title: 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.
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Shimei
authors.initials: S
authors.lastname: Qi
authors.forename: Yinqiang
authors.initials: Y
authors.lastname: Xin
authors.forename: Yingtao
authors.initials: Y
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Diao
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Kou
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D009573:Nitrites / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C106407:ampelopsin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone