Pharmacological modes of plant-derived compounds for targeting inflammation in rheumatoid arthritis: A comprehensive review on immunomodulatory perspective.

Background: Rheumatoid arthritis (RA) is one of the most prevalent autoimmune, chronic, inflammatory disease characterized by joint inflammation, synovial swelling, loss of articular structures, swelling, and pain. RA is a major cause of discomfort and disability worldwide, associated with infectious agents, genetic determinants, epigenetic factors, advancing age, obesity, and smoking. Although conventional therapies for RA alleviate the symptoms, but their long-term use is associated with significant side effects. This necessitates the urge to discover complementary and alternative medicine from natural products with minimum side effects.

Purpose: In this review, natural product's potential mechanism of action against RA has been documented in the setting of in-vivo, in-vitro and pre-clinical trials, which provides new treatment opportunities for RA patients. The bioefficacy of these natural product's bioactive compounds must be further studied to discover novel natural medications for RA with high selectivity, improved effectiveness, and economic replacement with minimum side effects.

Study Design And Methods: The current review article was designed systematically in chronological order. Plants and their phytochemicals are discussed in an order concerning their mode of action. All the mechanisms of action are depicted in diagrams which are thoroughly generated by the Chembiodraw to maintain the integrity of the work. Moreover, by incorporating the recent data with simple language which is not incorporated previously, we tried to provide a molecular insight to the readers of every level and ethnicity. Moreover, Google Scholar, PubMed, ResearchGate, and Science Direct databases were used to collect the data.

Solution: Traditionally, various plant extracts and bioactive compounds are effectively used against RA, but their comprehensive pharmacological mechanistic actions are rarely discussed. Therefore, the objective of this study is to systematically review the efficacy and proposed mechanisms of action of different plants and their bioactive compounds including Tripterygium wilfordii Hook F (celastrol and triptolide), Nigella sativa (thymoquinone), Zingiber officinale (shogaols, zingerone), Boswellia serrata (boswellic acids), Curcuma longa (curcumin), and Syzygium aromaticum (eugenol) against rheumatoid arthritis.

Conclusion: These plants have strong anti-inflammatory, anti-oxidant, and anti-arthritic effects in different study designs of rheumatoid arthritis with negligible side effects. Phytomedicines could revolutionize pharmacology as they act through alternative pathways hence seeming biocompatible.