基于网络药理学方法探究药对人参-熟地黄抗衰老的作用及分子机制

Anti-aging effects and molecular mechanisms of ginseng-rehmannia glutinosa based on network pharmacology

目的:探讨人参-熟地黄药对抗衰老的网络药理学作用及分子机制。方法:运用中药系统药理学数据库平台(Traditional Chinese Medicine System Pharmacology Database Platform,TCMSP)筛选人参、熟地黄的潜在活性化合物及靶点蛋白,在蛋白质数据库(Uniprot)中进行基因转换,借助人类基因数据库(GeneCards)检索与衰老相关的基因,导入Cytoscape 3.6.1软件构建“成分-基因-疾病”网络图,采用蛋白质相互作用数据库(String)构建蛋白质相互作用网络(Protein-protein Interaction Network,PPI),利用“CentiScape 2.2”功能进行网络拓扑属性分析,筛选出核心靶点,最后进行生物功能注释(Gene Ontology,GO)基因分析和京都基因及基因组百科全书(Kyoto Gene and Genome Encyclopedia,KEGG)代谢通路富集分析。结果:共检索出人参-熟地黄药对18种潜在活性化合物和115个相应靶基因,以及4511个衰老相关靶基因,通过Cytoscape 3.6.1软件进行网络构建,共获得17种与疾病相关的活性成分及75个靶点基因,结合PPI网络互作图,人参-熟地黄药对主要通过调控RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、转录因子P65(RELA)、丝裂原激活蛋白激酶8(Mitogen-activated Protein Kinases 8,MAPK8)、核因子κB抑制剂α(NFKBIA)等靶点,TNF信号通路、Toll样信号通路等信号通路发挥抗衰老作用。结论:人参-熟地黄药对抗衰老的作用是多成分、多靶点、多途径的,这为实验室及临床进一步探究药对抗衰老作用的机制提供了一定依据。

Objective:To explore the network pharmacological effects and molecular mechanisms of ginseng-rehmannia glutinosa on aging.Methods:The potential active compounds and target proteins of ginseng and rehmannia glutinosa was screened by TCMSP.The gene conversion was performed in Uniprot,and the genes related to aging were retrieved by GeneCards database and imported Cytoscape 3.6.1 software to build a component-gene-disease network diagram.A PPI was constructed by String database,and network topology attribute analysis was performed by CentiScape 2.2 function,to screen out core targets point,and finally to perform GO gene analysis and KEGG metabolic pathway enrichment analysis.Results:18 potential active compounds and 115 corresponding target genes and 4511 senescencerelated target genes were retrieved from ginseng-rehmannia glutinosa.Accroding to the network construction of Cytoscape 3.6.1 software,17 disease-related active ingredients and 75 target genes were obtained.Combined with PPI network interaction mapping,ginseng-rehmannia glutinosa medicines play an anti-aging role by regulating AKT1,TNF,RELA,MAPK8,NFKBIA and other targets,TNF signal pathway,Tolllike signal pathway and other signal pathways.Conclusion:The anti-aging effect of ginseng-rehmannia glutinosa is multi-component,multitarget and multi-path,which provides a certain basis for further investigation of the anti-aging mechanism of drugs in the laboratory and clinic.