基于网络药理学探讨葛根黄芩黄连汤治疗2型糖尿病的机制

Mechanism of Gegen Huangqin Huanglian Decoction in the Treatment of Type 2 Diabetes Based on Network Pharmacology

目的 采用网络药理学和分子对接技术共同探讨葛根黄芩黄连汤(GHHT)对2型糖尿病及其并发症的治疗机制。方法 使用中药系统药理学数据库与分析平台(TCMSP)筛选葛根、黄芩、黄连、甘草4味中药所含的活性成分。利用GeneCards数据库搜索与2型糖尿病相关的蛋白靶点;利用Pharmmapper平台,预测GHHT所含活性成分所作用的人类蛋白靶点。分析二者靶点的重复情况,并将重复靶点进行靶点蛋白相互作用(PPI)分析,利用Cytoscape软件构建药物-成分-靶点的网络图。通过Enrichr平台对关键基因作用的靶向细胞进行富集分析。结果 筛选得到活性成分101种,相关靶点155种,与2型糖尿病相关靶点500种,共有26种靶点重复。结论 GHHT可通过调节胰岛素分泌水平、改善胰岛素抵抗等机制治疗2型糖尿病;并通过调节转化生长因子β(TGF-β)/转化生长因子β受体1(TGFβR1)改善糖尿病肾病;通过调节血管内皮生长因子(VEGF)/血管内皮生长因子受体(KDR)通路改善糖尿病视网膜病变和糖尿病血管并发症。

Objective To explore the therapeutic mechanism of Gegen Huangqin Huanglian Decoction(GHHT) in the treatment of type 2 diabetes and its complications by using network pharmacology and molecular docking technology.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to screen the active ingredients of four traditional Chinese medicines,namely,Pueraria lobata,Scutellaria baicalensis,Coptis chinensis and Glycyrrhiza uralensis. GeneCards database was used to search for protein targets related to type 2 diabetes.Pharmmapper platform was used to predict the human protein targets affected by the active ingredients in GHHT. The duplication of the targets screened in the above two searches was analyzed. The duplicated targets were analyzed by proteinprotein interaction(PPI). And the drug-component-target network diagram was constructed by using Cytoscape software.Enrichment analysis of targeted cells with key gene effects was performed by using Enrichr platform. Results A hundred and one active ingredients,155 targets related to the active ingredients in GHHT and 500 targets related to type 2 diabetes were screened,with a total of 26 target replicates. Conclusion GHHT can treat type 2 diabetes by regulating insulin secretion and improving insulin resistance,improve diabetic nephropathy by regulating transforming growth factor-β(TGF-β) and TGF-beta receptor type-1(TGFβR1),and improve diabetic retinopathy and diabetic vascular complications by regulating vascular endothelial growth factor(VEGF) and vascular endothelial growth factor receptor(KDR) pathway.