title: 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.
authors.affiliation: Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Wu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yu
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wu
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D008297:Male; D051381:Rats; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured / Q000166:cytology; D002867:Chromones / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007511:Ischemia / Q000473:pathology; D009025:Morpholines / Q000494:pharmacology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051267:NF-E2-Related Factor 2 / Q000378:metabolism
chemical_list: C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000975:Antioxidants; D002867:Chromones; D003474:Curcumin; D004791:Enzyme Inhibitors; D005947:Glucose; D009025:Morpholines; D016660:NAD(P)H Dehydrogenase (Quinone); D018696:Neuroprotective Agents; C507703:NQO1 protein, rat; D010100:Oxygen; D051057:Proto-Oncogene Proteins c-akt; D051267:NF-E2-Related Factor 2
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