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Inhibition of PAI-1 release from human endothelial cells by Angelica keiskei Koidzumi (Ashitaba) chalcones is structure-dependent

Naoki Ohkura, Hiroaki Oiwa, Katsunori Ohnishi, Masahiko Taniguchi, Kimiye Baba, Gen-ichi Atsumi.

Abstract
Angelica keiskei Koidzumi (Ashitaba) is a traditional herbal medicine and it is also regarded in Japan as a health food that might have antithrombotic properties. Ashitaba exudate suppresses lipopolysaccharide (LPS)-induced plasma plasminogen activator inhibitor 1 (PAI-1), a risk factor for thrombotic diseases in mice. Xanthoangelol (XA) and 4-hydroxyderricin (4-HD) comprise > 95% of total chalcones from Ashitaba exudates that also contain trace amounts of other chalcone subtypes. The present study aimed to determine the effects of Ashitaba chalcones including xanthoangelols B (XB), D (XD), E (XE), F (XF) and XA as well as 4-HD on PAI-1 levels in the medium of stimulated human EA.hy926 endothelial cells. Xanthoangelol (10 M) inhibited PAI-1 production at a rate of 77.1%, whereas the inhibition rates of XB, XD, XE and 4-HD were not significant. Xanthoangelol F was highly cytotoxic and thus its ability to inhibit PAI-1 production could not be evaluated. The side hydrocarbon chain of XA played an important role in the excretion of inhibitory activity. Small modifications of the hydrocarbon chain or small functional groups on the A ring measurably influenced the inhibitory activity of xanthoangelols. These findings warrant future research towards an understanding of the mechanism of antithrombotic action of Ashitaba as herbal medicine or antithrombotic health food.

Key words: thrombosis, health supplement, endothelial cells, fibrinolysis


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