Computational Network Pharmacology, Molecular Docking, and Molecular Dynamics to Decipher Natural Compounds of Alchornea laxiflora for Liver Cancer Chemotherapy

Abstract

<b>Background:</b><i>Alchornea laxiflora</i> (Benth.) Pax & K. Hoffm. (<i>A. laxiflora</i>) is utilized as a traditional herb for treating several diseases. <b>Objective</b>: Our study aims to identify the active phytochemical candidates from <i>A. laxiflora</i> and analyses to predict their anticancer activity mechanism by employing network pharmacology, molecular docking, and molecular dynamics (MD). <b>Methods</b>: The phytoconstituents of <i>A. laxiflora</i> were retrieved from the literature, and phytoconstituent-related targets implicated in hepatocellular carcinoma (HCC) were collected from respective databases. Computational methods were employed to recognize essential compounds, hub gene targets, and signaling pathways. <b>Results</b>: Our study has identified 12 potentially bioactive compounds, 150 potential anti-HCC targets, and 15 hub gene targets for <i>A. laxiflora</i>. Molecular docking results recognized the better binding energy values of below -5.6 kcal/mol. Further, MD simulations of the three of the top-scoring protein-ligand complexes (MAPK-3-acetylursolic acid, AKT1-quercetin, and AKT1-3-acetylursolic acid) allowed us to validate the docking results, evaluate the stability of the complexes, and associated conformational changes. <b>Conclusions</b>: Our research claims that phytoconstituents of <i>A. laxiflora</i> are crucial for treating liver cancer, and the recognized protein targets can serve as biomarkers, respectively.