Neurobehavioural Mechanism of Antidepressant Effect of Methanol Stem Bark Extract of Adansonia Digitata (Linn) in Tail Suspension Test in Mice
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Advances in Pharmacology and Pharmacy 7(1): 5-13, 2019 http://www.hrpub.org DOI: 10.13189/app.2019.070102 Neurobehavioural Mechanism of Antidepressant Effect of Methanol Stem Bark Extract of Adansonia digitata (Linn) in Tail Suspension Test in Mice Akinpelu Lateef Abiola1,*, Adebayo Muritala Ayofe2, Adesola Adedoyin1 1Department of Pharmacology and Toxicology, Dora Akunyili College of Pharmacy, Igbinedion University, Nigeria 2Department of Pharmacognosy, Dora Akunyili College of Pharmacy, Igbinedion University, Nigeria Copyright©2019 by authors, all rights reserved. Authors agree that this article remains permanently open access under the terms of the Creative Commons Attribution License 4.0 International License Abstract Aim: An earlier study has demonstrated the depression is among the top ten causes of morbidity, and in-vivo antidepressant effect of methanol stem bark extract mortality world over [1], and it is envisaged to be the of Adansonia digitata, using soxhlet extraction protocol, leading cause of morbidity and mortality by the year 2030 but there is a lack of scientific data on its neurobehavioural [2, 3]. Patients with depression have symptoms that reflect mechanism of action. This study, therefore, investigated its a functional deficit in brain monoamine neurotransmitters, antidepressant potentials, using cold maceration method, specifically norepinephrine, serotonergic [4] and and determined the probable neurobehavioural mechanism dopaminergic systems [5]. Other neurotransmitters such as of its antidepressant-like effect. Methodology: The GABA acting via GABAB receptor [6], β adrenoceptors [7], antidepressant-like effect of the extract was evaluated in muscarinic cholinergic receptor [8], glutaminergic via tail suspension test, at graded doses in mice. Subsequently, NMDA receptor [9], and nitric oxide signaling pathways [8] the probable neurobehavioural mechanism of the have been implicated in depression. antidepressant-like effect of the extract was investigated by Despite the availability of synthetic antidepressant drugs, intraperitoneal pretreatment with adrenergic, serotonergic, depression remains a major medical problem [10]. This is dopaminergic, and muscarinic cholinergic receptor because the currently available antidepressant drugs are antagonists; GABA agonist; nitric oxide precursor and associated with a numerous side effect which includes inhibitors; and using a putative neuromodulator at NMDA weight gain, hypopiesia, sexual dysfunction, and cardiac receptors prior to the extract administration. Results and toxicity and sleep disorder [11, 12, 13]. Therefore, herbal discussion: The extract at all the doses used, significantly therapies should be considered alternative or (p<0.05) and dose-dependently decreased the immobility complementary medicines [14]. Among the demonstrated time in tail suspension test without significant (p>0.05) herbal therapies effective for the treatment of depression alteration on locomotor behaviour in mice. However, the are Hypericum perforatum L. [15], Cordyceps sinensis [16], anti-immobility potential of the extract was significantly and Perilla frutescens [17]. (p<0.05) reversed by prazosin, yohimbine, sulpiride, Adansonia digitata L. (Bombacaceae), otherwise called methylene blue, L-arginine and baclofen, suggesting the baobab, is a large iconic tree indigenous to Africa, where it involvement of adrenergic, dopaminergic, GABAerargic is found in many African countries [18]. The African and nitergic pathways. Conclusion: This study, therefore, species Adansonia digitata is indigenous to, and widely concluded that the extract may possess antidepressant distributed throughout the savannas and savanna effect and its mechanism may involve multiple pathways. woodlands of sub-Saharan Africa [19]. Numerous ethnomedicinal values are attributed to the Keywords Adansonia digitata, Cold Maceration, various plant parts of Adansonia digitata [18]. For example, Antidepressant, Neurobehavioural Mechanism, Multiple stem bark is used in the treatment of neuropsychiatric Receptor Pathways disorder [20], depression [21], malaria [19], wound healing [22], among other indications in Africa traditional medicine and have been evaluated as a substitute for imported western drugs [23, 24]. 1 . Introduction The different parts of Adansonia digitata have numerous biological properties including antimicrobial, antiviral [25], According to The World Health Organization, antioxidant [26], hepatoprotective [27], anti-inflammatory, 6 Neurobehavioural Mechanism of Antidepressant Effect of Methanol Stem Bark Extract of Adansonia digitata (Linn) in Tail Suspension Test in Mice analgesic and antipyretic activities [24]. commercial diet (Guinea feeds brand, Bendel Feeds According to the World Health Organisation, depression Nigeria) and water ad libitum. The animals were will be the second leading cause of disability in the acclimatized to the laboratory condition for at least one developed countries in 2020 [28], and the continuous use of week before the commencement of the behavioural the currently available synthetic antidepressant drugs experiments. The experimental procedures employed in acting via multiple neurotransmitters system [29], have this study are in accordance with the approved institutional been associated with some severe side effects [30]. guidelines and within the confine of internationally Therefore, a continuous search for new affordable accepted principles for Laboratory Animal Use and Care therapeutic agents with minimal side effects from (EEC Directive of 1986; 86/609/EEC) [31]. All efforts medicinal plants is imperative. Although the antidepressant were made to reduce animal sufferings and to use the effect of Adansonia digitata stem bark has been minimum number of animals in this study. demonstrated using hot extraction protocol on forced swimming (FST) and tail suspension (TST) tests [21], but 2.4. Acute Toxicity Test there is lack of scientific data on its probable neurobehavioural mechanism of action, therefore, the Acute Oral Toxicity Study objective of this study was to investigate the antidepressant The acute oral toxicity test of MSAD was conducted effect of the stem bark extract using cold extraction according to the Organization for Economic Cooperation protocol, as well as determine its neurobehavioural and Development (OECD) guidelines 425 of 2008. The mechanism of action in TST. experimental procedures were carried out in two phases. In the first phase, a single female mouse was orally administered 2000 mg/kg of MSAD after 3 h of fasting. 2. Materials and Methods The mouse was observed for any signs of acute behavioural toxicity within the first 24 h. Based on the outcome of the Adansonia digitata stem bark was collected in Bode Osi first phase; another 4 female mice were orally administered in Ola Oluwa Local Govt area of Osun State. It was the same dose of MSAD and subsequently observed for authenticated by Mr. G. A. Ademoriyo of the Herbarium any sign of delayed toxicity or death in the next 14 days Unit, Department of Botany, Faculty of Science, OAU, [32]. Based on the outcome of the experiment, the two Ile-Ife and herbarium voucher Ife 17705 was obtained and phases of the experiments were repeated for 5000 mg/kg. herbarium specimen deposited. 2.5. Pharmacological Experiments 2.1. Preparation of Plant Materials Effect of MSAD in Tail Suspension Test (TST) Adansonia digitata stem barks were air dried at room temperature. The dried stem barks were pulverized, and The TST employed for screening the potential 300 g of the powdered material, was extracted with 1.5 antidepressants effect of MSAD was carried out as litres of eighty percent (80%) methanol for 72 h. The previously done elsewhere [33]. Mice were randomly filtrate was then concentrated in vacuo at a temperature of divided into 5 groups, containing 5 mice per group (n=5). 40oC and further freeze-dried to yield 2.3 g (0.77 %) crude Group I (Vehicle): mice received normal saline p.o (10 extract and coded MSAD. mL/kg); Groups II-IV (Treatment groups): mice received 200, 400 and 800 mg/kg, p.o of MSAD, and Group V (received the reference drug): mice received fluoxetine (20 2.2. Drugs mg/kg, i.p.). One hour after oral ingestion of MSAD and 30 Prazosin hydrochloride, cyproheptadine hydrochloride, min after intraperitoneal injection of fluoxetine, each yohimbine hydrochloride, fluoxetine hydrochloride, mouse was suspended on the edge of a table, 50 cm above propranolol hydrochloride, baclofen, (±) sulpiride, the floor with the help of adhesive tape placed atropine sulphate, L-arginine, L-NG-Nitroarginine, approximately 1 cm from the tip of the tail. Immobility methylene blue and ascorbic acid were all from Sigma duration was recorded for the last 4 minutes during 6 Aldrich, St. Louis, MO, USA; and normal saline (Unique minutes period in different groups. The mouse animal was Pharmaceutical Limited, Lagos, Nigeria). MSAD and other considered immobile, when it did not show any movement drugs were dissolved in normal saline and freshly prepared of the body, and hanged passively. on each day of the experiment. 2.6. Mechanism of Action of MSAD in TST 2.3. Animals Involvement of Noradrenergic Pathway Male adult albino mice weighing 18–25 g were obtained Mice were randomly divided into 5 groups containing 5 from the Animal House, Igbinedion University, Okada, mice per group (n=5). Group I: mice in this group received Edo State, Nigeria. The animals were fed with a standard normal saline p.o (10 mL/kg); Groups II: mice