基于网络药理学和分子对接技术探讨丹灯通脑软胶囊治疗中风的作用机制  

Dandeng Tongnao Soft Capsules in the Treatment of Stroke Based on Network Pharmacology and Molecular Docking

作　　者：高艺菲 黄佳奇 郭思宇 陶晓宇 金政森 陈美琳 伍超 黄志鸿 赵若琪 吴嘉瑞[1] GAO Yifei;HUANG Jiaqi;GUO Siyu;TAO Xiaoyu;JIN Zhengsen;CHEN Meilin;WU Chao;HUANG Zhihong;ZHAO Ruoqi;WU Jiarui(School of Chinese Material Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中药学院,北京102488

出　　处：《中国医院用药评价与分析》2024年第4期401-407,共7页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金资助项目(No.82074284);国家中医药传承创新团队子项目(No.ZYYCXTD-C-202005-10);中国民族医药学会科研立项项目(No.2020MZ298-110101)。

摘　　要：目的:基于网络药理学和分子对接技术,探讨丹灯通脑软胶囊治疗中风的活性成分和作用机制。方法:借助中药系统药理学数据库与分析平台、中国台湾中医药资料库、BATMAN-TCM数据库以及文献,筛选丹灯通脑软胶囊相关成分,在成分靶点预测数据库中预测其作用靶点,结合药物与疾病数据库、人类孟德尔遗传综合数据库、治疗靶点数据库和DisGeNET数据库中得到的中风靶点构建网络,通过STRING数据库对共同靶点进行蛋白质-蛋白质相互作用(PPI)分析,筛选关键靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,并利用Autodock Tools 1.5.7软件进行分子对接,预测核心成分和关键靶点间的结合活性。结果:共检索到丹灯通脑软胶囊相关成分161个,对应靶点856个,中风相关靶点234个,取交集得到86个共有靶点,构建PPI网络并进行拓扑学分析得到30个关键靶点,其富集分析得到2712个GO功能进程和122条KEGG通路。分子对接结果显示,核心成分槲皮素、木犀草素可以与核心靶点前列腺素内过氧化物合酶2、蛋白激酶B、基质金属蛋白酶(MMP)9、半胱天冬酶-3和MMP2稳定结合。结论:本研究预测了丹灯通脑软胶囊可能是通过调节炎症反应,改善糖尿病并发症中的晚期糖基化终末产物(AGE)-AGE受体信号通路等途径治疗中风,表明丹灯通脑软胶囊通过多成分介导多靶点、作用于多通路来治疗中风的复杂机制,为进一步深入研究奠定了基础。OBJECTIVE:To probe into the active components and mechanism of Dandeng Tongnao soft capsules in the treatment of stroke based on network pharmacology and molecular docking.METHODS:Based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,Taiwan Traditional Chinese Medicine database of China,BATMAN-TCM database and literature,the targets were predicted by component target prediction database.The network was constructed by combining stroke targets obtained from DrugBank,On-line Mendelian Inheritance in Man,Therapeutic Target Database and DisGeNET database.Protein-protein interaction(PPI)network of the common targets were analyzed by STRING.Key targets were screened for gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Autodock Tools 1.5.7 was used for molecular docking to predict the binding activity between core components and key targets.RESULTS:A total of 161 related components of Dandeng Tongnao soft capsules were retrieved,with 856 corresponding targets and 234 apoplexy-related targets,and 86 common targets were obtained from the intersection.The PPI network was constructed and topological analysis was performed to obtain 30 key targets.The enrichment analysis showed 2712 GO processes and 122 KEGG pathways.Molecular docking results showed that the core components quercetin and luteolin could stably bind to the core targets prostaglandin-endoperoxide synthase 2,serine/threonine protein kinase 1,matrix metalloproteinase(MMP)9,cysteine asparaginase-3,and MMP2.CONCLUSIONS:This study predicts that Dandeng Tongnao soft capsules might treat stroke by regulating inflammatory response and improving advanced glycated end(AGE)products-AGE receptor signaling pathway in diabetes complications,indicating the complex mechanism of Dandeng Tongnao soft capsules in the treatment of stroke by mediating multiple targets through multiple components,laying a foundation for further research.

关 键 词：丹灯通脑软胶囊 中风 网络药理学 分子对接 

分 类 号：R932[医药卫生—生药学]