基于生物信息学与网络药理学分析薯蓣皂苷治疗阿尔茨海默病和新型冠状病毒肺炎的靶点研究OACSTPCD
Bioinformatics and network pharmacology identify the therapeutic role and potential targets of diosgenin in Alzheimer disease and COVID-19
目的:基于生物信息学、网络药理学及分子对接技术探究薯蓣皂苷治疗阿尔茨海默病(alzheimer disease,AD)和新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的靶点.方法:利用生物信息学对AD和COVID-19的共有的差异表达基因(differential expression gene,DEGs)进行富集分析.接着,通过转录因子(transcription Factor,TF)调控网络分析,并利用Cytoscape使其网络可视化,进一步通过DGIdb数据库预测能同时治疗AD和COVID-19的药物,与CTD数据库中AD、COVID-19相关治疗药物进行 韦 恩 图 分 析,确 定 薯 蓣 皂 苷 作 为 治 疗 AD、COVID-19 的 潜 在 药 物.使 用 SEA、SuperPred、SwissTargetPrediction、TCMSP对薯蓣皂苷进行靶点预测,并将其分别与AD、COVID-19的DEGs进行韦恩图交集分析,确定薯蓣皂苷治疗AD、COVID-19的靶点,对其进行基因本体论(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,并构建这些药物靶点的蛋白相互作用(Protein Protein Interaction,PPI)网络,筛选出关联度最高的核心靶点.利用分子对接分析薯蓣皂苷与这些核心靶点的结合情况.结果:通过富集和聚类分析,发现AD、COVID-19共有DEGs所富集的生物过程、通路、疾病均与炎症和免疫调节相关.利用这些共有DEGs与Trust数据库构建了AD和COVID-19 TFs调控网络.通过网络药理学预测到薯蓣皂苷是治疗AD和COVID-19的潜在药物,并揭示了薯蓣皂苷治疗AD的36个靶点和27个治疗COVID-19的靶点.用CytohHubba计算得分,分别选取各自关联度最高的6个的核心靶点与薯蓣皂苷进行分子对接.结论:本研究首次揭示了AD和COVID-19共有TFs调控网络,预测并验证了薯蓣皂苷是治疗AD和COVID-19的潜在药物.且通过分子对接确定了薯蓣皂苷与治疗AD和COVID-19的核心药理靶点的结合情况,为开辟临床治疗 AD 和COVID-19新的途径提供了理论依据.
Objective:To explore the targets of diosgenin in treatment of Alzheimer′s disease(AD)and Coronavirus Dis-ease 2019(COVID-19)based on bioinformatics,network pharmacology and molecular docking techniques.Methods:Differential expression genes(DEGs)shared by AD and COVID-19 were enriched by bioinformatics.Secondly,key genes in transcription fac-tor(TF)of AD and COVID-19 were found by analysis of regulatory networks,and Cytoscape was used to visualize the networks.Based on this,the DGIdb database was further used to predict the drugs that can treat AD and COVID-19 at the same time,and the Venn diagram analysis was conducted with the drugs related to AD and COVID-19 in the CTD database to determine diosgen-in as a potential drug for the treatment of AD and COVID-19.SEA,SuperPred,SwissTargetPrediction and TCMSP were used to predict the target of diosgenin in the treatment of AD and COVID-19,and the target of diosgenin in the treatment of AD and COVID-19 was determined by Wayne diagram intersection analysis with the differentially expressed genes of AD and COVID-19.Their Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were analyzed jointly.The Protein Protein Interaction(PPI)network of these drug targets was constructed,and core targets with the highest correlation were screened out.The binding of diosgenin to these core targets was analyzed by molecular docking.Results:Through enrichment and cluster analy-sis,it was found that the biological processes,pathways and diseases enriched by DEGs in AD and COVID-19 were all related to inflammation and immune regulation.These common DEGs and Trust databases were used to construct regulatory networks of AD and COVID-19 TFs.Diosgenin was predicted as a potential drug for the treatment of AD and COVID-19 by network pharma-cology,and 36 targets of diosgenin for the treatment of AD and 27 targets for COVID-19 were revealed.The six core targets with the highest correlation were selected for molecular docking with diosgenin using CytohHubba to calculate the scores.Conclusions:This study reveal for the first time the common TF regulatory network of AD and COVID-19,and predicted and verified diosgen-in as a potential drug for the treatment of AD and COVID-19.The binding of diosgenin to the core pharmacological targets for the treatment of AD and COVID-19 was determined by molecular docking,which provides a theoretical basis for developing a new ap-proach to clinical treatment of AD and COVID-19.
张华雄;张明惠;李红燕
新疆维吾尔自治区人民医院 神经内科,新疆 乌鲁木齐 830000新奇康药业股份有限公司,新疆 乌鲁木齐 830000
中医学
生物信息学网络药理学薯蓣皂苷阿尔茨海默病新型冠状病毒肺炎
BioinformaticsNetwork pharmacologyDiosgeninAlzheimer's diseaseCOVID-19
《海南医学院学报》 2024 (001)
39-49 / 11
This study was supported by Research and Development and Industrialization Demonstration of Xinjiang Special Medicinal Materials,Antiinfective Drugs and Disinfection Products-Construction of Xinjiang Special Resource Antiinfective Drug Research and Development Platform(2021A03002-4) 新疆特色药材抗感染药物及消毒产品研发及产业化示范-新疆特色资源抗感染药物研发平台建设(2021A03002-4)
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