半夏泻心汤治疗胃食管反流病的作用机制探讨

Discussion on the Mechanism of Banxia Xiexin Decoction in the Treatment of Gastroesophageal Reflux Disease

目的:基于网络药理学和分子对接技术,探讨半夏泻心汤治疗胃食管反流病的作用机制。方法:从TCMSP数据库筛选出半夏泻心汤的药物靶点,通过GeneCards数据库检索胃食管反流病疾病靶点,运用STRING数据库构建PPI网络图。通过Cytoscape3.8.2软件中CytoNCA插件筛选关键靶点,利用ClusterProfiler程序包进行GO和KEGG富集分析,并通过Cytoscape3.8.2软件构建半夏泻心汤药物-成分-靶点-通路网络,最后利用AutoDock、PyMOL软件进行分子对接验证。结果:筛选得到半夏泻心汤中活性成分148种,对应潜在靶点211个,网络图显示槲皮素、甘草查耳酮A、汉黄芩素等是半夏泻心汤治疗胃食管反流病的关键成分,EGFR、TP53、STAT3、MAPK3等是该方治疗胃食管反流病的核心靶点。GO富集分析结果显示这些靶点富集在生物过程中显著的条目有对金属离子响应、对脂多糖的响应、对细胞外刺激的响应等生物学过程。KEGG富集分析显示主要涉及脂质与动脉粥样硬化、AGE-RAGE信号通路、IL-17信号通路等多种与胃食管反流病相关的通路。分子对接结果表明半夏泻心汤中主要活性成分与核心作用靶点对接后,结合能均小-8kcal/mol,表明其具有较为稳定的结合活性。结论:本研究初步揭示了半夏泻心汤多成分、多靶点、多通路治疗胃食管反流病的机制,为半夏泻心汤的临床开发利用提供了依据。

Objective:To explore the mechanism of Banxia Xiexin Decoction in the treatment of gastroesophageal reflux disease based on network pharmacology and molecular docking technology.Methods:The drug targets of Banxia Xiexin Decoction were screened from the TCMSP database,and the targets of gastroesophageal reflux disease were retrieved through the GeneCards database,and the PPI network diagram was constructed using the STRING database.The key targets were screened by the CytoNCA plug-in in Cytoscape3.8.2 software,GO and KEGG enrichment analysis was performed by the ClusterProfiler package,and the drug-component-target-pathway network of Banxia Xiexin Decoction was constructed by Cytoscape3.8.2 software,and finally AutoDock was used.,PyMOL software for molecular docking verification.Results:148 active ingredients in Banxia Xiexin Decoction were screened,corresponding to 211 potential targets.The network diagram showed that quercetin,licochalone A,wogonin,etc.are the effective components of Banxia Xiexin Decoction in the treatment of gastroesophageal reflux.EGFR,TP53,STAT3,MAPK3,etc.are the core targets of this prescription for the treatment of gastroesophageal reflux disease.The GO enrichment analysis results showed that these targets were enriched in significant biological processes,such as the response to metal ions,the response to lipopolysaccharide,and the response to extracellular stimuli.KEGG enrichment analysis showed that lipid and atherosclerosis,AGE RAGE signaling pathway,IL-17 signaling pathway and other pathways related to gastroesophageal reflux disease were mainly involved.Molecular docking results showed that after the main active components in Banxia Xiexin Decoction were docked with the core target,the binding energy was as small as-8kcal/mol,indicating that it has relatively stable binding activity.Conclusion:This study preliminarily revealed the multi-component,multi-target and multi-channel mechanism of Banxia Xiexin Decoction in the treatment of gastroesophageal reflux disease,and provided a basis for the clinical development and utilization of Banxia Xiexin Decoction.