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Molecules 2014, 19(10), 15786-15798;

Pinocembrin Protects the Brain against Ischemia-Reperfusion Injury and Reverses the Autophagy Dysfunction in the Penumbra Area

Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Author to whom correspondence should be addressed.
Received: 31 July 2014 / Revised: 6 September 2014 / Accepted: 15 September 2014 / Published: 30 September 2014
(This article belongs to the Section Medicinal Chemistry)
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The aim of this study was to investigate the effects of pinocembrin on brain ischemia/reperfusion (I/R) injury and the potential involvement of autophagy activity changes in the penumbra area in the mechanisms of pinocembrin activity. Focal cerebral I/R model was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h reperfusion. Pinocembrin was administered intravenously at different doses (1, 3, and 10 mg/kg, respectively) at the onset of reperfusion. Neurological function, brain infarction and brain swelling ratio were evaluated. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and immunohistochemical analysis (Caspase-3) were used to evaluate apoptosis in the penumbra cortex. Two key proteins of autophagy, LC3B and Beclin1, were detected by western blot. The results showed that pinocembrin-treatment could significantly reduce neurological deficit scores, infarct volume, cerebral edema and improve pathological lesion in the I/R rats. Pinocembrin-treatment could also reduce the number of TUNEL-positive and Caspase-3-positive neurons, and upregulate the expression of LC3B and Beclin1 in penumbra area. These results suggested that pinocembrin could protect the brain against I/R injury, and the possible mechanisms might be attributed to inhibition of apoptosis and reversed autophagy activity in penumbra area. View Full-Text
Keywords: pinocembrin; ischemia/reperfusion; penumbra; autophagy pinocembrin; ischemia/reperfusion; penumbra; autophagy

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Zhao, G.; Zhang, W.; Li, L.; Wu, S.; Du, G. Pinocembrin Protects the Brain against Ischemia-Reperfusion Injury and Reverses the Autophagy Dysfunction in the Penumbra Area. Molecules 2014, 19, 15786-15798.

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