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Ethyl caffeate suppresses NF‐κB activation and its downstream inflammatory mediators, iNOS, COX‐2, and PGE2in vitro or in mouse skin

2005/07/25 by Yi‐Ming Chiang, Chiu‐Ping Lo, Yiping Chen +5 · 27 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Biochemistry #Biology #Chemistry #Enzyme #Genomics, phytochemicals, and oxidative stress #Kinase #Molecular biology #NF-κB #NF-κB Signaling Pathways #Natural product bioactivities and synthesis #Nitric oxide #Nitric oxide synthase #Pharmacology #Phosphorylation #Signal transduction

paper · pdf · doi:10.1038/sj.bjp.0706343

openalex publication_date 2005/07/25 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/26

Abstract

Ethyl caffeate, a natural phenolic compound, was isolated from Bidens pilosa, a medicinal plant popularly used for treating certain inflammatory syndromes. The purpose of this study was to investigate the structural activity, and the anti-inflammatory functions and mechanism(s) of ethyl caffeate. Ethyl caffeate was found to markedly suppress the lipopolysaccharide (LPS)-induced nitric oxide (NO) production (IC(50) = 5.5 microg ml(-1)), mRNA and protein expressions of inducible nitric oxide synthase (iNOS), and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Transient gene expression assays using human cox-2 promoter construct revealed that ethyl caffeate exerted an inhibitory effect on cox-2 transcriptional activity in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells. Immunohistochemical studies of mouse skin demonstrated that TPA-induced COX-2 expression was significantly inhibited by ethyl caffeate with a superior effect to that of celecoxib, a nonsteroidal anti-inflammatory drug. The phosphorylation and degradation of inhibitor kappaB (IkappaB) and the translocation of nuclear transcription factor-kappaB (NF-kappaB) into the nucleus, as well as the activation of mitogen-activated protein kinases (MAPKs) induced by LPS in macrophages, were not affected by ethyl caffeate. Ethyl caffeate, however, could inhibit NF-kappaB activation by impairing the binding of NF-kappaB to its cis-acting element. These results suggest that ethyl caffeate suppresses iNOS and COX-2 expressions partly through the inhibition of the NF-kappaB.DNA complex formation. Structure-activity relationship analyses suggested that the catechol moiety and alpha,beta-unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF-kappaB.DNA complex formation. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory and therapeutic properties of ethyl caffeate.

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