Methyl p-Hydroxycinnamate Suppresses Lipopolysaccharide-Induced Inflammatory Responses through Akt Phosphorylation in RAW264.7 Cells.

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-1β and TNF-α. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-κB 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.

• Authors: Van Anh Vo, Jae-Won Lee, Seung-Yeon Shin, Jae-Hyun Kwon, Hee Jae Lee, Sung-Soo Kim, Yong-Soo Kwon, Wanjoo Chun
• Journal: Biomolecules & therapeutics (Biomol Ther (Seoul)) Vol. 22 Issue 1 Pg. 10-6 (Jan 2014) ISSN: 1976-9148 [Print] Korea (South)
• PMID: 24596616 (Publication Type: Journal Article)