Anxiolytic Effect of Sesamol, Possibly Through the GABAkine Interaction Pathway

Plant-based components have helped generate novel lead molecules and scaffolds for anxiety research in psychopharmacology. The present study examined the anxiolytic properties of sesamol (SES), a phenolic lignan derived from Sesamum indicum, employing both in vivo and computational methods to understand its mechanisms of action. In this experiment, adult Swiss albino mice received various doses of SES (25 and 50 mg/kg, p.o.) orally. Afterward, a series of behavioral assessments, including open field, swing, hole cross, and light-dark testing, were conducted. The impact of the GABAergic agonist diazepam (DZP-1 mg/kg, i.p.) along with the antagonist flumazenil (FLU-0.1 mg/kg, i.p.) has been studied as provided concurrently with the SES-50 group. Computational studies were performed to comprehend the interaction between SES and GABA_A receptor subunits (α₂ and α₃). The results of our investigation revealed that SES dose-dependently and significantly (p < 0.05) 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-50 significantly reduced all these parameters, while altering with FLU-0.1. The molecular docking analysis showed that the SES has a relatively good binding score (-5.03 ± 0.15 and -5.25 ± 0.23 kcal/mol) with GABA_A receptor α₂ and α₃ subunits, respectively. The SES triggers anxiolytic effects via GABA_A receptor α₂ and α₃ subunit interactions. Furthermore, precise and comprehensive preclinical research must be considered to validate potential SES targets for anxiolytic impact, clinical trial efficacy, and safety.