Network Pharmacology and Molecular Docking Reveal the Active Compounds and Key Targets of JiaWei SiNi San in Hepatocellular Carcinoma

Background This study aims to investigate the potential anti-tumor efficacy and mechanisms of JiaWei SiNi San (JWSNS) against hepatocellular carcinoma via network pharmacology. Methods The predicted active compounds of JWSNS were used to construct a TCM-active compound-target network. The drug targets were then subjected to pathway enrichment analysis and were intersected with differentially expressed genes (DEGs). Based on the resulting overlapping genes targets, a protein-protein interaction (PPI) network was developed. Cell experiments were performed to measure the expression levels of five key genes in hepatocellular carcinoma (HCC) cells. Immune infiltration analysis and gene set enrichment analysis (GSEA) were performed based on the identified key genes. Molecular docking was used to predict the binding affinity. Results Overlapping targets between the drug targets and DEGs were used to construct a protein-protein interaction (PPI) network, from which five key genes ( ESR1 , MMP9 , FOS , CDKN2A , and CDK1 ) were identified. Particularly, MMP9 was highly expressed in HCC cells, and its knockdown significantly inhibited cell viability, migration, and invasion. Additionally, molecular docking predicted that the active compounds of JWSNS, including quercetin, nobiletin, and luteolin, could bind to the MMP9 protein. However, these findings are mainly based on bioinformatics analysis and require further validation in vitro and in vivo . Conclusion Network pharmacology analysis showed the anti-HCC effects of JWSNS, providing a novel basis for further experimental verification.