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Phosphorylation of Akt Mediates Anti-Inflammatory Activity of 1-p-Coumaroyl ${\beta}$-D-Glucoside Against Lipopolysaccharide-Induced Inflammation in RAW264.7 Cells

  • Vo, Van Anh (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Lee, Jae-Won (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kim, Ji-Young (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Park, Jun-Ho (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Lee, Hee Jae (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kim, Sung-Soo (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kwon, Yong-Soo (College of Pharmacy, Kangwon National University) ;
  • Chun, Wanjoo (Department of Pharmacology, College of Medicine, Kangwon National University)
  • Received : 2013.11.20
  • Accepted : 2013.12.31
  • Published : 2014.02.28

Abstract

Hydroxycinnamic acids have been reported to possess numerous pharmacological activities such as antioxidant, anti-inflammatory, and anti-tumor properties. However, the biological activity of 1-p-coumaroyl ${\beta}$-D-glucoside (CG), a glucose ester derivative of p-coumaric acid, has not been clearly examined. The objective of this study is to elucidate the anti-inflammatory action of CG in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In the present study, CG significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. CG also inhibited LPS-induced secretion of pro-inflammatory cytokines, IL-$1{\beta}$ and TNF-${\alpha}$. In addition, CG significantly suppressed LPS-induced degradation of $I{\kappa}B$. To elucidate the underlying mechanism by which CG exerts its anti-inflammatory action, involvement of various signaling pathways were examined. CG exhibited significantly increased Akt phosphorylation in a concentration-dependent manner, although MAPKs such as Erk, JNK, and p38 appeared not to be involved. Furthermore, inhibition of Akt/PI3K signaling pathway with wortmannin significantly, albeit not completely, abolished CG-induced Akt phosphorylation and anti-inflammatory actions. Taken together, the present study demonstrates that Akt signaling pathway might play a major role in CG-mediated anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells.

Keywords

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