Cerebral ischemia is a neurological disorder with high mortality. Quercetin is a flavonoid compound that is abundant in vegetables and fruits. It exerts anti-inflammatory and anti-apoptotic effects. This study investigated the neuroprotective effects of quercetin in focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) to induce focal cerebral ischemia. Quercetin or vehicle was injected 30 min before the onset of ischemia. A neurological function test, brain edema measurement, and 2,3,5-triphenyltetrazolium chloride staining were performed to elucidate the neuroprotective effects of quercetin. Western blot analysis was performed to observe caspase-3 and poly ADP-ribose polymerase (PARP) protein expression. MCAO leads to severe neuronal deficits and increases brain edema and infarct volume. However, quercetin administration attenuated the MCAO-induced neuronal deficits and neuronal degeneration. We observed increases in caspase-3 and PARP protein levels in MCAO-operated animals injected with vehicle, whereas quercetin administration attenuated these increases in MCAO injury. This study reveals the neuroprotective effect of quercetin in an MCAO-induced animal model and demonstrates the regulation of caspase-3 and PARP expression by quercetin treatment. These results suggest that quercetin exerts a neuroprotective effect through preventing the MCAO-induced activation of apoptotic pathways affecting caspase-3 and PARP expression.

Cerebral ischemia is a major cause of death and neurological disability. It also leads to severe brain tissue damage by excessive generation of oxidative stress. Quercetin is a bioflavonoid substance that acts an antioxidant agent and exerts a neuroprotective effect against cerebral ischemia. The aim of this study was to detect specific proteins that are differentially expressed in response to quercetin treatment in focal cerebral ischemia. Adult male rats were intraperitoneally injected with vehicle or quercetin (10 mg/kg) 30 min prior to right middle cerebral artery occlusion (MCAO). Brain tissues were collected 24 h after MCAO surgery and right cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry. MCAO leads to neurological behavior disorders, infarction, and histopathological change. However, quercetin treatment alleviated MCAO-induced neuronal deficits and damages. We identified specific proteins differentially expressed between vehicle- and quercetin-treated animals. Among these detected proteins, isocitrate dehydrogenase [NAD], adenosylhomocysteinase, pyruvate kinase, and ubiquitin carboxy terminal hydrolase L1 were decreased in vehicle-treated animals, while quercetin administration alleviated the MCAO-induced decreases in these proteins. However, 60 kDa heat shock protein and collapsin response mediator protein 2 were increased in the vehicle-treated animals, and quercetin treatment attenuated increases in these proteins. The expression changes in these proteins were confirmed by Western blot and reverse transcription-PCR analyses. These proteins are associated with cellular differentiation, metabolism, and oxidative stress related proteins. These results suggest that quercetin reduces ischemic injury by modulating the expression of various proteins in focal cerebral ischemia.

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Quercetin is a plant flavonoid that has anti-oxidant, anti-inflammatory, anti-cancer, and anti-ischemic properties. Moreover, quercetin exerts neuroprotective effects against focal cerebral ischemia. Protein phosphatase 2A (PP2A) is a form of serine/threonine phosphatase that modulates various biological functions. Among PP2A subunit types, subunit B exists abundantly in brain tissue and plays an essential function in nervous system. We previously reported the decrease of PP2A subunit B in focal cerebral animal model. This study explored the change of PP2A subunit B expression by quercetin treatment in cerebral ischemic animal model and glutamate-treated hippocampal-derived (HT22) cell culture. Quercetin (10 mg/kg) or vehicle was injected intraperitoneally into male rats before 30 min of middle cerebral artery occlusion (MCAO), and cerebral cortices were isolated 24 hr after MCAO. MCAO induced the neurological behavioral deficit and increased infarct volume. However, quercetin treatment attenuated the increase of neurological deficit and infarction. We detected the alleviation of MCAO-induced the decrease in PP2A subunit B by quercetin treatment using a proteomic approach. Reverse-transcription PCR and Western blot analyses confirmed lower PP2A subunit B expression levels in MCAO group with vehicle. However, quercetin treatment attenuated MCAO-induced this reduction. We also observed the neuroprotective effect of quercetin and the change of PP2A subunit B expression in glutamate-exposed HT22 cells. Glutamate exposure dramatically reduced cell viability and PP2A subunit B expression, and quercetin treatment significantly improved these decreases. We clearly showed that quercetin performs a neuroprotective function and modulates down-regulation of PP2A subunit B against MCAO injury and glutamate toxicity. Thus, our finding suggests that the regulation of PP2A subunit B by quercetin contributes to neuroprotective function in ischemic brain injury.

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