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

Abstract

BackgroundKainic 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.MethodsRodents (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.ResultsTreatment 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.ConclusionsTaken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

Sesamin attenuates neurotoxicity in mouse model of ischemic brain stroke

“…In line of these results, our data show that MCAO increased COX-2 levels in brain tissue and SES treatment reduced COX-2 levels in MCAO animals following SES treatment. These results support previous studies that reported suppressive effect of SES on COX-2 level in different experimental models (Chiang et al, 2014;Hsieh et al, 2011). Post-ischemic inflammation is triggered by activation of pro-inflammatory genes such as tumor necrosis factor (TNF-a) and interleukin (IL-6), promoting accumulation of neutrophils, macrophages and activated microglia at the site of injury (Tang et al, 2014).…”

“…Sesamin (SES) is one of the most abundant ligand in sesame seeds (Phitak et al, 2012). It has been shown to exhibit multiple biological functions, such as inhibition of inflammation (Lin et al, 2014), carcinogenesis (Deng et al, 2013) and oxidative stress (Hsieh et al, 2011). In addition, sesamin has been reported to attenuate hypertension (Matsumura et al, 1995), serum and hepatic cholesterol (Hirata et al, 1996), serum triglycerides (Fukuda et al, 1998), cerebral thrombogenesis (Noguchi et al, 2004), and neuroinflammation (Bournival et al, 2012b).…”

Anti-Colitic Effects of Kanjangs (Fermented Soy Sauce and Sesame Sauce) in Dextran Sulfate Sodium-Induced Colitis in Mice

“…55 In addition, genistein, daidzein, and sesamin reduce COX-2 activity in vitro. [57][58][59] Based on these results, we suggest that fermented sauces have anti-inflammatory effects on DSS-induced UC.…”

Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase

“…Celecoxib, a selective COX-2 inhibitor, could attenuate neuronal death in the hippocampus 16. In another study, COX-2 inhibition ameliorated brain injury and oxidative stress in kainic acid model of SE 17. However, the possible anticonvulsive effects of licofelone on SE has not been yet investigated.…”