Curcumin as a multi-target therapy for osteoarthritis in rats: a systematic review and meta-analysis.

Osteoarthritis (OA) represents a significant unmet clinical need, where current management strategies primarily alleviate symptoms but fail to halt disease progression and are often associated with adverse effects. Curcumin, a natural polyphenol, has emerged as a promising therapeutic candidate. To systematically evaluate its efficacy and mechanisms, we conducted a systematic review and meta-analysis of studies from databases including PubMed, Web of Science, CNKI, and Wanfang up to October 2025. Nineteen preclinical studies meeting the inclusion criteria were analyzed. The results demonstrated that curcumin significantly improved OARSI scores (MD = - 3.36), knee diameter (SMD = - 4.40), paw withdrawal threshold (MD = 4.36), and reduced apoptotic chondrocytes (SMD = - 9.50). Mechanistically, it enhanced antioxidant defense via SOD activity (SMD = 5.17) and suppressed the TLR4/NF-κB pathway, reducing key upstream signaling mediators (TLR4: SMD = - 1.41; NF-κB: SMD = - 3.72) and downstream pro-inflammatory cytokines (TNF-α: SMD = - 3.37; IL-6: SMD = - 10.19). Furthermore, it preserved cartilage metabolism by increasing type II collagen (SMD = 2.00) and decreasing MMP-13 (SMD = - 3.51) and COMP (SMD = - 2.95). These findings indicate that curcumin exerts multi-target protective effects in OA by mitigating oxidative stress, suppressing the TLR4/NF-κB inflammatory pathway, and reducing cartilage degradation, providing a theoretical foundation for its clinical translation. Future research employing standardized methodologies will be crucial to fully elucidate the mechanistic basis of curcumin's action and optimize its therapeutic potential for clinical applications.