Role of polyphenolics in the management of rheumatoid arthritis through intracellular signaling pathways: a mechanistic review

Inflammation of the joints, bone erosion, and cartilage destruction are the main characteristics of rheumatoid arthritis (RA) which causes joint malfunction, structural distortion, and long-term impairment of function. According to various studies, RA affects 0.1–2.0% of people globally. It is unclear what causes RA, but multiple pathways have been associated with its pathophysiology. Non-steroidal anti-inflammatory drugs; NSAIDs (diclofenac, celecoxib, and ibuprofen), disease-modifying antirheumatic drugs; DMARDs (methotrexate, azathioprine, and cyclosporine), immunological compounds (rituximab, anakinra, and infliximab), and immune suppressants are the currently available options. However, they are associated with major side effects, like hypertension, hepatotoxicity, gastric ulcers, and kidney dysfunction which results in their limited use. To treat RA effectively, there is an urgent need for treatment options that offer minimal side effects. The dietary polyphenols have therapeutic effects on RA based on their antioxidant, apoptotic, anti-inflammatory, immunosuppressive, and immunomodulatory characteristics. At the molecular level, interleukin (IL)-6, mitogen-activated protein kinase (MAPK), tumor necrosis factor-alpha (TNF-alpha), interleukin 1b, c-Jun N-terminal kinase (JNK), and nuclear factor k light-chain-enhancer of activated B-cell (NF-kB) pathways play a critical role in modulation. Various polyphenolic compounds have been studied for their potential efficacy against RA, including genistein, resveratrol, carnosol, curcumin, epigallocatechin gallate, kaempferol, and hydroxyl tyrosol. However, it is noted that most of the studies are investigated on animal models of RA. The present review article discusses the underlying mechanisms that lead to RA and explores the promising role of polyphenols as potential therapeutic agents.