基于网络药理学探讨高良姜治疗胃溃疡的活性成分及作用机制  

Study on the Active Ingredients and Mechanism of Alpinia officinarum in the Treatment of Gastric Ulcer Based on Network Pharmacology

作　　者：秦贞苗[1] 张力立 陈德梅[1] 王宁[1] 陈莹子 吴鑫福 张俊清[1] QIN Zhenmiao;ZHANG Lili;CHEN Demei;WANG Ning;CHEN Yingzi;WU Xinfu;ZHANG Junqing(School of Pharmacy,Hainan Medical University,Haikou 571199,China;Dept.of Cardiovasology,Hainan Provincial People’s Hospital/Hainan Hospital Affiliated Hainan Medical University,Haikou 570311,China)

机构地区：[1]海南医学院药学院,海口571199 [2]海南省人民医院/海南医学院附属海南医院心血管内科,海口570311

出　　处：《中国药房》2020年第12期1440-1445,共6页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81560721);2019年海南医学院大学生创新创业训练计划项目(No.X201911810073)。

摘　　要：目的:探讨高良姜治疗胃溃疡的活性成分及作用机制。方法:采用网络药理学方法,通过中药系统药理学分析平台、中药综合数据库检索[口服生物利用度(OB)≥30%和类药性(DL)≥0.18]和文献挖掘,筛选出高良姜的活性成分和作用靶点;另在TTD、CTD、OMIM、PubMed、DrugBank、DisGeNet数据库中获取胃溃疡的相关靶点,使用Venny 2.1软件筛选高良姜活性成分与胃溃疡的共同靶点;借助STRING数据库获得共同靶点的蛋白-蛋白相互作用(PPI)关系,使用Cytoscape 3.7.1软件构建PPI网络并分析;采用ClusterProfiler R功能包对共同靶点进行基因本体(GO)功能和KEGG通路富集分析;使用Cytoscape 3.7.1软件构建"活性成分-靶点-通路"网络并分析。结果:经筛选得到高良姜活性成分19个,活性成分作用靶点和胃溃疡相关靶点分别有209、195个,两者共同靶点35个。共同靶点PPI网络的平均节点度值为18、平均介数为16.9,关键靶点共有11个,分别为PTGS2、VEGFA、IL6、IL1B、CCL2、MYC、MMP9、EGFR、HIF1A、ESR1,BCL2L1。共同靶点主要富集于血小板α颗粒腔、线粒体外膜等细胞组分,氧化应激反应、炎症反应调节等生物过程以及蛋白磷酸酶结合、生长因子受体结合等分子功能,并富集于磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)、低氧诱导因子1(HIF-1)等信号通路。"活性成分-靶点-通路"网络显示,高良姜中的槲皮素、芹菜素、山柰酚、高良姜素等活性成分是主要的药效物质基础,可能通过作用于PTGS2、NOS2、BCL2、IL6、VEGFA、IL1B、MMP9、BCL2L1等基因靶点,参与调控PI3K/Akt、HIF-1、肿瘤坏死因子、白细胞介素17、核转录因子κB等细胞增殖、血管生成、炎症反应相关信号通路,从而起到抗胃溃疡的功效。结论:高良姜具有多成分、多靶点、多通路抗胃溃疡的作用特点。OBJECTIVE:To explore the potential active ingredients and mechanism of Alpinia officinarum in the treatment of gastric ulcer. METHODS:By network pharmacology method,the active ingredients and action targets of A. officinarum were screened through TCMSP and TCMID database retrieval [oral bioavailability(OB)≥30% and drug like(DL)≥0.18] and literature mining. Targets of gastric ulcer were obtained in the TTD,CTD,OMIM,PubMed,DrugBank and DisGeNet databases. Venny 2.1 software was used to screen common targets for the active ingredients of A. officinarum and gastric ulcer. Then,the protein-protein interaction(PPI)of the common targets was obtained by STRING database,and the PPI network was constructed and analysed by using Cytoscape 3.7.1 software. GO function and KEGG pathway enrichment analysis of the common targets were performed by using ClusterProfiler R package. Finally,Cytoscape 3.7.1 software was used to construct and analyze the network diagram of"active ingredients-targets-pathways". RESULTS:Totally 19 active ingredients of A. officinarum,209 active ingredients targets and195 gastric ulcer related targets,involving 35 common targets,were screened out. The average node degree of PPI network of common targets was 18,and the average intermediate number was 16.9. There were 11 key targets,i.e. PTGS2,VEGFA,IL6,IL1 B, CCL2, MYC, MMP9, EGFR, HIF1 A, ESR1, BCL2 L1. The common targets were mainly concentrated in the cell constituents such as the platelet α granule lumen and mitochondria outer membrane,involved in the biological processes as oxidative stress,inflammatory response regulation,and molecular functions as protein phosphatase binding,growth factor receptor binding. They were also enriched in the signal pathways such as PI3K/Akt,HIF-1. The network of"active ingredients-targetspathways"showed the active ingredients such as quer-cetin,apigenin,kaempferol and galangin in A. officinarum played an anti-gastric ulcer effect by acting on PTGS2,NOS2,BCL2,IL6, VEGFA, IL1 B, MMP9, BCL2 L1 and other targets to joi

关 键 词：网络药理学 高良姜 胃溃疡 活性成分 作用机制 

分 类 号：R656.62[医药卫生—外科学]