Cinnamophilin reduces oxidative damage and protects against transient focal cerebral ischemia in mice.

Abstract

Acute neuroprotective effects of cinnamophilin (CINN; (8R, 8'S)-4, 4'-dihydroxy-3, 3'-dimethoxy-7-oxo-8, 8'-neolignan), a novel antioxidant and free radical scavenger, were studied in a mouse model of transient middle cerebral artery (MCA) occlusion. CINN was administered intraperitoneally either 15 min before (pretreatment) or 2 h after the onset of MCA occlusion (postischemic treatment). Relative to vehicle-treated controls, animals pretreated with CINN, at 20-80 mg/kg, had significant reductions in brain infarction by 33-46% and improvements in neurobehavioral outcome. Postischemic administration with CINN (80 mg/kg) also significantly reduced brain infarction by 43% and ameliorated neurobehavioral deficits. Additionally, CINN administration significantly attenuated in situ accumulation of superoxide anions (O2-) in the boundary zones of infarct at 4 h after reperfusion. Consequently, CINN-treated animals exhibited significantly decreased levels of oxidative damage, as assessed by immunopositive reactions for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE), and the resultant inflammatory reactions at 24 h post-insult. It is concluded that CINN effectively reduced brain infarction and improved neurobehavioral outcome following a short-term recovery period after severe transient focal cerebral ischemia in mice. The finding of a decreased extent of reactive oxygen species and oxidative damage observed with CINN treatment highlights that its antioxidant and radical scavenging ability is contributory.

• Authors: E-Jian Lee, Hung-Yi Chen, Ming-Yang Lee, Tsung-Ying Chen, Yun-Shang Hsu, Yu-Ling Hu, Guan-Liang Chang, Tian-Shung Wu
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 39 Issue 4 Pg. 495-510 (Aug 15 2005) ISSN: 0891-5849 [Print] United States
• PMID: 16043021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Free Radical Scavengers
• Lignans
• Reactive Oxygen Species
• cinnamophilin
• Guaiacol

Topics

• Animals
• Antioxidants (therapeutic use)
• Brain Ischemia (drug therapy, prevention & control)
• Cerebral Cortex (blood supply)
• Cerebrovascular Circulation (drug effects)
• Free Radical Scavengers (therapeutic use)
• Guaiacol (analogs & derivatives, therapeutic use)
• Infarction, Middle Cerebral Artery (physiopathology)
• Lignans (therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (antagonists & inhibitors)
• Reperfusion Injury (prevention & control)
• Time Factors