Deguelin inhibits IL-1β-induced chondrocyte inflammation in vitro and ameliorates murine osteoarthritis in vivo

Osteoarthritis (OA), a prevalent age-related degenerative joint disorder, is characterized by progressive articular cartilage degradation accompanied by subchondral bone remodeling, synovitis, and reactive osteophytosis. Discovering natural medicines capable of inhibiting inflammatory response of chondrocytes and cartilage degeneration is necessary for OA treatment. Emerging investigations have systematically demonstrated deguelin's multimodal anti-inflammatory efficacy mechanistically across multiple pathological contexts. However, its effect on chondrocytes remains unknown. Through a dual-level investigation combining in vitro mechanistic analysis and in vivo disease modeling, this study delineates deguelin's chondroprotective mechanisms in primary murine chondrocytes, while demonstrating potent disease-modifying effects in surgically induced OA pathogenesis. Deguelin demonstrated significant anti-inflammatory activity in IL-1 beta-activated chondrocytes. It diminished cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNA and protein levels, and it prevented extracellular matrix (ECM) catabolism by reducing matrix metalloproteinases (MMPs) expression. Mechanistically, deguelin exerted anti-inflammatory effects through targeted suppression of NF-kappa B pathway activation, as confirmed by immunofluorescence and western blot analyses. Consistent with the in vitro findings, deguelin treatment protected against articular cartilage erosion and subchondral bone loss in OA murine model in vivo, suggesting its potential as an effective agent for treating OA.