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Thirty minutes after treatment, each animal was subjected to tail suspension and forced swimming tests, and their immobility time (IMT) was counted for 5\u2009min. <jats:styled-content style=\"fixed-case\">In silico<\/jats:styled-content> studies were performed with the GABA<jats:sub>A<\/jats:sub> receptor \u03b11, \u03b12, \u03b13, \u03b15, and \u03b32 subunits and 5HT<jats:sub>1A<\/jats:sub> to investigate possible molecular mechanisms. Additionally, in\u00a0vitro GABA activity of PHY and\/or reference drugs was also performed by using the colorimetric method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results demonstrated that PHY and\/or DZP significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and concentration\u2010dependently inhibited GABA, while FLU alone or its combination with PHY reversed it. In mice, PHY dose\u2010dependently reduced the IMT in both protocols, while FLUX\u201020 showed lower IMT compared to the control and DZP, indicating elevated locomotion in mice. It showed a reduced IMT value in male animals than in female animals. In both sexes, PHY at 75\u2009mg\/kg significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) increased the IMT values with DZP\u20102, while reducing this parameter with FLU\u20100.1. <jats:italic>In silico<\/jats:italic> studies demonstrated that PHY exhibited higher binding affinities with the \u03b12 and \u03b13 subunits of the GABA<jats:sub>A<\/jats:sub> and 5HT<jats:sub>1A<\/jats:sub> receptors by \u22126.5, \u22127.2 and 6.7\u2009kcal\/mol, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Taken together, PHY exerted sedative\u2010<jats:italic>like<\/jats:italic> antidepressant effects in mice and modulated the effects of GABAergic drugs DZP and FLU and serotonergic drug FLUX. PHY may be a potential candidate for the management of depression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70350","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T10:42:12Z","timestamp":1742726532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Possible <scp>GABAkine<\/scp>\u2010Mediated Sedative\u2010Like Antidepressant Effects of Phytol: Molecular Interventions Through In\u00a0Vitro, In\u00a0Vivo and In Silico Approaches"],"prefix":"10.1111","volume":"31","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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannatul","family":"Ferdous","sequence":"additional","affiliation":[{"name":"Bioinformatics and Drug Innovation Laboratory BioLuster Research Center Ltd.  Gopalganj Bangladesh"},{"name":"Department of Biotechnology and Genetic Engineering Gopalganj Science and Technology University  Gopalganj Bangladesh"},{"name":"Microbial Biotechnology Division National Institute of Biotechnology  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-9720","authenticated-orcid":false,"given":"Md. Shimul","family":"Bhuia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Gopalganj Science and Technology University  Gopalganj Bangladesh"},{"name":"Bioinformatics and Drug Innovation Laboratory BioLuster Research Center Ltd.  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Amirul","family":"Islam","sequence":"additional","affiliation":[{"name":"Pharmacy Discipline Khulna University  Khulna Bangladesh"},{"name":"Department of Pharmacy East West University  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md.","family":"Saifuzzaman","sequence":"additional","affiliation":[{"name":"Pharmacy Discipline Khulna University  Khulna Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2021.106007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn943"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra073096"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2021.06.037"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010009\u20100650\u20107"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1520-6394(2000)12:1 <2::AID-DA2>3.0.CO;2-4"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14596"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.10.025"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1114350"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.109195"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001362"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.2.368"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152707780363294"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903590111"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2023.06.009"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.10.009"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2008.08030395"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.8139"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1745017901006010001"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.12980\/APJTB.4.2014C1147"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phyplu.2021.100041"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202301615"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/1028415X.2020.1764290"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.08.032"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2015.07.010"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.06.055"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/187220830803150605162745"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2013.12.003"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116481"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2016.01.115"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00428203"},{"issue":"2","key":"e_1_2_10_33_1","first-page":"327","article-title":"Behavioral Despair in Mice: A Primary Screening Test for Antidepressants","volume":"229","author":"Porsolt R. 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