Abstract
Oxidative stress and neurodegeneration are involved in the initiation of epileptogenesis and progression of epileptic seizures. This study was aimed at investigating the anticonvulsant, antioxidant, and neuroprotective properties of active fractions isolated from Anthocleista djalonensis root barks in pentylenetetrazole mouse models of epileptic seizures. Bioactive-guided fractionation of Anthocleista djalonensis (AFAD) extracts using acute pentylenetetrazole (90 mg/kg) induced generalised tonic-clonic seizures, which afforded a potent anticonvulsant fraction (FPool 5). Further fractionation of AFAD was performed by high-performance liquid chromatography, which yielded fifteen subfractions, which were chemically characterised. In addition, AFAD was tested against convulsions or spontaneous kindled seizures induced, respectively, by acute (50 mg/kg) or subchronic (30 mg/kg) injection of pentylenetetrazole. Finally, oxidative stress markers, brain GABA content, and neuronal cell loss were evaluated in AFAD-treated pentylenetetrazole-kindled mice. Administration of AFAD significantly protected mice against acute pentylenetetrazole (90 mg/kg)-induced convulsions. In acute pentylenetetrazole (50 mg/kg)-induced hippocampal and cortical paroxysmal discharges, AFAD significantly decreased the number of crisis, the cumulative duration of crisis, and the mean duration of crisis. Additionally, AFAD significantly decreased the number of myoclonic jerks and improved the seizure score in subchronic pentylenetetrazole-induced kindled seizures. The pentylenetetrazole-induced alteration of oxidant-antioxidant balance, GABA concentration, and neuronal cells in the brain were attenuated by AFAD treatment. This study showed that AFAD protected mice against pentylenetetrazole-induced epileptic seizures possibly through the enhancement of antioxidant defence and GABAergic signalling. These events might be correlated with the amelioration of neuronal cell loss; hence, AFAD could be a potential candidate for the treatment of epilepsy.
Highlights
Grand mal seizures are a complex type of neurological disorders commonly found in the tropical area of Africa and are characterised by an abnormal, hypersynchronous discharger of a population of neurons in the brain that can lead to a loss of consciousness, violent muscle contractions, and eventually oxidative stress leading to the neuronal cell loss [1, 2]. ere are a significant number of studies indicating strong evidence linking kindled seizures, Evidence-Based Complementary and Alternative Medicine epileptogenesis, and oxidative stress leading to a neuronal cell loss [3, 4]
The crude extract was chromatographed with highperformance liquid chromatography, and 148 fractions were obtained. e fractions were pooled and tested for their anticonvulsant activities using 90 mg/kg pentylenetetrazoleinduced tonic-clonic convulsions. e more potent anticonvulsant fractions (FPool 5) were selected based on the highest latency to convulsion (20.84 ± 01.82), highest % surviving animals (20%), and lowest percentage of mice exhibiting convulsion (70%) (Table 1) and pooled to afford standardised active fractions from Anthocleista djalonensis (AFAD) constituted with fifteen chemical compounds in which some of them were identified. e purity and structures of isolated compounds were confirmed using standards (97%) by HPLC, 13C NMR, and 1H-NMR
active fractions of Anthocleista djalonensis (AFAD) has shown a protective effect against pentylenetetrazole-induced generalised tonic-clonic convulsions possibly through the enhancement of cortical antioxidant defence, GABAergic signalling, and the reduction of neuronal cell loss
Summary
Grand mal seizures are a complex type of neurological disorders commonly found in the tropical area of Africa and are characterised by an abnormal, hypersynchronous discharger of a population of neurons in the brain that can lead to a loss of consciousness, violent muscle contractions, and eventually oxidative stress leading to the neuronal cell loss [1, 2]. ere are a significant number of studies indicating strong evidence linking kindled seizures, Evidence-Based Complementary and Alternative Medicine epileptogenesis, and oxidative stress leading to a neuronal cell loss [3, 4]. Ere are a significant number of studies indicating strong evidence linking kindled seizures, Evidence-Based Complementary and Alternative Medicine epileptogenesis, and oxidative stress leading to a neuronal cell loss [3, 4]. Excitotoxicity, accumulation of lipid peroxidation, and the increase of DNA and protein damages encourage oxidative stress and are associated with an imbalance of neuronal excitation and inhibition and the activation of excitable neural network. In patients who have a brain injury associated with a high risk of epilepsy occurring months to years later, it may be possible to intervene pharmacologically to prevent epileptogenesis and eventually epilepsy [9,10,11,12]. No antiepileptic drug is free from adverse effects, but there are significant differences in type, frequency, and duration of adverse effects caused by individual medications [13]. With about 26 different medications available, selection of an antiepileptic drug is a much more complex process [14]
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