六味地黄丸治疗糖尿病视网膜病变网络药理学与分子对接分析  

Network Pharmacology and Molecular Docking Analysis of Liuwei Dihuang Pills(六味地黄丸)in the Treatment of Diabetic Retinopathy

作　　者：罗颖琳 黄发义 滕月 李晓洁 刘求红[2] LUO Yinglin;HAUNG Fayi;TENG Yue;LI Xiaojie;LIU Qiuhong(Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China)

机构地区：[1]广州中医药大学,广东广州510405 [2]广州中医药大学第一附属医院,广东广州510405

出　　处：《辽宁中医药大学学报》2023年第1期57-65,F0003,共10页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82174441);广东省医学科学技术研究基金项目指令性课题(C2019127)。

摘　　要：目的 基于网络药理学研究六味地黄丸治疗糖尿病视网膜病变(diabetic retinopathy,DR)的潜在机制并利用分子对接进行验证。方法 通过TCMSP数据库平台筛选六味地黄丸的有效成分以及相关靶点,通过疾病数据库(GeneCards、OMIM、Drugbank、TTD数据库)获取DR相关靶标并预测六味地黄丸治疗DR的潜在靶点。通过STRING网站和Cytoscape3.7.2软件绘制“复方活性成分-交集靶点”网络结构,同时建立PPI网络模型并找到关键靶点。对六味地黄丸治疗DR的靶标进行基因本体(GO)富集分析与京都基因与基因组百科全书(KEGG)通路富集分析,最后采用AutoDock软件实现分子对接。结果 (1)获得六味地黄丸活性成分69个,有效成分靶点蛋白203个,DR相关基因3326个,交集靶点121个,核心靶标13个。(2)与DR治疗相关的生物学进程(biological process,BP)包括对脂多糖、氧化应激、化学应激的反应等,KEGG富集分析提示关键的通路涵盖AGE-RAGE、PI3K-Akt、HIF-1信号通路等。(3)分子对接显示槲皮素、薯蓣皂苷、山柰酚、β-谷甾醇与核心靶点有良好的亲和力(结合能≤-5.0 kJ·mol-1)。结论 AGEs-RAGE、PI3K-Akt、HIF-1、TNF、IL-17等信号通路具有诱导氧化应激、加重炎症刺激、促进新生血管形成的功能,在DR病程中扮演重要的角色,六味地黄丸中的槲皮素、薯蓣皂苷、山柰酚、β-谷甾醇通过作用于以上通路,达到对DR的干预效果,延缓病程发展,展现出多组分-多环节-多靶点的优势。Objective Based on network pharmacology,explore the potential mechanism of Liuwei Dihuang Pills(六味地黄丸)in the treatment of diabetic retinopathy(DR)and verify the results by molecular docking.Methods To screen the effective ingredients and corresponding targets of Liuwei Dihuang Pills by the TCMSP database.To obtain DR relevant targets from disease databases(including Gene Cards,OMIM,Drugbank,TTD database)and predict the potential targets of Liuwei Dihuang Pills in the treatment of DR.The network of"drug active components-intersection target"was established by Cytoscape 3.7.2 software.The protein-protein interaction(PPI)network was constructed through the STRING database to find the core target.The intersection targets were analysis by Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Finally,Auto Dock software was used to verify.Results(1)69 active components of Liuwei Dihuang Pills,203 corresponding targets,3326 DR-related genes,121 intersection targets,13 core targets were screened out.(2)Biological processes include the response to lipopolysaccharide,oxidative stress,chemical stress,etc.The KEGG enrichment analysis suggests that the key pathways include AGE-RAGE,PI3K-Akt,and HIF-1 signaling pathways,etc.(3)The result of molecular docking indicate that quercetin,diosgenin,kaempferol,andβ-sitosterol have good affinity with the core targets(binding energy≤-5.0 k J·mol-1).Conclusion AGEs-RAGE,PI3K-Akt,HIF-1,TNF,IL-17 and other signaling pathways have the functions of inducing oxidative stress,aggravating inflammation,and promoting neovascularization,and play an important role in DR.Quercetin,diosgenin,kaempferol,andβ-sitosterol in Liuwei Dihuang Pills act on above pathways to achieve the intervention effect on DR,delay the development of DR,and show the advantage of multiple components-multiple links-multiple targets.

关 键 词：六味地黄丸 糖尿病视网膜病变 网络药理学 分子对接 作用机制 

分 类 号：R587.2[医药卫生—内分泌] R774.1[医药卫生—内科学]