抗支糖浆治疗咳嗽变异性哮喘作用机制网络药理学分析

Network pharmacological analysis on the mechanism of Kangzhi Syrup in treating cough variant asthma

目的基于网络药理学探讨抗支糖浆治疗咳嗽变异性哮喘(CVA)的靶点和作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)获取抗支糖浆中主要活性成分及其相关靶点,通过在线人类孟德尔遗传数据系统(OMIM)、Gene Cards数据库获取CVA相关靶点,采用Venny 2.1绘制抗支糖浆靶点与CVA疾病靶点的韦恩图,采用Cytoscape 3.6.1软件构建中药靶点网络,并应用STRING平台构建蛋白相互作用网络,应用R语言软件对关键靶点进行GO富集分析和KEGG通路富集分析。结果共获得136个活性成分,160个药物与CVA相关靶点,主要活性成分为豆甾醇、β-谷固醇、槲皮素、儿茶素、木犀草素、山奈酚等。PPI网络中核心基因为蛋白激酶B(AKT1)、白细胞介素(IL)-6、半胱氨酸蛋白酶3(CASP3)、IL-1β、JUN等;GO功能富集后富集数目较多的有受体-配体活性、细胞因子受体结合、细胞因子活性、血红素结合等;KEGG富集通路分析显示抗支糖浆治疗CVA主要通路有脂质与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路以及IL-17信号通路、肿瘤坏死因子信号通路等为主;KEGG通路与基因之间的网络图中关联数量较多的基因主要有IL-1β、NFKBIA、IL-6、CHUK、CXCL8、JUN、CASP3等。结论初步验证了抗支糖浆的药效基础,主要成分及靶点均显示具有较好的结合性能,可为抗支糖浆治疗CVA提供理论基础。

Objective To explore the therapeutic target and mechanism of Kangzhi Syrup in the treatment of cough variant asthma(CVA)based on network pharmacology.Methods The main active ingredients and related targets in Kangzhi Syrup were obtained through Traditional Chinese Medicine Systems Pharmacology(TCMSP),and CVA related targets were obtained through On-line Mendelian Inheritance in Man(OMIM)and Gene Cards databases.Venny 2.1 was used to draw the Venn diagram of Kangzhi Syrup target and CVA disease target,Cytoscape 3.6.1 software was used to build the Traditional Chinese Medicine-target network,STRING platform was used to construct the protein interaction network,and R language was used to perform GO enrichment analysis and KEGG pathway enrichment analysis on key targets.Results A total of 136 active components,and 160 drug-targets related to CVA were obtained.The main active components were stigmasterol,β-sitosterol,quercetin,(+)-catechin,luteolin,kaempferol,etc.The core genes in PPI network included AKT1,IL-6,CASP3,IL-1β,JUN etc.After GO function enrichment,there were more receptor-ligand activity,cytokine receptor binding,cytokine activity,heme binding and so on.KEGG pathway enrichment analysis showed that the main pathways of Kangzhi Syrup in the treatment of CVA were lipid and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,TNF signaling pathway and other pathways.The genes with more associations in the network map between KEGG pathway and genes included mainly IL-1β,NFKBIA,IL-6,CHUK,CXCL8,JUN,CASP3,etc.Conclusion The pharmacodynamic basis of Kangzhi Syrup is preliminarily verified.The main components and targets showed good binding properties,which can provide a theoretical basis for the treatment of CVA with Kangzhi Syrup.