{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:50:45Z","timestamp":1790823045430,"version":"4.1.0"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"13","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373942"],"award-info":[{"award-number":["81373942"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tibet Autonomous Region","award":["XZ201801-GA-16"],"award-info":[{"award-number":["XZ201801-GA-16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Insomnia is an anabatic epidemiology, while the mechanism is extremely complicated; it remains one of the major scientific challenges in life sciences. Because of the advantage of having a similar genetic background and circadian rhythm as those of humans, the Drosophila melanogaster model organism is hugely popular in sleep-related drug screening studies. Seven-day-old virgin D. melanogaster was used to establish the sleep deprivation model by repeated light stimulation at night. Using PySolo activity monitoring system and Drosophila activity as indices, the effective fractions of Zhi-Zi-Hou-Po decoction (ZZHPD) for insomnia were screened; the content of monoamine neurotransmitters dopamine (DA), 5-hydroxyindole-3-acetic acid (5-HIAA), Homovanillic acid (HVA), and 5-hydroxytryptamine (5-HT) in the brain of D. melanogaster were determined by high-performance liquid chromatography-electro-chemical detection. The herb-compound-target-disease target network were further constructed through network pharmacology to identify the potential targets and pathways of ZZHPD in the intervention of insomnia. Finally, the molecular docking method was used for evaluating the binding characteristics of important compounds from ZZHPD with related targets. The results showed that a certain dose of ZZHPD and its petroleum ether, dichloromethane, ethyl acetate, and n-butanol fractions could improve sleep. The dichloromethane fraction from ZZHPD extracts showed the best anti-insomnia effect among all extracts. It can also reduce the content of DA and HVA in the brain of D. melanogaster and increase 5-HT and 5-HIAA levels. The network pharmacology showed that the main active ingredients in ZZHPD included magnolol, honokiol, hesperidin, and so forth. According to the screening conditions, there were 71 targets and the result of KEGG enrichment analysis revealed that 73 pathways were associated with insomnia, which were primarily involved in inflammatory response, central neurotransmitter regulation, and apoptosis to relieve insomnia. The molecular docking results clarified that naringenin and apigenin have an intimate relationship with GABAA receptor, histamine H1, orexin receptor type 2, and interleukin-6. The mechanism of relieving insomnia is the result of the interaction of multi-components, multi-targets, and multi-pathways, which provides a certain theoretical basis for the treatment of insomnia and related diseases as well as clinical research.<\/jats:p>","DOI":"10.1021\/acsomega.1c00445","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T10:42:00Z","timestamp":1616582520000},"page":"9176-9187","source":"Crossref","is-referenced-by-count":15,"title":["Integrated Screening of Effective Anti-Insomnia Fractions\nof Zhi-Zi-Hou-Po Decoction via\n                    <i>Drosophila melanogaster<\/i>\n                    and Network Pharmacology Analysis of the Underlying Pharmacodynamic\nMaterial and Mechanism"],"prefix":"10.1021","volume":"6","author":[{"given":"Yu","family":"Sun","sequence":"first","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiting","family":"Ni","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Cao","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Qu","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiange","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3649-2428","authenticated-orcid":true,"given":"Chenning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yikun","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine , , ,","place":["Beijing, China, 102488"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"2026081414132319700_cit1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.12710","article-title":"The impact of stress on sleep: pathogenic\nsleep reactivity as a vulnerability to insomnia and circadian disorders","volume":"27","author":"Kalmbach","year":"2018","journal-title":"J. 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Rev."},{"key":"2026081414132319700_cit3","doi-asserted-by":"publisher","first-page":"8549237","DOI":"10.1155\/2019\/8549237","article-title":"Amygdala changes in\nchronic insomnia and their association with sleep and anxiety symptoms:\ninsight from shape analysis","volume":"2019","author":"Gong","year":"2019","journal-title":"Neural Plast."},{"key":"2026081414132319700_cit4","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.5665\/sleep.4170","article-title":"Insomnia\nsymptoms and risk for unintentional fatal injuries-the HUNT Study","volume":"37","author":"Laugsand","year":"2014","journal-title":"Sleep"},{"key":"2026081414132319700_cit5","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1378\/chest.14-1617","article-title":"The pathophysiology\nof insomnia","volume":"147","author":"Levenson","year":"2015","journal-title":"Chest"},{"key":"2026081414132319700_cit6","doi-asserted-by":"publisher","first-page":"367","DOI":"10.2147\/nss.s198812","article-title":"Impact of phenotypic heterogeneity of Insomnia on the\npatients\u2019response to cognitive-behavioral therapy for insomnia:\ncurrent perspectives","volume":"11","author":"Galbiati","year":"2019","journal-title":"Nat. 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Med.\nChem."},{"key":"2026081414132319700_cit33","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.3390\/ijms18091989","article-title":"Quercetin\nattenuates manganese-induced\nneuroinflammation by alleviating oxidative stress through regulation\nof apoptosis, iNOS\/NF-\u03baB and HO-1\/Nrf2 Pathways","volume":"18","author":"Bahar","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"2026081414132319700_cit34","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1111\/j.1476-5381.2011.01389.x","article-title":"Kaempferol\nacts through mitogen-activated protein kinases and protein kinase\nB\/AKT to elicit protection in a model of neuroinflammation in BV2\nmicroglial cells","volume":"164","author":"Park","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"2026081414132319700_cit35","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.imbio.2018.12.005","article-title":"Geniposide\nregulates the miR-101\/MKP-1\/p38 pathway and alleviates atherosclerosis\ninflammatory injury in ApoE mice","volume":"224","author":"Cheng","year":"2019","journal-title":"Immunobiology"},{"key":"2026081414132319700_cit36","doi-asserted-by":"publisher","first-page":"2875","DOI":"10.1080\/21691401.2019.1626406","article-title":"Geniposide protects PC12 cells from\nlipopolysaccharide-evoked inflammatory\ninjury via up-regulation of miR-145-5p","volume":"47","author":"Ma","year":"2019","journal-title":"Artif.\nCells, Nanomed., Biotechnol."},{"key":"2026081414132319700_cit37","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.molimm.2018.11.008","article-title":"Magnolol attenuates the inflammation\nand enhances phagocytosis through the activation of MAPK, NF-\u03baB\nsignal pathways in vitro and in vivo","volume":"105","author":"Chen","year":"2019","journal-title":"Mol. 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Immunopharmacol."},{"key":"2026081414132319700_cit40","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.steroids.2018.03.005","article-title":"Antidepressant\neffects of magnolol in a mouse model of depression induced by chronic\ncorticosterone injection","volume":"135","author":"Yang","year":"2018","journal-title":"Steroids"},{"key":"2026081414132319700_cit41","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.12841","article-title":"The key role\nof insomnia and sleep loss in the dysregulation of multiple systems\ninvolved in mood disorders: A proposed model","volume":"28","author":"Palagini","year":"2019","journal-title":"J. Sleep Res."},{"key":"2026081414132319700_cit42","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1002\/biof.1385","article-title":"Neuroprotective\neffects of honokiol: from chemistry to medicine","volume":"43","author":"Talarek","year":"2017","journal-title":"Biofactors"},{"key":"2026081414132319700_cit43","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1111\/j.1476-5381.2012.02010.x","article-title":"Honokiol\npromotes\nnon-rapid eye movement sleep via the benzodiazepine site of the GABA\u00ad(A)\nreceptor in mice","volume":"167","author":"Qu","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"2026081414132319700_cit44","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.4103\/1673-5374.213550","article-title":"Relationship\nof no cturnal concentrations\nof melatonin, gamma-aminobutyric acid and total antioxidants in peripheral\nblood with insomnia after stroke: study protocol for a prospective\nnon-randomized controlled trial","volume":"12","author":"Zhang","year":"2017","journal-title":"Neural Regener.\nRes."},{"key":"2026081414132319700_cit45","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1523\/jneurosci.1931-17.2018","article-title":"Pronounced Hyperactivity,\nCognitive Dysfunctions, and BDNF Dysregulation\nin Dopamine Transporter Knock-out Rats","volume":"38","author":"Leo","year":"2018","journal-title":"J. Neurosci."},{"key":"2026081414132319700_cit46","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.biopha.2018.07.095","article-title":"Therapeutic effects\nof honokiol on motor impairment\nin hemiparkinsonian mice are associated with reversing neurodegeneration\nand targeting PPAR\u03b3 regulation","volume":"108","author":"Chen","year":"2018","journal-title":"Biomed.\nPharmacother."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.1c00445","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/6\/13\/9176\/13098363\/ao1c00445.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/6\/13\/9176\/13098363\/ao1c00445.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:24:08Z","timestamp":1786731848000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/6\/13\/9176\/490333\/Integrated-Screening-of-Effective-Anti-Insomnia"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,24]]},"references-count":46,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,3,24]]},"published-print":{"date-parts":[[2021,4,6]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.1c00445","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,24]]}}}