Elucidation of the Mechanisms and Molecular Targets of Shuanglian Decoction for the Treatment of Hepatocellular Carcinoma Based on Network Pharmacology

Abstract

Shuanglian decoction (SLD) is traditionally used to treat hepatocellular carcinoma (HCC) in the clinical practice of traditional Chinese medicine. However, its mechanisms of action and molecular targets for the treatment of HCC are not clear. The active compounds of SLD were collected and their targets were identified. HCC-related targets were obtained by analyzing the differentially expressed genes between HCC patients and healthy individuals. Protein–protein interaction (PPI) data were then obtained and PPI networks of SLD putative targets and HCC-related targets were visualized and merged to identify the candidate targets for SLD against HCC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out. The gene-pathway network was constructed to screen the key target genes. In total, 35 active compounds and 31 targets of SLD were identified. In total, 245 differentially expressed genes with P values <0.005 and |log2 (fold change)| > 1 were identified between HCC patients and control groups, and 68 target genes associated with HCC were finally identified. Twenty-one pathways including cellular senescence, p53 signaling pathway, and cell cycle were significantly enriched. CYP3A4 was the core gene and other several genes including CYP1A2, PPP3CA, PTGS2, CCCNB1, and CDK1 were the key genes in the gene-pathway network of SLD for the treatment of HCC. The results indicated that SLD’s effects against HCC may relate to the regulation of an antioxidant function through specific biological processes and related pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of complex herbal formulations.