摘要
目的:基于网络药理学方法探讨银杏叶治疗脑梗死(CI)的潜在作用机制。方法:通过中药系统药理学数据库与分析平台筛选银杏叶高度活性化学成分,预测潜在靶点;通过GeneCards、人类在线孟德尔遗传数据库、DisGeNET、治疗靶点数据库和Drugbank数据库检索CI相关靶点。通过Uniprot数据库转换银杏叶有效成分潜在靶点,并与CI相关靶点取交集,得到银杏叶治疗CI的相关靶点。利用STRING 11.0数据库构建蛋白质-蛋白质相互作用网络图,筛选核心基因,并通过软件Metascape对银杏叶治疗CI的作用靶点进行基因本体功能富集分析和京都基因与基因组百科全书通路富集分析,最后借助Auto Dock Tools等软件进行分子对接验证。结果:共检测到银杏叶有效化学成分10种,有效成分靶标122个;CI相关靶点1109个;取交集后获得银杏叶治疗CI的潜在靶点43个。核心活性成分β-谷甾醇、芝麻素、豆甾醇、双[(2S)-2-乙基己基]苯-1,2-二羧酸酯、异戊环素和芫花素主要作用于核心靶点前列腺素内过氧化物合酶2(PTGS2),通过钙信号通路、弓形体病、心肌细胞中的肾上腺素能信号通路和磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K-Akt)信号通路等通路治疗CI,主要功能为改善血液循环等。分子对接结果表明核心活性成分与核心靶点之间均可较好结合。结论:银杏叶可能通过β-谷甾醇、豆甾醇和芝麻素等活性成分,作用于PTGS2等相关靶点,经钙信号、PI3K-Akt信号等通路参与炎症、氧化及凋亡等活动,从而发挥多成分、多靶点和多通路治疗CI的药理作用。
OBJECTIVE:To probe into the potential mechanism of Ginkgo biloba in the treatment of cerebral infarction(CI)based on the method of network pharmacology.METHODS:Through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform,the highly active chemical components of Ginkgo biloba were screened and the potential targets were predicted;the CI-related targets were retrieved by GeneCards,OMIM,DisGeNET,Therapeutic Targets Database and Drugbank database.The potential targets of active ingredients of Ginkgo biloba were converted by Uniprot database and intersected with CI-related targets to obtain the relevant targets of Ginkgo biloba for the treatment of CI.The protein-protein interaction network map was constructed to screen the core genes by using STRING 11.0 database,the gene ontology function enrichment analysis and Kyoto gene and genomic encyclopedia pathway enrichment analysis were performed on the active targets of Ginkgo biloba for the treatment of CI by using Metascape software,and finally the molecular docking verification was performed with the help of software such as Auto Dock Tools.RESULTS:Totally 10 active chemical components,122 active component targets and 1109 CI-related targets of Ginkgo biloba were detected;43 potential targets of Ginkgo biloba for the treatment of CI were obtained after the intersection.The core active ingredients includingβ-sitosterol,sesamin,stigmasterol,bis[(2 S)-2-ethylhexyl]benzene-1,2-dicarboxylate,isopimelanocycline and cgenkwanin were mainly act on the core target of prostaglandin endoperoxide synthase 2(PTGS2),and treated CI through calcium signaling pathway,adrenergic signaling pathway in toxoplasmosis and cardiac myocytes,phosphatidylinositol-3-kinase/protein kinase B(PI3 K-Akt)signaling pathway,with the main function of improving blood circulation.Results of molecular docking showed that the core active ingredients could bind well to the core targets.CONCLUSIONS:Ginkgo biloba may act on PTGS2 and other related targets throughβ-sitosterol,stigmasterol and sesamin,participate in inflammation,oxidation and apoptosis through the calcium signaling,PI3 K-Akt signaling and other pathways,thus exerting the pharmacological effects of multi-component,multi-target and multi-pathway in the treatment of CI.
作者
贾悠然
张树泉
秦升
JIA Youran;ZHANG Shuquan;QIN Sheng(College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250000,China;Dept.of Encephalopathy,Tai’an Hospital of Traditional Chinese Medicine,Shandong Tai’an 271000,China;College of Integrated Traditional Chinese and Western Medicine,Jining Medical University,Shandong Jining 272067,China)
出处
《中国医院用药评价与分析》
2022年第4期428-434,439,共8页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
山东省中医药科技发展计划项目(No.2019-0757)
泰安市科技发展计划(引导计划)项目(No.2018NS0113)。
关键词
网络药理学
银杏叶
脑梗死
分子对接
Network pharmacology
Ginkgo biloba
Cerebral infarction
Molecular docking
