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

Yi Ming Chiang, Chiu Ping Lo, Yi Ping Chen, Sheng Yang Wang, Ning Sun Yang, Yueh Hsiung Kuo, Lie Fen Shyur

研究成果: 雜誌貢獻文章

111 引文 (Scopus)

摘要

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 μg 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 κB (IκB) and the translocation of nuclear transcription factor-κB (NF-κB) 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-κB activation by impairing the binding of NF-κB to its cis-acting element. These results suggest that ethyl caffeate suppresses iNOS and COX-2 expressions partly through the inhibition of the NF-κB·DNA complex formation. Structure-activity relationship analyses suggested that the catechol moiety and α,β-unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF-κB·DNA complex formation. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory and therapeutic properties of ethyl caffeate.

原文英語
頁(從 - 到)352-363
頁數12
期刊British Journal of Pharmacology
146
發行號3
DOIs
出版狀態已發佈 - 十月 2005
對外發佈Yes

指紋

Nitric Oxide Synthase Type II
Prostaglandins E
Transcription Factors
Skin
Anti-Inflammatory Agents
Celecoxib
Tetradecanoylphorbol Acetate
Lipopolysaccharides
Bidens
Macrophages
ethyl caffeate
In Vitro Techniques
MCF-7 Cells
Structure-Activity Relationship
Medicinal Plants
Mitogen-Activated Protein Kinases
Nitric Oxide
Esters
Phosphorylation
Gene Expression

ASJC Scopus subject areas

  • Pharmacology

引用此文

Ethyl caffeate suppresses NF-κB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE 2 in vitro or in mouse skin. / Chiang, Yi Ming; Lo, Chiu Ping; Chen, Yi Ping; Wang, Sheng Yang; Yang, Ning Sun; Kuo, Yueh Hsiung; Shyur, Lie Fen.

於: British Journal of Pharmacology, 卷 146, 編號 3, 10.2005, p. 352-363.

研究成果: 雜誌貢獻文章

Chiang, Yi Ming ; Lo, Chiu Ping ; Chen, Yi Ping ; Wang, Sheng Yang ; Yang, Ning Sun ; Kuo, Yueh Hsiung ; Shyur, Lie Fen. / Ethyl caffeate suppresses NF-κB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE 2 in vitro or in mouse skin. 於: British Journal of Pharmacology. 2005 ; 卷 146, 編號 3. 頁 352-363.
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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 μg 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 κB (IκB) and the translocation of nuclear transcription factor-κB (NF-κB) 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-κB activation by impairing the binding of NF-κB to its cis-acting element. These results suggest that ethyl caffeate suppresses iNOS and COX-2 expressions partly through the inhibition of the NF-κB·DNA complex formation. Structure-activity relationship analyses suggested that the catechol moiety and α,β-unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF-κB·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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author = "Chiang, {Yi Ming} and Lo, {Chiu Ping} and Chen, {Yi Ping} and Wang, {Sheng Yang} and Yang, {Ning Sun} and Kuo, {Yueh Hsiung} and Shyur, {Lie Fen}",
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T1 - Ethyl caffeate suppresses NF-κB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE 2 in vitro or in mouse skin

AU - Chiang, Yi Ming

AU - Lo, Chiu Ping

AU - Chen, Yi Ping

AU - Wang, Sheng Yang

AU - Yang, Ning Sun

AU - Kuo, Yueh Hsiung

AU - Shyur, Lie Fen

PY - 2005/10

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N2 - 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 μg 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 κB (IκB) and the translocation of nuclear transcription factor-κB (NF-κB) 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-κB activation by impairing the binding of NF-κB to its cis-acting element. These results suggest that ethyl caffeate suppresses iNOS and COX-2 expressions partly through the inhibition of the NF-κB·DNA complex formation. Structure-activity relationship analyses suggested that the catechol moiety and α,β-unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF-κB·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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