Antidepressant Effect of Methanol Root Bark Extract of Acacia seyal: Involvement of Monominergic, Nitric Oxide and Opiodergic Pathways

Abstract

BackgroundDepression is a common mental disorder which affects more than 300 million people and is a leading cause of disability worldwide ( WHO, 2017). Available antidepressants are only effective in 50% of patients ( Simon, 2002). The treatment resistance has been linked to the multiple pathways involved in the pathology of depression. Acacia seyal root is used traditionally for the management of depression ( Shehu, 2017). However, there is no report of the scientific validation of this ethnomedicinal claim.ObjectiveTo determine the antidepressant activity of the methanol root bark extract of A. seyal (AS) and its possible mechanism(s) of antidepressant action.Materials and MethodsEthical Approval for the use of laboratory animals was sought and obtained from Ahmadu Bello University Committee on Animal Use and Care (ABUCAUC/2018/094). Antidepressant activity of AS was evaluated using tail suspension test (TST) at a dose of 250, 500 and 1000 mg/kg. For the mechanistic studies, mice were pretreated with Sulpiride (50 mg/kg), Prazosin (1 mg/kg), Yohimbine (1 mg/kg), Metergoline (1 mg/kg), Cyproheptadine (3 mg/kg), L‐Arginine (50 mg/kg), L‐NNA (50 mg/kg), atropine (1 mg/kg) and naloxone (2 mg/kg) 15 minutes prior to AS (500 mg/kg) administration, then assessed using TST one hour later.ResultsThe extract (at the doses of 250–1000 mg/kg) significantly (p<0.05) decreased the duration of immobility in the TST. Sulpiride (D2 receptor antagonist), Prazosin and Yohimbine (α1 and α2 receptor antagonists respectively), Metergoline, Cyproheptadine (5‐HT1 and 5‐HT2 receptor antagonist respectively), L‐Arginine and L‐NNA (substrate and inhibitor of nitric oxide synthase enzyme respectively) and naloxone (opioid receptor antagonist) significantly (p<0.05) reversed the antidepressant effect of ASConclusionThe methanol root bark extract of Acacia seyal possesses antidepressant activity possibly mediated via the dopaminergic, serotonergic, adrenergic, nitric oxide and opioidergic pathways.Effect of Methanol Root Bark Extract of Acacia seyal on Duration Immobility of Mice in Tail Suspension TestAnimals were acutely treated with AS (250, 500 or 1000 mg kg, po), distilled water (10 ml/kg, po), or Fluoxetine (20 mg/kg, po). Each column represents the mean ± SEM of 8 animals. Data was analyzed using one‐way ANOVA followed by Bonferroni post hoc test, *p≤0.05, **p≤0.001, ***p≤0.0001 significantly different from distilled water treated group.AS=Acacia seyal, DW= 10 ml/kg of Distilled water, FTX= FluoxetineFigure 1AcknowledgementThe technical assistance of staff of the Department of Pharmacology and Therapeutics, Ahmadu Bello University, Zaria‐Nigeria is acknowledged