基于网络药理学和分子对接技术探讨枸杞子治疗2型糖尿病的作用机制

The mechanism of Fructus lycii in the treatment of type 2 diabetes mellitus based on network pharmacology and molecular docking technology

目的:基于网络药理学和分子对接技术探讨枸杞子治疗2型糖尿病的机制。方法:利用TCMSP和Uniport数据库查询枸杞子的成分和靶点,Cytoscape 3.7.2软件构建“药物成分-疾病-靶点”网络图;DisGeNET、GeneCards检索2型糖尿病的靶点,筛选出药物与疾病交集靶点,绘制交集靶点韦恩图;String数据库对交集靶点构建PPI网络。Metascape数据库对靶点进行GO和KEGG信号通路富集分析。另外对核心靶点和枸杞子的成分进行分子对接,验证活性成分与核心靶基因的结合能力。结果:通过筛选枸杞子成分有45个,潜在靶点194个。2型糖尿病靶点3182个。将筛选出来的槲皮素靶点、枸杞子靶点与疾病靶点,运用Venny 2.1软件获得共同靶点101个。GO分析主要涉及氧化应激、脂多糖、药物反应和凋亡等。KEGG通路分析富集在癌症、脂质及动脉粥样硬化、AGE-RAGE等信号通路。分子对接结果显示,枸杞子的活性成分与核心靶点的分子对接亲和力均<-5 kcal/mol(1 kcal/mol=4.186 kJ/mol),表明结合活性好。结论:本研究基于网络药理学和分子对接技术探讨了枸杞子治疗2型糖尿病的作用机制,预测结果将有助于阐明枸杞子活性成分作为糖尿病用药的机理,但还需要更多的药理实验验证。

Objective:To explore the mechanism of Fructus lycii in the treatment of type 2 diabetes mellitus(T2DM)based on network pharmacology and molecular docking technology.Methods:The effective components and targets of Fructus lycii were screened using TCMSP and Uniport databases,and the"drug components-disease-targets"network map was constructed using Cytoscape3.7.2 software.DisGeNET and GeneCards databases were used to screen the targets of T2DM.And the common targets of drug and disease were obtained by Venny software.Protein-protein interaction(PPI)analysis of common targets was performed using String database.Metascape database was used for GO and KEGG analysis of common targets.Molecular docking was performed to verify the binding ability of active components to core targets.Results:There were 45 active components and 194 predicted targets in Fructus lycii.There were 3182 targets for T2DM.And 101 common targets of quercetin,Fructus lycii and T2DM were obtained by Venny software.GO analysis mainly involved oxidative stress,lipopolysaccharide,drug reaction and apoptosis.KEGG pathway analysis was enriched in Pathways in cancer,Lipid and atherosclerosis and AGE-RAGE signaling pathway.Results of molecular docking showed that the molecular docking affinity between the active components of Fructus lycii and the core targets were all<-5 kcal/mol(1 kcal/mol=4.186 kJ/mol),indicating that the binding activity was good.Conclusion:This study reveals the potential therapeutic mechanism of the active components of Fructus lycii in the treatment of T2DM based on network pharmacology and molecular docking technology,however,more pharmacological experiments are needed to verify the results.