Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 12, Issue 1, Pages 278-287Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2011.12.001
Keywords
Ampelopsin; ROS; Akt; NF-kappa B; RAW264.7 cells
Categories
Funding
- National Nature Science Foundation of China [81072433, 31071000, 81172798]
- Priority Academic Program Development of Jiangsu Higher Education Institutions [164320H106]
Ask authors/readers for more resources
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)-1 beta. IL-6 and tumor necrosis factor (TNF)-alpha in a dose-dependent manner. Consistent with NO inhibition, ampelopsin suppressed lipopolysaccharide (LPS)-induced expression of inducible NO synthase (iNOS) by inhibiting nuclear factor kappa B (NF-kappa B) activation, which highly correlated with its inhibitory effect on I kappa B kinase (IKK) phosphorylation, I kappa B phosphorylation and NF-kappa B 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/I kappa B/NF-kappa B-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/I kappa B 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-kappa B signaling pathways. (C) 2011 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available