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Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia

Yang, Chenhui ; Zhang, Xiangjian ; Fan, Hongguang ; Liu, Ying

Brain research, 2009-07, Vol.1282, p.133-141 [Periódico revisado por pares]

Amsterdam: Elsevier B.V

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Título:
Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia
Autor: Yang, Chenhui ; Zhang, Xiangjian ; Fan, Hongguang ; Liu, Ying
Assuntos: Animals ; Biological and medical sciences ; Brain - drug effects ; Brain - metabolism ; Brain - physiopathology ; Brain Edema - drug therapy ; Brain Edema - pathology ; Brain Edema - prevention & control ; Brain Infarction - drug therapy ; Brain Infarction - pathology ; Brain Infarction - prevention & control ; Brain Ischemia - drug therapy ; Brain Ischemia - metabolism ; Brain Ischemia - physiopathology ; Cerebral ischemia ; Curcumin ; Curcumin - pharmacology ; Curcumin - therapeutic use ; Cytoprotection - drug effects ; Cytoprotection - physiology ; Disease Models, Animal ; Enzyme Inhibitors - pharmacology ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - physiology ; Heme Oxygenase-1 - drug effects ; Heme Oxygenase-1 - genetics ; Heme Oxygenase-1 - metabolism ; Infarction, Middle Cerebral Artery - drug therapy ; Infarction, Middle Cerebral Artery - metabolism ; Infarction, Middle Cerebral Artery - physiopathology ; Male ; Medical sciences ; Neurology ; Neuroprotection ; Neuroprotective Agents - pharmacology ; NF-E2-Related Factor 2 - drug effects ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; Nuclear factor erythroid 2-related factor 2(Nrf2) ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger - analysis ; RNA, Messenger - metabolism ; Time Factors ; Up-Regulation - drug effects ; Up-Regulation - physiology ; Vascular diseases and vascular malformations of the nervous system
É parte de: Brain research, 2009-07, Vol.1282, p.133-141
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Descrição: Abstract Background: Oxidative and cytotoxic damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Curcumin is proved to elicit a vanity of biological effects through its antioxidant and anti-inflammatory properties. But the mechanisms underlying are poorly understood. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates expression of genes required for free radical scavenging, detoxification of xenobiotics, and maintenance of redox potential. This study evaluated the time course expression regularity of Nrf2, HO-1 and the curcumin's role in cerebral ischemia and its potential mechanism. Methods: Male, Sprague–Dawley rats were subjected to permanent focal cerebral ischemia by right MCA occlusion. Experiment 1 was used to evaluate the expression of Nrf2 and HO-1 in the cerebral ischemia, 6 time points was included. Experiment 2 was used to detect curcumin's neuroprotection in cerebral ischemia. At 24 h neurological deficit was evaluated using a modified six point scale; brain water content was measured; infarct size was analysed with 2, 3, 5-triphenyltetrazolium chloride (TTC). Immunohistochemistry, RT-PCR, Western blot, and confocal microscope were used to analyse the expression of Nrf2 and HO-1. Results: Compared with sham-operated, Nrf2 and HO-1 were upregulated at gene and protein level in ischemic brain, beginning at 3 h and peaking at 24 h after MCAO ( P < 0.05). Curcumin high dose (100 mg/kg) upregulated Nrf2 and HO-1 in MCAO-affected brain tissue and reduced infarct volume ( P < 0.05), brain water content ( P < 0.05) and behavioral deficits ( P < 0.05) caused by MCAO. Conclusions: Nrf2 and HO-1 were induced at the early stage after MCAO. Curcumin protected the brain from damage caused by MCAO, this effect may be through upregulation of the transcription factor Nrf2 expression. Nrf2 may be one of the strategic targets for cerebral ischemic therapies.
Editor: Amsterdam: Elsevier B.V
Idioma: Inglês

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Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia

Yang, Chenhui ; Zhang, Xiangjian ; Fan, Hongguang ; Liu, Ying

Amsterdam: Elsevier B.V

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