Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways.

is a triterpenoid compound extracted from a medicinal plant . It has been used as a highly efficient compound for the treatment of cancer and hyperlipidemia, as well as possessing potential antiinflammatory properties. However, its effects on bone metabolism and osteoporosis haven't been reported. The purpose of our research were to reveal the biomolecular effects of on osteoclasts, and its underlying molecular mechanisms regulating its effects on receptor activator of NF-κB ligand (RANKL)-induced signaling pathways. We found that inhibited multinucleated tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast differentiation and osteoclast induced bone loss. Real time PCR showed that reduced the expression of down-cascade target genes including , , , and . Western blot and luciferase reporter gene assays revealed that inhibits RANKL mediated NF-κB and NFATc1 signalings. Further, study demonstrated attenuates estrogen deficiency-induced bone loss in ovariectomized mice. MicroCT and histology analyses revealed that osteoclast numbers were significantly suppressed in treated groups. Furthermore, serum levels of TRAcP and CTX-1 were downregulated in treated groups. Taken together, our data show that can inhibit osteoclastic formation and reduce OVX-induced bone resorption through RANKL-activated NF-κB or NFATc1 signaling, suggesting that may be a potential and effective natural compound for the therapy of excessive RANKL-related osteolytic diseases.