Osteoarthritis (OA) is a degenerative joint disorder marked by the breakdown of cartilage and inflammatory responses. P2X7R is a switch of inflammation and also an activator of NLRP3 inflammasome and IL-1β. Recent studies have focused on plant extracts to prevent or delay OA development. Baicalein has been linked to positive effects for inflammation, and might be a potential therapeutic agent. In this study, we performed baicalein in an anterior cruciate ligament transection (ACLT) -induced OA rat model to evaluate its effects on cartilage histological changes, cartilage catabolism, pro-inflammatory cytokines, and NLRP3-indcued signaling pathway. Moreover, to further clarify the target of baicalein towards the upstream molecular of NLRP3, we used BzATP (a selective agonist of P2X7R) before baicalein administration both in OA rats and primary chondrocytes of rats. Our results show that baicalein relieves OA cartilage torn, including increased safranin O-fast green staining for proteoglycan and decreased OARSI score, as well as inhibiting MMP-13 and ADAMTS-5, which contribute to cartilage degradation. Additionally, baicalein downregulated the expression of P2X7 and NLRP3-induced axis both in vivo and in vitro; moreover, it reduces the contents of IL-1β, IL-6, IL-18, COX-2 and PGE-2, but increases IL-10. However, these results were reversed by BzATP partly. In conclusion, baicalein inhibits OA inflammation and cartilage catabolism through the P2X7-NLRP3 axis as an OA protective agent.

To Cite This Article: Zhang Z, Han Y, Du S, Lu A, Han L, Liu K, He P and Bai H, 2026. Baicalein suppresses NLRP3-mediated chondrocyte pyroptosis and extracellular matrix degradation in osteoarthritis via P2X7 receptor. Pak Vet J, 46(3): 638-644. http://dx.doi.org/10.29261/pakvetj/2026.052