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 traditional 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 suspension 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, 300mgkg(-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.

Keywords: Depression; Desipramine (PubChem CID: 2995): Fluoxetine (PubChem CID: 3386); Fluoxetine; Forced swim test; N(ω)-nitro- l-arginine methyl ester (PubChem CID: 135193); NMDA/glycine(B) modulators; Noradrenaline (PubChem CID: 439260); Reserpine (PubChem CID: 5770); Tail suspension test; d-cycloserine (PubChem CID: 6234); d-serine (PubChem CID: 71077); l-arginine (PubChem CID: 6322); p-Chlorophenylalanine (PubChem CID: 73610); α-Methyl-p-tyrosine (PubChem CID: 81824).