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标题：4-Hydroxykobusin Inhibits the Induction of Nitric Oxide Synthase by Inhibiting NF-κB and AP-1 Activation
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作者：Yuba Raj Pokharel ; Qing-He Liu ; Jae Wook Oh 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：6
页码：1097-1101
DOI：10.1248/bpb.30.1097
出版社：The Pharmaceutical Society of Japan
摘要：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 −1.59 kb 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.
关键词：4-hydroxykobusin;activator protein-1 (AP-1);Geranium thunbergii;inducible nitric oxide synthase (iNOS);nuclear factor-κB (NF-κB);nitric oxide