Phytochemicals targeting transforming growth factor (TGF)-β and inducible nitric oxide synthase to treat rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is characterized by inflammation, progressively affects joints and causes disability. The pathogenesis of RA consists of various steps including synovial hyperplasia, inflammation, and tissue damage, which at the end results in joint destruction. Transforming growth factor beta (TGF-β) and inducible nitric oxide synthase (iNOS) are the two key targets for the treatment of RA. TGF-β is a mediator protein that has multifaceted functions, and it possesses both proinflammatory and anti-inflammatory activities depending on certain conditions. TGF-β plays its proinflammatory role by the overexpression of cytokines like interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), which results in RA. TGF-β is also known as a chemoattractant for immune cells, which results in worsening inflammation in RA. While iNOS causes inflammation, it also causes tissue damage when produced in excess as in autoimmune disorders. There is an increase in levels of iNOS in the synovium of RA. Downregulation of iNOS reduces bone erosion and necrosis. We can reduce the progression of RA by targeting TGF-β and iNOS. Natural compounds targeting TGF-β and iNOS offer a potential approach to treat RA. Genkwanin, Kaempferol, Berberine, Rutin, Andrographolide, Arctigenin, 6-Shogaol, Curcumin, Chlorogenic acid, and Licochalcone A, Licochalcone C are the phytochemicals that reduce inflammation and give a potential therapeutic approach to treat RA. These phytoconstituents play the role by inhibiting NO, IL-1β, IL-6, and Prostaglandin E2 (PGE2) production, suppressing the NF-κB pathway also by influencing TNF-α and TGF-β levels and blocking JAK-2. Phytoconstituents offer promising therapeutic potential by modulating various inflammatory pathways and mediators.