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

E. Jian Lee, Hung Yi Chen, Yu Chang Hung, Tsung Ying Chen, Ming Yang Lee, Shu Ching Yu, Ying Hsin Chen, I. Chuan Chuang, Tian Shung Wu

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

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-α), 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 μM) 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.

Original languageEnglish
Pages (from-to)74-83
Number of pages10
JournalExperimental Neurology
Volume217
Issue number1
DOIs
Publication statusPublished - 2009 May

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

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