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Insomnia, one of the most prevalent disorders in contemporary society, significantly impacts people\u2019s daily lives. This study aims to explore the anti-insomnia effects of valerian volatile oil (VVO) and investigate its potential mechanism of action through chemical analysis, network pharmacology, molecular docking, molecular dynamics simulations, and experimental validation. Through gas chromatography\u2013mass spectrometry (GC-MS) analysis and drug-likeness screening, we identified 38 active compounds. Network pharmacology studies revealed that these 38 compounds might affect 103 targets associated with insomnia, such as monoamine oxidase B (MAOB), dopamine receptor D2 (DRD2), monoamine oxidase A (MAOA), interleukin 1\u03b2 (IL1B), solute carrier family 6 member 4 (SLC6A4), prostaglandin-endoperoxide synthase 2 (PTGS2), and 5-hydroxytryptamine receptor 2A (HTR2A), which contribute to regulating the neuroactive ligand\u2013receptor interaction, 5-hydroxytryptaminergic synapse, and calcium signaling pathways. The results of the molecular dynamics simulations indicated that bis[(6,6-dimethyl-3-bicyclo[3.1.1]hept-2-enyl)methyl] (E)-but-2-enedioate exhibited a stabilizing interaction with MAOB. The animal studies demonstrated that gavage administration of a high dose (100 mg\/kg) of VVO significantly diminished autonomous activity, decreased sleep latency, and extended sleep duration in mice. Furthermore, the results of the Western blot experiment indicated that VVO interacts with MAOB, resulting in decreased expression levels of MAOB in the cerebral cortex. This study demonstrates the protective mechanism of VVO against insomnia through chemical analysis, network pharmacology, and experimental validation and extends the possible applications of VVO, which is a potential therapeutic ingredient for use in insomnia treatment.<\/jats:p>","DOI":"10.3390\/ijms26041726","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T03:47:06Z","timestamp":1739850426000},"page":"1726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the Effects and Mechanisms of Valerian Volatile Oil in Treating Insomnia Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation-Based Approaches"],"prefix":"10.3390","volume":"26","author":[{"given":"Halimulati","family":"Muhetaer","sequence":"first","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huajian","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingna","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Cai","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0722-5680","authenticated-orcid":false,"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxian","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5932-8188","authenticated-orcid":false,"given":"Chuwen","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.5664\/jcsm.7172","article-title":"Insomnia in the Elderly: A Review","volume":"14","author":"Patel","year":"2018","journal-title":"J. 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