Isoquercetin activates the ERK1/2-Nrf2 pathway and protects against cerebral ischemia-reperfusion injury in vivo and in vitro

Abstract

Isoquercetin has exhibited a wide range of therapeutic properties, including antioxidant, anti-inflammatory and anti-allergic activities. The aim of the present study was to investigate the effect of isoquercetin on rats with 2 h middle cerebral artery occlusion (MCAO) and evaluate the neuroprotective effect of isoquercetin on a primary culture of rat hippocampal neuronal cells subjected to oxygen-glucose deprivation followed by reoxygenation (OGD/R). <i>In vivo</i>, the rats treated with isoquercetin exhibited a lower degree of neurological dysfunction and smaller infarct volume than the vehicle-treated rats. <i>In vitro</i>, it was found that isoquercetin prevented the OGD/R-induced increase in apoptosis, lactate dehydrogenase release and reduction in cell viability. Additionally, isoquercetin induced the upregulation of nuclear factor erythroid 2-related factor 2 gene and protein expression, and increased extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation. This indicates that the ERK1/2 pathway may contribute to the neuroprotective effect of isoquercetin against OGD/R-induced oxidative damage in rat hippocampal neurons. These findings suggest the potential importance of isoquercetin in the treatment of ischemia/reperfusion-related brain injury and associated diseases.