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Inhibitory effect of naringin on lipopolysaccharide (LPS)-induced endotoxin shock in mice and nitric oxide production in RAW 264.7 macrophages.

Abstract：

:Lipopolysaccharide (LPS) has been known to induce endotoxin shock via production of inflammatory modulators such as tumor necrosis factor alpha (TNF-alpha), or nitric oxide (NO). In this study, we have examined the effect of naringin (NG), one of the flavonoids, on LPS-induced endotoxin shock in mice and NO production in RAW 264.7 macrophages. For intraperitoneal (i.p., 20 mg/kg) injection of LPS at 48 h, the survival rate of mice administered with LPS alone (n=10) or pretreated with NG at 10, 30 and 60 mg/kg (i.p.) group (n=10) was 0% or 10%, 50% and 70%, respectively. NG dose-dependently suppressed LPS-induced production of TNF-alpha. LPS-induced production of NO at 6 h (125.89+/-16.35 microM), as measured by nitrite formation, was significantly reduced by NG at 30 or 60 mg/kg for 49.49+/-4.81 or 27.91+/-1.81 microM (P<0.01 vs. LPS alone), respectively. To further examine the mechanism by which NG suppresses LPS-induced endotoxin shock, we used an in vitro model, RAW 264.7 mouse macrophage cells. NG (1 mM) suppressed LPS (0.01, 0.1 or 1 microg/ml)-induced production of NO and the expression of inflammatory gene products such as inducible NO synthase (iNOS), TNF-alpha, inducible cyclooxygenase (COX-2) and interleukin-6 (IL-6) as determined by RT-PCR assay. NG was found to have blocked the LPS-induced transcriptional activity of NF-kappaB in electrophoretic mobility shift assay and reporter assay. These findings suggest that suppression of the LPS-induced mortality and production of NO by NG is due to inhibition of the activation of NF-kappaB.

journal_name

Life Sci

journal_title

Life sciences

authors

Kanno S,Shouji A,Tomizawa A,Hiura T,Osanai Y,Ujibe M,Obara Y,Nakahata N,Ishikawa M

doi

10.1016/j.lfs.2005.04.051

subject

Has Abstract

pub_date

2006-01-11 00:00:00

pages

673-81

issue

7

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(05)00702-2

journal_volume

78

pub_type

杂志文章

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