Curcumin in Arthritis: Molecular Mechanisms, Preclinical Evidence, and Clinical Applications

This review aims to provide a comprehensive and integrative evaluation of the therapeutic potential of curcumin in arthritis, focusing on its molecular mechanisms, preclinical evidence, and clinical applications. A systematic literature search was conducted across major databases, and a total of 165 studies were included in this review. Curcumin exerts multi-target effects on key pathogenic pathways involved in arthritis. At the molecular level, it inhibits inflammatory signaling pathways, particularly NF-κB, and reduces the production of pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, COX-2, and PGE2. In parallel, curcumin modulates oxidative stress by enhancing antioxidant defenses, including superoxide dismutase (SOD) and glutathione (GSH), while reducing lipid peroxidation. It also regulates cell death pathways, including apoptosis, autophagy, and emerging mechanisms such as pyroptosis and ferroptosis, and preserves cartilage integrity by inhibiting matrix metalloproteinases and ADAMTS while promoting extracellular matrix components. Preclinical studies consistently demonstrate anti-inflammatory, antioxidant, and chondroprotective effects across in vitro and animal models. Clinical evidence, particularly in osteoarthritis, indicates improvements in pain and functional outcomes, with some studies suggesting efficacy comparable to nonsteroidal anti-inflammatory drugs. However, this evidence remains limited and should be interpreted with caution. However, variability in formulations and limited bioavailability remain key challenges influencing clinical outcomes. Overall, curcumin represents a promising multi-target therapeutic agent for arthritis. Further large-scale, well-designed randomized controlled trials using standardized and bioavailable formulations are required to confirm its efficacy and optimize its clinical application.