Polyphenol amentoflavone affords neuroprotection against neonatal hypoxic-ischemic brain damage via multiple mechanisms

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

Research output: Contribution to journalArticle

58 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)561-572
Number of pages12
JournalJournal of Neurochemistry
Volume96
Issue number2
DOIs
Publication statusPublished - 2006 Jan 1
Externally publishedYes

Keywords

  • Apoptosis
  • Flavonoids
  • Hypoxia
  • Ischemia
  • Necrosis
  • Neuroprotection

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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