基于网络药理学和分子对接探讨健脾清热方治疗慢性萎缩性胃炎伴肠上皮化生的作用机制

Mechanism of action of Jianpi Qingre formula in treatment of chronic atrophic gastritis with intestinal metaplasia based on network pharmacology and molecular docking

中文关键词: 网络药理学  分子对接  健脾清热方  慢性萎缩性胃炎  肠上皮化生

英文关键词: network pharmacology  molecular docking  Jianpi Qingre formula  chronic atrophic gastritis  intestinal metaplasia

中文摘要:

      目的 借助网络药理学与分子对接,探索健脾清热方治疗慢性萎缩性胃炎(CAG)伴肠上皮化生(IM)的作用机制.方法 依据中药系统药理学数据库和分析平台及Uniprot数据库,对健脾清热方活性成分与靶点展开筛选;在Gene-Cards和OMIM数据库中进行检索,获取该方与CAG伴IM的交集靶点.Cytoscape搭建"药物-活性成分-疾病靶点";借助STRING平台,深入解析蛋白-蛋白相互作用关系,网络拓扑法确定核心靶点,开展GO和KEGG功能富集分析.Autodock软件实现活性成分与核心靶点的有效分子对接.结果 共筛选出健脾清热方潜在活性成分247种和靶点353个,CAG伴IM疾病靶点2 673个,网络拓扑分析得46个节点.富集分析通路247条,健脾清热方治疗CAG伴IM主要作用于AGE-RAGE、脂质与动脉粥样硬化、乙型肝炎、流体剪应力及动脉粥样硬化等信号通路.3个核心成分槲皮素、乌苏酸和β谷固醇与TP53、TNF、STAT3、AKT1和IL6进行分子对接,结合能均较低.结论 健脾清热方可能通过多成分、多靶点、多通路对CAG伴IM发挥疗效.

英文摘要:

      Objective To explore the mechanism of action of Jianpi Qingre formula in the treatment of chronic atrophic gastritis(CAG)with intestinal metaplasia(IM)based on network pharmacology and molecular docking.Methods The ac-tive ingredients and targets of the Jianpi Qingre formula were screened based on the Traditional Chinese Medicine Systems Phar-macology Database and Analysis Platform and the Uniprot database.The GeneCards and OMIM databases were searched to ob-tain the intersection targets of the Jianpi Qingre formula and CAG with IM.Cytoscape was used to construct the"drug-active ingredient-disease target"network.The STRING platform was used to analyze the protein-protein interaction relationship,and network topology was used to analyze the core targets.GO and KEGG functional enrichment analyses were carried out on the core targets.The molecular docking between the core targets and the active ingredients was analyzed by means of Autodock software.Results A total of 247 potential active ingredients and 353 targets of the formula were identified,and 2 673 potential disease targets for CAG with IM were obtained.Network topology analysis revealed 46 key nodes.Enrichment analysis identi-fied 247 pathways.The Jianpi Qingre formula in the treatment of CAG with IM mainly acts on signaling pathways such as AGE-RAGE signaling pathway,lipid and atherosclerosis pathway,hepatitis B pathway,and fluid shear stress and atherosclero-sis pathway.The three core ingredients(quercetin,ursolic acid and β-sitosterol)undergo molecular docking with TP53,TNF,STAT3,AKT1 and IL6,and their binding energies are all relatively low.Conclusion Jianpi Qingre formula may exert cura-tive effects on CAG with IM through multiple ingredients,multiple targets,and multiple pathways.