Neuroprotective effects of Withania somnifera on ischemic stroke are mediated via anti-inflammatory response and modulation of neurotransmitter levels

The present study was designed to evaluate the beneficial effects of hydroalcoholic root extract of Withania somnifera (WS) on ischemia-reperfusion injury (IRI) induced by Middle Cerebral Artery Occlusion (MCAO). MCAO animals showed increase in IL-6, TNF-α and MCP-1 levels in terms of mRNA and protein levels. Concomitantly, mRNA and protein levels for astrocyte and microglial activation markers; GFAP and IBA-1, were increased in MCAO animals. COX-2 and NF-kβ protein levels were also increased in the brains of MCAO animals. The levels of neurotransmitters; glutamate and GABA were increased in the MCAO animals. On the contrary, levels of catecholamines; dopamine, norepinephrine and serotonin were reduced in the MCAO animals. Additionally, MCAO animals showed reduced locomotor activity. However, pre-supplementation with WS hydro-alcoholic root extract at a dose of 300 mg/kg, body weight to MCAO animals reduced the expression of IL-6, TNF-α and MCP-1. In addition, WS also reduced the number of GFAP and Iba-1 positive cells in comparison to MCAO animals. WS pre-supplementation was also observed to inhibit MCAO induced increase in COX-2; NF-kβ proteins and reduce the glutamate levels. The levels of GABA, dopamine, norepinephrine and serotonin were increased in WS pre-supplemented MCAO animals. WS pre-supplementation also prevented motor deficits in the MCAO animals. Taken together, these findings suggest that WS is effective in attenuating IRI induced neuroinflammation, neurochemical alterations and motor deficits in MCAO model of ischemic stroke thereby suggesting its ameliorative role in ischemia-reperfusion injury.