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

TL;DR

This study shows that Hyptis crenata essential oil has anxiolytic effects in mice, possibly by inhibiting a brain protein linked to anxiety.

Contribution

The study provides new evidence that Hyptis crenata essential oil has anxiolytic properties, supported by both behavioral and in silico findings.

Findings

EOHc reduced anxiety-like behaviors in mice, similar to known anxiolytic drugs.

Molecular docking suggests EOHc constituents may inhibit the serotonin transporter (SERT).

EOHc showed no significant effects on food, water consumption, or weight in mice.

Abstract

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.

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