Okanin alleviates osteoarthritis by suppressing oxidative stress and pyroptosis via Nrf2/HO-1 activation.

Osteoarthritis (OA) is a chronic joint disorder characterized by degenerative cartilage and chondrocyte dysfunction. Oxidative stress and NLRP3 inflammasome-mediated pyroptosis play pivotal roles in OA progression. This study investigated the protective effects and mechanisms of Okanin, a natural flavonoid, in a mouse model of knee osteoarthritis. We found that Okanin effectively activated the Nrf2/HO-1 signaling pathway, significantly enhanced the antioxidant capacity of chondrocytes and scavenged excess ROS. Concurrently, Okanin inhibited the assembly and activation of the NLRP3 inflammasome, thereby suppressing the caspase-1/GSDMD-dependent pyroptosis pathway. In vivo experiments demonstrated that Okanin treatment improved articular cartilage morphology, reduced proteoglycan loss, and decreased OARSI scores in a destabilization of the medial meniscus (DMM) murine model. Mechanistically, Nrf2 was identified as a key target of Okanin through siRNA knockdown. This study is the first to reveal that Okanin exerts dual chondroprotective effects against oxidative stress and pyroptosis via the Nrf2/HO-1 axis, suggesting a novel strategy for OA treatment.