A sesquiterpene, dehydrocostus lactone, inhibits the expression of inducible nitric oxide synthase and TNF-alpha in LPS-activated macrophages.
Nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) are the major mediators produced in activated macrophages which contribute to the circulatory failure associated with septic shock. A sesquiterpene lactone compound (dehydrocostus lactone) isolated from the medicinal plant, Saussurea lappa, inhibited the production of NO in lipopolysaccharide (LPS)-activated RAW 264.7 cells by suppressing inducible nitric oxide synthase enzyme expression. This compound also decreased the TNF-alpha level in LPS-activated systems in vitro and in vivo. Thus, dehydrocostus lactone may be a possible candidate for the development of new drugs to treat endotoxemia accompanied by the overproduction of NO and TNF-alpha.
Lee
H J
HJ
College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
Kim
N Y
NY
Jang
M K
MK
Son
H J
HJ
Kim
K M
KM
Sohn
D H
DH
Lee
S H
SH
Ryu
J H
JH
D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D012717:Sesquiterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D007783:Lactones; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C083030:dehydrocostus lactone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse