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.