Search

Hydroxyhydroquinone or 1,2,4-benzenetriol (BT) detected in the beverages has a structure that coincides with the water-soluble form of a sesame lignan, sesamol. We previously showed that sesame antioxidants had neuroprotective abilities due to their antioxidant properties and/or inducible nitric oxide synthase (iNOS) inhibition. However, studies show that BT can induce DNA damage through the generation of reactive oxygen species (ROS). Therefore, we were interested to investigate the neuroprotective effect of BT in vitro and in vivo. The results showed that instead of enhancing free radical generation, BT dose-dependently (10-100 microM) attenuated nitrite production, iNOS mRNA and protein expression in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. BT significantly reduced LPS-induced NF-kappaB and p38 MAPK activation. It also significantly reduced the generation of ROS in H2O2-induced BV-2 cells and in H2O2-cellfree conditions. The neuroprotective effect of BT was further demonstrated in the focal cerebral ischemia model of Sprague-Dawley rat. Taken together, the inhibition of LPS-induced nitrite production might be due to the suppression of NF-kappaB, p38 MAPK signal pathway and the ROS scavenging effect. These effects might help to protect neurons from the ischemic injury.

The alpha-ketoglutarate dehydrogenase complex (KGDHC) is a mitochondrial enzyme in the TCA cycle. Inhibition of KGDHC activity by alpha-keto-beta-methyl-n-valeric acid (KMV) is associated with neuron death. However, the effect of KMV in microglia is unclear. Therefore, we investigated the effect of KMV on BV-2 microglial cells exposed to hypoxia or oxidative stress. The results showed that KMV (1-20 mM) enhanced the cell viability under hypoxia. KMV dose-dependently reduced ROS and LDH releases from hypoxic BV-2 cells. KMV also reduced ROS production and enhanced the cell viability under H2O2 but failed to reduce the SIN-1 and sodium nitroprusside (SNP) toxicity. KMV also reduced caspase-3 and -9 activation under stress. These results suggest that KMV protects BV-2 cells from stress and acts by reducing ROS production through inhibition of KDGHC.

Reactive oxygen species (ROS) has been proposed to play a pathogenic role in neuronal injury. Sesame antioxidants that inhibit lipid peroxidation and regulate cytokine production may suppress ROS generation. In this study, we focused on the effect of sesamolin on H2O2-induced neurotoxicity and ROS production in the murine microglial cell line BV-2. Results indicate that the H2O2 elicited BV-2 cell death in a concentration- and time-dependent manner. ROS generation in BV-2 cells was time-dependently increased by the H2O2 treatment. Sesamolin reduced ROS generation in BV-2 cells. p38 mitogen-activated protein kinase (MAPK) and caspase-3 were also activated in BV-2 cells under H2O2 stress. Sesamolin was able to inhibit H2O2-induced p38 MAPK and caspase-3 activation and cell death. In addition, sesamolin preserved superoxide dismutase and catalase activities in BV-2 cells under H2O2 stress. In conclusion, sesamolin protects microglia against H2O2-induced cell injury and this protective effect was accompanied by its inhibition of p38 MAPK and caspase-3 activation and ROS production.

Sesamin and sesamolin were tested for their ability to protect BV-2 microglia from hypoxia-induced cell death. These antioxidants dose-dependently reduced hypoxia-induced lactate dehydrogenase (LDH) release and dichlorofluorescein (DCF)-sensitive reactive oxygen species (ROS) production. Their effects on signaling pathway mitogen-activated protein kinases (MAPKs) and caspase-3 in hypoxia-induced cell death were further examined. Extracellular signal-regulated protein kinases (ERK1/2), c-jun NH(2)-terminal kinase (JNK), and p38 MAPKs were activated during hypoxia. The sesamin or sesamolin reduced caspase-3 and MAPK activation correlated well with diminished LDH release in BV-2 cells under hypoxia. Furthermore, they preserved superoxide dismutase (SOD) and catalase activities in BV-2 cells under hypoxia. Taken together, these results indicate that the mechanism of sesame antioxidants involves inhibition of MAPK pathways and apoptosis through scavenging of ROS in hypoxia-stressed BV-2 cells.

Sesame antioxidants have been shown to inhibit lipid peroxidation and regulate cytokine production. In this study, we focused on the effect of sesamin and sesamolin, on nitric oxide (NO) induction by lipopolysaccharides (LPS) in the murine microglial cell line BV-2 and rat primary microglia. The results showed that sesamin and sesamolin significantly inhibited NO production, iNOS mRNA and protein expression in LPS-stimulated BV-2 cells. Sesamin or sesamolin significantly reduced LPS-activated p38 MAPK of BV-2 cells. Furthermore, SB203580, a specific inhibitor of p38 MAP kinase, dose-dependently inhibited NO production in LPS-stimulated BV-2 cells. Taken together, the inhibition of NO production might be due to the reduction of LPS-induced p38 MAPK signal pathway by sesamin and sesamolin.