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Polyphenol amentoflavone affords neuroprotection against neonatal hypoxic-ischemic brain damage via multiple mechanisms
- Title
- Polyphenol amentoflavone affords neuroprotection against neonatal hypoxic-ischemic brain damage via multiple mechanisms
- Authors
- Shin D.H.; Bae Y.C.; Kim-Han J.S.; Lee J.H.; Choi I.Y.; Son K.H.; Kang S.S.; Kim W.-K.; Han B.H.
- Ewha Authors
- 김원기
- SCOPUS Author ID
- 김원기
- Issue Date
- 2006
- Journal Title
- Journal of Neurochemistry
- ISSN
- 0022-3042
- Citation
- Journal of Neurochemistry vol. 96, no. 2, pp. 561 - 572
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Flavonoids are naturally occurring polyphenolic compounds that have many biological properties, including antioxidative, anti-inflammatory and neuroprotective effects. Here, we report that amentoflavone significantly reduced cell death induced by staurosporine, etoposide and sodium nitroprusside in neuroblastoma SH-SY5Y cells. In post-natal day 7 rats, hypoxic-ischemic (H-I) brain damage induced by unilateral carotid ligation and hypoxia resulted in distinct features of neuronal cell death including apoptosis and necrosis. In this model, a systemic administration of amentoflavone (30 mg/kg) markedly reduced the H-I-induced brain tissue loss with a wide therapeutic time window up to 6 h after the onset of hypoxia. Amentoflavone blocked the activation of caspase 3, characteristic of apoptosis, and the proteolytic cleavage of its substrates following H-I injury. Amentoflavone also reduced the excitotoxic/necrotic cell death after H-I injury in vivo and after oxygen/glucose deprivation in mouse mixed cultures in vitro. Treatment of mouse microglial cells with amentoflavone resulted in a significant decrease in the lipopolysaccharide-induced production of nitric oxide and induction of inducible nitric oxide synthase and cyclo-oxygenase-2. Furthermore, amentoflavone decreased the inflammatory activation of microglia after H-I injury when assessed by the microglial-specific marker OX-42. These data demonstrate for the first time that amentoflavone strongly protects the neonatal brain from H-I injury by blocking multiple cellular events leading to brain damage. © 2005 International Society for Neurochemistry.
- DOI
- 10.1111/j.1471-4159.2005.03582.x
- Appears in Collections:
- 자연과학대학 > 화학·나노과학전공 > Journal papers
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