基于网络药理学和分子对接技术探讨熟地平颤方治疗帕金森病的分子机制  

Exploring the molecular mechanisms of Shu Di Ping Chan formula in treating Parkinson’s disease based on network pharmacology and molecular docking approaches

作　　者：邱添 李泰平[2] 肖红[2] 刘卫国[3] 康冰[4] 杨宁[4] QIU Tian;LI Tai-ping;XIAO Hong(Department of Pharmacy,Brain Hospital Affliated Nanjing Medical University,Nanjing 210029,China;不详)

机构地区：[1]南京医科大学附属脑科医院药剂科,210029 [2]南京医科大学附属脑科医院神经精神病学研究所,210029 [3]南京医科大学附属脑科医院神经内科,210029 [4]南京医科大学附属脑科医院中医科,210029

出　　处：《临床神经病学杂志》2022年第4期246-256,共11页Journal of Clinical Neurology

基　　金：国家自然科学基金资助项目(81571348);江苏省重点研发计划专项项目(BE2019611);江苏省中医药科技发展专项项目(2020ZX17);南京市卫生科技发展专项资金项目(YKK20094);南京市中医药青年人才培养项目(ZYQ20070,ZYQ20071)。

摘　　要：目的 利用网络药理学和分子对接技术预测熟地平颤方治疗帕金森病(PD)的主要活性成分、潜在靶点及其分子作用机制。方法 借助中药系统药理学数据库与分析平台(TCMSP)和TCM@TAIWAN台湾中医药资料库、PubChem、Swiss Target Prediction平台筛选熟地平颤方中药的主要化学成分及其作用靶点,利用GeneCards和DisGeNET数据库筛选PD的相关靶点,STRING和Cytoscape软件构建共同靶点蛋白相互作用网络(PPI)及中药-活性成分-靶点网络图。通过Metascape对关键靶点进行基因本体论(GO)、DisGeNET功能富集和京都基因与基因组百科全书数据库(KEGG)通路富集分析。运用iGEMDOCK软件进行批量分子对接实验。结果 筛选出熟地平颤方29个主要活性成分,178个与PD共有的作用靶点,主要核心靶点包括AKT1、ALB、MAPK3、CASP3和APP等。GO功能和KEGG通路富集显示该方调控蛋白丝氨酸/苏氨酸及酪氨酸蛋白激酶、神经递质受体、肽链内切酶等多种分子功能,通过神经活动配体-受体相互作用、cAMP、雌激素、磷脂酶D等多种信号通路发挥治疗PD的作用。DisGeNET功能富集结果表明熟地平颤方广泛参与了认知障碍、淀粉样变性、记忆缺陷、神经痛和成瘾行为等方面的改善。分子对接结果显示羊毛甾醇、胆固醇与前列腺素G/H合酶2(PTGS2),α1-谷甾醇与白蛋白(ALB)均有较强的结合活性。结论 网络药理学和分子对接技术初步揭示了熟地平颤方通过多成分、多靶点及多通路发挥PD的治疗作用,为其进一步研究提供了参考。Objective To precisely achieve the prediction of the major bioactive components,potential targets and molecular mechanisms of ShuDi PingChan(SDPC) formula in the treatment of Parkinson’s disease(PD) by network pharmacology and molecular docking approaches.Methods The main bioactive components of the SDPC formula with their targets were screened using TCMSP,TCM@TAIWAN,PubChem databases and the Swiss Target Prediction platform.GeneCards and DisGeNET databases were used to obtain PD-related targets.Protein-protein interaction(PPI) and active ingredient-target networks were constructed by STRING and Cytoscape softwares,respectively.Gene ontology(GO),DisGeNET functional enrichment,and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses were performed by Metascape using the common targets.Batch molecular docking experiments were performed using iGEMDOCK software.Results Twenty-nine main bioactive ingredients of the SDPC and 178 common PD-related targets were achieved,including the core targets(AKT1,ALB,MAPK3,CASP3 and APP).GO function and KEGG pathway enrichments showed that multiple molecular functions were regulated by SDPC formula,such as the activity of serine/threonine kinase,neurotransmitter receptor,tyrosine kinase and endopeptidase.Neuroactive ligand-receptor interaction,cAMP,estrogen,phospho-lipase D and other signaling pathways played an important role in the treatment of PD.DisGeNET functional enrichment indicated that SDPC was widely involved in the improvement of cognitive impairment,amyloidosis,memory deficit,neuralgia and addictive behavior.Molecular docking results showed that lanosterol,cholesterol with prostaglandin G/H synthase 2(PTGS2),and sitosterol α1 with albumin(ALB) had strong binding activity respectively.Conclusion The application of network pharmacology and molecular docking approaches preliminarily revealed that the SDPC formula exerts the therapeutic effects of PD through multi-component,multi-target and multi-pathway,which provides a reference for its further rese

关 键 词：熟地平颤方 网络药理学 分子对接 帕金森病 分子机制 

分 类 号：R742.5[医药卫生—神经病学与精神病学]