Esculetin alleviates pentylenetetrazole-induced seizures, cognitive impairment and pro-inflammatory cytokines and suppresses penicillin-induced epileptiform activity in rats

Abstract

Aims: To investigate the effects of different doses of esculetin on epileptiform activity, behavioral seizures, memory impairment, and cortical and hippocampal NF-Kappa B, as a mediator of pro-inflammatory gene induction, and pro-inflammatory cytokines in penicillin-and pentylenetetrazole(PTZ)-induced seizure models in rats. Main methods: Different doses of esculetin (5, 10, and 20 mg/kg), and diazepam (5 mg/kg) as a positive control, were tested in penicillin-and pentylenetetrazole(PTZ)-induced seizure models. In the PTZ model, cognitive function, behavioral seizures, and cortical and hippocampal pro-inflammatory biomarkers and survival factor was evaluated. In the penicillin model, the frequency and amplitude of electrophysiological epileptiform activity were assessed. Key findings: In the PTZ model, the 10 mg/kg esculetin displayed anticonvulsant effects by extending onset-times of myoclonic-jerk and generalized tonic-clonic seizure, and by diminishing seizure severity and duration of generalized tonic-clonic seizure. It also ameliorated PTZ-induced cognitive impairment, and cortical and hip-pocampal activin-A, IL-1 beta, IL-6 and NF-Kappa B levels. In the penicillin model, the 10 mg/kg esculetin decreased the frequency of spikes without changing the amplitude of spikes. As a positive-control, diazepam reversed all changes induced by both PTZ and penicillin. Significance: Esculetin exhibits anticonvulsant and memory-improving effects by alleviating the behavioral and electrophysiological characteristics of epileptic seizures. Additionally, esculetin exerts anti-neuroinflammatory actions in the PTZ-induced seizures model. Thus, esculetin may be a multi-targeted promising agent with anti-convulsant and anti-neuroinflammatory effects in the treatment of epilepsy.