Key points are not available for this paper at this time.
Ferroptosis-induced lipid peroxidation in chondrocytes exacerbates intra-articular inflammation, oxidative stress , and articular cartilage degradation, accelerating osteoarthritis (OA) progression. Effective anti-inflammatory and antioxidant interventions can alleviate both joint pain and cartilage damage. This study aims to elucidate the therapeutic effects of Notopterol (NP), a bioactive compound extracted from the rhizome of Notopterygium incisum , a traditional Chinese medicine known for its potent anti-inflammatory and antioxidant properties, in treating OA. An in vivo mouse model of OA was established through medial meniscus destabilization (DMM). Intra-articular injections of NP over a 4-week treatment period significantly alleviated pain and gait abnormalities, reduced subchondral osteosclerosis , and attenuated cartilage degradation compared to the untreated DMM group. In vitro, chondrocytes treated with IL-1β to simulate OA conditions exhibited increased viability following NP pretreatment, with concurrent reductions in apoptosis , reactive oxygen species (ROS) accumulation, and chondrocyte catabolic dysfunction, along with enhanced extracellular matrix (ECM) synthesis. Mechanistically, NP exerts its anti-OA effects by inhibiting PI3K/Akt phosphorylation, suppressing ferroptosis, and improving antioxidant defense via upregulation of glutathione (GSH) and glutathione peroxidase 4 (GPX4), thereby preventing lipid peroxidation . In conclusion, NP modulates the PI3K/Akt/GPX4 axis to protect against lipid peroxidation, inhibit ferroptosis, and preserve cartilage integrity, thus delaying OA progression. • Notopterol (NP) alleviates OA symptoms by inhibiting chondrocyte ferroptosis and reducing oxidative stress . • NP modulates the PI3K/Akt/GPX4 signaling axis, preventing lipid peroxidation and preserving cartilage integrity. • In vivo and in vitro studies confirm NP's potential to reduce pain, improve gait, and slow OA progression.
Zhou et al. (Thu,) studied this question.