Anticonvulsant Activity of Soxhlet Leaf Extracts of Ajuga Integrifolia Buch.Ham ex D.Don (Lamiaceae) in Mice
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Date
2021-11
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Addis Ababa University
Abstract
Epilepsy is one of the most common chronic neurological conditions that affect 70 million
people in different parts of the world. The leaves of Ajuga integrifolia Buch.ham ex D Don
have been used as anti-convulsant remedy in Ethiopian traditional medicine. However, the
evidence supporting this claim is sparse in the literature. This study was conducted to add to
the existing body of knowledge about the anti-convulsant activity of the plant. To this effect
successive Soxhlet extraction was performed using n-hexane, ethyl acetate, methanol and
water.
Anti-convulsant activity of the extracts was investigated in both acute (pentylenetetrazole,
PTZ; and maximal electroshock, MES) and chronic (PTZ kindling) seizure models. For the
acute model, various doses of the extract (100mg/kg, 200mg/kg and 400mg/kg) were
administered. Positive controls received sodium valproate (200mg/kg) for PTZ and
phenytoin (25mg/kg) for MES. Distilled water or 2% tween 80 was used for negative
controls. Kindling was induced by repeated alternate day intra-peritoneal administration of
sub-convulsive dose of PTZ (35 mg/kg) for 13 days and the most active extract (ethyl
acetate) was tested in this model. Parameters including onset of clonus and duration of hind
limb tonic extension were recorded. Moreover, total alkaloid, flavonoid and phenol contents
of the most active extract were determined.
Treatment of mice with ethyl acetate extract produced a superior effect among all solvent
extracts in both PTZ and MES model. The mean latency to clonic seizure was significantly
increased (p<0.01) with all doses of ethyl acetate extract in PTZ test compared to control and
n.hexane extract ranked next to ethyl acetate extract in increasing onset of clonus. It
significantly increased mean onset of clonus compared to controls, with a maximum increase
(12.67min, p<0.001) displayed by HA400 mg/kg. Methanol extract at 200mg/kg and 400
mg/kg also significantly delayed onset of clonus (p<0.001) in PTZ model.Once again, all
doses of ethyl acetate extract of the study plant significantly reduced (p<0.001) the mean
duration of hind limb tonic extension in MES test compared to control. Hexane extract at 200
mg/kg and 400 mg/kg also significantly reduced (p<0.001) duration of hind limb tonic
extension. Methanol extract at 200mg/kg and 400 mg/kg also significantly reduced (p<0.01)
mean duration of hind limb tonic extension (HLTE) compared to control in MES test.
Aqueous extract at all doses was devoid of any anti-convulsant effect in both models. A
similar type of study done on the leaf crude extract and solvent fractions collected from
different geographical location also reported anti-convulsant activity of the plant in acute
seizure models. Treatment of mice with 200mg/kg and 400mg/kg of ethyl acetate extract
along with alternate day PTZ injection significantly protected(p<0.01 for 200mg/kg and
p<0.001 for 400 mg/kg) against PTZ induced kindling compared to controls in chronic
model. Ethyl acetate extract of the plant was found to contain 10.002±0.119 mg atropine
equivalent per gram of dry extract of alkaloids, 9.045 ±0.8445 mg quercetin equivalent /g of
dry weight extract of flavonoids and 21.928 ±1.118 mg gallic acid equivalent / g of dry
weight of extract of phenols. This study indicated that the plant has anti-convulsant activity
in both acute and chronic model and it could be a potential source to develop a new anti epileptic drug for pharmacoresistant epilepsy.
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Keywords
Ajuga integrifolia, Anti-convulsant, Epilepsy, kindling, phytoconstituents, Seizure