Saucerneol D, a naturally occurring sesquilignan, inhibits LPS-induced iNOS expression in RAW264.7 cells by blocking NF-kappaB and MAPK activation.
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.
Moon
Tae Chul
TC
Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Canada AB T6G 252.
Kim
Jin Cheul
JC
Song
Seung-Eun
SE
Suh
Seok-Jong
SJ
Seo
Chang-Seob
CS
Kim
Youn Kyung
YK
Jin
Meihua
M
Yang
Ju Hye
JH
Son
Jong-Keun
JK
Jahng
Yurngdong
Y
Kim
Cheorl-Ho
CH
Chang
Hyeun Wook
HW
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*
D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases