UHPLC and Computational Studies of Chemical Constituents Derived from <i>Myrica esculenta</i> against NADPH Oxidase 2 (NOX2) Protein

Abstract Here, we employed a combination of UHPLC and in silico approaches to evaluate the inhibitory effects of compounds from the Myrica esculenta (M. esculenta) plant on NOX2 protein. Compounds from the methanol extract of this plant were examined using the UHPLC technique. Pharmacophore and ADMET studies used Ligandscout 4.4.5 and Swiss ADME tools respectively. Molecular docking, MD simulation (triplicate), and MMGBSA computation were performed using Schrödinger 2021–2 software. The UHPLC method demonstrated that methanol extract of M. esculenta contained six compounds: rutin, chlorogenic acid, fisetin, quercetin, myricetin, and fumaric acid. Pharmacophore modelling results revealed that all six compounds show a significant number of interacting functionalities in their pharmacophores, and ADMET suggested that they would be excellent drug leads for oral administration. In molecular docking studies, rutin had the highest docking score of −9.82 compared to reference compound ascorbic acid, which had a −7.80 docking score. The MD simulation data indicated that rutin was significantly stable within the binding pocket of NOX2, exploring tightly attachment throughout the simulation. Furthermore, the complex's Gibbs free energy was estimated using MMGBSA analysis, which validated its stability. We believe that our research has the potential to assist the scientific community in developing NOX2 inhibitors from M. esculenta for the management of ROS‐mediated diseases, with further use of in vitro and in vivo testing.