基于网络药理学与分子对接探讨蒙药查干乌日勒治疗慢性萎缩性胃炎的作用机制

Mechanism of action of mongolian medicine Chagan Wurile in treatment of chronic atrophic gastritis based on network pharmacology combined with molecular docking

目的:基于网络药理学和分子对接技术探讨蒙药查干乌日勒治疗慢性萎缩性胃炎(CAG)作用机制。方法:通过TCMSP数据库检索查干乌日勒3味植物药材的活性成分和作用靶点;从GeneCards、OMIM、Drugbank数据库收集慢性萎缩性胃炎的相关靶点,利用Venny在线平台得到查干乌日勒和慢性萎缩性胃炎共有靶点;使用STRING 11.5数据库和Cytoscape 3.9.1软件构建共有靶点的PPI网络图,并筛选出关键靶点;使用R语言的ClusterProfiler包,进行GO和KEGG通路富集分析;应用Autodock Tools 1.5.7软件对核心成分与关键靶点进行分子对接。结果:收集到查干乌日勒28个活性成分、作用靶点512个,慢性萎缩性胃炎的相关靶点829个,共有靶点111个,其共有靶点主要富集于720个生物功能及20条信号通路。分子对接表明核心成分山柰酚、异鼠李素、槲皮素、山柰素、橙皮素和胡椒碱与关键靶点AKT1、SRC有较强结合活性。结论:查干乌日勒能保护胃黏膜,对抗血管生成及调节异常免疫,可能通过作用于AKT1和SRC等核心靶点调控癌症通路、HIF-1等信号通路治疗CAG。

Objective:To explore the mechanism of action of Mongolian medicine Chagan Wurile in the treatment of chronic atrophic gastritis(CAG)based on network pharmacology and molecular docking technique.Methods:The active components and action targets of three kinds of plant herbs were searched by TCMSP database;the related targets of chronic atrophic gastritis were collected from GeneCards,OMIM and Drugbank databases,and the common targets of Chagan Wurile and chronic atrophic gastritis were obtained by Venny online platform;the PPI network map of common targets was constructed by STRING11.5 database and Cytoscape3.9.1 software,and the key targets were screened out.The ClusterProfiler package of R language was used to analyze the enrichment of GO and KEGG pathways,and the Autodock Tools1.5.7 software was used to dock the core components with key targets.Results:A total of 28 active components and 512 targets of Chagan Wurile and 829 related targets of chronic atrophic gastritis were collected,with a total of 111 targets,which were mainly enriched in 720 biological functions and 20 signal pathways.Molecular docking showed that the core components kaempferol,isorhamnetin,quercetin,kaempferol,hesperetin and piperine had strong binding activity with key targets AKT1 and SRC.Conclusion:Chagan Wurile can protect gastric mucosa,against angiogenesis and regulate abnormal immunity.It may regulate cancer pathways,HIF-1 and other signaling pathways by acting on core targets such as AKT1 and SRC to treat CAG.