Prediction of Multi-targeting Pharmacological Activity of Bioactive Compounds from Medicinal Plants Against...

The primary objective of this study was to identify bioactive compounds from four medicinal plants with multi-targeting activity against hepatocellular carcinoma (HCC). A comprehensive analysis led to the identification of a subset of compounds possessing favorable drug-likeness, pharmacokinetics, and absence of toxicity profiles. Target analysis for 42 phytochemicals revealed 210 potential targets associated with HCC. Protein-protein interaction (PPI) analysis of these targets uncovered five critical hub genes, STAT3, SRC, AKT1, MAPK3, and EGFR, in our study. Correlation analysis of these hub genes indicated a strong positive correlation between EGFR, MAPK3, and SRC expression highlighting their interconnected roles in HCC. Survival analysis underscored the significant prognostic role of these hub genes in HCC underscoring their potential as biomarkers. The co-expression analysis unveiled an intricate network of interactions among the hub genes, while the enrichment analysis demonstrated their enrichment in diverse biological and signaling pathways related to HCC. Molecular docking analysis between the seven phytochemicals and five identified targets revealed that bauerenol exhibited good affinity towards all the targets. Subsequent molecular dynamics (MD) simulations demonstrated that bauerenol formed stable complexes with STAT3, AKT1, EGFR, and MAPK3, suggesting its potential as a multi-targeted inhibitor. Our research suggests that bauerenol shows promise as an inhibitor for HCC targets and stands out as a notable lead compound. However, further experimental studies are necessary to confirm its activity and to evaluate its potential as a therapeutic agent for HCC.