目的 运用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱（UPLC-Q-Exactive Focus MS/MS）技术鉴定枣仁安神胶囊化学成分，结合网络药理学和分子对接对枣仁安神胶囊治疗失眠的质量标志物（Q-Marker）进行预测。方法 采用UPLC-Q-Exactive Focus MS/MS技术在正、负离子模式下对枣仁安神胶囊中化学成分进行定性分析；将所得成分导入SwissADME数据库检索成分靶点；利用GeneCards、OMIM数据库收集失眠相关疾病靶点，取交集后利用Cytoscape 3.7.2软件构建“成分-疾病-靶点”网络，STRING数据库建立蛋白质-蛋白质相互作用（PPI）网络并筛选核心成分与核心靶点。利用DAVID数据库对共同靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，借助分子对接预测核心成分和关键靶点的结合能力，初步探索枣仁安神胶囊的Q-Marker。结果 通过UPLC-Q-Exactive Focus MS/MS共鉴定了枣仁安神胶囊中147种化学成分，结合数据库得到35个具有作用靶点的活性成分，644个与失眠相关靶点。其中，戈米辛E、表丹参隐螺内酯、五味子酯乙、五味子醇甲、五味子醇乙、五味子酯甲、木兰箭毒碱为枣仁安神胶囊治疗失眠的核心成分，蛋白激酶B (AKT1)、肿瘤坏死因子（TNF）、信号传导子及转录激活子3(STAT3)、B细胞淋巴瘤/白血病-2蛋白（BCL2）、胱天蛋白酶3(CASP3)为枣仁安神胶囊治疗失眠的核心靶点。作用于失眠与神经退行性变的途径、生长激素的合成、趋化因子信号通路等15条信号通路。分子对接结果表丹参隐螺内酯、戈米辛E、五味子醇乙、木兰箭毒碱4个核心成分与相关核心靶点的结合活性较好可作为枣仁安神胶囊的Q-Marker。结论 预测枣仁安神胶囊可能通过表丹参隐螺内酯、戈米辛E、五味子醇乙、木兰箭毒碱等关键成分，作用于AKT1、TNF、STAT3和BCL2等靶点，通过干预neurodegenerationmultiple diseases、Chemokine、FoxO等通路发挥治疗失眠的作用。

Objective To establish a high-resolution mass spectrometry method for rapid identification of chemical constituents of Zaoren Anshen Capsules. To predict and analyze the quality markers（Q-Markers） of Zaoren Anshen Capsules based on ultra-high performance liquid chromatography coupled with quadrupole/electrostatic field orbital trap high resolution mass spectrometry（UPLCQ-Exactive Focus MS/MS technology） and network pharmacology. Methods UPLC-Q-Exactive Focus MS/MS technology was used to qualitatively analyze the chemical components of Zaoren Anshen Capsules in both positive and negative ion modes. The identified components were imported into the SwissADME database to retrieve their target proteins. Targets related to insomnia were collected from GeneCards and OMIM databases, and a "component-disease-target" network was constructed using Cytoscape 3.7.2 software. Protein-protein interaction（PPI） networks were established through the STRING database to screen core components and core targets. Gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses of shared targets were conducted using the DAVID database. Molecular docking was employed to predict the binding affinity of core ingredients and key targets. The Q-Markers of Zaoren Anshen Capsules were preliminarily explored. Results A total of 147 chemical constituents in Zaoren Anshen Capsules were identified through UPLC-Q-Exactive Focus MS/MS. Database integration generated 35 active components with target proteins and 644 insomnia-related targets. Among them, gomisin E, epi-cryptoacetalide, schisandrin B, schisandrol A, schisandrol B, schisandrin A, and magnoflorine were identified as core components for treating insomnia. Protein kinase B（AKT1）, tumor necrosis factor（TNF）, signal transducer and activator of transcription 3（STAT3）, B-cell lymphoma/leukemia-2 protein（BCL2）, and Caspase-3（CASP3） were identified as core targets. These components acted on 15 signaling pathways, including those related to neurodegeneration, growth hormone synthesis, and chemokine signaling. Molecular docking results indicated that epicryptoacetalide, gomisin E, schisandrol B, and magnoflorine exhibited strong binding activity with core targets, making them potential Q-Markers of Zaoren Anshen Capsules. Conclusion Zaoren Anshen Capsules may exert therapeutic effects on insomnia through key components such as epi-cryptoacetalide, gomisin E, schizandrin B, and magnoflorine, by acting on targets such as AKT1, TNF, STAT3, and BCL2, and by intervening in pathways such as neurodegeneration-multiple diseases, Chemokine, and FoxO.

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“陕西省中医药管理局双链融合”中青年科研创新团队项目（2022-SLRH-YQ-003）；陕西省中医药管理局“医研校企”中医药传承创新平台项目（中医药创新药物/器械“研发-转化-推广”平台，2023）；陕西省中医药管理局中医药全省性专款专项项目（2021-QYZL-01）