基于网络药理学探讨肝舒胶囊治疗砷中毒的作用机制

A study on the mechanism of treating arsenic poisoning with the Ganshu capsules based on network pharmacology

目的:通过网络药理学方法分析肝舒胶囊治疗砷中毒的潜在机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)、有机小分子生物活性数据库(PubChem)、化源网等数据库,结合相关文献研究筛选和预测肝舒胶囊有效活性成分和作用靶点,利用Cytoscape 3.9.1软件绘制药物-有效化合物-潜在作用靶点网络图。通过GeneCards、OMIM、PharmGkb、Drugbank数据库和相关文献筛选砷中毒的相关靶点,使用STRING数据库和Cytoscape软件对交集靶点构建蛋白质-蛋白质互作网络,并绘制韦恩图。通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)方法进行基因功能注释和信号通路分析,将结果进行可视化。结果:本研究共筛选得到肝舒胶囊相关活性成分131个、药物靶点454个,砷中毒相关靶点786个,交集靶点170个。进一步对交集靶点进行蛋白质-蛋白质相互作用网络分析,得到肿瘤蛋白p53(Tumor Protein p53,TP53)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、信号传导与转录激活因子3(Signal Transducer and Acctivator of Transcription 3,STAT3)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)和白细胞介素(Interleukin,IL)-6等核心靶点。GO富集分析发现肝舒胶囊可参与调控砷中毒进展中的激素反应、蛋白质磷酸化和氮化合物反应等生物进程。KEGG富集分析发现肝舒胶囊可通过磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)等信号通路调控砷中毒进展。结论:文章通过网络药理学方法探讨肝舒胶囊治疗砷中毒的现代医学机制,为肝舒胶囊对砷中毒药效靶点的发现和分子作用机制的阐明提供参考依据。

Objective:To analyze the potential mechanism of treating arsenic poisoning with the Ganshu capsules(肝舒胶囊)by network pharmacology.Methods:The active ingredients and targets of the Ganshu capsules were screened and predicted from TCMSP,PubChem,Chemsrc and other databases combined with relevant literature.Cytoscape 3.9.1 software was used to plot the network diagram of drug-effective compounds-potential targets.GeneCards,OMIM,PharmGkb,Drugbank and related literature were used to screen the related targets of arsenic poisoning.STRING database and Cytoscape software were used to construct the protein-protein interaction network of intersection targets,and Venn diagram was drawn.Gene function annotation and signal pathway analysis were conducted through GO and KEGG methods,and the results were visualized.Results:Based on different database analysis,131 activity component and 454 related targets of the Ganshu capsules,and 786 related targets of arsenic poisoning were screened.There were 170 intersection targets of the Ganshu capsules and arsenic poisoning.Further protein-protein interaction network analysis of intersection targets obtained core targets such as TP53,AKT1,STAT3,EGFR and IL-6.GO enrichment analysis found that the Ganshu capsules can regulate biological processes such as response to hormone,protein phosphorylation and cellular response to nitrogen compound.KEGG pathway analysis showed that the Ganshu capsules may act on pathways such PI3K-Akt signaling pathway.Conclusion:This study explored the modern mechanism of treating arsenic poisoning with the Ganshu capsules through network pharmacology,providing reference for exploring the drug efficacy targets and molecular action mechanisms of treating arsenic poisoning with the Ganshu capsules.