Malibatol A Attenuates Ischemia/Reperfusion Injury In Stroke Via Inhibition Of Oxidative Stress

Background:Stroke is the second most common cause of mortality worldwide. The mechanisms leading to cellular damage from cerebral ischemia-reperfusion (I/R) injury are multi-factorial, including oxidative stress led by the imbalance between oxidants and antioxidants. Malibatol A (MA), a resveratrol oligomer, has shown potential neuroprotection effect against cerebral I/R injury.Objectives:The aims of this study are:(1) to investigate the antioxidant effects of MA in I/R injury; (2) to explore the mechanism underlying of MA in I/R-induced oxidative stress.Methods:The mice were randomly distributed into four groups:the Sham group, the Sham+MA group, the middle cerebral artery occlusion (MCAO) group, and the MCAO+MA group. MA (20mg/Kg) was given within 15min of reperfusion(2h post-occlusion). The reactive oxygen species (ROS) production were measured by DCFH-DA. Neurotrophin-3 (3-NT), and 4-Hydroxynonenal (4-HNE), and 8-hydroxy-2-de-axyguanine (8-OHdG) were measured by the ELISA. The activities of mitochondrial respiratory enzyme complex were measured by chromatometry. The expressions of Bcl-2, Bax, and cytochrome c were measured by western blot. The activities of Caspase-9 and Caspase-3 were measured by spectrophotography. Statistical analyses were performed using ANOVA and post hoc Fisher’s PLSD tests, with P< 0.05 considered statistically significant.Results:MA decreased reactive oxygen species (ROS) level and protein, lipid peroxidative products in mice cortex, which were significantly altered in MCAO group. The activities of respiratory enzyme complex Ⅰ and Ⅲ were effectively preserved compared with MCAO group through MA treatment. Western blot analysis showed a marked increase in the expression of Bcl-2 and decrease of Bax as a result of MA treatment. Moreover, the attenuation of content of cytochrome c and activities of Caspase-9/3 could be observed in MA treated group.Conclusion:These findings highlight the promising therapeutic effect of MA against cerebral I/R injury through anti-oxidant and anti-apoptotic mechanisms.