α-Lipoic Acid Promotes Neurological Recovery After Ischemic Stroke by Activating the Nrf2/HO-1 Pathway to Attenuate Oxidative Damage.

Alpha-lipoic acid (α-LA) has been demonstrated to be protective against cerebral ischemia injury. Herein, we investigate the neuroprotective effect and underlying mechanisms of α-LA. In vivo study, α-LA was administered intravenously upon reperfusion of transient middle cerebral artery occlusion. Garcia score was used to evaluate neurologic recovery. Infarct volume was examined by TTC staining, and oxidative damage was evaluated by ELISA assay. In an in vitro study, neurons were pretreated with α-LA at different doses and then subjected to OGD. Lentiviral vectors were applied to knockdown nuclear factor-erythroid 2-related factor-2 (Nrf2) or heme oxygenase-1 (HO-1). Cell viability was measured using CCK8. Protein expression was evaluated using western blot, and immunofluorescence staining was assessed. α-LA significantly reduced the infarct volume, brain edema, and oxidative damage and promoted neurologic recovery in rats. Pretreatment of α-LA caused an obvious increase in cell viability and a decrease in intracellular reactive oxygen species. Western blot analyses and immunofluorescence staining demonstrated a distinct increase in Nrf2 and HO-1 protein expression. Conversely, knockdown of Nrf2 or HO-1 resulted in the down-regulation of HO-1 protein and inhibited the neuroprotective effect of α-LA. α-LA treatment is neuroprotective and promotes functional recovery after ischemic stroke by attenuating oxidative damage, which is partially mediated by the Nrf2/HO-1 pathway.

Lv C ，Maharjan S ，Wang Q ，Sun Y ，Han X ，Wang S ，Mao Z ，Xin Y ，Zhang B ... -  《-》

Neuroprotection by acetyl-11-keto-β-Boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway.

Ding Y ，Chen M ，Wang M ，Wang M ，Zhang T ，Park J ，Zhu Y ，Guo C ，Jia Y ，Li Y ，Wen A ... -  《Scientific Reports》

Protocatechualdehyde Protects Against Cerebral Ischemia-Reperfusion-Induced Oxidative Injury Via Protein Kinase Cε/Nrf2/HO-1 Pathway.

Guo C ，Wang S ，Duan J ，Jia N ，Zhu Y ，Ding Y ，Guan Y ，Wei G ，Yin Y ，Xi M ，Wen A ... -  《-》

Neuroprotective Effect of Swertiamain on Cerebral Ischemia/Reperfusion Injury by Inducing the Nrf2 Protective Pathway.

Wang H ，Wei W ，Lan X ，Liu N ，Li Y ，Ma H ，Sun T ，Peng X ，Zhuang C ，Yu J ... -  《ACS Chemical Neuroscience》

Neuroprotective role of fucoxanthin against cerebral ischemic/reperfusion injury through activation of Nrf2/HO-1 signaling.

In the present study, an attempt was made to determine whether administration of fucoxanthin could attenuate cerebral ischemic/reperfusion (I/R) injury and its possible mechanisms using an in vivo middle cerebral artery occlusion (MCAO) model and an in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) model. Fucoxanthin was intragastrically administrated in different doses (30 mg/kg, 60 mg/kg, and 90 mg/kg, respectively) to the rats 1 h before MCAO induction. The neurological function, infarct area and brain water content of rats were then evaluated. Rat cortical neuron were pretreated with different doses of fucoxanthin (5 μM, 10 μM, and 20 μM) and then subjected to OGD/R. Expression levels of proteins in the brain tissues and cultured cells were determined by western blotting. Our results demonstrated that fucoxanthin pretreatment improved the neurologic deficit score, lowered the infarct volume and reduced the expression of apoptosis-associated proteins in brain tissues. In addition, fucoxanthin also suppresses OGD/R-induced apoptosis and ROS accumulation in cultured neurons. Furthermore, we found that fucoxanthin could significantly activate the Nrf2/HO-1 signaling through inducing Nrf2 nuclear translocation with enhanced HO-1 expression, and Nrf2 knockdown obviously abrogated the beneficial role of fucoxanthin in OGD/R-treated neurons. These findings suggested that fucoxanthin could be exploited as a therapeutic target for protecting neurons from cerebral I/R injury.

Hu L ，Chen W ，Tian F ，Yuan C ，Wang H ，Yue H ... -  《-》