Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway.
Mol Med Rep
; 12(3): 3688-3696, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26016839
ABSTRACT
The present study provided experimental evidence for the neuroprotective effects of quercetin using a rat model of global brain ischemic/reperfusion (I/R) injury. Pretreatment with quercetin (5 or 10 mg/kg orally (p.o.); once daily) induced a dosedependent reduction in I/Rinduced hippocampal neuron cell loss, with 10 mg/kg/day being the lowest dose that achieved maximal neuroprotection. Administration of 10 mg/kg quercetin over at least 3 days prior to I/R was required to improve the survival rate of I/R rats. Fluorescenceassisted cell sorting, hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling indicated neuronal cell loss in the CA1 hippocampus. Rats that had undergone transient global cerebral ischemia for 15 min followed by 1 h of reperfusion exhibited a significant increase in reactive oxygen species (ROS) production in the hippocampus. The I/Rinduced ROS overproduction in the hippocampus at 1, 12 and 24 h following I/R was significantly decreased by quercetin pretreatment. Western blot analysis revealed that the neuroprotective effects of quercetin (5 and 10 mg/kg/day, p.o.) were associated with an upregulation of the I/Rinduced suppression of Bcell lymphoma2 (Bcl2), Bcl extra large and survivin expression as well as phosphorylation of Bcl2associated death promoter. Furthermore, the neuroprotective effects of quercetin (5, 10 mg/kg/day) in the brain were associated with an upregulation of Akt signaling. These findings suggested that the inhibition of I/Rinduced brain injury by quercetin likely involves a transcriptional mechanism to enhance antiapoptotic signaling.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Quercetina
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Encéfalo
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Daño por Reperfusión
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Isquemia Encefálica
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Apoptosis
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Fármacos Neuroprotectores
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Proteínas Proto-Oncogénicas c-akt
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Med Rep
Año:
2015
Tipo del documento:
Article