Neuropharmacological effects of the petroleum ether/ethyl acetate stem bark extract of Maerua Angolensis D.C (Capparaceae)
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Date
JUNE, 2016
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Abstract
The search for novel lead compounds from medicinal plants to ameliorate or cure various
disorders is still important and valid. There is a greater and unmet medicinal need when it
comes to central nervous system (CNS) disorders. Maerua angolensis is a useful medicinal
plant found in most parts of the West-African sub-region including Ghana. It has been
employed in the treatment of various CNS disorders including epilepsy and psychosis. The
present study examined the anxiolytic, antidepressant and anticonvulsant potential of the
petroleum ether/ethyl acetate extract of the stem bark (MAE) in murine and zebrafish models.
Preliminary neuropharmacological investigations in the Irwin test showed analgesic effects as
well as a general reduction in fear response and motor activity. Further characterization
indicated a general CNS depressant effect in the spontaneous locomotor activity and
pentobarbitone-induced sleep tests. There was also a trend with respect to protection against
death in the seizure liability test although statistical significance was absent when compared to
control.
Based on the findings of the preliminary study, the anxiolytic potential was assessed in the
elevated plus maze (EPM), Suok test (ST) and open field test (OFT) in mice. MAE (30-300
mg kg
-1
), similar to diazepam, showed a significant increase in % open arm entries, a decrease
in % protected head-dips and % stretch-attend postures. Oral administration of MAE also
reduced anxiolytic parameters in the Suok test without affecting significantly motor
coordination. However, MAE treatment revealed significant anxiolytic effects by increasing
% centre time, whilst caffeine (anxiogenic agent) reduced % time spent in the central arena.
The anxiolytic effects was further evaluated in the novel tank and light-dark zebrafish models.
MAE (0.1-1.0 mg mL
-1
) treatment similar to fluoxetine and desipramine showed anxiolytic
iv
effects in both paradigms. Similar treatment with MAE also proved to be effective in
reversing ethanol withdrawal-induced anxiety and anxiety induced by chronic unpredictable
stress. The anxiolytic effect in the novel tank and light-dark tests was reversed by pretreatment
with granisetron (a 5-HT3
antagonist), cyproheptadine (a 5-HT2A antagonist), methysergide (a
5-HT2B/2C
antagonist) and pizotifen (a 5-HT2A/2C
and 5-HT1
antagonist). Also concomitant
administration of MAE after flumazenil (a GABA
A
receptor antagonist) treatment suppressed
the anxiolytic effect. Taken together, this suggest that the extract possesses true modulation of
the serotonergic and GABAergic systems.
Acute administration of the extract (100-1000 mg kg
-1
, p.o.) exhibited antidepressant effects
by reducing the duration of immobility in both the forced swim test (FST) and tail suspension
test (TST). Comparing the degree of reduction in immobility after treatment revealed that the
efficacy of MAE was higher than that of fluoxetine but lower than after imipramine treatment
in both tests. Significant increase in climbing and curling duration in the FST and TST
respectively is suggestive of serotonergic and opioidergic interaction of MAE.
The anticonvulsant effects of MAE and possible mechanisms involved were further explored
in the pentylenetetrazole-induced seizure model in rats. MAE (300 mg kg
-1
, p.o.) similar to
diazepam significantly delayed the onset as well as decreased the duration and frequency of
PTZ-induced seizures. The GABA
A
receptor antagonist, flumazenil, reversed the
anticonvulsant effect of MAE, further suggesting the possible involvement of the GABAergic
system in its action. Furthermore, the anticonvulsant effect of MAE (300 mg kg
-1
, p.o.) was
reversed by pre-treatment with a sub-effective doses of L-arginine or sildenafil indicating a
possible interaction with the nitricoxidergic system in the anticonvulsant effects.
v
In the in vitro antioxidant assay , the extract (0.02-0.2 mg mL
-1
) exhibited significant DPPH
scavenging activity (E
max=48.46 ± 3.652 %, IC50 =0.1817 mg mL
-1
), superoxide scavenging
activity (E
max=74.13 ± 8.199 %, IC50 =0.004357 mg mL
-1
) and reduced the degree of lipid
peroxidation (E
max=50 ± 0.00 %, IC50
=0.8245 mg mL
-1
). However, the in vitro antioxidant
properties of MAE was less potent than ascorbic acid, the reference antioxidant, although their
efficacies were comparable. Pretreatment with MAE before pentylenetetrazole administration
reduced significantly oxidative parameters suggesting the ability to prevent the damaging
effects of free radicals in the brain. These findings reveal that the extract has antioxidant
properties which may account for some of its neuropharmacological effects.
Results from this study suggests that MAE possesses sedative, anxiolytic, anticonvulsant,
antidepressant and significant antioxidant effects
Description
A thesis submitted in partial fulfillment of the requirements for the degree of Master of Philosophy in the Department of Pharmacology,