基于网络药理学和分子对接研究黄葵胶囊治疗糖尿病肾病的作用机制

Mechanism of Huangkui Capsules in the Treatment of Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接方法分析黄葵胶囊治疗糖尿病肾病的作用机制。方法:通过化源网数据库、中药与化学成分数据库、PubChem数据库以及文献查阅,搜集黄葵胶囊化学成分,运用Swiss ADME数据库筛选出黄葵胶囊活性成分,依据Swiss Target Prediction数据库预测黄葵胶囊各活性成分靶点;通过GeneCards数据库和在线人类孟德尔遗传数据库(OMIM)检索糖尿病肾病疾病相关靶点,利用韦恩图获取黄葵胶囊治疗糖尿病肾病的关键靶点,通过R3.6.2软件对靶蛋白进行基因本体(GO)生物过程富集分析和京都基因和基因组百科全书(KEGG)通路富集分析。通过Cytoscape 3.7.2软件构建黄葵胶囊治疗糖尿病肾病的“关键活性成分-重要靶点-通路”网络,最后利用AutoDock进行分子对接,计算最低结合能。结果:黄葵胶囊治疗糖尿病肾病的核心活性成分为4′,5,7,8-四甲氧基黄酮、槲皮素、没食子酸、原儿茶酸等,核心靶点PIK3R1、PIK3CA、AKT1、SRC、ESR1等,活性成分与关键靶点分子对接的最低结合能均接近-5 kcal/mol。黄葵胶囊治疗糖尿病肾病的作用机制可能与内分泌抵抗、缺氧诱导因子-1(HIF-1)信号通路、表皮生长因子受体(EGFR)酪氨酸激酶抑制剂耐药机制、雌激素信号通路等有关。结论:本研究初步验证黄葵胶囊可通过多成分、多靶点、多通路治疗糖尿病肾病的作用,为黄葵胶囊的进一步研究提供理论依据。

Objective:To explore the mechanism of Huangkui Capsules in the treatment of diabetic nephropathy based on network pharmacology and molecular docking.Methods:The chemical components of Huangkui Capsules were collected from ChemSrc,Chinese medicine and chemical component database,PubChem,and available literature.The active ingredients of Huangkui Capsules were screened from Swiss ADME and the target genes of the active ingredients in Huangkui Capsules were predicted by Swiss Target Prediction.The genes associated with diabetic nephropathy were obtained from GeneCards and Online Mendelian Inheritance in Man(OMIM).Venny2.1.0 was used to identify the key targets shared by Huangkui Capsules and diabetic nephropathy.R3.6.2 was used to perform gene ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genome(KEGG)pathway enrichment for the key targets.Cytoscape 3.7.2 was employed to establish an“active ingredient-target-pathway”network for Huangkui Capsules in the prevention and treatment of diabetic nephropathy.Finally,AutoDock was used for molecular docking between active ingredients and key targets and calculating the lowest binding energy.Results:The major active ingredients of Huangkui Capsules in the treatment of diabetic nephropathy were 4′,5,7,8-tetramethoxyflavone,quercetin,gallic acid,and protocatechuic acid,and the key targets were PIK3R1,PIK3CA,AKT1,SRC,and ESR1.The lowest binding energy between the active ingredients and the key targets was close to-5 kcal/mol.Huangkui Capsules may treat diabetic nephropathy via endocrine resistance,epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor resistance,hypoxia-inducible factor-1(HIF-1)signaling pathway,and estrogen signaling pathway.Conclusion:Huangkui Capsules can treat diabetic nephropathy through multiple ingredients,targets,and signaling pathways,which provides a theoretical basis for further research on Huangkui Capsules.