蒙药阿那尔四味散治疗功能性消化不良的作用机制研究

Research on the function mechanism of Mongolian medicine Anaer Siwei Powder in the treatment of functional dyspepsia

目的运用网络药理学和分子对接的方法探讨蒙药阿那尔四味散治疗功能性消化不良(FD)的潜在作用机制。方法本研究通过中药系统药理学数据库与分析平台(TCMSP)数据库及文献挖掘筛选出阿那尔四味散的主要活性成分,利用PharmMapper服务器、GeneCards数据库预测和筛选出主要活性成分的作用靶点。借助Gephi构建药物-活性成分-关键作用靶点网络,并将获得的靶点信息利用GlueGO进行基因通路的富集分析。采用String数据库和Cytoscape软件绘制蛋白相互作用网络,并通过Ledock对阿那尔四味散活性成分与靶点进行分子对接,分析结合活性。结果共收集到阿那尔四味散57个活性成分,其中Pipernonaline、Sylvatine、Retrofractamide-B、Alnusone、Quercetin等为关键作用成分。预测得到的196个靶标中与FD相关重复靶标46个,其中白蛋白(ALB)、丝裂原活化蛋白激酶(MAPK1、MAPK14、MAPK8)、雌激素受体1(ESR1)、表皮生长因子受体(EGFR)、半胱天冬酶3(CASP3)等为关键作用靶标。这些关键靶标显著富集在丝裂原活化蛋白激酶(MAPK)活性、一氧化氮合酶调节活性、对雌激素刺激的反应、周期蛋白依赖性激酶活性调节、血管内皮细胞增殖等生物过程,以及幽门螺杆菌感染的上皮细胞信号传导、受体蛋白酪氨酸激酶信号通路、雌激素信号通路等通路上。分子对接从计算机模拟层面上验证了前期预测结果的准确性。结论蒙药阿那尔四味散可能通过抗炎、抗幽门螺杆菌感染、保护胃肠黏膜、调节胃肠运动及调节雌激素水平等多方面发挥对FD的治疗作用。

Objective To investigate the potential function mechanism in the treatment of functional dyspepsia(FD)with the method of network pharmacology and molecular docking.Methods In this research,the main active components of Anaer Siwei Powder were screened through database and literature mining of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the function targets of the main active components were predicted and screened by PharmMapper server and GeneCards database.With the help of Gephi,a drug-active ingredient-key target network was constructed,and the obtained target information was enriched and analyzed by GlueGO.The protein interaction network was drawn by using String database and Cytoscape software,and the active components of Anaer Siwei Powder were molecularly docked with the target through Ledock,and the binding activity was analyzed.Results A total of 57 active components of Anaer Siwei Powder were collected,in which Pipernonaline,Sylvatine,Retrofractamide-B,Alnusone and Quercetin were the key components.In the predicted 196 targets,there are 46 repeated targets related to FD,in which albumin(ALB),mitogen-activated protein kinase(MAPK1,MAPK14,MAPK8),estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR)and caspase-3(CASP3)were the key function targets.These key targets were significantly enriched in biological processes such as mitogen-activated protein kinase(MAPK)activity,nitric oxide synthase regulation activity,response to estrogen stimulation,cyclin-dependent kinase activity regulation,vascular endothelial cell proliferation and so on,and signal transduction of epithelial cells infected by Helicobacter pylori,receptor protein tyrosine kinase signal pathway,estrogen signal pathway and so on.Molecular docking verifies the accuracy of the previous prediction results from the computer simulation level.Conclusion The Mongolian medicine Anaer Siwei powder may play a therapeutic role on FD through anti-inflammation,anti-Helicobacter pylori infection,protection of gastrointestinal mucosa,regulation of gastrointestinal motility and regulation of estrogen level.