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Background  Japanese herbal medicines can be used as alternatives to estrogen therapy and are sometimes prescribed for menopausal syndrome because they have fewer side effects and are associated with better compliance than estrogen therapy, but little is known about the pharmacological mechanisms of such treatments. This study aimed to explore the mechanisms responsible for the estrogen-like effects of five widely prescribed Japanese herbal medicines  (unkeito ,  kamishoyosan ,  nyoshinsan ,  keishibukuryogan , and  tokishakuyakusan ).    Methods  We evaluated the estrogenic activity of these five Japanese herbal medicines and their metabolites using an estrogen receptor (ER)-dependent cell proliferation bioassay and an ER-dependent reporter assay. We also investigated the estrogenic activity of the crude drugs within the medicines and attempted to detect inter-crude drug synergistic effects using the ER-dependent reporter assay.    Results  We found that  unkeito ,  kamishoyosan , and  nyoshinsan  exhibited estrogenic activity, and they displayed stronger estrogenic activity after being metabolized. Then, we focused on investigating the estrogenic activity of the crude drugs present within  unkeito . We found that glycyrrhizae radix, cinnamomi cortex, evodiae fructus, and zingiberis rhizoma demonstrated ERβ-dependent estrogenic activity. The combined use of evodiae fructus and glycyrrhizae radix, or evodiae fructus and cinnamomi cortex produced synergistic ERβ-dependent estrogenic activity.    Conclusion  It was suggested that  unkeito ,  kamishoyosan , and  nyoshinsan  exert estrogenic activity, and hence, might be useful for treating menopausal syndrome. Furthermore, synergistic estrogenic effects were detected between some of the crude drugs present within  unkeito .

bmc complementary and alternative medicine

The in vitro estrogenic activity of the crude drugs found in Japanese herbal medicines prescribed for menopausal syndrome was enhanced by combining them