UPLC-Q-Orbitrap HRMS结合网络药理学分析宁心养神膏化学成分及治疗失眠的作用机制*

作者：粟洁莹1，赵湘培1，卢蓉萍1，孙宗喜1，杨 梅1，2

单位：1.广西中医药大学附属国际壮医医院壮瑶医药研究实验室，广西 南宁 530201； 2.广西壮医龙路病重点研究室，广西 南宁 530201

引用：引用：粟洁莹，赵湘培，卢蓉萍，孙宗喜，杨梅.UPLC-Q-Orbitrap HRMS结合网络药理学分析宁心养神膏化学成分及治疗失眠的作用机制[J].中医药导报,2025,31(12):90-97.

DOI：10.13862/j.cn43-1446/r.2025.12.014

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摘要：目的：运用网络药理学和分子对接方法探讨宁心养神膏治疗失眠的相关靶点及其作用机制。方法：通过UPLC-Q-Orbitrap HRMS液质联用得到宁心养神膏的化合物成分，在SwissADME网站筛选并获取宁心养神膏的主要活性成分及其作用靶点；利用疾病基因网络（DisGeNet）、人类基因综合数据库（GeneCards）、药物靶标数据库（Drug Bank）、治疗靶点数据库（Therapeutic Target Database）、人类孟德尔遗传数据库（OMIM）和蛋白质数据库（Uniprot）检索失眠相关靶点；绘制韦恩图获取药物与疾病的共同靶点；以String在线分析平台分析药物与疾病共同靶点，进行蛋白质-蛋白质相互作用（PPI）网络构建；利用DAVID生物信息数据库对药物与疾病共同靶点进行基因本体论（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，并利用Cytocsape 3.10.2软件构建“药物-成分-靶点-疾病”网络图。通过AutoDock软件进行分子对接，并采用PyMol软件进行可视化分析。结果：宁心养神膏中共筛选出48个有效化学成分，其核心成分与失眠交集靶点615个。GO和KEGG分析结果显示宁心养神膏治疗失眠的作用机制主要涉及长时程抑制、β-丙氨酸代谢、脂肪酸降解、内分泌和神经元投射形态发生、常染色质、γ-氨基丁酸门控氯离子通道活性等调节通路。分子对接结果显示宁心养神膏中的化学成分黄芩苷元、山柰酚、棕榈酸、邻苯二甲酸二丁酯、橙皮素、棕榈油酸与丝裂原活化蛋白激酶3（MAPK3）、前列腺素内过氧化物合酶2（PTGS2）、过氧化物酶体增殖物激活受体γ（PPARG）、半胱天冬酶3（CASP3）、雌激素受体α（ESR1）等核心靶点有较高的亲和力。结论：宁心养神膏中黄芩苷元、山柰酚、棕榈酸、邻苯二甲酸二丁酯、橙皮素、棕榈油酸等有效成分为治疗失眠的相关靶点，可通过调控失眠的信号通路以及其相关蛋白发挥缓解失眠的作用。

关键词：失眠；宁心养神膏；UPLC-Q-OrbitrapHRMS；网络药理学；分子对接

Abstract：

Objective: To explore the related targets and mechanisms of action of the medicine Ningxin Yangshen Gao in treating insomnia by network pharmacology and molecular docking methods. Methods: The main active components of Ningxin Yangshen Gao were screened and obtained through UPLC-Q-Orbitrap HRMS liquid chromatography-mass spectrometry. The main active ingredients and their action targets of Ningxin Yangshen Gao were Screened and obtained on the SwissADME website. Insomnia-related targets were retrieved using DisGeNet, GeneCards, Drug Bank, Therapeutic Target Database, OMIM, and Uniprot databases. The targets of drugs and diseases were plotted in a Venn diagram to obtain common targets. The protein-protein interaction (PPI) network was constructed using the String online analysis platform for the common targets of drugs and diseases. DAVID database was used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the common targets of drugs and diseases, and Cytoscape 3.10.2 software was used to construct a "drug-component-target-disease" network diagram. Molecular docking was performed using AutoDock software and visualization analysis was conducted using PyMol software. Results: A total of 48 effective chemical components were screened out from Ningxin Yangshen Gao, and their core components intersected with 615 insomnia targets. GO and KEGG analysis results showed that the mechanism of action of Ningxin Yangshen Gao in treating insomnia mainly involves long-term inhibition, β-alanine metabolism, fatty acid degradation, endocrine and neuronal projection morphogenesis, constitutive chromatin, GABA-gated chloride channel activity, etc. Molecular docking results showed that the chemical components of Ningxin Yangshen Gao such as baicalin, kaempferol, palmitic acid, dibutyl phthalate, naringenin and palmitoleic acid exhibit high affinity with the core targets such as mitogen-activated protein kinase 3 (MAPK3), prostaglandin-endoperoxide synthase 2 (PTGS2), peroxisome proliferator-activated receptor gamma (PPARG), Caspase 3 (CASP3), and estrogen receptor alpha (ESR1). Conclusion: The effective components of Ningxin Yangshen Gao such as baicalin, kaempferol, palmitic acid, dibutyl phthalate, naringenin and palmitoleic acid, act on insomnia-related targets by regulating insomnia pathways and related proteins to alleviate insomnia.

Key words：insomnia; Ningxin Yangshen Gao; UPLC-Q-Orbitrap HRMS; network pharmacology; molecular docking

发布时间：2025-12-31

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