{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:58Z","timestamp":1790618278589,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973684"],"award-info":[{"award-number":["81973684"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2023NSFSC1760"],"award-info":[{"award-number":["2023NSFSC1760"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Insomnia is a pathological sleep disorder marked by persistent sleep\u2010onset difficulties. This study explored the therapeutic effects and underlying mechanism of Banxia Shumi Decoction (BXSMD) in treating insomnia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study used network pharmacology to predict the core targets and signaling pathways of BXSMD in insomnia intervention. A rat insomnia model was constructed via 4\u2010Chloro\u2010DL\u2010phenylalanine (PCPA) to assess BXSMD's behavioral impacts. ELISA, qRT\u2010PCR, Western blot, and IHC were applied to detect the expression of 5\u2010hydroxytryptamine (5\u2010HT), melatonin (MT), MT1\/MT2 receptors, and related factors (CLOCK, PER1, CaMKII, p\u2010CREB\/CREB, GABARAP, mGLuR1, ADAM10) in the rat suprachiasmatic nucleus (SCN), hippocampus, and serum. The non\u2010selective melatonin receptor antagonist luzindole was administered to explore its influence on BXSMD\u2010regulated expression of the above molecules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the model group, the BXSMD group showed shortened sleep latency and prolonged sleep duration. BXSMD significantly elevated 5\u2010HT, MT, and MT1\/MT2 levels. BXSMD upregulated the mRNA and protein expression of downstream effector molecules including CLOCK, PER1, CaMKII, and GABARAP, downregulated mGLuR1 expression, and increased the expression of ADAM10. Notably, CREB mRNA expression remained unchanged, while BXSMD significantly increased the p\u2010CREB\/CREB protein ratio. The regulatory effects of BXSMD on all altered molecules were significantly reversed by luzindole.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BXSMD effectively alleviates PCPA\u2010induced insomnia in rats. The mechanism relies on MT1\/MT2 as core targets, which mediate the regulation of sleep\u2010related molecules (CLOCK, PER1, CaMKII, p\u2010CREB\/CREB, GABARAP, and mGluR1), as well as the membrane protein shedding\u2010related molecule ADAM10.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70988","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T07:10:25Z","timestamp":1789888225000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Banxia Shumi Decoction Alleviates\n                    <scp>PCPA<\/scp>\n                    \u2010Induced Insomnia and Regulates\n                    <scp>ADAM10<\/scp>\n                    Expression via Melatonin Signaling in Rats"],"prefix":"10.1002","volume":"32","author":[{"given":"Baojun","family":"Guo","sequence":"first","affiliation":[{"name":"Department of TCM Henan Provincial People's Hospital, Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1413-2007","authenticated-orcid":false,"given":"Yuqin","family":"Tang","sequence":"additional","affiliation":[{"name":"Clinical Bioinformatics Experimental Center Henan Provincial People's Hospital, Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1033-1132","authenticated-orcid":false,"given":"Yongqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henan Academy of Innovations in Medical Science Henan Academy of Medical Sciences  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeke","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Stomatology Hospital of Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranran","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of TCM Henan Provincial People's Hospital, Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00046.2019"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0170772"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-018-1808-6"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01029-2"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleepx.2025.100138"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/NSS.S546410"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.04.017"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12961"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbs.2024.109280"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14194087"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1715457"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12674"},{"key":"e_1_2_13_14_1","volume-title":"Sleep Medicine","author":"Arrigoni E.","year":"2025"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115800"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(19)30077-9"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43141-021-00224-0"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.120.000131"},{"key":"e_1_2_13_19_1","first-page":"e19045","article-title":"Some Twist of Molecular Circuitry Fast Forwards Overnight Sleep Hours: A Systematic Review of Natural Short Sleepers' Genes","volume":"13","author":"Yook J. 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