Molecular insights into phytochemicals exhibiting anti-arthritic activity: systematic review: John Di Battista

Introduction Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with an unclear etiology causing severe inflammation, joint pain, and destruction that increases the chance of disability over time. Dysregulation of various immune signaling cascades regulates the formation of synovial hyperplasia and pannus formation. Imbalance in cytokine levels, predominantly proinflammatory cytokines like TNF-α, IL-1, IL-6, IL-17, and IL-12p70 profoundly influences the disease's pathogenesis. Even though various strategies are adopted to treat arthritis, their side effects and cost limit their usage. This review discusses the multiple pathways involved in the pathogenesis of rheumatoid arthritis, provides a systematic analysis of various phytochemicals, and discusses their potential molecular targets in RA treatment. Methods The literature mining was done from scientific databases such as PubMed, Europe PMC, Web of Science, Scopus, etc. The terminologies used for literature mining were Rheumatoid arthritis, phytochemicals, cell signaling pathways, molecular mechanism, etc. Results NF-κB, MAPKs, and JAK–STAT are the key pathways potentially targeted for RA treatment. However, specific susceptible pathways and potential targets remain unexplored. Besides, the phytochemicals remain an immense source to be exploited for the effective treatment of RA, overcoming the demerits of the conventional strategies. Various in vitro and in vivo findings suggest that polyphenols and flavonoids effectively treat RA conditions overcoming the demerits, such as limitations in usage and toxicity. The phytochemicals should be explored in par with the pathological mechanisms with all the available targets to determine their therapeutic efficacy. Through the established therapeutic efficacy, phytochemicals can help developing therapeutics that are safe and efficacious for RA treatment.