EXPLORING THE ROLE OF PHYTOCHEMICALS INDUCED JAK2 INHIBITION IN RHEUMATOID ARTHRITIS TREATMENT

Abstract

Rheumatoid Arthritis (RA) is a chronic autoimmune disease that mostly affects the joints, and causes the weakening of tendons and ligaments. The common symptoms of RA include tender joints, fever, fatigue, and often rheumatoid nodules under the skin. JAK2 is a tyrosine kinase that regulates the expression of pro-inflammatory cytokines. Persistent activation of the JAK-STAT pathway is due to the dysregulation of cytokine signaling contributing to synovial inflammation. Therefore, JAK2 inhibitors are required to treat the underlying disease rather than only curing symptoms. The phytochemicals such as ellagic acid, quercetin, curcumin and andrographolide have shown anti-inflammatory effects through modulation of the JAK-STAT pathway. These phytochemicals inhibits the phosphorylation of JAK2, which in turn reduces STAT transcription protein phosphorylation, regulating the overall JAK/STAT signalling, thus attenuating inflammation. So, for this we use ligands i.e. ellagic acid, quercetin, curcumin etc. which inhibits the activity of JAK2 protein, thus reducing the symptoms of RA. We are essentially assessing the interaction between the ligand and the protein while working on molecular docking. In-silico, assays demonstrated that curcumin reduced arthritis scores and enhanced inflammatory infiltration. Docking studies can show the binding affinity between ligands and proteins, thus providing predictions on the strength of their potential interaction. So, using molecular docking we infer that phytochemicals taken have a higher negative binding affinity than approved JAK inhibitor tofacitinib and can target RA symptoms.