基于系统药理学与分子对接探讨太子参抗Ⅱ型糖尿病作用机制

Mechanism in Anti-Type 2 Diabetes of Radix Pseudostellariae Based on Systems Pharmacology and Molecular Docking

目的运用系统药理学方法筛选太子参抗Ⅱ型糖尿病潜在活性成分及靶点并进行分子对接,探讨太子参抗Ⅱ型糖尿病作用机制。方法 TCMSP、TCMID数据库筛选太子参活性成分,Drugbank、TCMSP、SwissTargetPrediction数据库预测并构建成分靶点集,与DisGeNET、GeneCards、MalaCards、OMIM数据库中Ⅱ型糖尿病相关靶点取交集。STRING数据库构建蛋白互作网络,通过clusterProfiler进行富集分析,利用Cytoscape构建成份-靶点-通路网络图,Autodock Vina对候选化合物与核心靶标进行分子对接。结果从太子参中筛选得到59个候选成分,相关靶点蛋白229个;筛选糖尿病相关靶点552个,韦恩映射得到63个交集基因,蛋白互作网络筛选6个关键靶标ALB、IL6、AKT1、TNF、PPARG、TP53,涉及糖尿病并发症中的AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化、胰岛素抵抗、胰岛素信号通路、IL-17信号通路、Th17细胞分化等通路。结论太子参具有多成分、多靶点、多途径调节Ⅱ型糖尿病的作用特点,与糖尿病并发症中的AGE-RAGE信号通路、胰岛素抵抗、胰岛素信号通路等关联度较高。

OBJECTIVE To explore the potential active targets and anti-type 2 diabetes mechanism of Radix Pseudostellariae through molecular docking and systems pharmacology.METHODS TCMSP and TCMID databases were used to screen the active ingredients of Radix Pseudostellariae.The Drugbank, TCMSP and Swiss Target Prediction databases were used to predict and construct a set of component targets, which were intersected with the type Ⅱ diabetes-related targets in the DisGeNET,GeneCards, MalaCards, and OMIM databases, and proceeded through the clusterProfiler pack enrichment analysis;Construction of component-target-pathway network by using Cytoscape, and use Autodock Vina to perform molecular docking between candidate compounds and core targets.RESULTS 59 candidate components of Radix Pseudostellariae and 229 corresponding proteintargets are obtained.Screening 552 type 2 diabetes targets, then Venn diagramm and 63 intersection genes received.Screened 6 key targets ALB,IL6,AKT1,TNF,PPARG,TP53 through protein interaction network, involving AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, insulin resistance, insulin signaling pathway, IL-17 signaling pathway and Th17 cell differentiation pathway can play a role in the regulation of anti-type 2 diabetes.CONCLUSION Radix Pseudostellariae has the characteristics of multi-component, multi-target, and multi-channel regulation of type 2 diabetes.Through the target of type 2 diabetes screening, AGE-RAGE signaling pathway in diabetic complications, insulin resistance, insulin signaling pathway have a higher degree of association with type 2 diabetes.