基于网络药理学方法探讨半边莲治疗2型糖尿病的作用机制

Network pharmacology-based study on the mechanisms of chinensis lobelia in the treatment of type 2 diabetes mellitus

目的采用网络药理学方法探讨半边莲治疗2型糖尿病的潜在作用机制。方法在中药系统药理学分析平台查找并筛选半边莲的活性成分,通过文献检索补充半边莲中具有药理活性的成分;采用Swiss Target prediction数据库预测活性成分相关靶标;采用OMIM、TTD和Drug Bank数据库查找2型糖尿病相关靶标蛋白,采用Uniprot数据库查询靶标蛋白对应的基因名称,采用Venny图映射得到半边莲调控的2型糖尿病靶点;采用Metascape数据库进行GO富集分析及KEGG通路分析;采用Cytoscape 3.7.2软件构建“有效成分-活性靶点-代谢通路”网络并分析三者相互作用;采用STRING数据库分析蛋白相互作用;采用Discovery Studio软件对网络药理学分析结果进行验证。结果得到半边莲活性成分17个,通过文献补充半边莲具有降糖药理活性的成分2个;半边莲活性成分靶标152个;2型糖尿病相关靶点716个;半边莲调控的2型糖尿病靶点25个;GO富集条目20条,其中生物过程条目13条,分子功能条目3条,细胞组成条目4条;KEGG代谢通路8条;“有效成分-活性靶点-代谢通路”网络分析得知槲皮素、金合欢素、香叶木素和金圣草黄素是半边莲治疗糖尿病的关键成分;蛋白相互作用分析得知CYP1A2、CYP1A1和CYP2D6是半边莲治疗2型糖尿病的关键靶点;Discovery Studio分子对接结果表明,半边莲活性成分与关键靶点的结合活性较好。结论通过网络药理学的方法预测了半边莲治疗2型糖尿病可能的药效物质基础及其作用机制,解释了半边莲能发挥多靶点、多通路协同治疗糖尿病的作用,为半边莲治疗2型糖尿病进一步的实验研究提供理学基础和新的思路。

ObjectiveA network pharmacology approach was used to explore the potential mechanism of action of Chinese lobelia for the treatment of type 2 diabetes mellitus.MethodsHe active constituents of Chinese lobelia were identified and screened in the Traditional Chinese Medicine Systematic Pharmacology Platform,and the pharmacologically active constituents in Chinese lobelia were supplemented by literature search;the SwissTarget prediction database was used to predict the active constituent-related targets;the OMIM,TTD and Drug Bank databases were used to find the type 2 diabetes-related target.By using the Uniprot database to search for the gene names corresponding to the target proteins,and the Venny diagram mapping to obtain the type 2 diabetes targets modulated by Chinese lobelia.Metascape database was used for GO enrichment analysis and KEGG pathway analysis.The network of"active ingredient active target metabolton"was constructed by using Cytoscape 3.7.2 software,and the interaction among them was analyzed.The results of the network pharmacological analysis were validated by using Discovery Studio software.ResultsTo obtain 17 active ingredients in Chinese lobelia,2 ingredients with hypoglycemic pharmacological activity through literature supplementation;152 active ingredient targets of Chinese lobelia;716 type 2 diabetes-related targets;25 type 2 diabetes targets regulated by Chinese lobelia;20 GO enriched entries,including 13 biological process entries,3 molecular function entries and 4 cellular composition entries;8 KEGG metabolic pathways;the“active ingredient-active target-metabolic pathway”network analysis showed that Quercetin,Acacetin,Diosmetin and Chryseriol are the key components of Chinese lobelia for the treatment of diabetes;protein interaction analysis revealed that CYP1A2,CYP1A1 and CYP2D6 are the key targets of Chinese lobelia for the treatment of type 2 diabetes.Discovery Studio molecular docking results showed that the active ingredients of Chinese lobelia bound well to the key targets.ConclusionThe pharmacokinetic basis and mechanism of Chinese lobelia in the treatment of type 2 diabetes mellitus were predicted by network pharmacology,and explained that Chinese lobelia can play a multi-target and multi-pathway synergistic role in the treatment of diabetes,providing a scientific basis and new ideas for further experimental studies of Chinese lobelia in the treatment of type 2 diabetes.