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