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- Title
Polyphenol amentoflavone affords neuroprotection against neonatal hypoxic-ischemic brain damage via multiple mechanisms.
- Authors
Dong Hoon Shin; Young Chul Bae; Jeong Sook Kim-Han; Ji Hyun Lee; In Young Choi; Kun Ho Son; Sam Sik Kang; Won-Ki Kim; Byung Hee Han
- 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.
- Subjects
FLAVONOIDS; BRAIN damage; ANTINEOPLASTIC agents; NEUROBLASTOMA; CELL death; NECROSIS; MICROGLIA
- Publication
Journal of Neurochemistry, 2006, Vol 96, Issue 2, p561
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2005.03582.x