Available online 9 February 2023, 100640

Docking studies of various phytoestrogen with IκBα/NF-κB complex, key signalling complex for RA.

Comparative study between phytoestrogen and known synthetic inhibitors to be potential drugs.

Bavachin is the most effective phytoestrogen based on docking and in silico pharmacological studies.

PPI, GO and KEGG enrichment of Bavachin targets and respective molecular docking with Bavachin.

Bavachin targeting Vitamin D3 receptor is the most potent interaction in RA prevention

Causation of inflammation in chronic inflammatory diseases like Rheumatoid arthritis (RA) is mostly through NF-κB signaling pathway that has its activation via phosphorylation of IκBα/NF-κB complex leading to immediate polyubiquitination of IkB proteins causing NF-κB translocation followed by release of inflammatory cytokines. In this investigation, IκBα/NF-κB 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-κB.

The structure of IκBα/NF-κB 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-κB inhibitor drugs were then compared with IκBα/NF-κB complex demonstrating the potency of phytoestrogens to target NF-κB 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.

Bavachin, a flavonoid found in Psoralea corylifolia emerge as the most potent phytoestrogen to target NF-κB 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.

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.

Phytoestrogen

Rheumatoid arthritis

Inflammation

Molecular docking

phytomedicine

Bavachin

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