Phytochemical study of oleuropein and its therapeutic effects in improving seizure, oxidative stress and cognitive disorder in pentylenetetrazole kindling mouse model of epilepsy

Abstract

Prolonged epileptic seizures are the cause of neuronal death and brain damage. Lesions in different regions of the brain can lead to memory loss and cognitive disorders. It is therefore essential to seek out new neuroprotective drugs. Our aim was to investigate the therapeutic effects of oleuropein to improve seizure, oxidative stress and cognitive disorder in pentylenetetrazole (PTZ) kindling mouse model of epilepsy. Mice were randomly assigned to four groups; (1) PTZ group that intraperitoneally received PTZ for 10 days, (2) oleuropein group that received oleuropein (20mg/kg) 30 minutes before PTZ administration, (3) diazepam group that received diazepam 30 minutes before PTZ administration and (4) flumazenil group that was administered with flumazenil and then oleuropein 30 minutes before PTZ administration. Epilepsy severity was determined after final administration of PTZ. Then, the hippocampal tissue was removed and stored at -70°C to measure the interleukin-1 (IL-1) and glutamate transporter 1 (GLT-1) gene expression. Oleuropein treatment caused a significant increase in seizure latency and a significant decrease in total frequencies of head ticks, head and upper limbs seizures, the whole body seizures, frequent spinning and jumping and tonic seizures in PTZ receiving mice. IL-1 expression decreased and GLT-1 levels did not change significantly in oleuropein group. Oleuropein treatment caused significant improvement of passive avoidance memory in PTZ receiving mice in shuttle box test. Oleuropein can decrease PTZ-induced seizures and memory disorders due to its antioxidant and anti-inflammatory properties and thus can be used to produce antiepileptic drugs.