title: Phosphorylation of Akt Mediates Anti-Inflammatory Activity of 1-p-Coumaroyl β-D-Glucoside Against Lipopolysaccharide-Induced Inflammation in RAW264.7 Cells.
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 β-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 RAW264.7 macrophage cells. In the present study, CG significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein expression of iNOS and COX-2. CG also inhibited LPS-induced secretion of pro-inflammatory cytokines, IL-1β and TNF-α. In addition, CG significantly suppressed LPS-induced degradation of IκB. 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.
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Van Anh
authors.initials: VA
authors.lastname: Vo
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
keywords: 1-p-coumaroyl β-D-glucoside (CG); Akt; COX-2; Lipopolysaccharide; NF-κB; RAW264.7 cells; iNOS