Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation

Journal of Neuroinflammation

Kee-Ching Jeng²  Ming-Hong Chang³  Ya-Yun Chao³  Ching-Huei Lin³  Mei-Lin Shen³  Yu-Fen Peng⁴  Szu-Pei Wu⁴  Pei-Wun Yao⁴  Chien-Wei Hou⁴  Peiyuan F Hsieh¹ 

[1] Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Nantou, Taiwan;Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan;Division of Neurology, Taichung Veterans General Hospital, Taichung, Taiwan;Department of Biotechnology, Yuanpei University, Hsinchu, Taiwan

关键词: COX-2;    mitogen-activated protein kinases;    superoxide dismutase;    nitric acid;    thiobarbituric acid reactive substances;    reactive oxygen species;    kainic acid;    sesamin;    BV-2 cells;    PC12 cells;    Status epilepticus;   

Others  :  1213336
DOI  :  10.1186/1742-2094-8-57

 received in 2010-12-14, accepted in 2011-05-24,  发布年份 2011

【 摘 要 】

Background

Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied.

Methods

Rodents (male FVB mice and Sprague-Dawley rats) were fed with sesamin extract (90% of sesamin and 10% sesamolin), 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA), neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12 cells and microglial BV-2 cells.

Results

Treatment with sesamin extract (30 mg/kg) significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA) from 145% to 117% (p = 0.017) and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p = 0.013). The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca²⁺, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE₂ production from both cells under KA-stimulation.

Conclusions

Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

【 授权许可】

   
2011 Hsieh et al; licensee BioMed Central Ltd.

【 图 表 】

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