Orientin suppresses osteoclastogenesis and ameliorates ovariectomy‐induced osteoporosis via suppressing ROS production

The aberrant differentiation of osteoclasts is a key feature the pathogenesis osteoporosis, which has devastating impact on human health. While effects Orientin (Ori) particularly RANKL-stimulated osteoclast production and activation, remain still unclear, Ori been found to display several biological activities, including antioxidant anti-inflammatory. In this work, we investigated possible pathways through suppressed RANKL-induced development showed for first time that it does so. macrophages from bone marrow (BMMs) were cultivated then treated with after being stimulated RANKL. Then, TRAP-positive multinucleated cells counted, F-actin ring analysis was used assess Ori's mature development. addition, dihydroethidium (DHE) staining evaluate reactive oxygen species (ROS). performed western blotting quantitative RT-PCR investigate probable causes these downregulation effects. We discovered inhibits creation osteoclasts, gene protein expressions unique ROS production. By activating Nrf2 other ROS-scavenging enzymes, reduces intracellular levels. expression main transcription factor development, c-Fos, downregulated together NFATc1, CTSK, NFATc2, thanks inhibition NF-κB. Consistent its in vitro antiosteoclastogenic action, therapy ovariectomized (OVX) rat model also able restore mass improve microarchitecture distal femurs. Together, our results demonstrate flavonoid molecule therapeutic promise illnesses associated such as osteoporosis.