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Antidepressant Effect of Methanol Root Bark Extract of Acacia Seyal Del

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Antidepressant Effect of Methanol Root Bark Extract of Acacia Seyal Del Shehu et al Tropical Journal of Pharmaceutical Research July 2020; 19 (7): 1459-1464 ISSN: 1596-5996 (print); 1596-9827 (electronic) © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v19i7.18 Original Research Article Antidepressant effect of methanol root bark extract of Acacia seyal Del. (Fabaceae): Possible involvement of the inflammatory pathway Aishatu Shehu*, Bishio Anyip, Mohammed Garba Magaji Department of Pharmacology and Therapeutics, Ahmadu Bello University, Zaria, Nigeria *For correspondence: Email: [email protected]; Tel: +234-803-6028298 Sent for review: 22 February 2020 Revised accepted: 14 June 2020 Abstract Purpose: To study the involvement of inflammatory pathways in the antidepressant activity of Acacia seyal in mice. Methods: The median lethal dose (LD50) of the extract Acacia seyal (AS) was determined using OECD guideline 425. The antidepressant activity of AS was assessed against BCG (0.2 mg/kg, ip)-induced depression in mice using Tail suspension test (TST) and open field test (OFT) at 4, 24 and 48 hours post BCG administration. Results: The median lethal dose (LD50) for the extract was > 5000 mg/kg orally. The extract AS at all tested doses (250 – 1000 mg/kg) significantly (p ≤ 0.001) decreased the duration of immobility in TST but increased the number of line crossing in OFT post-BCG. Conclusion: The antidepressant activity of the methanol root bark extract of Acacia seyal in mice may involve an inflammatory mechanism. Thus, the extract of Acacia seyal may be suitable for the management of depression in humans resistant to other conventional antidepressant agents. However, further studies are required to ascertain this Keywords: Depression, Acacia seyal, Tail suspension test, Open field test, Bacillus Calmette-Guerin This is an Open Access article that uses a fund-ing model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus, International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts INTRODUCTION response [3]. Heterogeneity in depression hinders progress in treatment and research [4]. Depression is an incapacitating psychiatric Although a number of drugs are available for the ailment that has been estimated to affect 21% of treatment of depressive disorders, most of drugs the world population [1]. Depression can occur at produces poor response, relapse and remission any age from childhood to late life and is a conferring great challenge [5]. Inflammatory tremendous burden to the society. The disorder pathways play a role in the pathophysiology of causes severe distress and disruption of life depression and this can be highly beneficial in linked to all-cause mortality [2]. Depression is a forming basis for new treatment approaches [6]. highly complicated disorder with heterogeneity The release of pro-inflammatory cytokines leads observed in etiology, diagnosis and treatment to neuroinflammation, which contributes to ----------------------------------------------------------------------------------------------------------------------------------------------------- © 2020 The authors. This work is licensed under the Creative CommonsTrop Attribution J Pharm 4.0 Res, International July 2020; License19(7): 1459 Shehu et al depression [7]. Inflammation reduces the conditions and procedures stipulated in availability of serotonin in the brain [8]. international guidelines [12]. An ethical approval Therefore, antidepressant drugs required was obtained from the Ahmadu Bello University activation of the inflammatory pathways to Animal Ethics Committee (no. ABUCAUC/ increase the synaptic availability of serotonin. 2017/022). Antidepressants are likely to be less effective in the presence of inflammatory stimulus to reduce Acute toxicity study the depressive symptoms especially in major depression [9]. Excessive production of Median lethal dose (LD50) was determined using inflammatory mediators by macrophages has Organization for Economic Co-operation and been linked to suicidal attempts [10]. Thus, an Development (OECD) guideline in mice [13]. Two urgent need to target inflammatory pathways as groups of three mice each were fasted 3 h prior an alternative approach to the management of to administration of methanol root bark extract of depression. Acacia seyal is reported useful in the Acacia seyal and 2 h after the administration of management of depression elicited via the extract. In limit test, 5000 mg/kg was given to monoaminergic, neuroendocrine and neurotro- one mouse and observed for 48 h. The first phic pathways [11]. mouse survived, thereafter, two more mice were given same dose of extract. In all case, mice However, the involvement of the anti- were observed during the first 30 min of inflammatory mechanism in the antidepressant treatment and then at intervals over 24 h and activity of the plant has not been reported. This then daily for 14 days. The animals were study therefore aimed to determine the monitored for tremor, convulsion, salivation, antidepressant effect of methanol root bark diarrhoea, sleep, behavioural changes and extract of Acacia seyal against Bacillus Calmette- coma. The time of onset of toxic symptoms and Guerin (BCG) induced depression in mice. disappearance were also noted. The weights of animals were determined weekly for 14 days EXPERIMENTAL individually. Plant preparations and extraction Treatments The whole plant Acacia seyal was collected in On the day of injection, fresh solution of BCG March 2018 from Sabon Gari Local Government was prepared and administered intraperitoneally Area of Kaduna State. It was taken to Herbarium to forty mice at the dose of 0.2 mg/kg. Rectal Section of the Department of Botany, Ahmadu temperatures were taken at 0, 4, 24 and 48 h Bello University, Zaria where it was authenticated after BCG administration. The mice were divided by Mr Namadi Sanusi. A voucher specimen (no. into 5 groups of 8 mice each, then monitored for 900347) was deposited in the Herbarium of signs of motion sickness for a period of 4 h. Department of Botany, Ahmadu Bello University, Three hours after BCG treatment, Group 1 mice Zaria. were given distilled water (10 ml/kg) and group 2 with fluoxetine (20 mg/kg) via the oral route. Mice The root bark extract of Acacia seyal collected in groups 3, 4 and 5 received methanol root bark was dried and sized reduced using mortar and extract of Acacia seyal at dose of 250, 500 and pestle. Two hundred grams of the dried 1000 mg/kg per orally respectively. Mice in all powdered material was extracted with 1500 groups were then subjected to tail suspension milliliters of methanol by cold maceration and open field test 1 h after treatment, with technique for 2 days with occasional shaking. another hour interval allowed between each test. The resultant extract was evaporated to dryness over a water bath which gave a brown solid Behavioural tests mass. All solutions for administrations were freshly prepared using distilled water. Tail suspension test Animals Tail suspension test (TST) was performed according to the method described by [14]. Mice Male Swiss albino mice (18 - 20 g) were obtained in all the groups were subjected to tail from the Animal House of the Department of suspension test by individual suspension of the Pharmacology and Therapeutics, Ahmadu Bello mouse 60 cm above the surface of the table with University Zaria, Nigeria. They were housed in an adhesive tape placed 1 cm away from the tip cages and kept under natural day and light cycle. of the tail and a cylindrical rubber stopper. Mice Standard laboratory animal diet was provided were considered immobile only when they hung and water ad libitum and followed experimental passively and were completely motionless. Trop J Pharm Res, July 2020; 19(7): 1460 Shehu et al Experiments were video-taped for 6 min. This fluoxetine (20 mg/kg) and Acacia seyal (AS 500 test was done at 4, 24 and 48 h post BCG and 1000 mg/kg) 4 h post-BCG administration. injection. There were also significant (p ≤ 0.01) and dose- dependent decrease in the duration of immobility Open field test at all the tested doses when compared to the distilled water group 24 hours post-BCG Each mouse was placed in a white wooden open injection. However, only the highest dose of field apparatus (70 × 70 × 35 cm, length × extract and fluoxetine were able to significantly (p breadth × height), one side and floor were made ≤ 0.05) decrease the duration of immobility 48 h up of transparent plexiglas, with the floor divided post-BCG injection when compared to the into 16 visible squares (15 × 15 cm) with a distilled water group (Figure 2). central square. Peripheral and central square crossing behaviour of each mouse was recorded for 6 min with the aid of a camera suspended at the top of the apparatus [15]. This test was done at 4, 24 and 48 h after BCG administration. Statistical analysis All values are expressed as mean ± SEM. Values for rectal temperature were analysed using repeated measures ANOVA followed with Bonferroni post hoc test. The differences in the mean of immobility from tail suspension test, and mean number of line crossing activities from open field studies among different treated groups were analysed using one-way ANOVA followed Figure 1: Effect of methanol root bark extract of by Bonferroni post hoc test using SPSS version Acacia seyal on BCG-induced changes in rectal 20.0. A value of p < 0.05 was considered temperature of mice. Note: Each column represents significant.
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