A sesquiterpene lactone, costunolide, from Magnolia grandiflora inhibits NF-kappa B by targeting I kappa B phosphorylation.
A sesquiterpene lactone, costunolide (CTN), was identified from Magnolia grandiflora together with parthenolide (PTN) by its strong inhibition of LPS-induced NF-kappa B activation. CTN, which showed more potent inhibition than PTN in the NF-kappa B activation, strongly suppressed nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. RT-PCR and Western blot analyses demonstrated that CTN suppressed the expression of iNOS mRNA and protein in a dose-dependent manner. CTN also significantly inhibited LPS-induced DNA-binding activity of NF-kappa B as well as the LPS-induced degradation of I kappa B-alpha and -beta. Furthermore, CTN inhibited LPS-induced phosphorylation of I kappa B-alpha. These findings support that CTN inhibits NO production by down-regulating iNOS expression, at least, in part through the inhibition of I kappa Bs' phosphorylation and degradation, which are essential for the activation of NF-kappa B.
Koo
T H
TH
Anti-Cancer Agent Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea.
Lee
J H
JH
Park
Y J
YJ
Hong
Y S
YS
Kim
H S
HS
Kim
K W
KW
Lee
J J
JJ
D000818:Animals; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D012717:Sesquiterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D007783:Lactones
D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D012717:Sesquiterpenes; C002669:parthenolide; C002602:costunolide; D007783:Lactones; C496317:Nos2 protein, mouse