Protective Effects of Anthocleista djalonensis Extracts against Pentylenetetrazole-Induced Epileptic Seizures and Neuronal Cell Loss: Role of Antioxidant Defense System.

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.

Anticonvulsant activity of an active fraction extracted from Crinum jagus L. (Amaryllidaceae), and its possible effects on fully kindled seizures, depression-like behaviour and oxidative stress in experimental rodent models.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaf extract of Crinum jagus L. (Amaryllidaceae) is widely used in traditional Cameroonian medicine as antiepileptic remedy and for the treatment of convulsion, depression and mood disorders associated with epilepsy. AIM OF THE STUDY: Hence, this study was conducted to evaluate the effects of an active fraction extracted from the leaves of Crinum jagus against seizures, depression-like behaviour and oxidative stress in pentylenetetrazole (PTZ)-induced kindling in mice. MATERIALS AND METHODS: Bioactive-guided fractionation of the leaf extract of Crinum jagus by using 70mg/kg PTZ-induced convulsions in mice, afforded a potent anticonvulsant fraction (flavonol kaempferol; C4.4). The effects of C4.4 on 30mg/kg PTZ-induced kindling, kindling-induced depression like-behaviour and oxidative stress was evaluated. Mice were injected PTZ (30mg/kg, i.p.) once every alternate day (48±1h) until the development of kindling. Depression was assessed using tail suspension test and forced swim test while the oxidative stress parameters were estimated in the whole brain at the end of experiments. Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of C4.4. Acute toxicity of C4.4 was also assessed in mice. RESULTS: Convulsions-induced by 70mg/kg PTZ were strongly antagonized by C4.4. Oral administration of C4.4 significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure mean stage and decreased the number of myoclonic jerks in PTZ-kindled mice. The data indicated also that C4.4 significantly reduced the immobility times in the tail suspension test and the forced swim test. This active fraction has also antioxidant properties by decreasing the lipid peroxidation, and augmenting endogenous antioxidant enzymes in brain. C4.4 administered (12.5-50mg/kg) did not alter the locomotion of animals in the open-field or rotarod tests, which suggest a lack of a central depressant effect. The animals did not exhibit any acute toxicity to C4.4 at the therapeutic doses. CONCLUSION: These results suggest that pretreatment with C4.4 ameliorates convulsions-induced by PTZ, protects mice against kindling development, depression-like behaviour and oxidative stress in PTZ-kindled mice. These finding provides scientific rationale for the use of Crinum jagus extracts for the amelioration of epilepsy observed in traditional medicine in Cameroon.

Anticonvulsant effects of iridoid glycosides fraction purified from Feretia apodanthera Del. (Rubiaceae) in experimental mice models of generalized tonic-clonic seizures.

BACKGROUND: Despite the increasing number and variety of antiepileptic drugs, nearly 30 % of epileptic patients who receive appropriate medical attention have persisting seizures. Anticonvulsant activity has been demonstrated for different iridoid glycoside-rich plant extracts. This study was designed to investigate the anticonvulsant effects of iridoid glycosides purified from Feretia apodanthera and to explore the possible mechanisms involved in antiepileptic activity. METHODS: The anticonvulsant effects of iridoid glycosides extracts were investigated against 2.7 mg/kg bicuculline- and 70 mg/kg pentylenetetrazole-induced convulsions. The behavioural and electroencephalographic manifestations of 50 mg/kg pentylenetetrazole-induced seizures in mice as a model of generalized tonic-clonic seizures were also evaluated. Finally, the extracts were tested on the course of kindling development, kindled-seizures and oxidative stress markers in 30 mg/kg pentylenetetrazole-kindled mice. Their effects on brain GABA content were also determined. RESULTS: The iridoid glycosides (30-90 mg/kg) protected mice against bicuculline-induced motor seizures in all pre-treated animals. Behavioural seizures- and mortality-induced by 70 mg/kg pentylenetetrazole were strongly antagonized by the extracts (60-90 mg/kg). The number of crisis (n/20 min), the cumulative duration of crisis (sec/20 min), and the mean duration of crisis (sec) recorded in 50 mg/kg pentylenetetrazole-treated mice were significantly decreased in all pre-treated mice with the extracts (60-90 mg/kg). Administration of the extracts (30-90 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure mean stage and decreased the number of myoclonic jerks in 30 mg/kg pentylenetetrazole-kindled mice. Pentylenetetrazole kindling induced significant oxidative stress and brain GABA content alteration that was reversed by pretreatment with the extracts in a dose-dependent manner. CONCLUSIONS: The results indicate that pretreatment with the iridoid glycosides extracts of Feretia apodenthera improves generalized tonic-clonic seizures-induced by chemo-convulsants, protects mice against kindling development and oxidative stress, and improves brain GABA content in pentylenetetrazole-kindled mice.

Antipsychotic and sedative effects of the leaf extract of Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) has been used as a medicine for the treatment of epilepsy, insomnia, dementia and psychotic disorders in Cameroonian traditional medicine. AIM OF THE STUDY: This study was designed to examine whether the aqueous extract and the alkaloid fraction prepared from the leaves of Crassocephalum bauchiense possess antipsychotic and sedative properties in rodents. MATERIALS AND METHODS: The rectal temperature of mice was recorded with a probe thermometer at a constant depth. Novelty-induced rearing behavior is used to evaluate a central excitatory locomotor behavior in mice. The antipsychotic effects of the extracts were assessed using the apomorphine animal model of psychosis. The catalepsy test was tested based on the ability of the leaves extracts of Crassocephalum bauchiense to alter the duration of akinesia by placing the naive mice with both forelegs over a horizontal bar. The extracts of Crassocephalum bauchiense effects were evaluated on sodium pentobarbital-induced sleeping time. In addition, gamma-aminobutyric acid concentrations in the brain treated mice were also estimated. RESULTS: The aqueous extract and the alkaloid fraction from Crassocephalum bauchiense caused dose-dependent inhibition of novelty-induced rearing behavior, decreased the apomorphine-induced stereotypy and fighting, and had significant fall of the body temperature. The aqueous extract prolonged the sodium pentobarbital sleeping time. This prolongation was not reversed by bicuculline, a light-sensitive competitive antagonist of GABA(A) receptors complex. However, the effect of the aqueous extract on sodium pentobarbital-induced sleeping time was blocked by N-methyl-ß-carboline-3-carboxamide, a partial inverse agonist of the benzodiazepine site in the GABA(A) receptor complex and flumazenil, a specific antagonist of the benzodiazepine site in the GABAA receptor complex. In biochemical experiments, the concentration of the inhibitory amino acid, gamma-aminobutyric acid, was significantly increased in the brain of animals treated with the aqueous extract of Crassocephalum bauchiense and sodium valproate. CONCLUSIONS: The results show that the antipsychotic and sedative properties of Crassocephalum bauchiense are possibly mediated via the blockade of dopamine D-2 receptors and GABAergic activation, respectively. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for these neuropharmacological actions and also to identify the active substances present in the extracts of Crassocephalum bauchiense.