Pinocembrin protects the brain against ischemia-reperfusion injury and reverses the autophagy dysfunction in the penumbra area.

Abstract

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.

• Authors: Gang Zhao, Wen Zhang, Li Li, Song Wu, Guanhua Du
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 19 Issue 10 Pg. 15786-98 (Sep 30 2014) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 25271424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavanones
• Neuroprotective Agents
• pinocembrin
• Caspase 3

Topics

• Animals
• Autophagy (drug effects)
• Brain Edema (drug therapy, etiology)
• Brain Infarction (drug therapy, pathology)
• Brain Ischemia (drug therapy, metabolism, pathology, physiopathology)
• Caspase 3 (metabolism)
• Disease Models, Animal
• Flavanones (administration & dosage, pharmacology)
• Male
• Neuroprotective Agents (administration & dosage, pharmacology)
• Rats
• Reperfusion Injury (drug therapy, metabolism, pathology)