Autophagy and pyroptosis in chondrocytes contribute to cartilage degeneration in osteoarthritis (OA). Capsaicin (Cap), a bioactive compound derived from chili peppers, exhibits anti-inflammatory and antioxidant properties. However, the underlying mechanisms by which Cap exerts its chondroprotective effects in OA remain poorly understood. This study aims to elucidate the molecular basis of Cap-mediated chondroprotection. OA models were established using SD rats and primary rat chondrocytes to evaluate the effects of Cap on extracellular matrix (ECM) degradation, inflammation, pyroptosis, autophagy, and the AMPK/mTOR signaling pathway. To investigate the mechanisms underlying Cap’s chondroprotective effects, 3-Methyladenine and dorsomorphin were employed to inhibit autophagy and AMPK signaling, respectively. Cap mitigates cartilage damage and alleviates pain through activation of the AMPK/mTOR signaling pathway, while promoting chondrocyte autophagy and suppressing NLRP3 inflammasome activation and subsequent inflammatory responses. Notably, inhibition of autophagy or AMPK signaling in chondrocytes partially abrogates the protective effects of Cap on cartilage. Our findings demonstrate that Cap exerts its therapeutic effects in OA by activating the AMPK/mTOR pathway and enhancing autophagy in chondrocytes, thereby sequentially inhibiting pyroptosis and ECM degradation.

To Cite This Article: Zhang Z, Yang L, Du S, Han L, Liu K, Lu A, Ma T, Gao R and Bai H, 2025. Capsaicin regulates pyroptosis and autophagy in chondrocytes associated with osteoarthritis in rat models via the AMPK/mTOR signaling pathway. Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.297