Anxiolytic activity of Psidium guajava in mice subjected to chronic restraint stress and effect on neurotransmitters in brain

The anxiolytic activity of Psidium guajava L. leaf ethanolic extract (PLE) and its effect on neurotransmitter systems was investigated. PLE, extracted using Soxhlet apparatus, was subjected to preliminary qualitative and quantitative (flavonoids and phenols) analyses. The anxiolytic activity at 100, 200, and 400 mg/Kg doses were assessed in mice using elevated plus maze (EPM) and light/dark transition (LDT) test models on days 1 and 16. Neurotransmitters such as monoamines (serotonin, norepinephrine, and dopamine), γ‐aminobutyric acid (GABA), and glutamate were estimated in different regions of the brain (cortex, hippocampus, and cerebellum and brain stem). Phytoconstituents identified using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry were analyzed in silico to evaluate their potential binding mode(s) to GABA A and 5‐HT 1A receptors. Phytochemical studies showed the presence of alkaloids, tannins, flavonoids, saponins, anthraquinone glycosides, carbohydrates, and proteins, whereas total flavonoid and phenol contents were estimated to be 64.96 ± 0.95 and 206.58 ± 1.60 mg/g of dried extract, respectively. PLE treatment significantly enhanced exploratory activity of mice in EPM and LDT models with significant effects on monoamines, GABA and glutamate levels in the brain. The in silico studies suggested the interaction(s) of PLE component(s) with GABA A /5‐HT 1A receptors as a potential mechanism of its anxiolytic activity.