Xanthoangelol D isolated from the roots of Angelica keiskei inhibits endothelin-1 production through the suppression of nuclear factor-kappaB.
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.
Sugii
Masato
M
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Ohkita
Mamoru
M
Taniguchi
Masahiko
M
Baba
Kimiye
K
Kawai
Yu
Y
Tahara
Chiyoko
C
Takaoka
Masanori
M
Matsumura
Yasuo
Y
D029969:Angelica / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology; D047188:Chalcones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D019332:Endothelin-1 / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D018517:Plant Roots / Q000737:chemistry*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D047188:Chalcones; D019332:Endothelin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002599:Chalcone; C068244:xanthoangelol