Potential Mechanisms Involved in the Anticonvulsant Effect of Walnut Extract on Pentylenetetrazole-Induced Seizure

Abstract

Objective: It was the aim of this study to determine the potential effect of walnut kernel extract (WKE) on experimentally induced seizures in rats and to evaluate the role of benzodiazepines and ethosuximide (ESM) within these pathways. Materials and Methods: Male Wistar rats were selected and divided into eight groups. Seizures were evoked by intravenous infusion of pentylenetetrazole (PTZ; 2 mg/ml/min). In combination with PTZ, animals were treated with vehicle or WKE (100 mg/kg i.p.), with or without cotreatment with either flumazenil (FMZ; 5 mg/kg i.p.), ESM (150 mg/kg i.p.) or diazepam (DPZ; 0.5 mg/kg i.p.). Results: WKE administration significantly increased the PTZ dose needed to induce the first myoclonic jerk (13.09 ± 1.29 vs. 49.71 ± 12.03 mg/kg; p < 0.001), decreased the severity of seizure grades and reduced the mortality rate to 0%. FMZ did not significantly reduce the anticonvulsant effect of WKE. The combination of DPZ and WKE showed a synergic anticonvulsant effect, whereas ESM had no significant influence (p > 0.05) on the WKE effects. Conclusion: These findings indicated that WKE was effective at reducing seizure severity, at increasing the dose to the first myoclonic jerk and highly efficacious at preventing mortality, because 100% of animals were protected. It seems that this positive effect could apply through signaling pathways other than benzodiazepine-mediated γ-aminobutyric acid receptors and may at least in part be similar to ESM.

Protective Effects of Crude Flavonoids And Alkaloids Extracts of Matricaria Chamomilla L. in Chicks against Pentylenetetrazole-induced Convulsions

“…PTZ is a well-known convulsing used, exerting its effect by blockade of GABA A receptors, leading to decrease inhibitory GABA and increase excitatory glutamate levels in the brain tissue (Shimada and Yamagata, 2018). Thus, it brings the membrane potential closer to seizure threshold and firing action potentials (Asadi-Shekaari et al, 2014). The present results are in line with Wang et al (2021), who found that PTZ provoked convulsions by reducing the level of GABA and elevating glutamate level in the brain tissue.…”

“…In the present study, the preliminary phytochemical screening tests were carried out on the crude flavonoids and alkaloids extracts, and the phytochemical screening confirmed the presence of flavonoids in the crude flavonoids The effects of crude flavonoids together with alkaloids extracts on convulsive behaviors and brain tissue neurotransmitters PTZ, a GABA A receptor antagonist, is widely used to induce convulsive seizures by lowering the seizure threshold, and to assess the efficacy of anticonvulsant substances in experimental animals (Asadi-Shekaari et al, 2014). The results of the present experiment showed that the PTZ induced obvious convulsive behaviors such as tonic, myclonic, clonic, and tonic-clonic convulsive seizures.…”

“…PTZ is a GABA A receptor antagonist, used to chemically induced convulsive seizures, and screening and evaluating the potential effects of anticonvulsant substances (Shimada and Yamagata, 2018). It caused convulsive seizures by impairing inhibitory GABA and enhancing the activity of excitatory glutamate neurotransmitters in the brain tissue (Asadi-Shekaari et al, 2014). Consequently, resulted in considerable metabolic stress and alteration of electrolyte gradients, which further increase the neural and neuromuscular excitability during seizures (Borowicz-Reutt and Czuczwar, 2020).…”

Effect of Captopril on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice<br />

“…These researchers also reported that pretreatment with walnut kernel extract reduced mortality rate to 0%. 21 In the present research also the convulsions caused by PTZ were associated with a significant increase in mortality rate of mice (100% of mice). Pretreatment with all three doses of captopril significantly reduced mortality rate of mice.…”

Medicinal plants with anticonvulsant activities with emphasis on their mechanisms of action

“…The combination of diazepam (DPZ; 0.5 mg/kg ip) and WKE showed a synergic anticonvulsant effect, whereas ethosuximide (ESM) had no significant influence (p > 0.05) on the WKE effects. It seemed that the anticonvulsant effect attributed to signaling pathways other than benzodiazepine mediated γ-aminobutyric acid receptors [66][67].…”