基于网络药理学与分子对接技术探讨釜底抽薪散治疗儿童急性上呼吸道感染发热的机制

Mechanism of Fudi Chouxin Powder in the Treatment of Acute Upper Respiratory Tract Infection with Fever in Children Based on Network Pharmacology and Molecular Docking Technology

目的:基于网络药理学和分子对接技术,探讨釜底抽薪散治疗儿童急性上呼吸道感染发热的分子机制。方法:通过中药系统药理学数据库和分析平台(TCMSP)检索釜底抽薪散各组成药物的化学成分及靶点;通过在线人类孟德尔遗传(OMIM)、GeneCards等数据库查找急性上呼吸道感染发热的疾病靶点;通过STRING数据库绘制蛋白相互作用(PPI)网络,筛选出核心靶点;通过DAVID数据库对核心靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析;采用AutoDock软件进行活性成分与靶点的分子对接验证。结果:共检索到釜底抽薪散活性成分61个,成分相关靶点211个,急性上呼吸道感染发热相关靶点3874个,映射后获得潜在靶点131个。分析后最终获得釜底抽薪散治疗急性上呼吸道感染发热的主要活性成分(槲皮素、β-谷甾醇、异鼠李素、小檗碱、芦荟大黄素、黄藤素等)和27个核心靶点。GO功能富集分析得到GO条目287个,KEGG通路富集筛选得到62个信号通路,主要涉及炎症、病毒感染相关信号通路。分子对接显示槲皮素、β-谷甾醇等主要成分与关键靶点结合稳定。结论:釜底抽薪散通过多组分、多靶点及多通路协调作用治疗儿童急性上呼吸道感染发热,方中槲皮素、β-谷甾醇等成分可与AKT1、白细胞介素(IL)-6、IL-1β等多个靶点结合,通过肿瘤坏死因子(TNF)、IL-17、低氧诱导因子-1(HIF-1)、丝裂原活化蛋白激酶(MAPK)等信号通路调控炎症反应、抗病毒等生物学过程发挥治疗作用。

Objective:To explore the molecular mechanism of Fudi Chouxin powder in the treatment of acute upper respiratory tract infection with fever in children based on network pharmacology and molecular docking.Methods:The chemical components and targets of Fudi Chouxin powder were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The disease targets of acute upper respiratory tract infection with fever were searched through Online Mendelian Inheritance in Man(OMIM),GeneCards and other databases.The protein-protein interaction(PPI)network was plotted by STRING database and the core target was screened out.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for core targets by using the DAVID database.AutoDock software was used to verify the molecular docking between the active components and targets.Results:A total of 61 active components were selected,including 211 components related targets,3,874 acute upper respiratory tract infection with fever related targets,and 131 potential targets were obtained after mapping.The main active components(quercetin,β-sitosterol,isorhamnetin,berberine,aloe-emodin and palmatine)and 27 core targets of Fudi Chouxin powder in the treatment of acute upper respiratory tract infection with fever were finally obtained.Totally 287 items were obtained by GO functional enrichment analysis,and 62 signal pathways were obtained by KEGG pathway enrichment screening,mainly including inflammation and viral infection related signaling pathways.Molecular docking showed that quercetin,β-sitosterol and other major components bound to the receptor stably.Conclusion:Fudi Chouxin powder can treat acute upper respiratory tract infection with fever through multi-component,multi-target and multi-pathway coordination.The active components,such as quercetin,β-sitosterol,can bind to AKT1,interleukin-6(IL)-6,IL-1βand other targets,through tumor necrosis factor(TNF),IL-17,hypoxic-induced-factor-1(HIF-1),mitogen-activated protein kinase(MAPK)and other signaling pathways to regulate inflammatory response,antiviral and other biological processes to play its therapeutic role.