基于网络药理学研究三棱-莪术药对治疗肝细胞癌的作用机制

Mechanism of Sanleng(Sparganii Rhizoma)-Ezhu(Curcumae Rhizoma)Herbal Pair in Treatment of Hepatocellular Carcinoma Based on Network Pharmacology

目的:应用网络药理学的方法,研究三棱-莪术药对治疗肝细胞癌的作用机制。方法:通过中药系统药理数据库及分析平台(TCMSP)数据库以及手工查阅相关文献,搜集并整理三棱-莪术药物的活性成分及其靶标。通过人类孟德尔遗传数据库(OMIM)和人类基因数据库(Genecards)获得三棱-莪术药对治疗肝细胞癌潜在的靶标基因。使用Cytoscape 3.7.2软件建立相应的“成分-靶标”网络。结合String(functional protein association networks)数据库,构建其蛋白质相互作用网络。运用Bioconductor工具、R统计编程软件进行三棱-莪术药对的作用靶标进行相应的基因本体论(GO)分类富集分析以及京都基因与基因组百科全书(KEGG)通路富集分析。结果:共筛选得到6个活性成分,包括豆甾醇、β-谷固醇、丁芒柄花黄素等和39个作用靶标,包括雌激素受体1、雄激素受体、核受体共激活剂2、核受体亚家族3C组成员1、孕激素受体等,主要涉及神经活性配体-受体相互作用、雌激素信号转导途径、胆碱能突触等主要信号通路。结论:本研究基于网络药理学的方法初步预测了三棱-莪术药对治疗肝细胞癌的可能作用机制,三棱-莪术治疗肝细胞癌主要通过神经活性配体-受体相互作用、雌激素信号转导途径、胆碱能突触等信号通路发挥作用。

Objective:To study the possible action mechanism of Sanleng(Sparganii Rhizoma)-Ezhu(Curcumae Rhizoma)herbal pair on the treatment of hepatocellular carcinoma by means of network pharmacology.Methods:Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database and manual review of relevant literature,the active ingredients and their targets of Sanleng-Ezhu herbal pair were collected and sorted.Through Online Mendelian Inheritance in Man(OMIM)database and The Human Gene Database(Genecards)database,the potential target genes of Sanleng-Ezhu herbal pair for the treatment of liver cancer were obtained.Cytoscape 3.7.2 software was used to establish the corresponding“component-target”network.String(functional protein association networks)database was combined to construct its protein interaction network.Bioconductor tools and R statistical programming software were used to carry out the corresponding Gene Ontology(GO)classification and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis for the target of Sanleng-Ezhu herbal pair.Results:A total of 6 active ingredients were screened,including stigmasterol,β-sitosterol,formononetin,etc.and total 39 targets,including estrogen receptor 1,androgen receptor,nuclear receptor co-activator 2,nuclear receptor subfamily 3C group member 1,progesterone receptor,etc.,mainly involved in neuroactive ligand-receptor interactions,estrogen signal transduction pathways,cholinergic synapses and other major signal paths.Conclusions:Based on the method of network pharmacology,this study preliminarily predicted the possible action mechanism of Sanleng-Ezhu herbal pair on the treatment of hepatocellular carcinoma.Sanleng-Ezhu treat the disease mainly through the neuroactive ligand-receptor interaction and estrogen signal transduction pathways and signal pathway of cholinergic synapses,etc.