基于网络药理学及分子对接揭示芦荟大黄素的降糖机制

Network pharmacology and molecular docking reveal hypoglycemic mechanism of aloe-emodin

该文通过网络药理学结合分子对接的技术研究了芦荟大黄素改善Ⅱ型糖尿病的作用机制。利用数据库平台筛选出芦荟大黄素的潜在靶点和改善治疗Ⅱ型糖尿病的相关靶点,将二者取交集获得芦荟大黄素改善Ⅱ型糖尿病的潜在靶点;构建共同靶点间的蛋白互作网络,并对共同靶点进行GO功能注释和KEGG通路富集分析;通过筛选主要通路并构建“芦荟大黄素-Ⅱ型糖尿病-通路”网络图,对芦荟大黄素与通路及各通路所富集的靶点间的联系进行可视化分析,通过分子对接,研究芦荟大黄素与关键靶点的结合机制。结果表明,芦荟大黄素具有63个改善治疗Ⅱ型糖尿病的相关靶点,并根据蛋白互作网络筛选出AKT1、PIK3CA、HRAS和MAPK8等22个核心靶点,这些靶点主要富集在PI3K/AKT和胰岛素抵抗等信号通路,芦荟大黄素主要通过氢键、范德华力和π-π相互作用等分子间作用力与靶点结合,从而调控靶点的表达,改善Ⅱ型糖尿病。

The mechanism of action of aloe-emodin for improving typeⅡdiabetes was investigated by network pharmacology combined with molecular docking technique.The potential targets of aloe-emodin and the related targets for improving the treatment of typeⅡdiabetes were screened by using the database platform,and the potential targets of aloe-emodin for improving typeⅡdiabetes were obtained by intersecting the two.The protein interaction network between the common targets was constructed,and the GO function annotation and KEGG pathway enrichment analysis were performed for the common targets.By screening the main pathways and constructing a network diagram of“aloe-emodin-typeⅡdiabetes-pathway”,this study visualized the linkage between aloe emodin and the pathways and the targets enriched by each pathway and studied the binding mechanism between aloe-emodin and the key targets through molecular docking.Results showed that aloe-emodin had 63 targets for improving the treatment of typeⅡdiabetes,and 22 core targets,including AKT1,PIK3CA,HRAS,and MAPK8,were identified based on the protein interaction network,which was mainly enriched in PI3K/AKT and insulin resistance signaling pathways.Aloe-emodin bound to the targets mainly through intermolecular forces such as hydrogen bonding,van der Waals forces,andπ-πinteractions,thus regulating the expression of the targets and improving typeⅡdiabetes.