Altered muscarinic receptor expression in the cerebral cortex of epileptic rats: restorative role of Withania somnifera

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-kappa B, and TNF-alpha, 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.