Ginsenosides, the main active components of ginseng, have been reported possessing anti-osteoporosis activity in ovariectomized rats. However, the active ingredient and the mechanisms underlying the anti-osteoporosis activity of GSS have not been clearly elucidated.

In the present study, we determined the effect of ginsenoside Rb1, a major component of ginsenosides, on receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation.

Ginsenoside Rb1 inhibited RANKL-induced osteoclast differentiation from Raw264.7 cells without cytotoxicity. Ginsenoside Rb1 also inhibited RANKL-induced TNFα mRNA expression in Raw264.7 cells.

Pretreatment with ginsenoside Rb1 significantly inhibited RANKL-induced the gene expression of c-Fos and nuclear factor of activated T-cells c1 (NFATc1), which are two essential and crucial transcription factors for osteoclast formation.

Rb1 inhibited RANKL-induced nucleus translocation and activation of NF-κB, the upstream factor of c-Fos and NFATc1.

Among the three well known mitogen-activated protein kinases (MAPKs), Rb1 inhibited RANKL-induced JNK and p38 phosphorylation, but not ERK1/2.

Taken together, our data suggest that ginsenoside Rb1 is one of the effective components of ginsenosides for the anti-osteoporosis activity and can inhibit osteoclastogenesis by suppressing RANKL-induced activation of both JNK and p38 MAPKs and NF-κB pathways, and consequently down-regulating the gene expression of c-Fos and NFATc1 in osteoclast precursors.

Source: Cheng B, Li J, Du J, Lv X, Weng L, Ling C. Ginsenoside Rb1 inhibits osteoclastogenesis by modulating NF-κB and MAPKs pathways. Food Chem Toxicol. 2012 May;50(5):1610-5