基于UPLC-LTQ-Orbitrap-MS和网络药理学探讨六味地黄丸治疗AD潜在作用机制  

Based on UPLC-LTQ-Orbitrap-MS and network pharmacology methods to explore the potential mechanism of Liuwei Dihuang pills in the treatment of AD

作　　者：王迪[1] 张宁[2] 陈雪 薛傲 丁立新[1] 雷霞 WANG Di;ZHANG Ning;CHEN Xue;XUE Ao;DING Li-xin;LEI Xia(Jiamusi University,Jiamusi 154007,China;Jiamusi College,Heilongjiang University of Traditional Chinese Medicine,Jiamusi 154007,China;Wuxi Affiliated Hospital,Nanjing University of Traditional Chinese Medicine,Wuxi 214071,China)

机构地区：[1]佳木斯大学,佳木斯154007 [2]黑龙江中医药大学佳木斯学院,佳木斯154007 [3]南京中医药大学无锡附属医院,无锡214071

出　　处：《药物分析杂志》2022年第4期580-589,共10页Chinese Journal of Pharmaceutical Analysis

基　　金：黑龙江省属高校科技成果研发、培育项目(TSTAU-C2018020);哈尔滨市应用技术研究与开发项目(青年后备人才A类)(2017RAQXZ113);黑龙江中医药大学博士创新基金(2017BS09)。

摘　　要：目的:鉴定六味地黄丸入血入脑化学成分,采用网络药理学方法探讨六味地黄丸治疗阿尔茨海默症(AD)潜在作用机制。方法:通过超高效液相色谱-线性离子阱/静电场轨道阱组合式高分辨质谱联用(UPLC-LTQ-Orbitrap-MS)技术鉴定入血入脑成分,通过TCMSP、Swiss Target Prediction、OMIM、GeneCards、TTD、DisGeNET、DrugBank数据库预测成分和疾病作用靶点,通过String数据库、Cytoscape软件筛选核心靶点并构建“成分-靶点-疾病-通路”相互作用网络;采用Metascape数据库对核心靶点进行京都基因与基因组百科全书分析(Kyoto encyclopedia of genes and genomes,KEGG)、基因本体分析(gene ontology,GO)。结果:测得六味地黄丸入血入脑成分21个,涉及AD相关靶点蛋白169个。KEGG共富集175条代谢通路,主要涉及神经活性配体-受体相互作用信号通路、糖尿病并发症中AGE-RAGE信号通路、阿尔茨海默症信号通路等。GO功能富集分析主要涉及突触、细胞对氮化合物反应,G蛋白偶联受体活性等过程。结论:六味地黄丸治疗AD具有多靶点、多通路特点,其可能通过改善体内神经活性配体-受体异常、胰岛素受损等过程进行干预,为进一步实验验证其作用机制提供参考依据。Objective:To identify the chemical components of Liuwei Dihuang pills into the blood and brain,and to explore the potential mechanism of Liuwei Dihuang pills in the treatment of Alzheimer’s disease(AD)by meansof network pharmacology.Methods:Using ultra performance liquid chromatography-linear quadrupole ion trap-orbitrap high resolution mass spectrometry(UPLC-LTQ-Orbitrap-MS)technology,the components into the blood and brain was identified.Using TCMSP,Swiss Target Prediction,OMIM,GeneCards,TTD,DisGeNET and DrugBank database,composition and disease targets was predicted.Using String database and Cytoscape software,core targets were screened and a"component-target-disease-pathway"interaction network was constructed.Using Metascape database,Kyoto encyclopedia of genes and genome(KEGG)analysis and gene ontology(GO)were performed.Results:There were 21 components into blood and brain of Liuwei Dihuang pills,involving 169 AD-related target proteins.KEGG enriched a total of 175 metabolic pathways,which mainly involved neural active ligand-receptor interaction signaling pathways,AGE-RAGE signaling pathways in diabetic complications,and Alzheimer’s disease signaling pathways.GO functional enrichment analysis mainly involved processes such as synapses,cell responses to nitrogen compounds,and G protein coupled receptor activity.Conclusion:Liuwei Dihuang pills have the characteristics of multiple targets and multiple pathways in the treatment of AD.It may interfere with processes such as abnormal neuroactive ligand-receptor and insulin damage in the body,and provide a reference for further experimental verification of its mechanism of action.

关 键 词：阿尔茨海默病 六味地黄丸 化学成分鉴定 超高效液相色谱-线性离子阱/静电场轨道阱组合式高分辨质谱联用 网络药理学 靶点 通路 

分 类 号：R917[医药卫生—药物分析学]