基于网络药理学探讨四逆散治疗功能性消化不良的作用机制

Mechanism of Sini Powder in the Treatment of Functional Dyspepsia Based on Network Pharmacology

目的:本研究基于网络药理学和分子对接方法探讨四逆散治疗功能性消化不良的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)搜索四逆散中中药的活性成分与作用靶点,利用GeenCard、OMIM数据库搜索功能性消化不良的疾病靶点,利用R语言取得药物与疾病的共同靶点,通过Cytoscape3.7.2构建药物-疾病靶点网络,利用STRING平台构建蛋白质-蛋白质相互作用(PPI)网络图,通过DAVID进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。通过Autodock Tools 1.5.6对核心靶点和核心成分进行对接验证。结果:共筛选出四逆散活性成分144个,有效作用靶点223个,药物疾病共同靶点152个。PPI网络发现AKT1、IL-6、MARK、JUN、STAT3等可能是四逆散治疗功能性消化不良的关键靶点。GO功能富集发现了795个GO条目,KEGG通路富集分析共筛选出作用通路127条,主要富集基因数量较大的通路有PI3K-AKT信号通路、MAPK信号通路、TNF信号通路等。分子对接验证显示核心靶点和核心成分有较强的结合活性。结论:四逆散中的有效成分主要通过AKT1、IL-6、MARK、JUN、STAT3等靶点调节多条信号通路从而发挥治疗功能性消化不良的作用。

Objective:To explore the mechanism of Sini powder in the treatment of functional dyspepsia based on network pharmacology and molecular docking method.Methods:The effective components and corresponding target proteins of Sini Powder were screened by TCMSP,and the target of functional dyspepsia were screened by the GeenCards and OMIM data base.R software was used to obtain the common targets of drugs and diseases,and the“component-target-disease”network diagram was constructed by Cytoscape3.7.2 software.The STRING datebase was used to draw the protein interaction(PPI)network,and the DAVID was used to perform GO function and KEGG pathway enrichment analysis on effective targets.AutodockTools1.5.6 was used for docking verification of core targets and core components.Results:The result showed that 144 components were screened and 233 effective targets were screened.The 152 common targets were obtained.The PPI network found that AKT1,IL-6,MARK,JUN,STAT3,etc.may be the key targets for Sini Powder in treatment of functional dyspepsia.The GO function analysis found 795 items.The KEGG parhway analysis found 127 items,including enriched pathways with a large number of genes PI3K-Akt signaling pathway,MAPK signaling pathway,TNF signaling pathway and other pathways.The molecular docking shows that the core target and the core components have strong binding activity.Conclusion:The active components in Sini Powder mainly regulate multiple signaling pathways through targets such as AKT1,IL-6,MARK,JUN and STAT3,thus playing a role in the treatment of functional dyspepsia.