摘要
目的:运用网络药理学方法和分子对接技术探讨炙甘草汤减轻心肌缺血再灌注损伤(MIRI)的作用机制。方法:利用中医药系统药理学数据库与分析平台(TCMSP)与中药分子机制生物信息学分析工具(BATMAN-TCM)获取炙甘草汤有效成分并预测其作用靶点,然后应用人类基因综合(GeneCards)与人类疾病相关基因和突变信息的综合平台(DisGeNET)数据库预测MIRI靶点,通过Venny在线绘图软件获取炙甘草汤抗MIRI潜在作用靶点。利用蛋白质相互作用分析数据库(STRING数据库)平台构建蛋白互作(PPI)网络,并通过Cytoscope 3.9.1软件可视化、筛选出核心靶点,利用Metascape基因功能分析平台对筛选出的核心靶点进行基因本体(GO)富集分析与京都基因与基因组百科全书(KEGG)信号通路富集分析,探究炙甘草汤抗MIRI机制,再次利用Cytoscape 3.9.1软件构建活性成分-疾病-核心靶点-通路网络。最后利用分子对接程序AutoDock vina对炙甘草汤主要活性成分与其核心靶点结合活性进行验证。结果:经筛选获得炙甘草汤147个活性成分、865个基因靶点,MIRI 144个靶标,通过Venny数据库获取炙甘草汤抗MIRI潜在作用靶点79个;经PPI网络分析并筛选出40个关键靶点,其中肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、蛋白激酶B(AKT1)、血管内皮生长因子A(VEGFA)、一氧化氮合酶3(NOS3)、过氧化氢酶(CAT)、CC趋化因子配体2(CCL2)、髓过氧化物酶(MPO)均与炎症反应或氧化应激有关。经GO富集分析发现氧化应激、炎症反应与此生物学过程密切相关;经KEGG分析探究炙甘草汤抗MIRI的通路,共映射出178条信号通路。将炙甘草汤活性成分-疾病-核心靶点-通路网络中排名居前3位的成分及其关键靶点进行验证,结果显示炙甘草汤主要活性成分与关键作用靶点结合活性很强,能形成稳定的化合物。结论:甘草查尔酮A、人参皂苷Rh2、6-醛基异麦冬黄酮B、山柰酚、芒柄�
Objective:To explore the mechanism of action of Honey-fried Licorice Decoction on myocardial ischemia/reperfusion injury(MIRI)based on network pharmacology and molecular docking.Methods:The active components of Honey-fried Licorice Decoction were obtained and its target was predicted by the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and the Traditional Chinese Medicine Molecular mechanism bioinformatics analysis tool(BATMAN-TCM).The target of MIRI was predicted by the integrated platform of human Gene Synthesis(GeneCards)and human disease-related gene and mutation information(DisGeNET)database,and the potential target of Honey-fried Licorice Decoction anti-MIRI was obtained by Venny online software.The protein interaction(PPI)network was constructed using the Protein Interaction Analysis Database(String database)platform,and the core targets were screened and visualized by Cytoscope 3.9.1 software.The anti-MIRi mechanism of Honey-fried Licorice Decoction was investigated by Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis for the selected core targets by Metascape gene function analysis platform.The molecular docking program AutoDock vina was used to verify the binding activity of the main active ingredients of Honey-fried Licorice Decoction and its core target.Results:After screening,147 active ingredients,865 gene targets,and 144 MIRI targets of Honey-fried Licorice Decoction were selected.Seventy-nine potential anti-MIRI targets were obtained through Venny database.Forty core targets were screened by PPI network analysis,which showed that tumor necrosis factor(TNF),interleukin-6(IL-6),protein kinase B-α(AKT1),vascular endothelial growth factor A(VEGFA),endothelial nitric oxide synthetase(NOS3),catalase(CAT),CC chemokine ligand 2(CCL2),and myeloperoxidase(MPO)were related to inflammatory response or oxidative stress.GO enrichment analysis showed that oxidative stress and inflammation were close
作者
任海云
蔚蓁
REN Haiyun;WEI Zhen(College of Traditional Chinese Medicine and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong 030619,Shanxi,China)
出处
《中西医结合心脑血管病杂志》
2024年第3期402-409,共8页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
山西省基础(自由探索类)研究项目(No.202203021221203)
山西省重点实验室项目(No.04010910029)
山西中医药大学博士科研启动基金(No.2020BK03)。
关键词
心肌缺血再灌注损伤
炙甘草汤
网络药理学
分子对接
作用机制
myocardial ischemia-reperfusion injury
Honey-fried Licorice Decoction
network pharmacology
molecular docking
mechanism
