基于系统药理学方法探究荆花胃康胶丸干预幽门螺杆菌所致炎症反应机制

Systematic Pharmacological Methodology-based Investigation on Interventional Mechanism of Jinghua Weikang Capsule Protecting against Helicobacter Pylori-induced Inflammatory Responses

目的:探究荆花胃康胶丸(Jinghua Weikang capsule, JWC)干预幽门螺杆菌(Helicobacter pylori, Hp)所致炎症反应的作用机制。方法:采用Schr9dinger(2018)平台的QikProp模块过滤不符合ADME参数的JWC成分,用R语言factoextra和Facto MineR包对剩余成分进行主成分分析。借助Pharm Mapper Server和SwissTarget Prediction平台预测阳性药的作用靶点,并与OMIM、Genecards和DisGeNET数据库获得的Hp感染靶点取交集,获得阳性药对Hp感染的治疗靶点。采用Schr9dinger软件探究潜在活性成分对Hp感染治疗靶点的作用效果,借助R语言的pheatmap包构建对接结果的聚类分析热图。利用Cytoscape软件构建"药效成分-疾病靶点"网络模型,借助CluoGO插件分析JWC治疗Hp感染的作用通路。将水团花主要成分与BabA进行分子对接,探究水团花对Hp粘附的抑制作用。结果:13个候选活性化合物主要来自于土荆芥,分别作用于核心靶点TAK1、TAB1、RELB、MAPK14、MAPK11、JNK1、IKKB和ERK1。靶点映射得到KEGG通路28条,其中NF-κB/MAPK信号通路的富集靶点数最多。对接结果显示,水团花可能通过竞争性抑制黏附素BabA发挥抗Hp疗效。结论:JWC可能通过调控黏附素-MAPK/NF-kB信号通路干预Hp感染所致炎症反应。

Objective: To explore the mechanism of action of Jinghua Weikang capsule(JWC) in the intervention of inflammation caused by Helicobacter pylori(Hp). Methods: Firstly, the QikProp module of Schrodinger(2018) was used to filter the JWC components that did not conform to ADME parameters, and the remaining components were analyzed by the factoextra and Factominer packages of R language.Secondly, the targets of positive drugs were predicted using PharmMapper online database and SwissTarget Prediction, and intersected with the targets of anti-Hp function obtained from OMIM, GeneCards and DisGeNET database to acquire the treatment targets of positive drugs for Hp infection.Thirdly, Schrodinger software was used to explore the effects of 34 potential active ingredients treating the treatment targets of positive drugs for Hp infection, and the cluster analysis heatmap of the results was constructed by package pheatmapof R language.Fourthly, "medicinal composition and disease targets" network model was constructed by Cytoscape software and the interventional mechanism of JWC treating HP infection was analysed by CluoGO plug-in.Finally, the Molecular docking was conducted between the main components of Adina rubella Hance and BabA to explore the inhibitory effect of Adina rubella Hance on Hp adhesion.Results: It is shownd that most of the top 13 key pharmacodynamic molecules come from Chenopodium Ambrosioides L., which acted on the core targets TAK1、TAB1、RELB、MAPK14、MAPK11、JNK1、IKKB and ERK1. These targets were mapped to 28 KEGG pathways, of which the NF-κB/MAPK signaling pathway has the largest number of targets. Meanwhile, the results of molecular docking suggested that Adina rubella may exert anti-Hp effect through competitively inhibiting adhesin BabA. Conclusion: The mechanism of JMC in the intervention of inflammation caused by HP may be related to regulating adhesion-NF-κB/MAPK signaling pathway.