Abstract |
Transcription factor nuclear factor-kappa B ( NF-kappaB) has been demonstrated to be important in regulating various gene expressions such as cytokines, adhesion molecules, and endothelin-1 (ET-1) in vascular endothelial cells. In the present study, we show the effects of xanthoangelol, xanthoangelol D, E, and F, which isolated from the root of Angelica keiskei KOIDZUMI (Umbelliferae), on NF-kappaB activation and ET-1 gene expression in cultured porcine aortic endothelial cells (PAECs). Treatments of xanthoangelol D but not xanthoangelol, xanthoangelol E and F markedly suppressed both of basal and tumor necrosis factor-alpha ( TNF-alpha)-induced NF-kappaB activation in PAECs. To clarify the mechanism of xanthoangelol D-induced suppression on NF-kappaB activation, we evaluated the effects of xanthoangelol D on phosphorylation and degradation of IkappaBalpha, an inhibitory protein bound to NF-kappaB, and obtained evidence that xanthoangelol D selectively suppresses the phosphorylation of IkappaBalpha rather than the degradation of phosphorylated IkappaBalpha. In addition, xanthoangelol D significantly attenuated basal and TNF-alpha-induced prepro ET-1 mRNA expression in PAECs. These results suggest that xanthoangelol D may be useful for the treatment of various vascular diseases involved NF-kappaB activation.
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Authors | Masato Sugii, Mamoru Ohkita, Masahiko Taniguchi, Kimiye Baba, Yu Kawai, Chiyoko Tahara, Masanori Takaoka, Yasuo Matsumura |
Journal | Biological & pharmaceutical bulletin
(Biol Pharm Bull)
Vol. 28
Issue 4
Pg. 607-10
(Apr 2005)
ISSN: 0918-6158 [Print] Japan |
PMID | 15802795
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chalcones
- Endothelin-1
- NF-kappa B
- Tumor Necrosis Factor-alpha
- Chalcone
- xanthoangelol
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Topics |
- Angelica
(chemistry)
- Animals
- Cells, Cultured
- Chalcone
(analogs & derivatives, pharmacology)
- Chalcones
(pharmacology)
- Dose-Response Relationship, Drug
- Endothelial Cells
(drug effects)
- Endothelin-1
(biosynthesis)
- Gene Expression Regulation
(drug effects)
- Molecular Structure
- NF-kappa B
(metabolism)
- Plant Roots
(chemistry)
- Swine
- Tumor Necrosis Factor-alpha
(physiology)
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