基于网络药理学和分子对接探讨六味地黄丸治疗糖尿病的作用机制

The mechanism of Liuwei Dihuang pill in treating diabetes mellitus based on network phar⁃macology and molecular docking

目的:运用网络药理学和分子对接探究六味地黄丸治疗糖尿病的作用机制。方法:运用中药网络药理学数据库与分析平台(TCMSP)筛选出六味中药的主要成分,通过SwissTargetPrediction、SEA和PharmMapper共同预测化合物的靶点,运用Cytoscape构建成分-靶点网络。通过DisGeNET、T-HOD和TTD数据库检索糖尿病相关基因,将成分靶点与疾病基因取交集。对交集基因进行Metascape聚类富集分析和生物学通路富集分析。运用Cytoscape的CytoHubba和MCODE插件进行关键靶点的选取。通过DAVID数据库进行KEGG通路分析。通过DockThor对选取的六味地黄丸主要活性成分和关键靶点进行分子对接。结果:共获得药物靶点663个,糖尿病相关靶点1131个,药物和疾病交集基因204个,最终获取CNR1、ADORA1、HRH3等10个关键靶点。靶点参与的功能主要有血液循环、胰岛素抵抗、对脂多糖反应等过程;KEGG通路富集分析结果显示,主要涉及胰岛素调节、免疫调节、抗肿瘤等途径。分子对接结果显示主要活性成分与关键靶点具有较好的结合活性。结论:六味地黄丸可能通过抑制胰岛素抵抗、调节血液循环和糖代谢,降低体内血糖含量,从而达到治疗糖尿病目的。

Objective:To explore the mechanism of Liuwei Dihuang pill in treating diabetes mellitus by network pharmacology and molecular docking.Methods:The main compounds of Liuwei Dihuang pill were screened by the TCMSP database,and the target of compounds were predicted by SwissTargetPrediction,SEA and Pharm-Mapper.A compound-target network was built by Cytoscape.Diabetes-related genes were searched by DisGeNET,T-HOD and TTD databases and the intersection of component targets and disease genes were taken.Metascape cluster and biological pathways enrichment analysis were performed on the intersection genes.Key targets were selected on CytoHubba and MCODE plug-ins of Cytoscape.KEGG pathway analysis was done by DAVID.Molecular docking of main active ingredients and key targets of Liuwei Dihuang pill were done by DockThor.Results:A total of663 targets of Liuwei Dihuang pill,1,331 diabetes mellitus relate-genes,204 intersection targets of drug and disease and 10 key targets such as CNR1,ADORA1,HRH3,etc.were identified.The targets were mainly involved in blood circulation,insulin resistance,reaction to lipopolysaccharide and other processes.Results of enrichment of KEGG mainly related to insulin regulation,immune regulation and anti-tumor pathway.Molecular docking indicatedthat the major active components had a good bonding activity with the key targets.Conclusion:Liuwei Dihuang pill may reduce blood-sugar content through inhibiting insulin resistance,and regulating blood circulation and sugar metabolism to treat diabetes mellitus.