title: Saucerneol D, a naturally occurring sesquilignan, inhibits LPS-induced iNOS expression in RAW264.7 cells by blocking NF-kappaB and MAPK activation.
abstract: We evaluated the ability of saucerneol D (SD), a tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, to regulate the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells. SD consistently inhibited nitric oxide (NO) production in a dose-dependent manner, with an IC(50) of 2.62 microM, and also blocked LPS-induced iNOS expression. SD potently suppressed both the reporter gene expression and DNA-binding activity of nuclear factor-kappaB (NF-kappaB). In addition, SD inhibited IkappaB-alpha degradation in a concentration- and time-dependent manner. SD also inhibited LPS-induced activation of various mitogen-activated protein kinases, including extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). These findings suggest that SD may inhibit LPS-induced iNOS expression by blocking NF-kappaB and MAPK activation.
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Canada AB T6G 252.
authors.forename: Tae Chul
authors.initials: TC
authors.lastname: Moon
authors.forename: Jin Cheul
authors.initials: JC
authors.lastname: Kim
authors.forename: Seung-Eun
authors.initials: SE
authors.lastname: Song
authors.forename: Seok-Jong
authors.initials: SJ
authors.lastname: Suh
authors.forename: Chang-Seob
authors.initials: CS
authors.lastname: Seo
authors.forename: Youn Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Meihua
authors.initials: M
authors.lastname: Jin
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Yang
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Yurngdong
authors.initials: Y
authors.lastname: Jahng
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D017705:Lignans / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*
chemical_list: D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases