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Millettia macrophylla  is used traditionally to treat menopause related symptoms. This plant was shown to exhibit estrogenic effects  in vitro  on human embryonic kidney cells and  in vivo  on ovariectomized rats. The present study aimed at elucidating underlying mechanisms by which  M. macrophylla  induced its estrogenic effects. To accomplish our goal, kidney Hek293T cells transiently transfected with estrogen alpha or beta receptor expression plasmids were cotreated with a pure antiestrogen ICI 182,780 and the dichloromethane or methanol soluble fractions of  M. macrophylla.  To follow up, we cotreated ovariectomized rats with both extracts and ICI 182,780 for 3 days in the classical uterotrophic assay. Animals were then sacrificed and the uterine wet weight, total protein levels in uteri, uterine, and vaginal epithelial heights, and mammary gland were assessed.  In vitro,  the results suggested that the induction of the estrogenic activity by  M. macrophylla  is due to the binding of its secondary metabolites to ER α  and ER β .  In vivo , the cotreatment of extracts and ICI 182,780 significantly abrogated the biological responses induced by the extracts alone. Taken together, these results indicate that the active principles of  M. macrophylla  induce their beneficial effects on menopausal symptoms by activating the ERs.

Elucidation of Underlying Mechanisms by WhichMillettia macrophyllaBenth Induces Its Estrogenic Activity