title: Ginsenoside Rb1 inhibits osteoclastogenesis by modulating NF-κB and MAPKs pathways.
abstract: Ginsenosides (GSS), 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 GSS 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.
authors.affiliation: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Cheng
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Xiang
authors.initials: X
authors.lastname: Lv
authors.forename: Li
authors.initials: L
authors.lastname: Weng
authors.forename: Changquan
authors.initials: C
authors.lastname: Ling
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D036145:Ginsenosides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D036145:Ginsenosides; D016328:NF-kappa B; C442759:ginsenoside Rb1