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Ethyl caffeate suppresses NF‐ κ B activation and its downstream inflammatory mediators, iNOS, COX‐2, and PGE 2 in vitro or in mouse skin
Author(s) -
Chiang YiMing,
Lo ChiuPing,
Chen YiPing,
Wang ShengYang,
Yang NingSun,
Kuo YuehHsiung,
Shyur LieFen
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706343
Subject(s) - chemistry , nitric oxide synthase , nitric oxide , kinase , biochemistry , nf κb , microbiology and biotechnology , phosphorylation , signal transduction , pharmacology , enzyme , biology , organic chemistry
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 μ g 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 κ B (I κ B) and the translocation of nuclear transcription factor‐ κ B (NF‐ κ B) 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‐ κ B activation by impairing the binding of NF‐ κ B to its cis ‐acting element. These results suggest that ethyl caffeate suppresses iNOS and COX‐2 expressions partly through the inhibition of the NF‐ κ B·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‐ κ B·DNA complex formation. This study provides an insight into the probable mechanism(s) underlying the anti‐inflammatory and therapeutic properties of ethyl caffeate.British Journal of Pharmacology (2005) 146 , 352–363. doi: 10.1038/sj.bjp.0706343