Integrated Chemical, In Silico, and Functional Neurobehavioral Evaluation of Three Essential Oils in Acute Anxiety-...

Essential oils are multicomponent natural products with potential neurobehavioral activity, but integrated comparative studies remain limited. This study compared the essential oils of Satureja brevicalyx, Peperomia dolabriformis, and Rosmarinus officinalis in relation to their chemical profiles, predicted target interactions, preliminary acute oral safety, anxiolytic-like and antidepressant-like effects, antagonist-sensitive behavioral patterns, and exploratory serum biomarkers. Oils were characterized by GC-MS, and their constituents were screened by molecular docking against anxiety-, depression-, sleep-, and stress-related targets. Independent cohorts of male BALB/c mice received oral essential oils (25-100 mg/kg) and were assessed in anxiety-related, depression-related, and locomotor behavioral paradigms, including the elevated plus maze, light-dark box, marble burying, tail suspension, forced swim, and open field tests. Flumazenil and WAY-100635 were used to examine whether the behavioral responses were sensitive to γ-aminobutyric acid type A (GABA-A)/benzodiazepine- and serotonin 1A (5-HT1A)-related pharmacological modulation, respectively. In a preliminary 24-h acute oral toxicity screen, no mortality was observed up to 5000 mg/kg. The three oils produced anxiolytic-like and antidepressant-like effects without reducing spontaneous locomotor activity. Within its experimental block, S. brevicalyx showed the most consistent flumazenil-sensitive anxiolytic-like pattern and FDR-significant reductions in corticosterone and TNF-α, together with increased IL-4. P. dolabriformis showed a broader predicted multitarget docking profile and antagonist-sensitive behavioral attenuation compatible with mixed pathway participation. R. officinalis produced significant but more moderate behavioral effects. WAY-100635 partially attenuated the antidepressant-like effects of all three oils. These findings support differentiated but convergent functional neurobehavioral profiles among the oils. The docking, antagonist, and biomarker results should be interpreted as hypothesis-generating evidence of possible pathway involvement, supporting further validation in chronic stress models, receptor-specific assays, pharmacokinetic studies, and expanded safety evaluations.