Pharmacological Screening of Mangifera indica Seeds for Antidepressant-like Action Along with a Mechanistic Study

[Image: see text] Depression is emerging as a major global issue. There are several antidepressants available in the market, but their efficacy is usually unpredictable. Therefore, there is a need to find an alternative therapeutic agent with better therapeutic efficacy and availability. In the current investigation, the antidepressant-like action of the aqueous methanolic extract of Mangifera indica seeds (25, 50, and 100 mg/kg) was evaluated by two predictive models like the tail suspension test and forced swimming test along with the determination of the mechanism of action working behind this action. The results of the acute treatment with the extract show a dose-dependent reduction in the duration of immobility in both models. The antidepressant-like action of the extract (100 mg/kg) was blocked by the administration of p-chlorophenyl alanine, α-methyl-p-tyrosine, prazosin, and sulpiride while remaining unaffected with propranolol. In contrast, the administration of d-serine along with the extract (a full agonist of glycine/N-methyl-d-aspartate, NMDA, receptors) diminished the anti-immobility action. The administration of the extract along with nitro-l-arginine-methyl ester synergizes into the anti-immobility action of the extract, and intake of l-arginine remained unable to effect this action, whereas sildenafil blocks the effect. The antidepressant-like action of the extract is probably due to the involvement of serotonergic and adrenergic (mainly α receptors are involved) systems, an NMDA receptor complex, and the nitric oxide pathway.