Drug target screening for Rheumatoid Arthritis by Curcuma caesia through computational approach

Abstract

Curcuma caesia has been a subject of inflammatory and autoimmune disease research, showing promising anti-inflammatory properties. The present research aims to investigate the anti-rheumatic potential of the rhizome through network pharmacology, molecular docking and molecular dynamic simulations approaches. Phytocompounds were retrieved from PubChem, and their targets were predicted using Swiss target prediction, SEA, SuperPred, and BindingDB. The 13 phytocompounds overlapping with its 41 predicted proteins and its related pathways generated a Cytoscape interaction network revealing that C. caesia may inhibit rheumatoid arthritis through different metabolic pathways. NFKB1, PRKCA, RAC1, STAT3, and TLR4 were identified as potential core targets while 13 compounds α-Terpineol, Ar-tumerone, 3,3,8,8-tetramethyl-tricyclo[5.1.0.0(2,4)] oct-5-ene-5-propanoic acid (TPA), Rosifoliol, 2-Nonanone, Terpinen-4-ol, Dihydrocarveol, 5-Nonanone, Camphene, Linalool, Bornyl acetate, Camphor were identified as potential core compounds. Molecular docking and Induced Fit Docking (IFD) analysis revealed that NFKB1, PRKCA, and RAC1, along with the newly discovered TPA compound, are the most significant targets and bioactive compounds, respectively. Furthermore, in interactions such as TPA-RAC1, TPA might be a potential "chelating ligand" and may play a role in lowering concentrations of metal in blood. In addition, the molecular dynamics simulation (MDS) studies for 200 ns elucidated the binding mechanism of TPA with NFKB1, PRKCA and RAC1. In conclusion, TPA has a promising inhibiting potential against Rheumatoid Arthritis and thus necessitates further validation through in vitro and in vivo experiments.Therefore, the present study revealed the main mechanisms behind the anti-rheumatic effects of C. caesia, paving the path for further research on these compounds.