基于网络药理学方法研究知母治疗2型糖尿病作用机制

A network pharmacology technology study on the mechanism of anemarrhena in the treat⁃ment of type 2 diabetes mellitus

目的使用网络药理学技术探讨知母治疗2型糖尿病(T2DM)作用机制。方法挖掘中药成分数据库中知母化学成分,获取化学成分的药代动力学参数用于构建药物的化学成分数据库;利用ADME模型筛选潜在活性分子;基于随机森林和支持向量机的方法预测活性分子作用靶点并构建知母化合物-靶点(C-T)网络;从多个人类疾病数据库检索T2DM相关靶点并构建疾病蛋白-蛋白相互作用(PPI)网络,构建知母活性-疾病靶点(C-D)网络;通过富集分析构建知母活性分子作用靶点-通路(C-D-M)网络。结果该研究得到的知母化学成分数据库一共有81个分子,通过ADME模型筛选得到15个活性分子,通过分析化合物作用靶点网络发现知母活性分子作用20个T2DM靶点蛋白,富集分析发现知母活性分子通过调控胰岛素通路、胰岛素抵抗通路、PI3K-Akt信号、NOS3通路、HIF-1通路、能量代谢等途径治疗T2DM。结论知母可通过多成分、多靶点、多途径的协同作用治疗T2DM。

Objective To investigate the mechanism of anemarrhena in the treatment of type 2 diabetes mellitus(T2DM)using network pharmacology technology.Methods Mining the chemical constituents of anemarrhena in the database of traditional Chinese medicines,and obtaining the pharmacokinetic parameters of the chemical constituents to construct the chemical constituents database of medicines;by used ADME model to screen potential active molecules;methods based on random forest and support vector machine to predict active molecules act on the target and construct the anemarrhena compound-target(C-T)network;retrieve T2DM-related targets from multiple human disease databases and construct a disease protein-protein interaction(PPI)network to construct the active molecule-disease target of anemarrhena network;Construction of anemarrhena activity-disease target(C-D)network;construction of anemarrhena activity molecular target-pathway(C-D-M)network by enrichment analysis.Results A total of 81 molecules were obtained from the database of chemical constituents of Anemarrhena in this study,15 active molecules were screened by ADME model.By analyzing the target network of compounds,it was found that anemarrhena active molecules act on 20 target proteins of T2DM.The enrichment analysis found that the active molecules of anemarrhena can treat T2DM by regulating insulin pathway,insulin resistance pathway,PI3K-Akt signaling pathway,NOS3 signaling pathway,HIF-1 signaling pathway,energy metabolism pathway and other pathways.Conclusion Anemarrhena can treat T2DM through the synergistic effect of multiple components,multiple targets and multiple pathways.