基于液质联用技术和网络药理学方法探讨神牡安神胶囊改善失眠的潜在药效成分和作用机制  

Potential pharmacodynamic components and mechanism of Shenmu Anshen capsules in improving insomnia based on UPLC-MS/MS combined with network pharmacology

作　　者：尤诗晴 徐畅 刘莹 陈静婷 肖驿泽 陈曦 王金朝 张薇 褚福浩[1,2] YOU Shi-qing;XU Chang;LIU Ying;CHEN Jing-ting;XIAO Yi-ze;CHEN Xi;WANG Jin-zhao;ZHANG Wei;CHU Fu-hao(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488;Beijing University of Chinese Medicine East Hospital Zaozhuang Hospital,Zaozhuang Shandong 277000;Vast Sky Biotechnology(Beijing)Technology Co.,Ltd.,Beijing 100020)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]北京中医药大学东方医院枣庄医院,山东枣庄277000 [3]瀚天生物(北京)科技有限公司,北京100020

出　　处：《中南药学》2024年第9期2355-2362,共8页Central South Pharmacy

基　　金：北京中医药大学青年科学家培育计划(No.BUCM-2019-QNKXJC008)。

摘　　要：目的研究神牡安神胶囊治疗神经衰弱引起失眠的药效物质基础及潜在作用机制。方法运用UPLC-QE-Orbitrap-MS并结合文献,对神牡安神胶囊的主要化学成分进行分析鉴定;通过TCMSP数据库及文献查阅对神牡安神胶囊的潜在有效成分进行筛选及补充;通过Swiss Target Prediction数据库预测活性成分潜在靶点;搜索OMIM、GeneCards及TTD数据库获取失眠症相关靶点;使用Venny软件收集成分靶点-疾病靶点交集,在Cytoscape软件中构建药物-成分-靶点网络图;利用STRING平台构建PPI网络,借助Metascape数据库对交集靶点进行GO富集分析与KEGG通路分析,利用Cytoscape构建成分-靶点-通路图。进一步建立对氯苯丙氨酸(PCPA)诱导的失眠小鼠模型,通过延长戊巴比妥钠睡眠时间实验考察神牡安神胶囊改善失眠动物模型睡眠的作用,通过ELISA法检测各组小鼠血清中5-羟色胺(5-HT)水平,考察神牡安神胶囊改善睡眠的可能机制。结果通过与数据库对比、文献分析以及质谱裂解规律解析,从神牡安神胶囊样品中鉴定出40个化合物;通过网络药理学共筛选出122个候选成分和917个预测靶点,与失眠共同靶点185个,关键靶点主要涉及TP53、EP300、HDAC1、TNF、APP等;KEGG富集分析预测神牡安神胶囊主要通过神经退行性病变相关信号通路(pathways of neurodegeneration-multiple diseases)、多巴胺能突触信号通路(dopaminergic synapse)、帕金森病信号通路(Parkinson disease)及5-羟色胺能神经突触信号通路(serotonergic synapse)等信号通路发挥治疗失眠作用。延长戊巴比妥钠睡眠时间实验中,与模型组相比,神牡安神胶囊中、高剂量组小鼠睡眠时间显著延长(P<0.01);小鼠血清中5-HT的含量也明显升高(P<0.05)。结论初步明确了神牡安神胶囊的化学组成及其治疗神经衰弱失眠症的作用机制,其改善小鼠失眠作用可能是通过激活脑内抑制性单胺类神经递质,增加中枢对睡�Objective To determine the potential pharmacodynamic components and mechanism of Shenmu Anshen capsules in improving insomnia.Methods The main chemical components of Shenmu Anshen capsules were identified by UPLC-QE-Orbitrap-MS information and literature data.Through TCMSP database and literature review,the potential active components of Shenmu Anshen capsule were screened and supplemented.The potential targets of active components were predicted by Swiss Target Prediction database.OMIM,GeneCards,and TTD databases were used to collect insomnia-related targets.Venny software was used to collect the intersection of components targets and drug targets.Cytoscape software was used to establish the interaction network of drug-compound-target.The STRING platform was used to establish the PPI network.Functional enrichment analysis of target GO and KEGG pathways conducted with the Metascape database,and the component-target-pathway diagram was established by Cytoscape.At last,the mouse model of insomnia caused by p-chlorophenylalanine was used to determine the effect of Shenmu Anshen capsules in improving sleep in the mouse model of insomnia.The serum level of 5-hydroxytryptamine(5-HT)was detected by ELISA.Results Through comparison with the database,literature analysis and mass spectrometry cleavage law analysis,40 compounds were identified from the samples of Shenmu Anshen capsules.Totally of 122 candidate components and 917 predicted targets were screened by network pharmacology.There were 185 common targets with insomnia.The key targets mainly involved TP53,EP300,HDAC1,TNF,APP,etc.Shenmu Anshen capsules mainly participated in the regulation of signaling pathways of neurodegeneration-multiple diseases,dopaminergic synapse,Parkinson disease and serotonergic synapses.Compared with the model group,Shenmu Anshen capsules at medium and high doses greatly prolonged sleep duration and increased the content of 5-HT in the serum.Conclusion The chemical components of Shenmu Anshen capsules and the mechanism of improving neurasth

关 键 词：神牡安神胶囊 失眠 网络药理学 超高效液相色谱-四极杆-静电场轨道 阱高分辨质谱法 神经衰弱 

分 类 号：R286[医药卫生—中药学]