基于网络药理学和分子对接技术探讨通脉糖眼明胶囊治疗糖尿病视网膜病变的作用机制

Mechanism of action of Tongmaitangyanming capsules in treatment of diabetic retinopathy:A study based on network pharmacology and molecular docking

目的:通过网络药理学和分子对接技术探讨通脉糖眼明胶囊对糖尿病视网膜病变(DR)的作用机制。方法:通过TCMSP、PubChem、Swiss Target Prediction等数据库和相关文献获取通脉糖眼明胶囊中药物的主要化学成分及其靶点,运用UniPort数据库进行基因名称统一,运用Cytoscape软件构建药物-化合物-靶点作用网络图;通过GeneCards数据库筛选DR的相关靶点,获取与药物作用靶点交集,基于STRING平台构建蛋白质-蛋白质相互作用(PPI)网络;通过Metascape平台对活性成分靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。运用AutoDock Vina对活性成分与关键靶点进行分子对接。结果:通脉糖眼明胶囊中含有99种活性成分,对应DR 92个靶点;主要通过肿瘤坏死因子(TNF)、丝氨酸/苏氨酸蛋白激酶(AKT1)、白细胞介素-6(IL-6)、血管内皮生长因子A(VEGFA)、白细胞介素-1β(IL-1β)、肿瘤蛋白P53(TP53)、趋化因子配体2(CCL2)等关键靶点发挥疗效,主要途径为糖尿病并发症中的晚期糖基化产物(AGE)-晚期糖基化终末产物受体(RAGE)信号通路、低氧诱导因子-1(HIF-1)信号通路、磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-Akt)信号通路、血管内皮生长因子(VEGF)信号通路、核因子-κB(NF-κB)信号通路等;具体生物学功能表现在正向调控细胞因子受体结合、蛋白质均二聚活性、转录共激活因子结合、氧化还原酶活性、激酶结合的调节等;分子对接结果显示,筛选的主要活性成分及靶点蛋白具有较好的结合活性。结论:本研究初步揭示了通脉糖眼明胶囊通过多成分、多靶点、多通路治疗DR的作用机制,为临床应用提供了理论依据。

[Abstract]Objective:To investigate the mechanism of action of Tongmaitangyanming capsules in the treatment of diabetic retinopathy(DR)based on network pharmacology and molecular docking.Methods:Databases including TCMSP,PubChem,and Swiss Target Prediction and related articles were used to obtain the main chemical components of Tongmaitangyanming capsules and their corresponding targets,and UniPort database was used to unify the names of genes.Cytoscape software was used to construct a drug-compound-target network.GeneCards database was used to obtain the targets associated with DR,and the intersecting targets were obtained.STRING platform was used to construct a protein-protein interaction network,and Metascape platform was used to perform gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the targets of active components.AutoDock Vina was used to perform molecular docking between the active components and the key targets.Results:There were 99 active components of Tongmaitangyanming capsules,which corresponded to 92 targets of DR.Tongmaitangyanming capsules exerted a therapeutic effect mainly through the key targets such as TNF,AKT1,IL-6,VEGFA,IL-1β,TP53,and CCL2.The main pathways included the AGE-RAGE signaling pathway,the HIF-1 signaling pathway,the PI3K-Akt signaling pathway,the VEGF signaling pathway,and the NF-κB signaling pathway.The specific biological functions were reflected in the positive regulation of cytokine receptor binding,protein homodimerization activity,binding of transcription coactivators,oxidation-reduction enzyme activity,and kinase binding.Molecular docking showed good binding activity between the main active components and the target proteins.Conclusion:This study shows that Tongmaitangyanming capsules exert a therapeutic effect on DR through multiple components,targets,and pathways,which provides a theoretical basis for clinical application.