The antidepressant effects of albizia zygia root extract in mice are mediated via catecholaminergic mechanisms

Abstract

There is a pressing need for novel medicines to better manage neuropsychiatric disorders such as depression since current options are limited by suboptimal efficacy, disabling side effects and low availability in certain regions. The roots of Albizia zygia (DC.) J.F. Macbr. (Leguminosae) are used to treat mental disorders in traditional African medicine. Nonetheless, there is limited scientific evidence to justify its use at present. Therefore, this study was designed to evaluate the antidepressant-like properties of the hydroethanolic root extract of Albizia zygia (AZE) in murine models for antidepressants. The extract was prepared from freshly harvested roots of Albizia zygia collected in Kumasi, Ghana (6◦40′31.8′′N 1◦34′44.1′′W). After authentication, the roots were cleaned, air-dried and milled into a coarse powder which was extracted by maceration (27-28 ◦C) in 70% (v/v) ethanol for 5 days. The supernatant was filtered, concentrated in a rotary evaporator (60 ◦C) and dried to yield a brown-coloured extract (9.03% w/w yield) which was stored at 2-8 ◦C until use. In order to assess the antidepressant activity of AZE, several tests were carried out. First, the antidepressant activity of AZE was evaluated in acute depression models: the forced swim test and tail suspension test, and a chronic model, the open space swim test. Next, the mechanisms involved in the observed antidepressant actions of AZE were investigated by selective depletion of various neurotransmitters using ˛-methyl-para-tyrosine (an inhibitor of catecholamine synthesis), para-chlorophenylalanine (an inhibitor of serotonin synthesis) and reserpine (an inhibitor of vesicular monoamine storage). Lastly, the effect of AZE on spontaneous locomotion was assessed in the open field test. Ethical approval for this study was obtained from the Department of Pharmacology Ethics Committee, Kwame Nkrumah University of Science and Technology.AZE (100-1000 mg kg-1, p.o.) reduced immobility in the forced swim and tail suspension tests (at least P< 0.05) similar to the control antidepressants, imipramine and fluoxetine. Alsoin the open space swim test, AZE (100-1000 mg kg-1, p.o.) reduced immobility (at least P< 0.05) while concomitantly increasing distance swum (P< 0.01). This suggests a significant antidepressant effect of AZE since a reduction in immobility is predictive of antidepressant activity. Furthermore, no significant increase in spontaneous locomotion was detected in AZE-treated mice, thus ruling out a psychostimulatory effect which could yield false positive results. Similar to imipramine, the antidepressant effects of AZE were abolished by ˛-methyl-para-tyrosine and reserpine pretreatment. However, unlike fluoxetine, the antidepressant effects of AZE persisted after para-chlorophenylalanine pretreatment. This finding supports the involvement of catecholaminergic rather than serotonergic mechanisms in the antidepressant actions of AZE.In summary, the results obtained indicate that the hydroethanolic root extract of Albizia zygia possesses antidepressant-like properties which are likely mediated via catecholaminergic mechanisms and support its traditional use in the treatment of depression.