Exploring the mechanism of dihydroquercetin in the treatment of Hepatocellular carcinoma based on network pharmacology and experimental verification

Abstract Objective To investigate the effects and potential molecular mechanisms of dihydroquercetin (DHQ) on hepatocellular carcinoma through network pharmacology combined with experimental validation. Methods The active components and potential targets of emodin were obtained from the TCMSP database, while hepatocellular carcinoma-related genes were extracted from the GeneCards and OMIM databases. Common targets between the drug and disease were identified using an online Venn diagram tool. The protein-protein interaction (PPI) network was constructed using the STRING database and subsequently analyzed for visualization and topological features using Cytoscape 3.7.1 software. Cluster analysis of the PPI network was performed using the MCODE plugin. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using the clusterProfiler package in R 4.2.1 to explore the potential mechanisms of the compound's therapeutic effects, followed by construction of a component-target-pathway-disease network using Cytoscape.A "drug active component-target-disease" network was established to elucidate the potential therapeutic effects of dihydroquercetin (DHQ) on hepatocellular carcinoma. Experimental validation was performed using CCK-8 assay, colony formation assay, and flow cytometry to evaluate the effects of DHQ on the proliferation of HepG2、Huh7 cell and its regulation of key target genes. Result This study identified 131 targets related to dihydroquercetin compounds and 1073 disease-related targets; 46 intersecting targets; GO functional enrichment analysis mainly enriched 680 BP entries, 38 CC entries for cell composition, and 80 MF entries for molecular function (p.aj < 0.05); KEGG pathway enrichment analysis identified 138 (P < 0.05) significant signaling pathways; Molecular docking showed good affinity for the screened core targets ALB, caspase9, HSP90, and NFκB in the compound. Conclusion Research has shown that dihydroquercetin has a potential mechanism for multi-target and multi pathway treatment of Hepatocellular carcinoma.