SOME PHARMACOLOGICAL STUDIES OF THE METHANOLIC ROOT BARK EXTRACT OF SECURINEGA VIROSA (ROXB. EX WILLD) BAILL. ON LABORATORY ANIMALS

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Date
2012-11
Authors
Mohammed, Garba MAGAJI
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Abstract
Securinega virosa is a commonly used medicinal plant in West Africa in the management of cancer, epilepsy and as a sedative in children. Previously, the crude methanolic root bark extract was found to possess anticonvulsant and sedative properties. In this work, the crude methanolic root bark extract was partitioned into chloroform, ethyl acetate and n-butanol fractions, and the fractions were evaluated for CNS depressant and anticancer activities. Purification of the n-butanol fraction led to the isolation of a compound which was subjected to chemical tests, melting point determination, nuclear magnetic resonance, mass spectroscopy and X-ray crystallography. The n-butanol (75, 150 and 300 mg/kg) and residual aqueous (125, 250 and 500 mg/kg) fractions were evaluated for anticonvulsant activities using maximal electroshock test in chicks, pentylenetetrazole, 4-Aminopyridine, strychnine and picrotoxininduced seizures in mice, and kindling model in rats. The n-butanol and residual aqueous fractions were also evaluated for sedative and anxiolytic potentials using hole board, diazepaminduced sleeping time, elevated plus maze, staircase and open field tests in mice. The effects of these fractions on motor coordination were assessed using beam walking assay in mice. The effect of the isolated compound on sleep and motor coordination were also evaluated. The crude methanolic extract and its fractions were evaluated for anticancer activity using kill study and phosphorylation assay on glioblastoma multiforme U-1242 MG cell line. Based on the results of the analysis of the isolated compound, it was concluded to be bergenin, an isocoumarin. The n-butanol and residual aqueous fractions did not protect chicks against maximal electroshock seizure. Against seizures induced by 4- Aminopyridine, strychnine and picrotoxin, the two fractions did not produce significant activities. Conversely, the two fractions afforded 66.67% protection against pentylenetetrazole-induced seizure in mice. Both - 7 - fractions did not significantly decrease the mean seizure duration and the behavioural seizure scores in the kindled rats at the dose tested. In the hole board test, both fractions significantly (P < 0.01) reduced the mean number of head dips. Similarly, both fractions significantly (P < 0.05- P < 0.01) decreased the number of rearings and increased the total number of upward stairs climbed in the staircase test. In the elevated plus maze test, both fractions did not significantly increase the total number of open arm entries and total time spent in the open arms. Similarly, they did not increase the total central square crossed in the open field test. In the beam walking assay, they did not increase the mean number of foot slips. Bergenin significantly (P < 0.05) reduce the mean onset of sleep without affecting the total duration of sleep. However, it did not increase the mean number of foot slips. The crude methanolic root bark extract and its fractions significantly (P < 0.001) and concentration-dependently decreased mean viability of glioblastoma multiforme cells. The methanolic root bark extract and its residual aqueous fraction also blocked the phosphorylation of the epidermal growth factor receptor at tyrosine 1045 and 1068 sites. They also blocked the phosphorylation of platelet derived growth factor receptor. Similarly, phorbol myristate acetate and platelet derived growth factor-induced transactivations of epidermal growth factor receptor at tyrosine 1068 were also blocked. Mitogen activated protein kinase phosphorylation was also blocked by the crude methanolic root bark extract. However, the extract and its fractions did not affect the phosphorylation of protein kinase B. The findings of this study further lend credence to the ethnomedical use of the root of the Securinega virosa in the management of epilepsy, cancer and as a sedative. Bergenin, isolated from the root of the plant for the first time could partly be responsible for the sedative activity of the root of Securinega virosa. - 8 - CONTENTS Title page - - - - - - - i Declaration - - - - - - - ii Certification - - - - - - - iii Dedication - - - - - - - iv Acknowledgements - - - - - - v Abstract - - - - - - - vi Contents - - - - - - - viii List of Tables - - - - - - - xii List of Figures- - - - - - - xiii List of Plates- - - - - - - xviii Appendices- - - - - - - - xix Abbreviations/Definitions - - - - xx Chapter 1 Introduction - - - - - - - 1 1.1 Background information- - - - - - 1 1.2 Justification - - - - - - - 5 1.3 Aim and objectives - - - - - - 6 1.3.1 Aim of the study - - - - - - 6 1.3.2 Specific objectives - - - - - - - 6 1.4 Research hypothesis - - - - - - 7 Chapter 2 Literature review - - - - - - 8 2.1 Overview of drugs used as sedative/hypnotics and in the management of epilepsy - - - - - 9 - 9 - 2.1.1 Drugs used in the management of Insomnia - - - 9 2.1.2 Drugs used in the management of Anxiety - - - 11 2.1.3 Drugs used in the management of Epilepsy - - - 16 2.2 An overview on glioblastoma mutiforme and its management
Description
A Dissertation Submitted to the School of Postgraduate Studies, Ahmadu Bello University, Zaria In Partial Fulfilment of the Requirements for the Award of Doctor of Philosophy Degree in Pharmacology
Keywords
PHARMACOLOGICAL STUDIES, METHANOLIC ROOT, BARK EXTRACT, SECURINEGA, VIROSA (ROXB. EX WILLD, BAILL. ON LABORATORY
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