Inhibitory effect of sesaminol glucosides on lipopolysaccharide-induced NF-kappaB activation and target gene expression in cultured rat astrocytes.
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.
Lee
Sun Young
SY
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Son
Dong Ju
DJ
Lee
Yong Kyoung
YK
Lee
Jae Woong
JW
Lee
Hwa Jung
HJ
Yun
Young Won
YW
Ha
Tae Youl
TY
Hong
Jin Tae
JT
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
D004149:Dioxoles; D005663:Furans; D005960:Glucosides; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; C066016:sesaminol; D052247:Nitric Oxide Synthase Type II