The Anti-Inflammatory Potential of Red Betel (Piper crocatum) Leaves Through Inhibitory Mechanism on Nfκb Signaling Pathway: Drug-Like Candidate Study

Abstract

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes inflammation of the synovial tissue bone as well as joint damage. Furthermore, an increase in the level of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α) due to overexpression in the nuclear factor-kappa B (NFκB) contributes to the progression of the disease. NFκB also plays an important role in the production, differentiation, and effector function of inflammatory T cells. Red betel (Piper crocatum) leaf (RBL) is an Indonesian herb, which contains bioactive compounds such as flavonoids, terpenoids, and phenolic compounds. It is widely used as an intervention for various diseases including inflammatory-related diseases. Therefore, this study aims to evaluate the therapeutic effect of RBL extract as an anti-inflammatory agent through inhibition on the TNF receptor 1(TNFR1), NFκB, and inhibitor kappa B kinase (IκK) by molecular docking study. Oral toxicity prediction was carried out before molecular docking. Molecular docking performed using PyRx 0.8 software. The amino acid residues analysis and visualization were conducted using the Biovia Discovery Studio and Pymol. The toxicity prediction using ProTox-II showed that RBL active compounds are categorized between the 4th-6th class. Furthermore, the compounds, specifically kaempferitrin and apigenin have greater binding affinity compared to the drug inhibitor in NFκB signalling pathway. Based on the results, RBL active compounds can potentially act as an anti-inflammatory agent in RA, but further studies must be carried out to explore the potency of RBL through in vitro and in vivo effects. Keywords: Red betel leaf, Molecular docking, Rheumatoid arthritis, Flavonoid