Methyleugenol reduces cerebral ischemic injury by suppression of oxidative injury and inflammation.
The present study tested the cytoprotective effect of methyleugenol in an in vivo ischemia model (i.e. middle cerebral artery occlusion (MCAO) for 1.5 h and subsequent reperfusion for 24 h) and further investigated its mechanism of action in in vitro cerebral ischemic models. When applied shortly after reperfusion, methyleugenol largely reduced cerebral ischemic injury. Methyleugenol decreased the caspase-3 activation and death of cultured cerebral cortical neurons caused by oxygen-glucose deprivation (OGD) for 1 h and subsequent re-oxygenation for 24 h. Methyleugenol markedly reduced superoxide generation in the ischemic brain and decreased the intracellular oxidative stress caused by OGD/re-oxygenation. It was found that methyleugenol elevated the activities of superoxide dismutase and catalase. Further, methyleugenol inhibited the production of nitric oxide and decreased the protein expression of inducible nitric oxide synthase. Methyleugenol down-regulated the production of pro-inflammatory cytokines in the ischemic brain as well as in immunostimulated mixed glial cells. The results indicate that methyleugenol could be useful for the treatment of ischemia/inflammation-related diseases.
Choi
Yoo Keum
YK
College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Cho
Geum-Sil
GS
Hwang
Sunyoung
S
Kim
Byung Woo
BW
Lim
Ji H
JH
Lee
Jae-Chul
JC
Kim
Hyoung Chun
HC
Kim
Won-Ki
WK
Kim
Yeong Sik
YS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005609:Free Radicals / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D009474:Neurons / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000276:immunology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005609:Free Radicals; D013481:Superoxides; C005223:methyleugenol; D005054:Eugenol; D005947:Glucose; D010100:Oxygen