Isobavachalcone prevents osteoporosis by suppressing activation of ERK and NF-KB pathways and M1 polarization of macrophages

Estrogen receptors alpha (ER?), a member of the nuclear receptor protein family, was found to play an important role in maintaining bone mass. Its downstream signaling proteins such as ERK and NF-KB were reported to be involved in development of osteoporosis, which meant that targeting ER? might be an effective strategy for searching for new drugs to prevent bone loss. In this study, we demonstrate that isobavachalcone (ISO), as one of bioactive compounds isolated from Psoralea corylifolia Linn, has high affinity with ER?. The effects of ISO are investigated on receptor activator of NF-KB ligand (RANKL)-induced osteocalstogenesis. It is reported that ISO inhibits the RANKL-mediated increase of osteoclast-related genes MMP9, cathepsink and TRAR in RAW264.7 cells. Moreover, in vitro experiment shows that ISO exhibits an inhibitory effect on ERK and NF-KB signaling pathway, and suppresses RANKL-induced expression of osteoclast-related transcription factors NFATc1 and cFos. However, the impact of ISO in these molecules is eliminated by the application of ER? antagonist AZD9496. We further verified pharmacological effects of ISO in ovariectomized osteoporotic mice, and ISO significantly prevented bone loss and decreased M1 polarization of macrophages from marrow and spleen. Collectively, our data suggest that ISO prevents osteoporosis via suppressing activation of ERK and NF-KB signaling pathways as well as M1 polarization of macrophages.

Automated summary

Our study demonstrates that isobavachalcone (ISO) can prevent osteoporosis by inhibiting the activation of ERK and NF-KB signaling pathways, as well as M1 polarization of macrophages.