Methyl p-Hydroxycinnamate Suppresses Lipopolysaccharide-Induced Inflammatory Responses through Akt Phosphorylation in RAW264.7 Cells.
- Author:
Van Anh VO
1
;
Jae Won LEE
;
Seung Yeon SHIN
;
Jae Hyun KWON
;
Hee Jae LEE
;
Sung Soo KIM
;
Yong Soo KWON
;
Wanjoo CHUN
Author Information
1. Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Republic of Korea. wchun@kangwon.ac.kr
- Publication Type:Original Article
- Keywords:
Methyl p-hydroxycinnamate;
RAW 264.7 cells;
Lipopolysaccharide;
iNOS;
COX-2;
NF-kappaB
- MeSH:
Cytokines;
Cytoplasm;
Dinoprostone;
Macrophages;
Neuroprotective Agents;
NF-kappa B;
Nitric Oxide;
Phosphorylation*;
Tumor Necrosis Factor-alpha
- From:Biomolecules & Therapeutics
2014;22(1):10-16
- CountryRepublic of Korea
- Language:English
-
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 PGE2 and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-1beta and TNF-alpha. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of IkappaB, which retains NF-kappaB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-kappaB 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.
