title: Inhibitory effect of sesaminol glucosides on lipopolysaccharide-induced NF-kappaB activation and target gene expression in cultured rat astrocytes.
abstract: The inflammatory reaction plays an important role in the pathogenesis of the neurodegenerative disorder including Alzheimer's disease (AD). Sesame lignan compounds such as sesaminol glucosides (SG) exhibit a range of pharmacological activities including anti-oxidative and anti-inflammatory action. In this study, we tried to elucidate possible effects of SG on lipopolysaccharide (LPS)-induced inflammatory reaction and its underlying mechanism in cultured astrocytes. SG (10-100 microg/ml) inhibited LPS-induced generation of nitric oxide (NO) and reactive oxygen species (ROS), as well as inhibited LPS-induced cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression dose-dependently. This inhibitory effect of SG on NO and ROS generation was enforced by addition of glutathione (GSH) in culture. In addition, SG prevented LPS-induced DNA binding and transcriptional activity of nuclear factor KappaB (NF)-kappaB. Consistent with the inhibitory effect on NF-kappaB activity, SG inhibits phosphorylation and degradation of inhibitory KappaB (IkappaB), thereby translocation of p50 of NF-kappaB. These data show that SG has an anti-inflammatory effect through inhibition of NF-kappaB, and may be a useful agent for prevention of inflammatory disease like AD.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Son
authors.forename: Yong Kyoung
authors.initials: YK
authors.lastname: Lee
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Lee
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Young Won
authors.initials: YW
authors.lastname: Yun
authors.forename: Tae Youl
authors.initials: TY
authors.lastname: Ha
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats
chemical_list: D004149:Dioxoles; D005663:Furans; D005960:Glucosides; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; C066016:sesaminol; D052247:Nitric Oxide Synthase Type II