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

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.

• 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
• Journal: Journal of neurochemistry (J Neurochem) Vol. 96 Issue 2 Pg. 561-72 (Jan 2006) ISSN: 0022-3042 [Print] England
• PMID: 16336627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Biflavonoids
• Flavonoids
• Neuroprotective Agents
• Phenols
• Polyphenols
• amentoflavone

Topics

• Animals
• Animals, Newborn
• Anti-Inflammatory Agents (pharmacology)
• Biflavonoids (pharmacology)
• Brain (drug effects, pathology)
• Brain Damage, Chronic (etiology, prevention & control)
• Brain Ischemia (complications, pathology)
• Cells, Cultured
• Flavonoids (pharmacology)
• Humans
• Hypoxia, Brain (complications, pathology)
• Mice
• Microglia (drug effects)
• Neuroprotective Agents (pharmacology)
• Phenols (pharmacology)
• Polyphenols
• Rats
• Rats, Sprague-Dawley