Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Methyl p-Hydroxycinnamate Suppresses Lipopolysaccharide-Induced Inflammatory Responses through Akt Phosphorylation 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) ;
  • Shin, Seung-Yeon (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kwon, Jae-Hyun (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 : 2013.11.11
  • Accepted : 2013.12.20
  • Published : 2014.01.31
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Abstract

Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited 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. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-$1{\beta}$ and TNF-${\alpha}$. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-${\kappa}B$ in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.

Keywords

References

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