Atractylenolide I Attenuates Glucocorticoid-Induced Osteoporosis via Inhibiting NF-κB Signaling Pathway

Long-term treatment with glucocorticoids significantly impacts bone health, with glucocorticoid-induced osteoporosis (GIOP) being the most prevalent consequence. Previous studies have established that Atractylenolide I (Atr I) possesses anti-inflammatory, antioxidant and anti-tumor properties, however, its specific effects on osteoclastogenesis and GIOP are still unclear. In this study, our in vitro results revealed that Atr I inhibited RANKL-stimulated osteoclast differentiation in a dose-dependent manner, disrupted the structure of the F-actin belt in mature osteoclasts, blocked RANKL-induced ROS production, and suppressed the expression of osteoclast-associated genes. Mechanistically, the findings indicated that Atr I inhibited the RANKL-induced activation of the NF-κB signaling pathway. In vivo, the micro-CT, bone histomorphometric analysis and histological data demonstrated that Dex administration led to significant bone loss, accompanied by a considerable increase in the number of osteoclasts on the bone surface. Conversely, treatment with Atr I effectively prevented these Dex-induced alterations. Taken together, this study suggests that Atr I may hold potential as a therapeutic agent for the treatment of GIOP.