Pyrus pashia fruit extract and its major phytometabolite chrysin prevent hippocampal apoptosis and memory impairment in PTZ-kindled mice

Abstract

ABSTRACT Objectives Epilepsy is a chronic neurological condition with recurrent seizures. One-third of epilepsy patients experience unacceptable side effects from antiepileptic drugs. Pyrus pashia is a deciduous tree from southern Asia. Ethnomedicinally, Malakand tribes use its fruits for epilepsy treatment. Our prior research demonstrated the anticonvulsive properties of ethanolic extract of Pyrus pashia (EPP) and its bioactive compound chrysin in acute seizure tests. This study aims to investigate the impact of EPP and chrysin on cognitive impairment in a PTZ-induced kindling mice model of epilepsy. Methods Swiss albino male mice were equally divided into four groups. The first group received 0.5% carboxy methyl cellulose dissolved in normal saline while the other three groups were pre-treated with Diazepam (DZP) (1 mg/kg, i.p.), EPP (200 mg/kg, p.o.) and chrysin (5 mg/kg, p.o.). After 30 min, all groups were administered PTZ (35 mg/kg, i.p.) and evaluated for seizure severity, cognitive function, and neuronal apoptosis. Western blot analysis was conducted to analyze the expressions of apoptosis biomarkers and memory-related genes, including cAMP response element-binding protein (CREB) and Brain Derived Neurotrophic Factor (BDNF). Results The therapeutic effects of EPP and Chrysin were comparable to DZP in terms of reducing seizure severity, but unlike DZP, they prevented PTZ-induced memory impairment in experimental animals. Additionally, they increased the levels of BDNF and CREB while reducing apoptotic biomarkers in the hippocampus of experimental animals. Conclusions Based on the leads offered by this study EPP and its major bioactive constituent, could be developed as the treatment option for epilepsy.