Pinocembrin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress induced apoptosis.

Endoplasmic reticulum stress (ER stress) is known to play a vital role in mediating ischemic reperfusion damage in brain. Our previous studies showed that pinocembrin alleviated cerebral ischemic injury in ischemia/reperfusion and vascular dementia animal models, but whether attenuation of ER stress-induced apoptosis contributes to the mechanisms remains to be elucidated. In this study, an attempt was therefore made to investigate the modulation effect of pinocembrin on ischemia/reperfusion-induced ER stress in brain. Focal cerebral ischemia/reperfusion rats were induced by middle cerebral artery occlusion (MCAO) for 2h followed by 6h reperfusion. Pinocembrin was administered in different doses (1mg/kg, 3mg/kg, and 10mg/kg, respectively) at the same time of onset of reperfusion. Neurological function and brain infarction were evaluated. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, and flow cytometer (FCM) were used to investigate cell apoptosis in penumbra cortex. DNA fragmentation assay was also performed using electrophoresis. The expression of ER stress proteins of GRP78, CHOP/GADD153, ATF4, eIF2α phosphorylation was detected by western blot, and caspase-12 was evaluated by immunohistochemical analysis. Our results demonstrate that pinocembrin-treatment (3mg/kg and 10mg/kg) significantly reduced neurological deficit scores, infarct volume, and neuron apoptosis in the ischemia/reperfusion rats. It can also significantly modulate the protein levels by increasing GRP78 (10mg/kg) and attenuating CHOP/GADD153 expression along with caspase-12 activation (3mg/kg and 10mg/kg). At the same time, eIF2α phosphorylation was restrained and the expression of ATF4 was reduced (3mg/kg and 10mg/kg). These results suggest that the attenuation of ER stress induced apoptosis may be involved in the mechanisms of pinocembrin.

Wu CX ，Liu R ，Gao M ，Zhao G ，Wu S ，Wu CF ，Du GH ... -  《-》

Augmentation of endoplasmic reticulum stress in cerebral ischemia/reperfusion injury associated with comorbid type 2 diabetes.

Srinivasan K ，Sharma SS 《-》

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

Zhao G ，Zhang W ，Li L ，Wu S ，Du G ... -  《MOLECULES》

Melatonin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress.

Lin YW ，Chen TY ，Hung CY ，Tai SH ，Huang SY ，Chang CC ，Hung HY ，Lee EJ ... -  《-》

Pinocembrin protects rat brain against oxidation and apoptosis induced by ischemia-reperfusion both in vivo and in vitro.

Liu R ，Gao M ，Yang ZH ，Du GH ... -  《BRAIN RESEARCH》