Anti-Inflammatory, Antioxidant, and Analgesic Effects of Nitrophenylthiazole Acetamide in a Papain-Induced Osteoarthritis Rat Model

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, inflammation, oxidative stress, and pain. This study aimed to evaluate the therapeutic potential of a nitrophenylthiazole acetamide, 6a, in a papain-induced OA rat model. OA was induced by intra-articular injection of papain, followed by oral administration of compound 6a at doses of 2.5, 5, and 10 mg/kg. Knee joint diameter and mechanical allodynia were assessed using caliper measurements and the Von Frey pain threshold test, respectively. Oxidative stress markers (MDA, SOD, and GSH), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and mRNA expression levels of NLRP3, ASC, and caspase-1 were also evaluated. Results demonstrated that compound 6a significantly reduced joint swelling and increased pain threshold in a dose-dependent manner. Biochemical analysis revealed a marked decrease in MDA levels, along with significant increases in SOD and GSH, indicating strong antioxidant activity. Furthermore, compound 6a suppressed the elevated levels of TNF-α, IL-1β, and IL-6 and downregulated the mRNA expression of NLRP3, ASC, and caspase-1, suggesting inhibition of inflammasome-mediated inflammation. In conclusion, compound 6a exhibited notable anti-inflammatory, antioxidant, and analgesic effects in the OA rat model, highlighting its potential as a promising therapeutic agent for osteoarthritis management.