基于网络药理学和分子对接探讨连梅颗粒治疗心血管疾病的作用机制  

Uncovering the Mechanisms of Lianmei Granules on the Treatment of Cardiovascular Diseases Based on Network Pharmacology and Molecular Docking

作　　者：蒋敏 蔡茹航 梅漫雪 龙颖欣 黄春霞[2,3,4] 吴钉红[2,3] 宋健平 JIANG Min;CAI Ruhang;MEI Manxue;LONG Yingxin;HUANG Chunxia;WU Dinghong;SONG Jianping(Artemisinin Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510403 Guangdong,China;Guangdong Provincial Hospital of Chinese Medicine,Guangzhou 510120 Guangdong,China;Basic Research Laboratory of Traditional Chinese Medicine Quality,Guangdong Provincial Hospital of Traditional Chinese Medicine,Guangzhou 510120 Guangdong,China;The Second Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)

机构地区：[1]广州中医药大学青蒿研究中心,广东广州510403 [2]广东省中医院,广东广州510120 [3]广东省中医院中药物质基础研究团队,广东广州510120 [4]广州中医药大学第二临床医学院,广东广州510405

出　　处：《中药新药与临床药理》2022年第1期80-90,共11页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省科技计划项目(2019B020201012);广东省中医药局科研项目(20201084)。

摘　　要：目的通过网络药理学和分子对接技术探讨连梅颗粒治疗心血管疾病(CVD)的作用机制。方法基于TCMSP、 SymMap、 ETCM、 TCM@taiwan等开源数据库获取连梅颗粒的活性成分,并通过DrugBank、TargetNet、PubChem等数据库预测成分靶点。通过人类基因数据库(GeneCards)、治疗靶点数据库(TTD)和基因疾病关联数据库(DisGeNET)等收集心血管疾病的作用靶点。通过比较毒性遗传学数据库(CTD)收集核心靶点相关的心血管疾病。利用Cytosacpe 3.8.0软件构建中药-成分、中药-成分-核心靶点-疾病网络,对网络进行拓扑结构分析,筛选出关键化合物和关键靶点。提取核心子网络,利用DAVID 6.8在线工具对核心子网络的靶点做基因本体(Gene Ontology, GO)分析和京东基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。利用分子对接方法分析关键化合物和关键靶点的相互作用关系。结果成分-靶点网络分析连梅颗粒得到9种重要的活性化合物,关键化合物为香草酸、槲皮素。药物、疾病网络的共同靶点MIF、TLR9是关键靶点,靶点-疾病网络显示连梅具有潜在治疗作用的主要疾病是高血压、心力衰竭和心肌梗塞。GO分析显示核心子网络与抗氧化、抗炎、调节免疫等多个生物学过程相关。KEGG富集分析连梅颗粒得到能量代谢相关通路,包括cAMP信号通路、钙信号通路和PPAR信号通路。分子对接显示,香草酸、槲皮素与MIF、TLR9可通过氢键结合形成相互作用。结论连梅颗粒及其关键成分香草酸、槲皮素可能通过以MIF、TLR9作为靶标发挥在高血压、心力衰竭和心肌梗塞疾病中的药效作用,其作用机制涉及能量代谢通路cAMP信号通路、钙信号通路和PPAR信号通路,以上结论有待进一步实验验证。Objective This study was designed to explore the mechanism of Lianmei granules on the treatment of cardiovascular diseases(CVD) through network pharmacology and molecular docking. Methods The chemical compositions of Lianmei granules(LMG)were obtained from TCMSP,SymMap,ETCM and TCM@taiwan databases.Then the targets of the ingredients were predicted through DrugBank, TargetNet, and PubChem databases.Subsequently, the targets of cardiovascular disease were collected via the Human Gene Database(GeneCards),Therapeutic Target Database(TTD)and the Gene Disease Association Database(DisGeNET). Finally,core targets of LMG were screened and then core target-related cardiovascular diseases were collected through the Comparative Toxicogenomics Database(CTD). Cytoscape 3.8.0 software was used to construct a network of herbs-components,herbs-components-core targets-diseases respectively, key compounds of LMG and its related key targets were screened after the topological structure analysis of the network. DAVID 6.8 online tool was applied to conduct Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis on the key targets. Ultimately, interactions between key compounds and key targets were analyzed by molecular docking methods. Results 9 important active compounds of LMG and 10 key targets were screened, the top 2 active compounds(according to degree value)were vanillic acid and quercetin, and the top 2 key targets(according to degree value)were MIF and TLR9. The target-disease network showed that LMG had potential therapeutic effects on hypertension,heart failure and myocardial infarction. GO analysis demonstrated that the core targets of LMG were related to multiple biological processes such as anti-oxidation,anti-inflammatory,and immune regulation. KEGG enrichment analysis suggested that the mechanism of LMG on cardiovascular diseases was related to energy metabolism pathway,including cAMP signaling pathway,calcium signaling pathway and PPAR signaling pathway.Molecular docking also

关 键 词：连梅颗粒 心血管疾病 网络药理学 分子对接 香草酸 槲皮素 MIF TLR9 

分 类 号：R285.5[医药卫生—中药学]