EXPLORING THE ROLE OF CURCUMIN INDUCED STAT3 INHIBITION IN RHEUMATOID ARTHRITIS TREATMENT

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune condition that mainly affects the joints, resulting in the degradation of tendons and ligaments. Typical symptoms of RA consist of inflamed and sensitive joints, fever, tiredness, and the formation of nodules beneath the skin called rheumatoid nodules. STAT3, which is a transcription factor, has a significant role in controlling the production of pro-inflammatory cytokines. The continuous activation of the JAK-STAT pathway, caused by cytokine signalling dysregulation, contributes to synovial inflammation. Hence, STAT3 inhibitors are essential to address the root cause of the disease rather than merely alleviating symptoms. Curcuma longa contains three primary curcuminoids: curcumin, desmethoxycurcumin, and bisdemethoxycurcumin. Curcumin, the active component, has demonstrated anti-inflammatory properties by modulating the JAK STAT pathway. It effectively inhibits STAT3 activation and downstream signalling by promoting its dephosphorylation. Consequently, curcumin serves as a ligand that inhibits STAT3 activity, thereby mitigating RA symptoms. This study focuses on evaluating the interaction between curcumin and STAT3 through molecular docking. In-silico assays have shown that curcumin reduces arthritis scores and enhances inflammatory infiltration. Docking studies can determine the binding affinity between ligands and proteins, offering predictions on the strength of their interaction. Our molecular docking analysis indicates that curcumin exhibits lower binding free energy compared to other well-known STAT3 inhibitors, suggesting its potential efficacy in targeting RA symptoms.