基于网络药理学的黄芩素、京尼平抗脑缺血作用机制研究  

Anti-cerebral ischemia mechanisms of baicalein and genipin based on network pharmacology

作　　者：向净匀 吴杰 王琰 高原雪 何林 李豪 李敏[1] 史永恒[1] 王斌[1] XIANG Jing-yun;WU Jie;WANG Yan;GAO Yuan-xue;HE Lin;LI Hao;LI Min;SHI Yong-heng;WANG Bin(Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]陕西中医药大学

出　　处：《中草药》2019年第23期5802-5811,共10页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目（81473385）;陕西省自然科学基金项目（2018JM7111）

摘　　要：目的采用网络药理学及分子对接技术,以灯盏花乙素苷元(scutellarein,SE)作为参照,预测黄芩素(baicalein,BE)、京尼平(genipin,GE)抗脑缺血作用靶点,为脑缺血疾病的临床防治和开发研究提供参考。方法利用TCMSP、Swiss Target Prediction和Stitch数据库检索和文献挖掘方法,预测SE、BE、GE作用靶点,同时应用DisGeNET、CTD、NCBI Gene、OMIM、DrugBank和PharmGkb数据库预测脑缺血疾病相关靶点。通过Cytoscape 3.3.0构建小分子-靶点网络图,用DAVID软件分析SE、BE、GE特有抗脑缺血靶点的GO功能富集和KEGG通路分析。采用AutodockVina软件对SE、BE、GE与抗脑缺血共同靶点分别进行对接研究,根据受体与配体的结合能和抑制浓度排序,选择最佳的靶点蛋白。结果SE、BE、GE分别预测出30、59、35个靶蛋白,SE与BE共同抗脑缺血疾病靶点有PIK3CG、CYP1A2、VEGFA、ALOX5、PTGS2,SE与GE共同抗脑缺血靶点为PTGS2。分子对接结果显示受体PTGS2与SE、BE、GE对接结合能及抑制浓度相对较低。GO功能富集结果显示BE-SE共同靶点主要分布于细胞质、细胞器膜、内质网膜等部位,具有与金属离子、阳离子结合功能及催化、氧化还原酶活性,参与细胞脂质、羧酸、含氧酸、有机酸代谢及脂肪酸合成等过程有关;KEGG分析结果显示受体PTGS2主要作用于花生四烯酸代谢通路和VEGF信号通路,BE与GE配伍治疗脑缺血疾病通过抑制PTGS2(COX-2)和VEGF蛋白的表达,从而减轻炎症因子造成的脑组织损伤并改善血脑屏障(Blood brain barrier,BBB)的通透性发挥脑保护作用。结论预测了BE与GE配伍治疗脑缺血疾病的潜在靶点,初步验证了治疗脑缺血疾病的作用机制,为进一步深入研究BE与GE配伍治疗脑缺血作用机制提供参考,也为下一步合成新的衍生物提供基础。Objective Using network pharmacology and molecular docking technology along with scutellarein(SE)as a reference,this study predicted the anti-cerebral ischemia targets of both baicalein(BE)and genipin(GE).It is hoped that these will provide a reference for clinical prevention and development of ischemic diseases.Methods SE,BE and GE targets were predicted using TCMSP,Swiss Target Prediction,Stitch database search and literature mining methods.Targets related to cerebral ischemia diseases could be predicted by DisGeNET,CTD,NCBI Gene,OMIM,DrugBank and PharmGkb databases.Cytoscape 3.3.0 was used to construct the small molecule-target network.GO function enrichment and KEGG pathway analysis of SE,BE and GE specific anti-cerebral ischemia targets were analyzed with the DAVID database.Autodock Vina software was used for molecular docking,testing the binding energy of BE,GE and SE to targets of cerebral ischemia.The optimal target protein was selected according to the binding energy and inhibition concentration of receptor and ligand.Results A total of 30 potential targets of SE,59 potential targets of BE and 35 potential targets of GE were found.Common anti-cerebral ischemia targets of SE and BE were PIK3CG,CYP1A2,VEGFA,ALOX5 and PTGS2,while common anti-cerebral ischemia targets of SE and GE were PTGS2.Molecular docking results demonstrated that the binding energy and inhibitory concentration of receptor PTGS2 to the three drugs were relatively low.Enrichment of GO function showed that common targets of BE-SE were mainly distributed in cytoplasm,organelle membrane,endoplasmic reticulum and other elements.These elements had binding functions with metal ions and cations,catalytic and oxidoreductase activities,and they participated in cell lipid,carboxylic acid,oxygenic acid,organic acid metabolism and fatty acid synthesis.Results of the KEGG analysis demonstrated that receptor PTGS2 mainly acted on the arachidonic acid metabolism pathway and the vascular endothelial growth factor signaling pathway.A combination of BE and

关 键 词：黄芩素 灯盏花乙素苷元 京尼平 脑缺血 网络药理学 分子对接 

分 类 号：R285.5[医药卫生—中药学]