Temporal lobe epilepsy involves a sequence of events that can lead to
neurotransmitter signalling alterations. There are many herbal extracts considered to be alternative therapeutic methods to manage
epilepsy. In this study, we investigated the effect of Withania somnifera (WS) root extract and
withanolide A (WA) in the management of
temporal lobe epilepsy. Confocal imaging of TOPRO-3-stained cortical sections showed severe damage in the epileptic brain. We also observed a reduced
antioxidant potential and increased
peroxide levels in the epileptic test group of rats. Oxidative stress resulted in the down-regulation of CREB, NF-κB, and TNF-α, and with up-regulation of the apoptotic factors
caspases 8 and 3 and Bax in the epileptic group. Epileptic condition also resulted in increased
muscarinic receptor binding and
mRNA expression in the cerebral cortex. Withania somnifera and
withanolide A significantly reversed the altered
muscarinic receptor expression and reversed the oxidative stress and resultant derailment in cell signalling. Thus our studies suggest that Withania somnifera and
withanolide A play important roles in central
muscarinic receptor functional balance and activation of the
antioxidant system in the cerebral cortex in
temporal lobe epilepsy. These findings can be of immense therapeutic significance for managing
epilepsy.