Inhibitory effect of Galgeun-tang on RANKL-induced osteoclast differentiation and bone loss in ovariectomized rats

Abstract

Galgeun-tang (GGT) is a traditional Korean medication known to have a diaphoretic effect and to improve cerebral circulation. The aim of this study was to investigate the effects of GGT on osteoclast differentiation and bone loss in ovariectomized (OVX) rats compared to Galgeun-tang fermented by Bifidobacterium breve (designated as GFT). GGT significantly and dose-dependently inhibited the receptor activator for nuclear factor κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in RAW264.7 cells. In addition, GGT significantly reduced RANKL-induced mRNA expression levels of TRAP, c-Src, and Cathepsin K. To examine the effect of GGT or GFT in OVX rats, we administered GGT or GFT (15 mL/kg/day) orally to OVX rats for 12 weeks. GGT administration significantly reduced body weight gain in OVX rats. GGT administration also significantly reduced total serum cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels in OVX rats. GFT administration significantly reduced serum LDL-cholesterol and triglyceride levels in OVX rats. Moreover, administration of GGT, but not GFT, significantly increased bone mineral density of the femur, which is normally decreased in OVX rats. In conclusion, these results suggest that GGT could have the potential to decrease ovariectomy-induced increases in body weight and lipid content and could prevent bone loss through its inhibitory effect on osteoclast differentiation.