Methyleugenol reduces cerebral ischemic injury by suppression of oxidative injury and inflammation

Abstract

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.

Keywords::

• Methyleugenol
• ischemic injury
• OGD
• ROS
• NO

Declaration of interest: This study was supported by a grant (#2009K001250 to W.-K. Kim) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology and a grant from the Oriental Medicine R&D Project (B080027 to W.-K. Kim) of the Ministry for Health, Welfare and Family Affairs, Republic of Korea.