Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, often arising from chronic liver diseases such as cirrhosis and hepatitis. Despite progress in existing treatments, therapeutic efficacy in advanced HCC remains limited. This study aims to investigate the therapeutic potential of jatrorrhizine, a naturally occurring isoquinoline alkaloid, against HCC using integrative computational approaches to elucidate its molecular targets, signaling pathways, and binding stability. A network pharmacology approach was employed to identify key molecular targets and signaling pathways associated with jatrorrhizine in HCC. Protein–protein interaction (PPI) network construction, Gene Ontology (GO) analysis, and KEGG pathway enrichment were performed to elucidate its multi-target regulatory mechanisms. Molecular docking studies were conducted to predict the binding affinity and interaction patterns of jatrorrhizine with core HCC-related proteins. Furthermore, molecular dynamics (MD) simulations were performed to evaluate the structural stability, conformational behavior, and dynamic interactions of the protein–ligand complexes over time. Network analysis revealed that jatrorrhizine interacts with multiple targets involved in cell proliferation, apoptosis, and inflammatory responses, including AKT1 and MAPK1. Enrichment analysis highlighted significant involvement of PI3K–Akt and MAPK signaling pathways. Molecular docking demonstrated favorable binding affinities with key oncogenic proteins, while MD simulation results confirmed the stability and persistence of jatrorrhizine within the binding pockets, supporting the reliability of the predicted docking poses. This integrative in-silico study suggests that jatrorrhizine may exert a multi-targeted therapeutic effect against HCC by modulating critical oncogenic pathways and maintaining stable protein–ligand interactions. These findings provide a robust computational foundation for future in vitro and in vivo validation studies.
MATE et al. (Fri,) studied this question.