泻白散作用靶点的生物信息学研究及活性成分解析

Bioinformatics Study on Targets of Xiebai Powder(泻白散)and Analysis of Active Components

目的:基于网络药理学以及高效液相色谱技术,探讨泻白散治疗哮喘的主要活性成分与药理作用机制。方法:构建大鼠哮喘病理模型,评价泻白散治疗哮喘的药理作用,借助TCMSP数据库检索泻白散活性成分及其相关作用靶点;利用Cytoscape 3.6.1软件构建“成分-疾病-靶点”交互作用网络,并筛选得到主要活性成分;运用Metascape数据库对关键靶点基因进行基因本体论(GO)分析与京都基因和基因组数据库(KEGG)通路分析;采用AutoDock Tools 1.5.6软件进行分子对接,结合高效液相色谱技术分析泻白散治疗哮喘的核心化合物。结果:泻白散能有效改善哮喘大鼠症状,泻白散治疗哮喘的靶点125个,通路16条,主要通过槲皮素、山奈酚、柚皮素、β-谷甾醇等15个小分子发挥治疗哮喘的作用。结论:泻白散能够有效缓解哮喘大鼠病理状态,并通过多个有效活性成分参与磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-Akt)、丝裂原活化蛋白激酶(MAPK)、白细胞介素(IL)-17等免疫、炎症信号通路,调控肿瘤坏死因子(TNF)、IL-6、丝氨酸激酶1(AKT1)、MAPK1等关键蛋白发挥泻白散抗哮喘的作用。

Objective:To explore the main active components and pharmacological mechanism of Xiebai Powder(泻白散)in the treatment of asthma based on network pharmacology and high performance liquid chromatography(HPLC).Methods:The pathological model of rat with asthma was established to evaluate the pharmacological effect of Xiebai Powder on asthma.The active components and their related targets of Xiebai Powder were searched by TCMSP database,and the“component-disease-target”interaction network was constructed by using Cytoscape 3.6.1 software to screen and obtain the main active components.Metascape database was used to conduct gene ontology(GO)analysis of key target genes and Kyoto Encyclopedia of Genes and Genome(KEGG)pathway analysis.AutoDock Tools 1.5.6 software was used for molecular docking and the key compounds of Xiebai Powder in the treatment of asthma were analyzed by HPLC.Results:Xiebai Powder can effectively improve the symptoms of asthmatic rats.There are total 125 targets of Xiebai Powder in the treatment of asthma and 16 pathways,mainly through 15 small molecules such as Quercetin,Kaempferol,Naringenin and 8-beta-sitosterol to treat asthma.Conclusions:Xiebai Powder can effectively alleviate the pathological state of asthmatic rats.It also participates in multiple immune and inflammatory signal pathways such as PI3K Akt,MAPK and IL-17 through multiple active ingredients,regulates key proteins such as TNF,IL6,AKT1 and MAPK1,and plays the antiasthmatic role of Xiebai Powder.