基于网络药理学和分子对接探讨瓜蒌皮注射液治疗冠心病的作用机制

To investigate the mechanism of Gualoupi Injection in the treatment of coronary heart disease based on network pharmacology and molecular docking

关键词:  网络药理学  分子对接  瓜蒌皮注射液  冠心病  作用靶点

Key words:  network pharmacology  molecular docking  Gualoupi Injection  coronary heart disease  action target

摘要:

[目的] 通过网络药理学及分子对接的方法，探究瓜蒌皮注射液治疗冠心病的分子机制。[方法] 首先通过查阅文献汇总瓜蒌皮注射液中的主要化学成分，通过中药系统药理学数据库与分析平台（TCMSP）、SwissADME数据库筛选其活性成分并预测其作用靶点，与在GeneCards数据库、OMIM数据库中获取的冠心病的相关靶点交集获得核心靶点；其次通过String数据库构建靶点蛋白互作网络，转换格式导入Cytoscape3.7.2软件构建蛋白互作网络和“相关活性成分-潜在作用靶点”网络并分析关键靶点蛋白与活性成分；然后通过Metascape数据库对靶点基因进行基因本体（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；最后通过AutoDock Vina软件将活性成分与核心靶点进行分子对接来对网络药理学预测的准确性进行虚拟验证。[结果] 研究获得瓜蒌皮注射液治疗冠心病的可能相关活性成分10个，核心靶点7个。瓜蒌皮注射液的活性成分可能通过调控蛋白激酶B抗体（AKT1）、表皮生长因子受体（EGFR）、非受体酪氨酸激酶（SRC）、热休克蛋白90AA1（HSP90AA1）、半胱氨酸蛋白酶3（CASP3）、雌激素受体1（ESR1）、纤溶酶原（PLG）等核心靶点及丝裂原活化蛋白激酶（MAPK）、白介素（IL）-17、叉头框蛋白O（FoxO）通路等信号通路以达到治疗冠心病的作用，分子对接结果表明活性成分与关键靶点蛋白结合稳定，AKT1与3，29-二苯甲酰基栝楼仁二醇、木犀草苷和槲皮苷等对接更为稳定。[结论] 瓜蒌皮注射液通过多靶点、多途径来干预冠心病，为进一步揭示瓜蒌皮注射液的药理作用机制提供理论基础。

Abstract:

[Objective] To explore the molecular mechanism of Gualoupi Injection in the treatment of coronary heart disease （CHD） by network pharmacology and molecular docking methods. [Methods] Firstly，the main chemical components in Gualoupi Injection were summarized by reviewing the literature，and the active components were screened and the target of this injection was predicted by the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform （TCMSP） and SwissADME database. The core target was obtained by intersections with the related targets of CHD obtained from GeneCards database and OMIM database. Secondly，the target protein interaction network was constructed by String database，Cytoscape 3.7.2 software constructed protein interaction network and “Related active ingredients-Potential Target” network were introduced into the conversion format，and key target proteins and active ingredients were analyzed. Then the target genes were enriched by GO function and KEGG pathway through Metascape database. Finally，AutoDock Vina software was used to perform molecular docking between active ingredients and core targets tovirtually verify the accuracy of network pharmacological prediction. [Results] In this study，10 possible related active ingredients and 7 core targets of Gualoupi Injection in the treatment of CHD were obtained. The active ingredients of Gualoupi Injection may regulate the core targets such as AKT1，EGFR，SRC，HSP90AA1，CASP3，ESR1，PLG and other signaling pathways such as MAPK，IL-17，FoxO pathway to achieve the therapeutic effect of CHD. Molecular docking results showed that the active component was stable in binding with key target proteins，and AKT1 was more stable in binding with 3，29-dibenzoyloxy- karounidiol，cynaroside and quercetrin. [Conclusion] Gualoupi Injection may intervene in CHD through multi-target and multi-pathway，providing a theoretical basis for further revealing the pharmacological mechanism of Gualoupi Injection.