Neuroprotection by Curcumin in Ischemic Brain Injury Involves the Akt/Nrf2 Pathway

Abstract

Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of curcumin against experimental stroke. Oxygen and glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular expression of NAD(P)H: quinone oxidoreductase1 (NQO1) induced by OGD was counteracted by curcumin post-treatment, which paralleled attenuated cell injury. The reduction of phosphorylation Akt induced by OGD was restored by curcumin. Consequently, NQO1 expression and the binding activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) to antioxidant response element (ARE) were increased. LY294002 blocked the increase in phospho-Akt evoked by curcumin and abolished the associated protective effect. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 60 minutes. Curcumin administration significantly reduced infarct size. Curcumin also markedly reduced oxidative stress levels in middle cerebral artery occlusion (MCAO) rats; hence, these effects were all suppressed by LY294002. Taken together, these findings provide evidence that curcumin protects neurons against ischemic injury, and this neuroprotective effect involves the Akt/Nrf2 pathway. In addition, Nrf2 is involved in the neuroprotective effects of curcumin against oxidative damage.

Maslinic acid promotes synaptogenesis and axon growth via Akt/GSK-3β activation in cerebral ischemia model

“…Changes in the phosphorylation of Akt were reported after cerebral ischemia induced by MCAO. These reports showed that ischemia/reperfusion significantly increased phosphorylation of Akt at Ser473 (Gu et al, 2013;Wu et al, 2013;Zhang et al, 2007), which was consistent with our study. In addition, the activation of Akt by phosphorylation at Ser473 facilitates the process of synaptic plasticity in the MCAO model (Chen et al, 2010),and is prone to promote axonal outgrowth and motoneuronal survival (Namikawa et al, 2000;Ransome and Turnley, 2008).…”

Enhanced Neuroprotection of Acetyl-11-Keto-β-Boswellic Acid (AKBA)-Loaded O-Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways

“…After 2 h, 0.5-ml neurobasal medium was added to each well. After 2 days in vitro, 5 μM cytosine arabinofuranoside was added to inhibit glial proliferation as previously described [24]. Neurons were cultured at 37°C in a humidified 5 % CO 2 atmosphere.…”

“…Subsequently, the release rate gradually slowed, and the cumulative release of drug was over 70 % within 96 h. The observed initial burst release might be due to the dissociation of surface absorbed drugs present in the polymeric matrix. Subsequently, sustained release activity of the drugs was due to the slow release of drugs entrapped inside the polymer matrix [24].…”

Benefits of Curcumin Supplementation on Antioxidant Status in β-Thalassemia Major Patients: A Double-Blind Randomized Controlled Clinical Trial

“…The β-diketone moiety and the hydroxyl/methoxy groups on phenyl rings in curcumin are responsible for its direct radical scavenging property [14,20]. Curcumin upregulates antioxidant enzymes by triggering the nuclear factor erythroid 2-related factor 2/antioxidant response element signaling pathway [17,38]. Based on the results obtained by Das and Vinayak [39], they believed that curcumin regulates the endogenous antioxidant system both at the transcriptional level and via post-translational modification of enzyme activity.…”