From osteoarthritis to rheumatoid arthritis: re-exploring the molecular pathways and therapeutic potential of diacerein

Diacerein, an anthraquinone derivative, is emerging as a promising disease-modifying agent in rheumatoid arthritis (RA), because of its potent anti-inflammatory and chondroprotective actions. Unlike nonsteroidal anti-inflammatory drugs, which primarily inhibit cyclooxygenase enzymes, diacerein suppresses interleukin-1β, a central mediator of synovial inflammation and cartilage degradation. It also modulates tumor necrosis factor-alpha and matrix metalloproteinases, thereby alleviating pain, decreasing inflammation, and preserving joint structure. This review of clinical and preclinical studies highlights the therapeutic potential of diacerein in RA management, focusing on its molecular mechanisms, clinical outcomes, and combination strategies with disease-modifying antirheumatic drugs (DMARDs) or biologics. Recent advances in drug delivery, including nanoparticle-based and sustained-release formulations, have further enhanced its bioavailability and efficacy. Diacerein effectively decreases joint swelling and stiffness, while demonstrating a superior gastrointestinal safety profile to nonsteroidal anti-inflammatory drugs. However, its slow onset of action and moderate efficacy as a monotherapy limit its standalone use. Combination therapy with DMARDs or biologics appears to potentiate its therapeutic benefits. Overall, diacerein is a valuable adjunctive agent in RA treatment. Further studies are warranted to optimize dosing regimens and delivery systems to improve clinical outcomes.