Background SiNiSan (SNS) is an ancient traditional Chinese medicine (TCM) used to treat liver and spleen deficiencies. We studied the unique advantages of using SNS to treat hepatocellular carcinoma (HCC) with multiple components and targets to determine its potential mechanism of action. Methods The active compounds from the individual herbs in the SNS formula and their targets were mined from Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). HCC-associated targets were collected from the TCGA and GEO databases and samples were collected from patients with stage III hepatocellular carcinoma. A compound-disease target network was constructed, visualized, and analyzed using Cytoscape software. We built a protein-protein interaction (PPI) network using the String database. We enriched and analyzed key targets using GSEA, GO, and KEGG in order to explore their functions. Autodock software was used to simulate the process of SNS molecules acting on HCC targets. Results A total of 113 candidate compounds were taken from SNS, and 64 of the same targets were chosen from HCC and SNS. The predominant targets genes were PTGS2, ESR1, CHEK1, CCNA2, NOS2 and AR; kaempferol and quercetin from SNS were the principal ingredients in HCC treatment. The compounds may work against HCC due to a cellular response to steroid hormones and histone phosphorylation. The P53 signaling pathway was significantly enriched in the gene set GSEA enrichment analysis and differential gene KEGG enrichment analysis. Conclusions Our results showed that the SNS component has a large number of stage III HCC targets. Among the targets, the sex hormone receptors, the AR and ESR1 genes, are the core targets of SNS component and the most active proteins in the PPI network. In addition, quercetin, which has the most targets, can act on the main targets (BAX, CDK1, CCNB1, SERPINE1, CHEK2, and IGFBP3) of the P53 pathway to treat HCC.

中文翻译：

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利用药物靶点与四逆散天然化合物之间的相互作用网络和分子对接确定新型候选抗肝细胞癌药物

背景 四逆散（SNS）是一种古老的传统中药（TCM），用于治疗肝脾不足。我们研究了使用 SNS 治疗多成分和靶点的肝细胞癌 (HCC) 的独特优势，以确定其潜在的作用机制。方法从中药系统药理学数据库（TCMSP）中挖掘SNS配方中单味药的活性成分及其作用靶点。HCC 相关靶点是从 TCGA 和 GEO 数据库中收集的，样本是从 III 期肝细胞癌患者中收集的。使用 Cytoscape 软件构建、可视化和分析复合疾病目标网络。我们使用 String 数据库构建了蛋白质-蛋白质相互作用 (PPI) 网络。我们使用 GSEA、GO 和 KEGG 丰富和分析了关键靶标，以探索其功能。采用Autodock软件模拟SNS分子作用于HCC靶点的过程。结果从SNS中总共筛选出113个候选化合物，从HCC和SNS中筛选出64个相同靶点。主要靶基因是PTGS2、ESR1、CHEK1、CCNA2、NOS2和AR；SNS 中的山奈酚和槲皮素是治疗 HCC 的主要成分。由于细胞对类固醇激素和组蛋白磷酸化的反应，这些化合物可能对抗肝癌。P53信号通路在基因集GSEA富集分析和差异基因KEGG富集分析中显着富集。结论 我们的结果表明，SNS 组件具有大量 III 期 HCC 靶标。其中，性激素受体AR和ESR1基因是SNS成分的核心靶点，也是PPI网络中最活跃的蛋白质。此外，靶点最多的槲皮素可以作用于P53通路的主要靶点（BAX、CDK1、CCNB1、SERPINE1、CHEK2和IGFBP3）来治疗HCC。