Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with limited therapeutic options and poor long-term survival. Hypericum japonicum Thunb. (Tianjihuang), a traditional Chinese medicine exhibits promising anticancer properties. This study aims to elucidate the multi-target mechanisms of Tianjihuang in treating HCC using network pharmacology and molecular docking techniques. METHODS: The active components of Tianjihuang and their targets were retrieved from TCMSP, PubChem, and Swiss Target Prediction databases. HCC-related targets were identified using GeneCard, OMIM, and TTD databases, and overlapping targets were analyzed. Protein-protein interaction (PPI) networks were constructed and analyzed using Cytoscape. Functional enrichment analysis of key targets was performed via GO and KEGG pathways. Kaplan-Meier curves assessed the clinical relevance of core targets, and molecular docking evaluated the binding affinities between Tianjihuang components and key targets. RESULTS: Tianjihuang contained seven bioactive components targeting 207 genes, with 77 overlapping HCC-related targets. PPI analysis identified key targets, including AKT1, STAT3, EGFR, and ESR1, which play pivotal roles in HCC pathogenesis. GO and KEGG analysis revealed that Tianjihuang's anti-HCC effects involve multiple biological processes and pathways, such as cell proliferation, apoptosis, and PI3K-Akt signaling. Molecular docking results showed high binding affinities of key components, such as quercetin and gallic acid, with core targets supporting their potential therapeutic effects. CONCLUSION: This study demonstrates that Tianjihuang exerts its anti-HCC effects through a multi-component, multi-target, and multi-pathway mechanism. These findings provide a scientific foundation for the clinical application of Tianjihuang and highlight its potential as a complementary therapy for HCC.