Xanthoangelol D Isolated from the Roots of Angelica keiskei Inhibits Endothelin-1 Production through the Suppression of Nuclear Factor-κB(Pharmacology)

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Transcription factor nuclear factor-kappa B (NF-κB) 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-κB 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-α (TNF-α)-induced NF-κB activation in PAECs. To clarify the mechanism of xanthoangelol D-induced suppression on NF-κB activation, we evaluated the effects of xanthoangelol D on phosphorylation and degradation of IκBα, an inhibitory protein bound to NF-κB, and obtained evidence that xanthoangelol D selectively suppresses the phosphorylation of IκBα rather than the degradation of phosphorylated IκBα. In addition, xanthoangelol D significantly attenuated basal and TNF-α-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-κB activation.
公益社団法人日本薬学会の論文
2005-04-01