Abstract
Our previous study reported that the in vitro osteogenic effects of 8-prenylgenistein (8PG) were more potent than its parent compound genistein. This study aimed to evaluate the osteoprotective effects of 8PG in ovariectomized (OVX) mice as well as to characterize its estrogenic effects in uterus. Mature OVX mice were treated with phytoestrogen-free diet containing 8PG or genistein. Trabecular bone mass and most of the micro-structural parameters were ameliorated at the distal femoral metaphysis in OVX mice upon treatment with genistein and both doses of 8PG. The beneficial effects of 8PG on trabecular bone were confirmed by safranin O and ABHO staining. 8PG markedly inhibited the ovariectomy-induced mRNA expressions of RANKL/OPG, ALP, COL, OCN, cathepsin K and ER-α in bone. In contrast, genistein further increased the ovariectomy-induced ER-α expression in bone. The uterus index was increased in genistein-treated group. Genistein up-regulated the expression of ER-α and PR, while 8PG significantly down-regulated the ER-α and C3 expression in uterus of OVX mice. Moreover, genistein, but not 8PG, increased expressions of ER-α, PCNA and C3 in Ishikawa cell. This study suggested that 8PG improved trabecular bone properties in OVX mice without exerting uterotrophic effects and its estrogenic actions were distinct from those of genistein.