Synergistic Anxiolytic Effects of Linalool and Sesamol Co‐Treatment on Swiss Albino Mice: A Potential GABAergic Intervention

Sesamol (SES) and linalool (LIN) are aromatic compounds that have neuroprotective effects. The main purpose of this study is to evaluate the anxiolytic activity of LIN and SES co-treatment on Swiss albino mice and analyze its possible mechanism through in silico study. In this sense, the mice were given the gamma-aminobutyric acid type A receptors (GABA_A) agonist diazepam (DZP; 3 mg/kg, p.o.) as a positive control. A vehicle (10 mL/kg) was served as control. The tested chemicals, single-dose LIN (50 mg/kg) and SES (50 mg/kg), as well as a combination (LIN + SES) and (DZP + LIN + SES), were administered orally in order to conduct several behavioral tests, including open-field, swings box, hole-crossing, and dark-resident time tests. Further, molecular docking studies of LIN, SES, and DZP were carried out through different software. The results showed that LIN and SES individually have significant anxiolytic-like activity in mice. Further, when LIN was combined with SES and with (SES + DZP), it exhibited a relatively lower locomotor activity in mice compared to individual treatment groups, indicating a synergistic action. In addition, the molecular docking analysis revealed that LIN and SES have a moderate binding affinity (-5.0 and -5.1 kcal/mol) toward the GABA_A receptor α3 subunit. In conclusion, our findings suggest that LIN and SES exerted synergistic anxiolytic activity on Swiss albino mice, possibly through the GABAergic interaction pathways.