TY - JOUR
T1 - Therapeutic window for cinnamophilin following oxygen-glucose deprivation and transient focal cerebral ischemia
AU - Lee, E. Jian
AU - Chen, Hung Yi
AU - Hung, Yu Chang
AU - Chen, Tsung Ying
AU - Lee, Ming Yang
AU - Yu, Shu Ching
AU - Chen, Ying Hsin
AU - Chuang, I. Chuan
AU - Wu, Tian Shung
N1 - Funding Information:
This research was supported by grants from the National Research Institute of Chinese Medicine (NRICM No. 95-002).
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.expneurol.2009.01.019
DO - 10.1016/j.expneurol.2009.01.019
M3 - Article
C2 - 19416670
AN - SCOPUS:64549162354
SN - 0014-4886
VL - 217
SP - 74
EP - 83
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -