vivo effect of rhubarb extract was studied using a vitellogenin assay system in the freshwater fish, Japanese medaka (Oryzias latipes). There were marked increases in serum vitellogenin levels in male medaka exposed to rhubarb extract. We conclude that lindleyin, a component of some herbal medicines, is a novel phytoestrogen and might trigger many of the biological responses evoked by the physiological estrogens.