Anxiolytic-Like Effect of Hyptis crenata Essential Oil: Behavioral Insights and In Silico SERT Modulation

Purpose: The essential oil of Hyptis crenata (EOHc) contains several terpenes, many of which have anxiolytic-like activity. Thus, the aim of this study was to extract, analyze the chemical composition, and evaluate the anxiolytic-like effect of EOHc in mice using experimental approaches (behavioral parameters) and in silico studies. Methods: Mice were divided into seven experimental groups: Group I (no stress); Group II, stress only (no treatment); Group III, Tween 80 (stress and 0.1%, vehicle); Group IV, Tween 80 (no stress and 0.1%, vehicle); Group V, mirtazapine (stress and 30 mg/kg); Group VI, citalopram (stress and 10 mg/kg); Group VII, essential oil of H. crenata (stress and EOHc, 100 mg/kg); Group VIII, essential oil of H. crenata (no stress and EOHc, 100 mg/kg); Group IX, essential oil of H. crenata (stress and EOHc, 300 mg/kg); and Group X, essential oil of H. crenata (no stress and EOHc, 300 mg/kg);. After eight stress days, the behavioral tests (open field, elevated plus maze, and RotaRod) were started. Furthermore, docking and molecular dynamics analysis were used. To evaluate the safe administration of EOHc, water consumption, food consumption, and weight parameters were evaluated during 7 days of treatment. Results: The oil yield was 1.0-1.5%. Chromatography revealed that the top 5 constituents were caryophyllene V1, azulene, α-pinene, bornanone, and viridiflorene. All the treatments reduced the crossover and the rearing (p-value ≤ 0.05; ANOVA; Tukey's post hoc test). During grooming time, neither stress nor treatments induced any changes. The stress altered the number of entries and the time spent in both open arm and closed effect that was reversed by all treatments except mirtazapine (p ≤ 0.05; ANOVA; Tukey's test). There was no significance in the evaluation of water consumption, food consumption, and weight. With the exception of the Tween group, the RotaRod Test showed no significance between the control, 100 mg/kg EOHc, and 300 mg/kg EOHc groups. Conclusion: It can be concluded that EOHc presents an anxiolytic effect experimentally, with the probable inhibition of Apo SERT, due to the terpenoid constituents present in the oil.