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

Introduction: Xylopia aethiopica (Dunal) A. Rich (Annonaceae) is a tropical plant that has been used traditionally to manage pain and CNS disorders like epilepsy [1]. This study evaluated the antidepressant potential of an ethanolic fruit extract of X. aethiopica (XAE).

Method: Antidepressant effect was evaluated by forced swim test (FST) [2] and tail suspension test (TST) [3] in mice. The effect on various monoamines was assessed through selective monoamine depletion [4].

Result: The extract (30 – 300 mg/kg) was as efficacious as fluoxetine and desipramine in FST (p < 0.035) (Fig. 1a) and as efficacious desipramine in TST (p < 0.001) (Fig. 1b).

Fig. 1: Dose response curves for XAE, fluoxetine and desipramine in forced swim test (a) and tail suspension test (b).

The antidepressant effect of XAE was significantly (p < 0.001) reversed after 5-hydoxytryptamine (5-HT) depletion with the tryptophan hydoxylase inhibitor; parachlorophenylalanine (pCPA) and after monoamine depletion with vesicular monoamine transporter inhibitor; reserpine (p < 0.001) as did fluoxetine (3 – 30 mg/kg) but not desipramine (3 – 30 mg/kg). It was however not affected by catecholamine depletion with tyrosine hydoxylase inhibitor; α-methylparatyrosine (AMPT) nor did it potentiate noradrenaline toxicity. Sub-effective dose (10 mg/kg) of XAE was potentiated (p < 0.005) by glycine B receptor partial agonist, D-cycloserine but antidepressant effect of XAE (30 – 300 mg/kg) was abolished by D-serine.

Conclusion: X. aethiopica has antidepressant potential largely due to effect on 5-HT neurotransmission with possible glutamatergic effect through the glycine co binding site.

Keywords: NMDA/gycine B complex, affective disorders, forced swim test

References:

[1] Souza and Dossa. (1988) Bull. Med. Trad. Pharm 2 (2) 181 – 196.

[2] Porsolt et al. (1977) Nature 266 (5604): 730 – 732.

[3] Steru et al. (1985) Psychopharmacology 85(3): 367 – 370.

[4] O'Leary et al. (2007) Psychopharmacology 192(3): 357 – 371.