Scheme 1. Schematic representation of the mechanism by which puerarin inhibits in vivo and in vitro osteoclastogenesis. RANKL induces osteoclastogenesis by binding to its receptor, RANK, thereby inducing ROS and activating the NF-κB and MAPK pathways and increased NFATc1 expression. Subsequently, the expression of osteoclast-specific genes, Ctsk, Acp5, Atp6v0d2, and Mmp9 are upregulated. Our results show that puerarin inhibits osteoclastogenesis by inhibiting intracellular ROS levels by inhibiting NOX1 and enhancing antioxidant enzymes like HO-1, subsequently inhibits the activation of the MAPK and NF-κB signaling pathways.