Introduction: Causation of inflammation in chronic inflammatory diseases like Rheumatoid arthritis (RA) is mostly through NF-kappa B signaling pathway that has its activation via phosphorylation of I kappa B alpha/NF-kappa B complex leading to immediate polyubiquitination of IkB proteins causing NF-kappa B translocation followed by release of inflammatory cytokines. In this investigation, I kappa B alpha/NF-kappa B complex was targeted by various selected phytoestrogens by in silico analysis to screen out the most appropriate phytoestrogen that may suppress the activity of NF-kappa B. Methods: The structure of I kappa B alpha/NF-kappa B complex and various phytoestrogens, screened by literature survey were retrieved from Protein Data Bank (PDB) database and PubChem database respectively followed by molecular docking analysis using AutoDock Vina. The docked results of commonly used NF-kappa B inhibitor drugs were then compared with I kappa B alpha/NF-kappa B complex demonstrating the potency of phytoestrogens to target NF-kappa B with nearly equivalent binding energies as that of popularly used synthetic drugs. Further pharmacological and preclinical trial analyses of the phytoestrogens were performed by SWISS ADME and PKCSM software. Results: Bavachin, a flavonoid found in Psoralea corylifolia emerge as the most potent phytoestrogen to target NF kappa B activation with highest binding energy of - 8.7 Kcal /mol and satisfying all the pharmacological parameters. Protein-protein interaction (PPI) networks of the potential targets of Bavachin associated to RA were constructed and GO and KEGG enrichment analysis were performed. Conclusion: Phytoestrogen Bavachin can be utilized as an alternative to commonly used synthesized drugs for targeting specific disease related targets leading to the reduction in inflammation in chronic diseases like RA with less or minimal side effects.

Assessment of the potential therapeutic benefits offered by naturally occurring phytoestrogens necessitate inspection of their potency and sites of action in impeding the chronic, systemic, autoimmune, joint destructing disorder Rheumatoid arthritis (RA). Possessing structural and functional similarity with human estrogen, phytoestrogen promisingly replaces the use of hormone therapy in eradicating RA symptoms with their anti-inflammatory, anti-oxidative, anti-proliferative, anti-angiogenesis, immunomodulatory, joint protection properties abolishing the harmful side effects of synthetic drugs. Scientific evidences revealed that use of phytoestrogens from different chemical categories including flavonoids, alkaloids, stilbenoids derived from different plant species manifest beneficial effects on RA through various cellular mechanisms including suppression of pro‐inflammatory cytokines in particular tumor necrosis factor (TNF-α), interleukin(IL-6) and nuclear factor kappa B (NF-κB) and destructive metalloproteinases, inhibition of oxidative stress, suppressing inflammatory signalling pathways, attenuating osteoclastogenesis ameliorating cartilage degradation and bone erosion. This review summarizes the evidences of different phytoestrogen treatment and their pharmacological mechanisms in both in vitro and in vivo studies along with discussing clinical evaluations in RA patients showing phytoestrogen as a promising agent for RA therapy. Further investigations and more clinical trials are mandatory to clarify the utility of these plant derived compounds in RA prevention and in managing oestrogen deficient diseases in patients.