Cinnamophilin reduces oxidative damage and protects against transient focal cerebral ischemia in mice.
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.
Lee
E-Jian
EJ
Neurophysiology Laboratory, Neurosurgical Service, Department of Surgery & Institute of Biomedical Engineering, National Cheng Kung University Medical Center and Medical School, Tainan, Taiwan.
Chen
Hung-Yi
HY
Lee
Ming-Yang
MY
Chen
Tsung-Ying
TY
Hsu
Yun-Shang
YS
Hu
Yu-Ling
YL
Chang
Guan-Liang
GL
Wu
Tian-Shung
TS
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D017705:Lignans / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000517:prevention & control; D013997:Time Factors
D000975:Antioxidants; D016166:Free Radical Scavengers; D017705:Lignans; D017382:Reactive Oxygen Species; C088121:cinnamophilin; D006139:Guaiacol