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Ampelopsin reduces endotoxic inflammation via repressing ROS-mediated activation of PI3K/Akt/NF-κB signaling pathways.

Abstract：

:Ampelopsin (AMP), a plant flavonoid, has potent anti-inflammatory properties in vitro and in vivo. The molecular mechanisms of ampelopsin on pharmacological and biochemical actions of RAW264.7 macrophages in inflammation have not been clearly elucidated yet. In the present study, non-cytotoxic level of ampelopsin significantly inhibited the release of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in a dose-dependent manner. Consistent with NO inhibition, ampelopsin suppressed lipopolysaccharide (LPS)-induced expression of inducible NO synthase (iNOS) by inhibiting nuclear factor κB (NF-κB) activation, which highly correlated with its inhibitory effect on IκB kinase (IKK) phosphorylation, IκB phosphorylation and NF-κB nuclear translocation. Further study demonstrated that ampelopsin suppressed LPS-induced activation of Akt without effecting mitogen-activated protein kinases (MAPKs) phosphorylation. A pharmacological inhibitor of the phosphoinositide 3-kinase (PI3K)-Akt pathway, LY294002, abrogated IKK/IκB/NF-κB-mediated iNOS gene expression. Finally, we certificated that ampelopsin reduced reactive oxygen species (ROS) accumulation and an anti-oxidant N-acetyl-L-cysteine (NAC) significantly repressed LPS-induced PI3K/Akt phosphorylation and the downstream IKK/IκB activation. NAC thereby inhibited LPS-induced iNOS expression and NO production. The present results suggest that the anti-inflammatory effect of ampelopsin is due to inhibiting the interconnected ROS/Akt/IKK/NF-κB signaling pathways.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Qi S,Xin Y,Guo Y,Diao Y,Kou X,Luo L,Yin Z

doi

10.1016/j.intimp.2011.12.001

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

278-87

issue

1

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(11)00463-2

journal_volume

12

pub_type

杂志文章

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