Gypenoside inhibits RANKL-induced osteoclastogenesis by regulating NF-κB, AKT, and MAPK signaling pathways.

Gypenoside (GP) is one of the most pharmacologically active components in Gynostemma pentaphyllum and possesses neuroprotective, anticancer, anti-oxidant, anti-inflammatory, anti-diabetic, and anti-osteoarthritis effects. However, the involvement of GP the osteoclast differentiation has not yet been investigated. In the present study, we examined the effect of GP on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Our results demonstrated that GP significantly inhibited the formation of osteoclast, as well as suppressed the expression of osteoclastogenesis-related marker proteins in RANKL-stimulated bone marrow macrophages (BMMs). For molecular mechanisms, GP inhibited RANKL-induced NF-κB and MAPK activation and AKT phosphorylation in BMMs. Collectively, these findings suggest that GP inhibits RANKL-induced osteoclastogenesis via regulating NF-κB, AKT, and MAPK signaling pathways. Therefore, GP may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis.