title: 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.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Van Anh
authors.initials: VA
authors.lastname: Vo
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Seung-Yeon
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701 ; Department of Radiology, Dongguk University Ilsan Hospital, Ilsan 410-773, Republic of Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
keywords: COX-2; Lipopolysaccharide; Methyl p-hydroxycinnamate; NF-κB; RAW 264.7 cells; iNOS