Estrogenic activity of isoflavonoids from the stem bark of the tropical tree Amphimas pterocarpoides, a source of traditional medicines.

Abstract Various preparations of the African tree Amphimas pterocarpoides Harms are traditionally used to treat endocrine- related adverse health conditions. In the ovariectomized rat, the enriched in phenolics fraction of the methanol extract of stem bark of A. pterocarpoides acted as vaginotrophic agent of considerably weaker uterotrophic activity compared to estradiol. Evaluation of the fraction and 11 isoflavonoids isolated therefrom using Ishikawa cells and estrogen receptor (ER) isotype-specific reporter cells suggested that the estrogenic activity of the fraction could be attributed primarily to daidzein and dihydroglycitein and secondarily to glycitein. The potency-based selectivity of daidzein, dihydroglycitein and glycitein for gene expression through ERβ versus ERα, expressed relative to estradiol, was 37, 27 and 20, respectively. However, the rank order of relative-to-estradiol potencies of induction of alkaline phosphatase in Ishikawa cells, a reliable marker of estrogenic activity, was daidzein > dihydroglycitein >> glycitein. The considerably higher estrogenic activity of dihydroglycitein compared to glycitein could be attributed to the partial agonist/antagonist activity of dihydroglycitein through ERβ. Calculation of theoretical free energies of binding predicted the partial agonism/antagonism of dihydroglycitein through ERβ. The fraction and the isolated isoflavonoids promoted lactogenic differentiation of HC11 mammary epithelial cells at least as effectively as premenopausal levels of estradiol. This data suggests that the estrogenic activity of the fraction likely depends on the metabolism of glycitein to dihydroglycitein; that the fraction could exert vaginotrophic activity likely without challenging endocrine cancer risk more than estrogen-alone supplementation; and that the fraction's safety for the reproductive track warrants a more detailed evaluation.