基于网络药理学和分子对接研究蒙药额尔敦-乌日勒对帕金森病的作用机制  

Study on the mechanism of Mongolian medicine Erdun-Wurile on Parkinson’s disease based on network pharmacology and molecular docking

作　　者：李晓锋 林玉凤 张雅蓓 陈向辉 赵蕊 朱伟 谢雅彬[1,3,4] 谢伟 巴德仁贵 姜树原[1,3,4,8] 刘晓蕾 邵国[1,3,4,9] 白海花 贾小娥[1,3,4,6] 杨志甫 LI Xiaofeng;LIN Yufeng;ZHANG Yabei;CHEN Xianghui;ZHAO Rui;ZHU Wei;XIE Yabin;XIE Wei;BADE Rengui;JIANG Shuyuan;LIU Xiaolei;SHAO Guo;BAI Haihua;JIA Xiaoe;YANG Zhifu(Baotou Medical College of Inner Mongolia University of Science and Technology,Baotou 014040;Department of Neurology,the First Affiliated Hospital of Baotou Medical College;Institute of Neuroscience,Baotou Medical College;Key Laboratory of Hypoxia Transformational Medicine in Inner Mongolia Autonomous Region;Puyang Oilfield General Hospital Emergency Department;School of Basic Medicine and Forensic Medicine,Baotou Medical College;School of Pharmacy,Baotou Medical College;School of Public Health,Baotou Medical College;The Third People’s Hospital of Longgang District;Genetic Testing Center of Affiliated Hospital of Inner Mongolia University for Nationalities)

机构地区：[1]内蒙古科技大学包头医学院,内蒙古包头014040 [2]包头医学院第一附属医院神经内科 [3]包头医学院神经科学研究所 [4]内蒙古自治区低氧转化医学重点实验室 [5]濮阳油田总医院急诊科 [6]包头医学院基础医学与法医学院 [7]包头医学院公共卫生学院 [8]包头医学院药学院 [9]深圳市龙岗区第三人民医院 [10]内蒙古民族大学附属医院基因检测中心

出　　处：《包头医学院学报》2024年第1期1-7,40,共8页Journal of Baotou Medical College

基　　金：国家自然科学基金项目(81901918);内蒙古自然科学基金(2021MS08053);2020年中央引导地方发展基金(2020ZY0040);2022年内蒙古人才开发基金;内蒙古自治区个体化用药工程技术研究中心开放课题(MDK2021057),包头医学院创新团队(bycxtd-04);内蒙古自治区卫生健康科技计划项目(202201422);自治区高等学校科学研究项目(NJZY23093);包头医学院青年科技人才发展计划(BYJJ-DXK2022042)。

摘　　要：目的:基于网络药理学方法挖掘蒙药额尔敦-乌日勒治疗帕金森病的主要活性成分和药物靶点,揭示其潜在的可能作用机制,并运用分子对接研究药物与靶点蛋白结合能力。方法:依据中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSCP)挖掘额尔敦-乌日勒的活性成分及对应靶点,以药动参数生物利用度(oral bioavailability,OB)≥30%、类药性(drug-likeness,DL)≥0.18:为条件进行筛选,运用GeneCards、OMIM和TTD数据库筛选出额尔敦-乌日勒活性成分治疗帕金森病的可能靶点,运用Cytoscape 3.9.1绘制Venn图,借助STRING数据库绘制蛋白互作(protein-protein interaction,PPI)网络图;应用微生信在线软件及Metascape数据库查找蒙药额尔敦-乌日勒潜在的活性成分及治疗帕金森病的潜在作用靶点,并将靶点进行基因本体(gene ontology,GO)及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,并将药物小分子和靶点蛋白进行分子对接。结果:蒙药额尔敦-乌日勒中筛选出DL及OB值好的活性成分118种,预测治疗帕金森病的靶点207个,GO功能富集分析及KEGG富集分析显示,蒙药额尔敦-乌日勒治疗帕金森病的机制主要涉及RNA聚合酶启动子转录的正调控、正调控DNA模板转录和调控基因表达等生物过程,其涉及的通路包括AKT1、TP53、TNF、VEGFA、CASP3等。结论:蒙药额尔敦-乌日勒治疗帕金森病是多成分、多靶点、多通路的作用结果,为蒙药额尔敦-乌日勒治疗帕金森病的进一步研究提供了理论依据。Objective:To explore the main active components and drug targets of Mongolian medicine Erdun-Wurile in the treatment of Parkinson’s disease and its potential action mechanism based on the network pharmacology,and study the binding ability of drugs and target proteins with molecular docking.Methods:The active components and corresponding targets of Eerdun-Wurile were mined based on the traditional Chinese medicine systems pharmacology database and analysis platform,TCMCSP).The mined data were screened under the term of pharmacokinetic parameters oral bioavailability(OB)≥30%,drug-likeness property(DL)≥0.18:.GeneCards,OMIM and TTD databases of human gene-disease related databases were used to screen out the possible targets in active components of Eerdun-Wurile in the treatment of Parkinson’s disease.The Venn diagram was drawn by Cytoscape 3.9.1,and PPI network diagram was drawn with STRING database.The Bioinformatics and Metascape database were used to search the potential active ingredients of Erden-Wurile and potential targets for the treatment of Parkinson’s disease,and GO function analysis and KEGG enrichment analysis was performed on screened targets with molecular docking of small drug molecules and target proteins.Results:118 kinds of active ingredients with good DL and oral absorption were screened from Eerdun-Wurile medicine,and 207 targets were predicted to treat Parkinson’s disease.GO function analysis and KEGG enrichment analysis showed that the mechanism of Mongolian medicine Eerdun-Wurile in treating Parkinson’s disease mainly involved with biological processes such as positive regulation of RNA polymerase II promoter transcription,positive regulation of DNA template transcription,positive regulation of gene expression.Pathways involved were AKT1,TP53,TNF,VEGFA,CASP3,etc.Conclusion:The effect of Mongolian medicine Eerdun-Wurile in treating Parkinson’s disease is the action result of multi-components,multi-targets and multi-channels,which provides theoretical basis for further research

关 键 词：蒙药 额尔敦-乌日勒 网络药理学 帕金森病 作用机制 分子对接 

分 类 号：R29[医药卫生—民族医学]