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.