A sesquiterpene lactone, costunolide, from Magnolia grandiflora inhibits NF-κB by targeting IκB phosphorylation

A sesquiterpene lactone, costunolide (CTN), was identified from Magnolia grandiflora together with parthenolide (PTN) by its strong inhibition of LPS-induced NF-kappaB activation. CTN, which showed more potent inhibition than PTN in the NF kappaB 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 kappaB as well as the LPS-induced degradation of I kappaB-alpha and -beta. Furthermore, CTN inhibited LPS-induced phosphorylation of I kappaB-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-kappaB.