Oxysophoridine promotes osteoarthritis repair via GSH system activation and ROS suppression

Osteoarthritis (OA) is a prevalent joint degenerative disease involving inflammation and oxidative stress, with reactive oxygen species (ROS) driving progression. Restoring joint redox balance mitigates cartilage damage. Osilyhizidine (OSR), from Sophora alopecuroides, has anti-inflammatory/antioxidant properties, but its OA-specific effects and mechanisms were unclear. In vitro experiments assessed OSR's impact on OA chondrocyte proliferation, repair, and inflammation, focusing on Glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) regulation. A murine OA model validated findings in vivo. OSR showed anti-inflammatory, antioxidant effects and promoted cartilage repair, enhancing chondrocyte functions under inflammation and suppressing pro-inflammation. It upregulated GPX4 (improving ROS detoxification) and SLC7A11 (facilitating glutathione synthesis for redox balance) at transcriptional and protein levels. These were confirmed in mice. OSR alleviates OA by activating GPX4/SLC7A11 to regulate ROS and oxidative stress, emerging as a promising OA therapeutic candidate, offering insights into redox-targeted interventions.