Biol. Pharm. Bull. 28(4) 607—610 (2005)

tory processes, where activation of the transcription factor nuclear factor-kappa B (NF-kB) plays a pivotal role by augmenting the expression of various genes such as cytokines, chemokines, leukocyte-adhesion molecules. NF-kB is found in the cytoplasm of most cells as an inactive complex bound to an inhibitory protein, inhibitor kappa B (IkB). It is also well known that treatment with a variety of stimuli including tumor necrosis factor-a (TNF-a) and reactive oxygen species (ROS) results in the rapid activation of NF-kB, through the phosphorylation of IkB and its subsequent proteolytic degradation by the proteasome-dependent pathway. Recent studies have shown that the inhibition of gene expressions through NF-kB activation is one of the favorable treatments in vascular and inflammatory diseases. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide purified from the supernatant of cultured porcine aortic endothelial cells (PAECs) and possesses a number of biological activities leading to vascular disorders. ET-1 biosynthesis and release appear to be regulated at the transcriptional level because ET-1 release from endothelial cells (ECs) is constitutive. Several studies have indicated that various substances such as thrombin, transforming growth factor-b1, and TNF-a stimulate the ET-1 gene expression in ECs by DNA binding of transcription factors such as activator protein-1 (AP-1) and nuclear factor-1 (NF-1). Recent studies have shown that NF-kB is also one of modulators in ET-1 production. Chalcones are obtained from various natural plant sources. It has been reported that chalcones possess various biological properties, including anti-inflammatory, analgesic, antioxidant, antibacterial, and antifungal activities. Our previous studies have demonstrated that the roots of Angelica keiskei KOIDZUMI are abundant in chalcones such as xanthoangelols and 4-hydroxyderricin. These roots have traditionally been used as a health food with diuretic, laxative, analeptic and galactagogic effects. Recent studies have also indicated that the extracted chalcones from the roots of Angelica keiskei KOIDZUMI have beneficial effects including vasodilatation, antitumor and antimetastatic activities. The purpose of the present study is to evaluate whether chalcones extracted from Angelica keiskei KOIDZUMI have an inhibitory effect on NF-kB activation. To attain this, we examined the effects of xanthoangelol, xanthoangelol D, E, and F on NF-kB activation in PAECs. In addition, we evaluate the effects of xanthoangelols on ET-1 production in PAECs.