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The present study examined the anxiolytic properties of sesamol (SES), a phenolic lignan derived from <jats:italic>Sesamum indicum<\/jats:italic>, employing both in vivo and computational methods to understand its mechanisms of action. In this experiment, adult <jats:italic>Swiss<\/jats:italic> albino mice received various doses of SES (25 and 50\u2009mg\/kg, p.o.) orally. Afterward, a series of behavioral assessments, including open field, swing, hole cross, and light\u2013dark testing, were conducted. The impact of the GABAergic agonist diazepam (DZP\u20101\u2009mg\/kg, i.p.) along with the antagonist flumazenil (FLU\u20100.1\u2009mg\/kg, i.p.) has been studied as provided concurrently with the SES\u201050 group. Computational studies were performed to comprehend the interaction between SES and GABA<jats:sub>A<\/jats:sub> receptor subunits (\u03b1<jats:sub>2<\/jats:sub> and \u03b1<jats:sub>3<\/jats:sub>). The results of our investigation revealed that SES dose\u2010dependently and significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) reduced the number of square crosses, hole crosses, swings, grooming, and rearing along with a reduction of light residence time in animals. When combined with DZP, SES\u201050 significantly reduced all these parameters, while altering with FLU\u20100.1. The molecular docking analysis showed that the SES has a relatively good binding score (\u22125.03\u2009\u00b1\u20090.15 and \u22125.25\u2009\u00b1\u20090.23\u2009kcal\/mol) with GABA<jats:sub>A<\/jats:sub> receptor \u03b1<jats:sub>2<\/jats:sub> and \u03b1<jats:sub>3<\/jats:sub> subunits, respectively. The SES triggers anxiolytic effects via GABA<jats:sub>A<\/jats:sub> receptor \u03b1<jats:sub>2<\/jats:sub> and \u03b1<jats:sub>3<\/jats:sub> subunit interactions. Furthermore, precise and comprehensive preclinical research must be considered to validate potential SES targets for anxiolytic impact, clinical trial efficacy, and safety.<\/jats:p>","DOI":"10.1002\/ddr.70028","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T05:51:43Z","timestamp":1733377903000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Anxiolytic Effect of Sesamol, Possibly Through the GABAkine Interaction Pathway"],"prefix":"10.1002","volume":"85","author":[{"given":"Md. 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