基于网络药理学探讨葛花-枳椇子药对治疗酒精性肝病的作用机制

Mechanism of Flos Puerariae and Hovenia dulcis Thunb on alcoholic liver disease based on network pharmacology

目的:基于网络药理学方法探讨葛花-枳椇子药对治疗酒精性肝病(ALD)的分子生物学作用机制。方法:利用TCMSP在线数据库检索并获取葛花-枳椇子的活性成分及各成分对应的作用靶点,再根据ADME筛选出合适的中药活性组分。通过检索GeneCards、OMIM、TTD、DRUGBANK、DisGeNET、CTD、PharmGkb及DiGSeE数据库,获得ALD相关疾病靶点。将药物与疾病共同靶点提取后利用STRING数据库进行蛋白互作网络分析并构建PPI网络;利用Cytoscape 3.7.1软件对关键靶点进行网络拓扑学分析,获取葛花-枳椇子治疗ALD的核心作用靶点,再利用DAVID在线工具对核心靶点进行GO及KEGG富集分析,最后构建“化学成分-核心靶点-关键通路”的多层次网络关联图。结果:共筛选出葛花-枳椇子药对活性成分23个,潜在靶点222个,ALD的相关潜在靶点1523个,药物-疾病的交集靶基因131个,主要活性成分为槲皮素、山奈酚、β谷甾醇、豆甾醇等,核心靶点有APP、NTRK1、TP53、EGFR、CUL3、XPO1、ESR1、MCM2、UBC、FN1、CDK2、HSP90AA1、COPS5、RNF2、MYC、CUL7、SIRT7、GRB2、CUL1、CAND1等,涉及624个生物学过程、111种分子功能、72个细胞组分、123条信号通路,作用机制可能与癌症通路、乙型肝炎、PI3K-Akt信号通路、肿瘤坏死因子信号通路等有关。结论:揭示了葛花-枳椇子药对治疗ALD的“多靶点-多通路-多作用”作用机制,为进一步验证该作用机制提供了基础,也为临床推广、运用葛花-枳椇子药对治疗ALD提供科学依据。

Objective:To explore the molecular biological mechanism of Flos Puerariae and Hovenia dulcis Thunb on alcoholic liver disease(ALD)based on network pharmacology.Methods:Tcmsp online database was used to search and obtain the active components of Flos Puerariae and Hovenia dulcis Thunb and the corresponding target of each component,and then the appropriate active components of traditional Chinese medicine were screened according to ADME.ALD related disease targets were obtained by searching GeneCards,OMIM,TTD,DrugBank,DisGeNET、CTD、PharmGkb and digsee databases.After extracting the common target of drugs and diseases,the protein interaction network was analyzed by string database and PPI network was constructed 3.7.1 software for network topology analysis of key targets,to obtain the core target of Flos Puerariae-Hovenia dulcis Thunb in the treatment of alcoholic liver disease,and then use DAVID online tool to analyze the core target for go and KEGG enrichment,and finally construct the multi-level network association diagram of"chemical composition core target key pathway".Results:a total of 23 active components,222 potential targets,1523 potential targets for alcoholic liver disease,131 target genes for drug disease intersection were screened.The main active components were quercetin,kaempferol,β-sitosterol,stigmasterol,etc.the core targets were APP,NTRK1,TP53,EGFR,CUL3,XPO1,ESR1,MCM2,UBC,FN1,CDK2,HSP90AA1,COPS5,RNF2,MYC,CUL7,SIRT7,GRB2,CUL1,CAND1,etc.Involve 624 biological processes,111 molecular functions,72 cell components and 123 signal pathways.The mechanism of action may be related to cancer pathway,hepatitis B,PI3K-Akt signaling pathway and tumor necrosis factor signaling pathway.Conclusion:This study preliminarily revealed the mechanism of"multi target-multi pathway-multi effect"of Flos Puerariae-Hovenia dulcis Thunb in the treatment of ALD,which provided the basis for further verification of the mechanism,and also provided scientific basis for clinical promotion and application of Flos Puerariae-Hovenia dulcis Thunb in the treatment of alcoholic liver disease.