Estrogenic effects of ginsenoside Rg1 in endometrial cells in vitro were not observed in immature CD-1 mice or ovariectomized mice model

Objective: The present study was designed to determine whether ginsenoside Rg1 could exert selective estrogenic effects by using both cell lines and an animal model. Methods: The endometrial Ishikawa cells and preosteoblastic MC3T3-E1 cells were treated with a different dose of Rg1. Immature CD-1 mice and ovariectomized (OVX) C57BL/6J mice were used to study the short-term and long-term estrogenic effects of Rg1, respectively. Results: Rg1 significantly increased estrogen receptor-dependent alkaline phosphatase activity, activated estrogen response element-luciferase activity, and induced the phosphorylation of mitogen-activated protein kinase kinase, extracellular-regulated kinase, and estrogen receptor-α in Ishikawa cells. In contrast, Rg1 did not induce any estrogenic responses in MC3T3-E1 cells. Administration of Rg1 to immature CD-1 mice did not alter their uterine weight or the estrogen-regulated gene expressions in the uterus. Treatment of OVX C57BL/6J mice with Rg1 via mini-osmotic pumps for 3 months did not alter the uterine weight or induce any transcriptional activation of estrogen receptor in the uterus. Rg1 induced Bcl-2 messenger RNA expression in the left ventricular tissue and striatum but failed to alter the bone mineral density in the femur and tibia of the OVX mice. Conclusions: Rg1 exerted potent estrogenic effects in endometrial cells in vitro as well as in heart and brain tissues in vivo. However, it did not exert any estrogenic effects on reproductive tissues in vivo, nor did it stimulate bone tissues in vitro or in vivo. Our results suggest that the estrogenic effects of Rg1 are distinct from those of estradiol and are cell type and tissue selective.