{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:43:03Z","timestamp":1792806183508,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine","award":["KLRCCM2302"],"award-info":[{"award-number":["KLRCCM2302"]}]},{"name":"Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine","award":["XN2314"],"award-info":[{"award-number":["XN2314"]}]},{"name":"Competitive research fund of Hubei University for Nationalities","award":["KLRCCM2302"],"award-info":[{"award-number":["KLRCCM2302"]}],"id":[{"id":"https:\/\/ror.org\/01q349q17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Competitive research fund of Hubei University for Nationalities","award":["XN2314"],"award-info":[{"award-number":["XN2314"]}],"id":[{"id":"https:\/\/ror.org\/01q349q17","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>With the increasing prevalence of insomnia-related diseases, the effective treatment of insomnia has become an important health research topic. Lavender (Lavandula angustifolia Mill.) essential oil (LEO) is a commonly used medicine for the treatment of insomnia and neurological disorders. However, neither the active components nor its sedative\u2013hypnotic mechanism have been fully discovered. This study aimed to screen the main active terpenes and discover the possible mechanism of LEO through network pharmacology in the treatment of insomnia-related diseases, as well as to verify our hypothesis in insomnia mice. The results showed that, in LEO\u2019s 15 potential active ingredients, beta-myrcene had strong sedative\u2013hypnotic effects through the serotonergic synaptic pathway according to the network pharmacological prediction. Further, PCPA(DL-4-chlorophenylalanine)-induced insomnia mice were treated with beta-myrcene for one day or seven days. The quiet state of insomnia mice was increased effectively, and the hypnotic effect was enhanced by anaobarbital sodium by prolonging sleep duration, decreasing sleep latency, and increasing the rate of falling asleep. Beta-myrcene reduced the damage to hypothalamic neuron cells induced by PCPA and increased neurotransmitter levels of GABA, 5-HT, and Glu in the serum and hypothalamus of insomnia mice. Meanwhile, beta-myrcene exerted an improvement in insomnia by upregulating relevant genes and protein expression in the serotonergic synaptic pathway. These results support the merit of the sedative\u2013hypnotic activity of LEO. Beta-myrcene, a terpene in LEO, may be the main source of its sedative\u2013hypnotic properties. It may serve as a good potential compound in future clinical studies on coping with insomnia.<\/jats:p>","DOI":"10.3390\/ph17091161","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T03:45:21Z","timestamp":1725248721000},"page":"1161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Beta-Myrcene as a Sedative\u2013Hypnotic Component from Lavender Essential Oil in DL-4-Chlorophenylalanine-Induced-Insomnia Mice"],"prefix":"10.3390","volume":"17","author":[{"given":"Luge","family":"Chen","sequence":"first","affiliation":[{"name":"National & Local Joint Engineering Research Center of High-Throughput Drug Screening Technology, Hubei University, Wuhan 430062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingwei","family":"Liu","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Research Center of High-Throughput Drug Screening Technology, Hubei University, Wuhan 430062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Xu","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Research Center of High-Throughput Drug Screening Technology, Hubei University, Wuhan 430062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhang","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Research Center of High-Throughput Drug Screening Technology, Hubei University, Wuhan 430062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Chen","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Research Center of High-Throughput Drug Screening Technology, Hubei University, Wuhan 430062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hubei University for Nationalities, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Sun","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Research Center of High-Throughput Drug Screening Technology, Hubei University, Wuhan 430062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1093\/brain\/awz030","article-title":"Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: A multicentre study","volume":"142","author":"Postuma","year":"2019","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.smrv.2017.06.010","article-title":"Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis","volume":"40","author":"Shi","year":"2018","journal-title":"Sleep Med. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ye, M., Lee, S., Yu, H.J., Kim, K.R., Park, H.J., Kang, I.C., Kang, S.A., Chung, Y.S., and Shim, I. (2023). Sedative-Hypnotic Effects of Glycine max Merr. Extract and Its Active Ingredient Genistein on Electric-Shock-Induced Sleep Disturbances in Rats. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087043"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Monroy, F. (2021). Ultrasound-Assisted Extraction of Lavender (Lavandula angustifolia Miller, Cultivar Rosa) Solid By-Products Remaining after the Distillation of the Essential Oil. Appl. Sci., 11.","DOI":"10.3390\/app11125495"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/01.HNP.0000343210.56710.fc","article-title":"Lavandula angustifolia miller: English lavender","volume":"23","author":"Denner","year":"2009","journal-title":"Holist. Nurs. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhong, Y., Zheng, Q., Hu, P., Huang, X., and Liu, S. (2019). Sedative and hypnotic effects of compound Anshen essential oil inhalation for insomnia. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2732-0"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115868","DOI":"10.1016\/j.jep.2022.115868","article-title":"Lavender essential oil fractions alleviate sleep disorders induced by the combination of anxiety and caffeine in mice","volume":"302","author":"Yue","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1139\/cjm-2020-0484","article-title":"Antifungal mechanisms of lavender essential oil in the inhibition of rot disease caused by Monilinia fructicola in postharvest flat peaches","volume":"67","author":"Xiong","year":"2021","journal-title":"Can. J. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hayani, M., Benabbouha, T., Naceiri Mrabti, N., Eljebri, S., Sabiri, M., and Zair, T. (2024). Bioactive Profiling, Antibacterial Efficacy and Computational Modelling of Myrtus Communis Essential Oil (Morocco). Chem. Biodivers., 21.","DOI":"10.1002\/cbdv.202302114"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e14314","DOI":"10.1111\/ppl.14314","article-title":"Ancient bayberry increased stress resistance by enriching tissue-specific microbiome and metabolites","volume":"176","author":"Li","year":"2024","journal-title":"Physiol. Plant"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"593","DOI":"10.5607\/en.2019.28.5.593","article-title":"3-Carene, a Phytoncide from Pine Tree Has a Sleep-enhancing Effect by Targeting the GABAA-benzodiazepine Receptors","volume":"28","author":"Woo","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"i264","DOI":"10.1093\/chemse\/bjh216","article-title":"Effects of Plant-derived Odors on Sleep\u2013Wakefulness and Circadian Rhythmicity in Rats","volume":"30","author":"Sadao","year":"2005","journal-title":"Chem. Senses"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1124\/mol.116.105080","article-title":"\u03b1-Pinene, a Major Constituent of Pine Tree Oils, Enhances Non-Rapid Eye Movement Sleep in Mice through GABAA-benzodiazepine Receptors","volume":"90","author":"Yang","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.pnpbp.2012.04.012","article-title":"The anxiolytic-like effect of an essential oil derived from Spiranthera odoratissima A. St. Hil. leaves and its major component, \u03b2-caryophyllene, in male mice","volume":"38","author":"Galdino","year":"2012","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lai, Y., Hua, L., Yang, J., Xu, J., Chen, J., Zhang, S., Zhu, S., Li, J., and Shi, S. (2023). The Effect of Chinese Agarwood Essential Oil with Cyclodextrin Inclusion against PCPA-Induced Insomnia Rats. Molecules, 28.","DOI":"10.3390\/molecules28020635"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2174\/1386207323666200401095008","article-title":"A Study on the Mechanism of Lavender in the Treatment of Insomnia Based on Network Pharmacology","volume":"23","author":"Wang","year":"2020","journal-title":"Comb. Chem. High. Throughput Screen."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1523\/JNEUROSCI.1925-17.2017","article-title":"Regulation of Lateral Hypothalamic Orexin Activity by Local GABAergic Neurons","volume":"38","author":"Ferrari","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.neuroscience.2015.09.038","article-title":"Tolerance to the sedative and anxiolytic effects of diazepam is associated with different alterations of GABAA receptors in rat cerebral cortex","volume":"310","author":"Ferreri","year":"2015","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9277","DOI":"10.1021\/acs.jafc.5b04141","article-title":"Lotus Leaf Alkaloid Extract Displays Sedative-Hypnotic and Anxiolytic Effects through GABAA Receptor","volume":"63","author":"Yan","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hassan, S.H., El-Nashar, H.A.S., Rahman, M.A., Polash, J.I., Bappi, M.H., Mondal, M., Abdel-Maksoud, M.A., Malik, A., Aufy, M., and El-Shazly, M. (2024). Sclareol antagonizes the sedative effect of diazepam in thiopental sodium-induced sleeping animals: In vivo and in silico studies. Biomed. Pharmacother., 176.","DOI":"10.1016\/j.biopha.2024.116939"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, S., Wang, C., Peng, D., Liu, X., Wu, C., Guo, P., and Wei, J. (2017). Agarwood Essential Oil Displays Sedative-Hypnotic Effects through the GABAergic System. Molecules, 22.","DOI":"10.3390\/molecules22122190"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.55730\/1300-0144.5670","article-title":"Propofol mitigates brain injury and oxidative stress, and enhances GABAA receptor \u03b11 subunit expression in a rat model of lithium chloride-pilocarpine induced status epilepticus","volume":"53","author":"Li","year":"2023","journal-title":"Turk. J. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yao, L., Lv, J., Duan, C., An, X., Zhang, C., Li, D., Li, C., and Liu, S. (2022). Armillaria mellea fermentation liquor ameliorates p-chlorophenylalanine-induced insomnia associated with the modulation of serotonergic system and gut microbiota in rats. J. Food Biochem., 46.","DOI":"10.1111\/jfbc.14075"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sheng, J.A., Bales, N.J., Myers, S.A., Bautista, A.I., and Handa, R.J. (2021). The Hypothalamic-Pituitary-Adrenal Axis: Development, Programming Actions of Hormones, and Maternal-Fetal Interactions. Front. Behav. Neurosci., 14.","DOI":"10.3389\/fnbeh.2020.601939"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118048","DOI":"10.1016\/j.jep.2024.118048","article-title":"Zhumian Granules improves PCPA-induced insomnia by regulating the expression level of neurotransmitters and reducing neuronal apoptosis","volume":"327","author":"Bao","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/13880209.2021.2019283","article-title":"A comprehensive study on the relieving effect of Lilium brownii on the intestinal flora and metabolic disorder in p-chlorphenylalanine induced insomnia rats","volume":"60","author":"Si","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yu, H., Yu, H., Si, L., Meng, H., Chen, W., Wang, Z., and Gula, A. (2022). Influence of warm acupuncture on gut microbiota and metabolites in rats with insomnia induced by PCPA. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267843"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e176329","DOI":"10.1172\/jci.insight.176329","article-title":"Distinct glutamatergic projections of the posteroventral medial amygdala play different roles in arousal and anxiety","volume":"9","author":"Li","year":"2024","journal-title":"JCI Insight"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.2147\/NDT.S443844","article-title":"Examining the Role of GLU\/GABA to GLN Metabolic Cycle in the Pathogenesis of Post-Stroke Depressive Disorder and Insomnia","volume":"19","author":"Zhang","year":"2023","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.smrv.2010.11.003","article-title":"Serotonin control of sleep-wake behavior","volume":"15","author":"JM","year":"2011","journal-title":"Sleep Med. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41398-024-02769-3","article-title":"Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses","volume":"14","author":"Bernabe","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1089\/107999099313244","article-title":"Interleukin-10 inhibits spontaneous sleep in rabbits","volume":"19","author":"Kushikata","year":"1999","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1177\/09645284231160193","article-title":"Electroacupuncture of the cymba concha alleviates p-chlorophenylalanine-induced insomnia in mice","volume":"41","author":"Zhang","year":"2023","journal-title":"Acupunct. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3408","DOI":"10.2174\/138161208786549281","article-title":"The role of cytokines in sleep regulation","volume":"14","author":"Krueger","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1124\/pr.109.002063","article-title":"Regulation of GABA(A) receptor subunit expression by pharmacological agents","volume":"62","author":"Korpi","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11064-023-04035-2","article-title":"Anti-insomnia Effect of a Polyherbal Formulation on P-chlorophenyalanine Induced Experimental Animal Model","volume":"49","author":"Sheethal","year":"2024","journal-title":"Neurochem. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3390\/cimb45010026","article-title":"Lavender Essential Oil Modulates Hepatic Cholesterol Metabolism in HepG2 Cells","volume":"45","author":"Martella","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"W356","DOI":"10.1093\/nar\/gkx374","article-title":"PharmMapper 2017 update: A web server for potential drug target identification with a comprehensive target pharmacophore database","volume":"45","author":"Wang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/bioinformatics\/14.8.656","article-title":"GeneCards: A novel functional genomics compendium with automated data mining and query reformulation support","volume":"14","author":"Rebhan","year":"1998","journal-title":"Bioinformatics"},{"key":"ref_41","first-page":"514","article-title":"Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders","volume":"33","author":"Ada","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/nar\/30.1.412","article-title":"TTD: Therapeutic Target Database","volume":"30","author":"Chen","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_43","first-page":"44","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"44","author":"Huang","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1007\/s11064-024-04102-2","article-title":"Cannabidiol Exerts Sedative and Hypnotic Effects in Normal and Insomnia Model Mice Through Activation of 5-HT1A Receptor","volume":"49","author":"Liu","year":"2024","journal-title":"Neurochem. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113627","DOI":"10.1016\/j.jep.2020.113627","article-title":"Sedative and hypnotic effects of Perilla frutescens essential oil through GABAergic system pathway","volume":"279","author":"Zhong","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"110324","DOI":"10.1016\/j.vetimm.2021.110324","article-title":"Sero-diagnostic efficacy of various ELISA kits for diagnosis of infectious bovine rhinotracheitis (IBR) in cattle and buffaloes in India","volume":"241","author":"Sarangi","year":"2021","journal-title":"Vet. Immunol. Immunopathol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1161\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:46:53Z","timestamp":1760111213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,1]]},"references-count":46,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ph17091161"],"URL":"https:\/\/doi.org\/10.3390\/ph17091161","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,1]]}}}