Xylopia aethiopica fruit extract exhibits antidepressant-like effect via interaction with serotonergic neurotransmission in mice

Abstract

Ethnopharmacological relevance: Xylopia aethiopica has been used traditionally to treat some central nervous system disorders including epilepsy. Aim of the study: Despite the central analgesic and sedative effects, there is little evidence for its tra- ditional use for CNS disorders. This study thus assessed the antidepressant potential of Xylopia aethiopica ethanolic fruit extract (XAE). Material and methods: Antidepressant effect was assessed in the forced swim test (FST) and tail sus- pension test (TST) models in mice. The role of monoamines in the antidepressant effects of XAE was evaluated by selective depletion of serotonin and noradrenaline, whereas involvement of NMDA/nitric oxide was assessed with NMDA receptor co-modulators; D-serine and D-cycloserine and NOS inhibitor, L- NAME. Results: Xylopia aethiopica (30, 100, 300 mg kg 1) dose dependently reduced immobility in both FST and TST. The reduced immobility was reversed after 5-hydroxytryptamine (5-HT) depletion with tryptophan hydroxylase inhibitor—p-chlorophenylalanine (pCPA) and after monoamine depletion with vesicular monoamine transporter inhibitor—reserpine. The observed antidepressant effect was not affected by catecholamine depletion with the tyrosine hydroxylase inhibitor, α-methyl-p-tyrosine (AMPT). Similarly XAE did not potentiate the toxicity of a sub-lethal dose of noradrenaline. XAE had a synergistic effect with the glycineB receptor partial agonist, D-cycloserine and nitric oxide synthase inhibitor, L-NAME. However established antidepressant effects of XAE were abolished by NMDA and NOS activation with D- serine and L-arginine. Conclusion: This study shows that Xylopia aethiopica has antidepressant potential largely due to effects on 5-HT neurotransmission with possible glutamatergic effect through the glycineB co-binding site and nitric oxide synthase inhibition