Contrasting Correlation in the Inhibition Response of ADP-induced Platelet Aggregation and the Anti coagulant Activities of Algal fucoidans Derived from Eisenia bicyclis and Undaria pinnatifida sporophylls (Mekabu)
1
조회
0
다운로드
4
인용
0
참고문헌
키워드
초록
Sulfated fucans are known to have both anti thrombotic and anti coagulant activities. In this study, the variation in platelet aggregation and anti coagulant activities was investigated in vitro with regard to administered dose, molecular weight distribution, sulfate content, and sugar composition in two algal fucoidans from Eisenia bicyclis and Undaria pinnatifida sporophylls (Mekabu). The anti coagulant activity largely correlated with sulfate content and with molecular weight distribution in a dose-dependent manner. However, both fucoidans demonstrated inhibitory responses to ADP-induced platelet aggregation in dose- and structure-dependent manners that contrasted with the anti coagulant activity. Neither molecular weight distribution nor sulfate content greatly affected platelet-aggregation inhibition (PA-inhibition) by the fucoidan fractions, whereas anti coagulant activity was sensitive to these structural factors. Interestingly, an E. bicyclis fucoidan fraction exhibited almost complete PA-inhibition at a treatment dose of 500 mg/mL while retaining weak anti coagulant activity. In conclusion, these observations suggest that fucoidan may be a useful anti thrombotic or anti platelet agent in various arterial thrombotic disorders, including post-vascular intervention with controlled bleeding complications, due to its anti coagulant modulating activity.
Abstract
Sulfated fucans are known to have both anti thrombotic and anti coagulant activities. In this study, the variation in platelet aggregation and anti coagulant activities was investigated in vitro with regard to administered dose, molecular weight distribution, sulfate content, and sugar composition in two algal fucoidans from Eisenia bicyclis and Undaria pinnatifida sporophylls (Mekabu). The anti coagulant activity largely correlated with sulfate content and with molecular weight distribution in a dose-dependent manner. However, both fucoidans demonstrated inhibitory responses to ADP-induced platelet aggregation in dose- and structure-dependent manners that contrasted with the anti coagulant activity. Neither molecular weight distribution nor sulfate content greatly affected platelet-aggregation inhibition (PA-inhibition) by the fucoidan fractions, whereas anti coagulant activity was sensitive to these structural factors. Interestingly, an E. bicyclis fucoidan fraction exhibited almost complete PA-inhibition at a treatment dose of 500 mg/mL while retaining weak anti coagulant activity. In conclusion, these observations suggest that fucoidan may be a useful anti thrombotic or anti platelet agent in various arterial thrombotic disorders, including post-vascular intervention with controlled bleeding complications, due to its anti coagulant modulating activity.
참고문헌 (23)
- Alywan, I.P., "Inhibition of platelet aggregation in baboons: therapeutic implications for xenotransplantation", Xenotransplantation, 7, pp.247~257 (2000)
- Amano, H., "Effect of seaweed mixture on serum lipid level and platelet aggregation in rats", Fisheries Sci., 71, pp.1160~1166 (2005)
- Anderson, L.O., "Anticoagulant pro-perties of heparin fractionated by affinity chro-matography on matrix-bound antithrombin III and gel filtration", Thromb. Res., 9, pp.575~580 (1974)
- Born,G.V.R, "Quantitative investigations into the aggregation of blood platelets", J. Physiol., 162, pp.927~929 (1962)
- Chauvet, P., "Inhibition of platelet neutrophil inter-actions by fucoidan reduces adhesion and vaso-constriction after acute arterial injury by angioplasty in pigs", J. Cardiovasc. Pharmacol, 34, pp.597~603 (1999)
- Colliec-jouault, S., "Effect of low molecular weight fucoidan on experimental arterial thrombosis in the rabbit and rat", pp.1114~1115 (2003), Int. Soc. on Thrombosis and Haemostasis
- Cumashi, A., "A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and anti-adhesive activities of nine different fucoidans from brown seaweeds", Glycobiology, 17, pp.541~552 (2007)
- Dubois, M., "Colorimetric method for determination of sugars and related substances", Anal. Chem., 28, pp.350~354 (1956)
- Durig, J., "Anticoagulant fucoidan fractions from Fucus vesiculosus induce platelet activation in vitro", Thromb. Res., 85, pp.479~491 (1997)
- Koo, J.G, "Structural characterization of purified fucoidan from Laminaria religiosa, sporophylls of Undaria pinnatifida, Hizikia fusirome and Sagassum fulvellum in Korea", J. Korean. Fish. Soc., 30, pp.128~131 (1997)
- Mauray, S., "Venous antithrombotic and anticoagualant activities of a fucoidan fraction", Thromb. Haemost, 74, pp.1280~1285 (1995)
- Melo, F.R., "Antithrombin-mediated anticoagulant activity of sulfated polysaccharides", J. Biol. Chem., 279, pp.20824~20835 (2004)
- Millet, J., "Antithrombotic and anticoagulant activites of a low molecular weight fucoidan by the subcutaneous route", Thromb. Haemost, 81, pp.391~395 (1999)
- Mourão, P.A.S, "Searching for alternatives to heparin: sulfated fucans from marine invertebrates", Trends. Cardiovasc Med., 9, pp.225~232 (1999)
- Nagasawa, K., "Chemical change involved in the oxidative-reductive depolymerization of heparin", Carbohydr. Res., 236, pp.165~180 (1992)
- Nishino, T., "Isolation, purification, and charac-terization of fucose-containing sulfated polysac-charides from the brown seaweed Ecklonia kurome and their blood-anticoagulant activities", Carbohydrate Research, 186, pp.119~129 (1989)
- Pereira, M.S., "Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans?", Gly-cobiology, 12, pp.573~580 (2002)
- Pomin, V.H., "Selective cleavage and anticoagulant activity of a sulfated fucan: stereospecific removal of a 2-sulfate ester from the polysaccharide by mild acid hydrolysis, pre-paration of oligosaccharides, and heparin cofactor II-dependent anticoagulant activity", Glycobiology, 15, pp.369~381 (2005)
- Théorêt, J.F., "Recombinant P-selectin glycoprotein-ligand-1 delays thrombin-induced platelet aggregation: a new role for P-selectin in early aggregation", Briti. J. Pharm., 148, pp.299~305 (2006)
- Thorlacius, H., "The polysaccharide fucoidan inhibits microvascular thrombus formation indepen-dently from P- and L-selectin function in vivo", Eur. J. Clin. Invest., 30, pp.804~810 (2000)
- Trento, F., "Antithrombin activity of an algal poly-saccharide", Thrombosis Res., 102, pp.457~465 (2001)
- Usui, T., "Isolation of highly purified fucoidan from Eisenia bicyclis and its anticoagulant and antitumor activities", Agric. Biol. Chem., 44, pp.1965~1966 (1980)
- Volpi, N., "Low molecular weight heparins (5 kDa) and oligoheparins (2 kDa) produced by gel permeation enrichment or radical process: Comparison of structures and phy-sicochemical and biological properties", Anal. Bio-chem., 200, pp.100~107 (1992)