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 mu M) 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. (C) 2009 Elsevier Inc, All rights reserved.
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Xuzhou Med Coll, Res Ctr Biochem & Mol Biol, Xuzhou 221002, Jiangsu, Peoples R China
Xuzhou Med Coll, Jiangsu Key Lab Brain Dis Bioinformat, Xuzhou 221002, Jiangsu, Peoples R ChinaXuzhou Med Coll, Res Ctr Biochem & Mol Biol, Xuzhou 221002, Jiangsu, Peoples R China
Yu, Chang-Zhou
Li, Chong
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Xuzhou Med Coll, Res Ctr Biochem & Mol Biol, Xuzhou 221002, Jiangsu, Peoples R China
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Li, Chong
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Pei, Dong-Sheng
Zong, Yan-Yan
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Hang, Dong
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Hang, Dong
Hou, Xiao-Yu
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Zhang, Guang-Yi
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