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Therapeutic window for cinnamophilin following oxygen-glucose deprivation and transient focal cerebral ischemia.

Abstract：

:Cinnamophilin (CINN, (8R, 8'S)-4, 4'-dihydroxy-3, 3'-dimethoxy-7-oxo-8, 8'-neolignan) protects against ischemic stroke in mice. While some anti-oxidative effects of CINN have been characterized, its therapeutic window and molecular basis for neuroprotection remain unclear. We evaluated antioxidant and anti-inflammatory properties and therapeutic window of CINN against brain ischemia using a panel of in vitro and in vivo assays. Data from lipid peroxidation and radical scavenging assays showed that CINN was a robust antioxidant and radical scavenger. CINN effectively inhibited the production of tumor necrosis factor alpha (TNF-alpha), nitrite/nitrate, interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 and BV2 cells (P<0.05, respectively). Relative to controls, CINN, administrated at 80 mg/kg, 2, 4, or 6 h postinsult, but not 12 h, significantly reduced brain infarction by 34-43% (P<0.05) and improved neurobehavioral outcome (P<0.05) following transient focal cerebral ischemia in rats. CINN (10-30 microM) also significantly reduced oxygen-glucose deprivation-induced neuronal damage (P<0.05) in rat organotypic hippocampal slices, even when it was administrated 2, 4, or 6 h postinsult. Together, CINN protects against ischemic brain damage with a therapeutic window up to 6 h in vivo and in vitro, which may, at least in part, be attributed by its direct antioxidant and anti-inflammatory effects.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Lee EJ,Chen HY,Hung YC,Chen TY,Lee MY,Yu SC,Chen YH,Chuang IC,Wu TS

doi

10.1016/j.expneurol.2009.01.019

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

74-83

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(09)00021-1

journal_volume

217

pub_type

杂志文章

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