Journal
PHARMACOLOGICAL RESEARCH
Volume 51, Issue 6, Pages 539-546Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2005.02.002
Keywords
amentoflavone; I-kappa B alpha; iNOS; nitric oxide; NF-kappa B
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Amentoflavone is a bi-flavonoid compound with anti-fungal and anti-inflammatory activities. We isolated amentoflavone from Selaginella tamariscina (Selaginellaceae) and studied its effects on nuclear factor-kappa B (NF-kappa B)-mediated inducible nitric oxide synthase (iNOS) gene expression in RAW 264.7 cells. Amentoflavone inhibited the production of nitric oxide in a concentration-dependent manner and also blocked the lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS). To clarify the mechanistic basis for its inhibition of iNOS induction, we examined the effect of amentoflavone on the transactivation of iNOS gene by luciferase reporter activity using - 1.59 kb flanking region. Amentoflavone potently suppressed the reporter gene activity. The LPS-induced activation of NF-kappa B was also found to be significantly blocked by amentoflavone, but APA activation was unaffected. Furthermore, the nuclear translocation of p65 by LPS was inhibited by amentoflavone. NF-kappa B activation is controlled by the phosphorylation and subsequent degradation of I-kappa B alpha, and the cytosolic degradation of I-kappa B alpha was found to be inhibited by amentoflavone. These findings suggest that the inhibition of LPS-induced NO formation by amentoflavone is due to its inhibition of NF-kappa B by blocking I-kappa B alpha degradation, which may be the mechanistic basis of the anti-inflammatory effects of amentoflavone. (c) 2005 Elsevier Ltd. All rights reserved.
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