基于网络药理学和分子对接技术探讨蒙药新黑苏嘎乌日勒治疗脑缺血再灌注损伤机制

Mechanism of Mongolian medicine Xinheisugawurile in the treatment of cerebral ischemia-reperfusion injury based on network pharmacology and molecular docking technology

目的:探究蒙药新黑苏嘎乌日勒治疗脑缺血再灌注损伤的作用机制。方法:通过TCMSP、BATMAN和GeneCards等数据库分别对药物及疾病靶点进行预测。利用Venny得到其共同靶点,并使用STRING软件构建PPI网络。运用David数据库开展GO生物及KEGG通路富集研究,并利用Cytoscape软件构建活性成分-关键靶点-重要通路网络。最后,利用Autodock等软件展开分子对接。结果:获得蒙药新黑苏嘎乌日勒治疗脑缺血再灌注损伤的关键靶点30个,重要生物过程15条,核心KEGG通路20条和主要活性成分10个。分子对接结果显示,主要活性成分与关键靶点结合能力值≤-1.2 kcal/mol。结论:网络药理学分析表明,蒙药新黑苏嘎乌日勒主要通过β-胡萝卜素、黄芩素、胡椒碱、金合欢素等有效成分作用于雌激素受体α(estrogen receptor 1,ESR1)、核因子-κBp65(uclear factor-κBp65,RELA)、肿瘤蛋白p53(tumor protein p53,TP53)和蛋白激酶B1(protein kinase B1,AKT1)等靶点,调节细胞凋亡、肿瘤坏死因子α(Tumor Necrosis Factorα,TNF-α)、低氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)、磷脂酰肌醇-3激酶(phosphatidylinositol-3 kinase,PI3K)-AKT、雌激素等信号通路,参与细胞凋亡的正负调控、炎症反应、血管生成、缺氧反应等生物过程,从而达到治疗脑缺血再灌注损伤的作用。

Objective:To explore the mechanism of Mongolian medicine Xinheisugawurile in the treatment of cerebral ischemia-reperfusion injury.Methods:The drug and disease targets were predicted by TCMSP,BATMAN and GeneCards databases,respectively.Venny was used to obtain their common targets,and STRING software was used to construct PPI network.The David database was used to carry out GO biological and KEGG pathway enrichment studies,and Cytoscape software was used to construct an active ingredient-key target-important pathway network.Finally,molecular docking was performed using Autodock and other software.Results:A total of 30 key targets,15 important biological processes,20 core KEGG pathways and 10 main active components were obtained for the treatment of cerebral ischemia-reperfusion injury by Mongolian medicine Xinheisugawurile.The results of molecular docking showed that the binding ability of the main active components to the key targets was≤1.2 kcal/mol.Conclusion:Network pharmacology analysis shows that Mongolian medicine Xinheisugawurile mainly acts on estrogen receptorα(ESR1),nuclear factor-κBp65(RELA),tumor protein p53(TP53)and protein kinase B1(AKT1)throughβ-carotene,baicalein,piperine,acacetin and other active ingredients.It regulates apoptosis,tumor necrosis factor alpha(TNF-α),hypoxia-inducible factor-1(HIF-1),phosphatidylinositol-3 kinase(PI3K)-AKT,estrogen and other signaling pathways,participates in the positive and negative regulation of apoptosis,inflammatory response,angiogenesis,hypoxia and other biological processes,so as to achieve the effect of treating cerebral ischemia-reperfusion injury.