Selective activation of heparin cofactor II by a sulfated polysaccharide isolated from the leaves of Artemisia princeps.
While checking anticoagulant activities in crude fractions from Wakan-Yakus (traditional herbal drugs), we detected antithrombin activity in the polysaccharide fraction of the leaves of Artemisia princeps Pamp. A sulfated polysaccharide purified from the crude fractions by ion-exchange chromatography on DEAE-cellulose and gel filtration on Sepharose 6B potentiated the heparin cofactor II (HC II)-dependent antithrombin activity but not the antithrombin activity of antithrombin III (AT III). The polysaccharide enhanced the HC II-thrombin reaction more than 6000-fold. The apparent second-order rate constant of thrombin inhibition by HC II increased from 3.8 x 10(4) (in the absence of the polysaccharide) to 2.5 x 10(8) M-1 min-1 in the presence of 25-125 micrograms/ml of the polysaccharide. In human plasma, the polysaccharide accelerated the formation of thrombin-HC II complex. The stimulating effect on HC II-dependent antithrombin activity was almost totally abolished by treatment with chondroitinase AC I, heparinase or heparitinase, while chondroitinase ABC or chondroitinase AC II had little or no effect. These results suggest that the polysaccharide is a glycosaminoglycan-like material with properties that are quite distinct from heparin or dermatan sulfate.
Hayakawa
Y
Y
Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan. hayakawa@ms.toyama-mpu.ac.jp.
Hayashi
T
T
Hayashi
T
T
Niiya
K
K
Sakuragawa
N
N
D000990:Antithrombin III / Q000494:pharmacology; D002808:Chondroitin Lyases / Q000494:pharmacology; D002848:Chromatography, DEAE-Cellulose; D002850:Chromatography, Gel; D015844:Heparin Cofactor II / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010936:Plant Extracts / Q000737:chemistry*; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D013431:Sulfates / Q000302:isolation & purification / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors
D010936:Plant Extracts; D011134:Polysaccharides; D013431:Sulfates; D015844:Heparin Cofactor II; D000990:Antithrombin III; D013917:Thrombin; D002808:Chondroitin Lyases