Evaluation of estrogenic/antiestrogenic activity of Onobrychis ebenoides extract -: Interaction with estrogen receptor subtypes ERα and ERβ

A protective effect of plant extract from Onobrychis ebenoides on ovariectomy-induced bone loss in rats has been shown. To investigate the molecular mechanisms that underly the beneficial effect of O. ebenoides (Onb) on bone loss, we studied its potential to activate ER subtypes (ER alpha and ER beta) on transiently transfected HeLa cells with HO-hER alpha or pSG5-hER beta and 3xERE-TATA-Luc expression vectors. Its impact to stimulate differentiation and mineralization of osteoblasts (KS483 cell line) by Alizarin Red-S staining was also examined. Furthermore we sought to induce for its potential the IGFBP3, a known estrogen-dependent marker in MCF7 breast cancer cells. 17 beta-Estradiol and the pure antiestrogen IC1182780 were included to serve as control samples of the estrogenic and antiestrogenic activity respectively. Our data revealed: (1) Onb extract displayed a significant estrogenic activity on both ER alpha and ER beta subtypes. (2) It exhibited direct action on osteoblasts by inducing mineralization. (3) It showed estrogenic activity in MCF7 cells. These findings suggest that the beneficial effect of Onb extract on bone loss is mediated through an estrogen-like action via activation of ER alpha-ERE and ER beta-ERE pathways and via direct action on the mineralization process of osteoblasts. (c) 2006 Elsevier Ltd. All rights reserved.