MEDICINAL PLANTS USED IN THE MANAGEMENT OF DEPRESSIVE ILLNESSES: ANTIDEPRESSANT ACTIVITY OF METHANOL STEM BARK EXTRACT OF ADANSONIA DIGITATA L. IN MICE
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ABSTRACT
Depression is a heterogeneous mood disorder that has been treated with a number of synthetic drugs. These drugs have adverse effects and delayed onset of action that compromise their therapeutic benefits. This makes it worthwhile to search for new antidepressant agents with proven efficacy and favourable benefit-to-risk ratio. Medicinal plants have enjoyed wide patronage among local people in the management of neuropsychiatric disorders including depression. The study therefore aimed at establishing a collection of medicinal plants used in the management of depressive illnesses by the traditional medical practitioners of Zaria, Nigeria, as well as provide scientific basis for their ethnomedical use in the management of depression and determine the antidepressant activity of the most promising of the collected plants and its possible mechanism of action. An ethnobotanical survey was conducted in December, 2015 in Zaria, Nigeria in which data were collected by interviewing traditional medical practitioners in Zaria with the aid of a questionnaire. Plant specimens were collected along the line, subsequently dried and mounted. They were taken for identification and authentication in the Herbarium Section of Botany Department, Ahmadu Bello University, Zaria where specimen vouchers were documented. Information on sources, safety, methods of preparation and administration, identity, local and botanical names of ten medicinal plants used in the management of depression by traditional medical practitioners were obtained. Nine of the medicinal plants were further collected and then extracted with methanol using soxhlet apparatus method of extraction. Thin layer chromatographic finger printing of the medicinal plants extract was conducted, followed by acute toxicity (LD50) studies using oral OECD 420 guidelines. Antidepressant activity of all the medicinal plant extracts was evaluated using tail suspension test (TST), followed by test for motor co-ordination deficit and stimulant activity using beam walking assay vii (BWA) and open field test (OFT) respectively. The most promising extract, methanol stem bark extract of Adansonia digitata was further subjected to forced swim test (FST), novel object recognition test (NORT) and chronic unpredictable mild stress (CUMS). Following the CUMS, the effect of extract was also assessed on sucrose preference test (SPT), OFT and TST. The possible mechanism(s) of action of Adansonia digitata extract was also determined. The plants used by the traditional practitioners in Zaria included Ficus platyphyllla, Caralluma dalzielli, Adansonia digitata, Acacia seyal, Tapinanthus dodeinofolius, Tapinanthus globiferus, Senna occidentalis, Olax manni, Combretum micranthum and Pancrantium africanum. The chromatographic profile of the extracts of these medicinal plants showed the presence of steroids, tannins, flavonoids, alkaloids, triterpenes, saponins in all the plants and anthraquinones in some of the medicinal plants. The oral median lethal doses of the methanol extracts of F. platyphylla, C. dalzielli and O. manni were found to be greater than 2000 mg/kg while that of others were greater than 5000 mg/kg. The methanol extracts of all the plants significantly (p<0.05) decreased the duration of immobility at all tested doses in the TST. The methanol extracts of the medicinal plants did not significantly increase the number of lines crossing and the number of foot slips in the OFT and BWA respectively. The methanol stem bark extract of A. digitata (MEAD) significantly and dose dependently decreased the duration of immobility in FST, with no alterations on cognition in the NORT when acutely administered. Following the CUMS, MEAD significantly (p<0.05) and dose dependently reversed weight loss of mice, the inhibited locomotor behaviour in the OFT, decreased sucrose consumption in SPT, reduced the duration of immobility in TST and reversed the impaired cognition in the NORT. The antidepressant activity produced by MEAD was significantly (p<0.05) reversed by sulpiride (D2/D3 receptor antagonist), metergoline (5- HT1 antagonist), cyproheptadine (5-HT2 antagonist), prazosin (α1 adrenergic antagonist), viii yohimbine (α2 adrenergic antagonist) and augmented by L-NNA (Nitric oxide synthase inhibitor) and atropine (muscarinic antagonist). MEAD significantly (p<0.05) and dose dependently increased the levels of brain derived neurotrophic factors (BDNF), decreased the levels of plasma cortisol, increased the levels of total superoxide dismutase (SOD) activity and decreased plasma malondialdehyde (MDA) levels in mice following CUMS. The findings from this study provide pharmacological rationale for the folkloric use of the medicinal plants in the management of depression by traditional medical practitioners in Zaria, Northwestern Nigeria. The methanol stem bark extract of Adansonia digitata possesses significant antidepressant activity in both acute and CUMS model of depression, possibly mediated via the monoaminergic, nitritergic, metabolic, neurotrophic and neuroendocrine systems.
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