A Sesquiterpene Lactone, Costunolide, from Magnolia grandiflora Inhibits NF-κB by Targeting IκB Phosphorylation

Abstract A sesquiterpene lactone, costunolide (CTN), was identified from MAGNOLIA GRANDIFLORA together with parthenolide (PTN) by its strong inhibition of LPS-induced NF-κB activation. CTN, which showed more potent inhibition than PTN in the NF-κB 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-κB as well as the LPS-induced degradation of IκB-α and -β. Furthermore, CTN inhibited LPS-induced phosphorylation of IκB-α. These findings support that CTN inhibits NO production by down-regulating iNOS expression, at least, in part through the inhibition of IκBs' phosphorylation and degradation, which are essential for the activation of NF-κB.