基于网络药理学的白及治疗胃溃疡的作用研究

Mechanism of Bletilla striata in the treatment of gastric ulcer based on network pharmacology

目的基于网络药理学方法探讨白及治疗胃溃疡可能的分子机制。方法通过中国知网、中药系统药理学数据库和分析平台(TCMSP)等数据库,以生物利用度≥30%及类药性≥0.18为筛选条件,收集白及药材的主要化学成分。用PubChem数据库获得白及各活性成分的SMILES结构或2D结构,通过Swiss Target Prediction和Drugbank数据库筛选出药物成分潜在作用靶点。用GeneCards数据库预测并筛选胃溃疡的潜在作用靶点,用FunRich软件绘制韦恩图,对药物靶点和疾病靶点进行匹配映射,获得白及治疗胃溃疡的潜在靶点。首先借助Cytoscape软件构建"活性成分-关键靶点"网络。通过STRING数据库结合Cytoscape软件绘制蛋白-蛋白互作网络图作用图,并进行网络拓扑参数分析,筛选白及治疗胃溃疡的关键靶点。再者用DAVID数据库对白及治疗胃溃疡的关键靶点进行基因本体富集分析及东京基因组百科全书通路富集分析,并构建"成分-靶点-通路"网络图。结果通过筛选得到9个白及活性成分,排除重复后共有452个潜在靶点;与胃溃疡的靶点匹配后得到41个关键靶点。通过富集分析得到,白及活性成分主要通过苏氨酸激酶1(Akt1)、丝裂原活化蛋白激酶3(MAPK3)、MAPK1、肿瘤坏死因子(TNF)等靶点和磷脂酰肌醇3激酶-苏氨酸激酶、TNF及MAPK信号通路等发挥保护胃黏膜的机制。结论白及治疗胃溃疡体现了中药通过多成分-多靶点-多通路共同发挥作用的特点。

Objective To explore the possible molecular mechanism of Bletilla striata in treating gastric ulcers with the network pharmacology method.Methods Through China Knowledge Network,Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and other databases,the main chemical components of Bletilla striata were collected with bioavailability≥30%and drug-like properties≥0.18 as the screening conditions.The PubChem database was used to obtain the SMILES structure or 2 D structure of each active ingredient of Bletilla striata,and the potential target of drug ingredients were screened by Swiss Target Prediction and Drugbank database.The GeneCards database was used to predict and screen the potential targets of gastric ulcer.FunRich software was used to draw a Wayne chart,which matched the drug targets and disease targets to obtain the potential targets for the treatment of gastric ulcer.First,build a network of"active ingredients-key targets"with the help of Cytoscape software.Through the STRING database combined with Cytoscape software,the protein-protein interaction network map was drew,and the treatment of gastric ulcer key targets were screened by network topology parameter analysis.In addition,the DAVID database was used to perform the gene ontology enrichment analysis and Tokyo Encyclopedia Enrichment analysis of the key targets for the treatment of gastric ulcers,and"component-target-pathway"network diagram was constructed.Results Nine active ingredients of Bletilla striata were obtained through screening,and 452 potential targets were eliminated after repeated elimination;41 key targets were obtained after matching with the target of gastric ulcer.By enrichment analysis,the active ingredients of Bletilla striata played their roles in the protection of gastric mucosa mainly through of the targets of threonine kinase 1(Akt1),mitogen-activated protein kinase 3(MAPK3),MAPK1,tumor necrosis factor(TNF)and others targets and the signaling pathways of phosphatidylinositol 3 kinase-threonine kinase,TNF and MAPK.Conclusion The treatment of Bletilla striata ulcers gastric ulcers reflects the characteristics of traditional Chinese medicine acting through multiple components-multiple targets-multiple pathways.