基于网络药理学对人参抗脓毒症效应的分子机制研究

Molecular Mechanism for Anti-Sepsis Effects of Ginseng Based on Network Pharmacology

目的:基于网络药理学方法研究人参抗脓毒症的分子机制,为新药研发及中药人参的拓展应用提供理论依据。方法:通过中药系统药理数据库及分析平台(TCMSP)获取人参的有效成分及有效成分作用靶点;通过GeneCards、DrugBank和OMIM数据库预测脓毒症相关靶点,并运用Uniprot数据库规范靶点的基因名称,利用STRING平台进行蛋白质相互作用分析,然后采用Cytoscape3.7.2软件构建“有效成分-靶点-信号通路”相互作用网络,最后采用Metascape平台进行GO(Gene Ontology)生物功能分析和KEGG(Kyoto Encyclopedia of Genes and Genomes)通路富集。结果:经筛选获得人参有效成分17种,人参-脓毒症交集靶点43个,其中核心靶点包括AKT1、TNF、CASP3、MAPK8、IL1B、PTGS2、JUN、ICAM1、NOS3、VCAM1、PPARG等。GO分析获得1064条生物过程(P<0.01),KEGG富集得到102条信号通路(P<0.01),其中直接与脓毒症相关的信号通路包括TNF、NF-κB、Th17细胞分化、IL-17以及Toll样受体等信号通路。结论:人参可能通过对物质代谢、信号转导、炎症反应等多靶点及多通路的调节从而发挥抗脓毒症效应。

Objective:To investigate the molecular mechanism for anti-sepsis effects of Ginseng based on network pharmacology,thus to provide theoretic basis for the development of new drug and extended application of Ginseng.Methods:The active ingredients and targets of Ginseng were studied by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The GeneCards,OMIM and DrugBank databases were searched to obtain target datasets for sepsis,and the gene name of the targets were standardized by using Uniprot database.With the help of Cytoscape software,a network model of"active ingredient-target-signal pathway"was constructed,and the protein-protein interaction(PPI)network was drawn using the STRING platform,and Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were also performed on the relevant targets of anti-sepsis effects of Ginseng by using Metascape platform.Results:After the screening,17 core active ingredients of Ginseng and 43 Ginseng-sepsis drug-disease common targets were obtained,of which AKT1,TNF,CASP3,MAPK8,IL1B,PTGS2,JUN,ICAM1,NOS3,VCAM1,PPARG may be the key regulatory genes of anti-sepsis effects of Ginseng.GO analysis obtained 1,064 signals(P<0.01).KEGG analysis obtained 102 signal pathways(P<0.01),of which the signal pathways related to sepsis included TNF signal pathway,NF-κB signal pathway,Th17 cell differentiation signal pathway,IL-17 signal pathway and Toll-like receptor signal pathway.Conclusion:Ginseng has a synergistic effect on the treatment of sepsis through multi-targets,multi-pathways and multiple signal pathways,such as substance metabolism,signal transduction and inflammation.