{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:27:21Z","timestamp":1780496841085,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T00:00:00Z","timestamp":1742688000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Citronellal (CTL), a monoterpenoid, exhibits notable neurological activity, including anxiolytic, and anticonvulsant effects, primarily through GABAergic pathways. Our current study aimed to explore CTL's sedative potential using in vitro, in vivo, and in silico approaches through the GABAergic pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The in vitro GABAergic activity of CTL was assessed via colorimetric assay, while acute toxicity was evaluated in\n                      <jats:italic>Swiss<\/jats:italic>\n                      mice per OECD guidelines with doses up to 2000\u00a0mg\/kg to establish safety margins. Sedative effects were assessed in\n                      <jats:italic>Swiss<\/jats:italic>\n                      mice using thiopental sodium (TS, 40\u00a0mg\/kg)\u2010induced sleep protocols. CTL was administered at 62.5, 125, and 250\u00a0mg\/kg doses, alone or combined with diazepam (DZP, 2\u00a0mg\/kg) or flumazenil (FLU, 0.1\u00a0mg\/kg). The in silico studies were also performed with GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptors (\u03b11 and \u03b22 subunits) to investigate the possible molecular mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results demonstrated that in vitro, CTL exhibited significantly concentration\u2010dependent GABAergic activity. Acute toxicity tests indicated a high safety margin (no behavioral or physiological abnormalities at 2000\u00a0mg\/kg dose). Additionally, CTL significantly (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05) and dose\u2010dependently reduced the latency and augmented sleep duration in animals, compared to the control group. It also significantly (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05) decreased the latency and increased the duration of sleep with DZP\u20102 while reducing this parameter with FLU\u20100.1. In in silico studies, CTL exhibited binding affinities (BAs) with the GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptor (\u03b11 and \u03b22 subunits) of \u20135.6\u00a0kcal\/mol.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      CTL demonstrated potent sedative effects in vitro and in vivo, with a strong safety profile and interaction with the GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptor (\u03b11 and \u03b22 subunits).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70446","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T03:02:05Z","timestamp":1742785325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Citronellal Exerts Sedative\u2010\n                    <i>Like<\/i>\n                    Effects and Augments Diazepam's Action in\n                    <i>Swiss<\/i>\n                    Mice, Possibly Through the GABAergic Pathway"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6392-3820","authenticated-orcid":false,"given":"Md. Torequl","family":"Islam","sequence":"first","affiliation":[{"name":"Pharmacy Discipline Khulna University  Khulna Bangladesh"},{"name":"Department of Pharmacy Gopalganj Science and Technology University  Gopalganj Bangladesh"},{"name":"Bioinformatics and Drug Innovation Laboratory BioLuster Research Center Ltd.  Gopalganj Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7560-4041","authenticated-orcid":false,"given":"Md. Sakib Al","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Gopalganj Science and Technology University  Gopalganj Bangladesh"},{"name":"Bioinformatics and Drug Innovation Laboratory BioLuster Research Center Ltd.  Gopalganj Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emon","family":"Mia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Gopalganj Science and Technology University  Gopalganj Bangladesh"},{"name":"Bioinformatics and Drug Innovation Laboratory BioLuster Research Center Ltd.  Gopalganj Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irfan Aamer","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddique Akber","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. 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