Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia

Abstract

Previous studies have demonstrated that quercetin, a bioflavonoid shows the inhibitory effect against ischemia and reperfusion-induced injury in various tissues including neural tissue. Quercetin is also reported to have an inhibitory effect against matrix metalloproteinases (MMPs). Because MMPs are known to play a main role in the pathophysiology of brain ischemic insult, their mechanisms of possible protective effect of quercetin against brain ischemia remain to be clarified. In the present study, C57BL/6 mice were subjected to 20 min transient global brain ischemia. Cerebral blood flow was monitored by laser doppler flowmeter. Animals were sacrificed 72 h after ischemia. Quercetin (50 mg/kg, dissolved in saline) was intraperitoneally administered to mice at 30 min before and immediately after ischemia and from the second day, quercetin was then administered once daily until sacrifice. The present study was undertaken to test the effect of quercetin on neuronal damage after transient cerebral ischemia. Neuronal damages were remarkable in the medial portion of CA1 and CA2 areas after ischemic insult. In quercetin-treated mice, delayed neuronal damage was significantly decreased compared with vehicle-treated mice. Mice treated with quercetin showed attenuated brain MMP-9 activity. Gelatin gel zymography showed an induction of MMP-9 protein after ischemia. Quercetin significantly inhibited ischemia-induced elevation of MMP-9. In situ zymography showed elevations in gelatinase activities after brain ischemia. Quercetin also inhibited TdT-mediated dUTP nick end labeling (TUNEL) staining in CA1 and CA2 areas. These results demonstrate that quercetin, a natural flavonoid reduces global ischemia-induced neuronal damage through inhibition of MMP-9 activity. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Quercetin; Global ischemia; Hippocampus; Matrix metalloproteinases