Exploring the role of polyphenols in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory and autoimmune disorder which is mainly characterized by inflammation in joints, bone erosions and cartilaginous destruction that leads to joint dysfunction, deformation, and/or permanent functional impairment. The prevalence of RA is increasing, incurring a considerable burden on healthcare systems globally. The exact etiology of RA is unknown, with various pathways implicated in its pathophysiology. Non-steroidal anti-inflammatory drugs (NSAIDs) including celecoxib, diclofenac and ibuprofen, disease-modifying anti-rheumatic drugs (DMARD) including azathioprine, methotrexate and cyclosporine, biological agents including anakinra, infliximab, and rituximab and immunosuppressants are used for symptomatic relief in patients with RA, but these medications have severe adverse effects such as gastric ulcers, hypertension, hepatotoxicity and renal abnormalities which restrict their use in the treatment of RA; new RA treatments with minimal side-effects are urgently required. There is accumulating evidence that dietary polyphenols may show therapeutic efficacy in RA through their antioxidant, anti-inflammatory, apoptotic, and immunosuppressant activities and modulation of the tumor necrosis factor-α (TNF-α), interleukin (IL)-6, mitogen-activated protein kinase (MAPK), IL-1β, c-Jun N-terminal kinase (JNK), and nuclear factor κ light-chain-enhancer of activated B cell (NF-κB) pathways. While resveratrol, genistein, carnosol, epigallocatechin gallate, curcumin, kaempferol, and hydroxytyrosol have also been studied for the treatment of RA, the majority of data are derived from animal models. Here, we review the various pathways involved in the development of RA and the preclinical and clinical data supporting polyphenols as potential therapeutic agents in RA patients. Our review highlights that high-quality clinical studies are required to decisively establish the anti-rheumatic efficacy of polyphenolic compounds.