4-Hydroxykobusin Inhibits the Induction of Nitric Oxide Synthase by Inhibiting NF-κB and AP-1 Activation(Pharmacology)

概要

論文の詳細を見る
We recently isolated a novel lignan, 4-hydroxykobusin from Geranium thunbergii (Liu et al., Arch. Pharm. Res., 29, 1109-1113, 2006). Here, we studied its effect on the expression of inducible nitric oxide synthase (iNOS) gene in RAW264.7 cells. 4-Hydroxykobusin inhibited nitric oxide (NO) production in a concentration-dependent manner and blocked the lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS). To identify the mechanistic basis for its inhibition of iNOS induction, we examined the effect of 4-hydroxykobusin on the transactivation of iNOS gene by luciferase reporter activity using -1.59kb flanking region. The lignan suppressed the reporter gene activity and the LPS-induced reporter activations of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) were also significantly blocked by 4-hydroxykobusin. These findings suggest that the inhibition of LPS-induced NO formation by 4-hydroxykobusin is due to its inhibition of NF-κB and AP-1 activation.
公益社団法人日本薬学会の論文
2007-06-01