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Influence of Fucoidans on Hemostatic System
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow, Russian Federation
Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya str. 10, 119121 Moscow, Russian Federation
Department of Physics, M.V. Lomonosov Moscow State University, Leninskie gory, 119991 Moscow, Russian Federation
Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe shosse, 24, 115478 Moscow, Russian Federation
* Author to whom correspondence should be addressed.
Received: 22 April 2013; in revised form: 20 May 2013 / Accepted: 25 June 2013 / Published: 12 July 2013
Abstract: Three structurally different fucoidans from the brown seaweeds Saccharina latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and a synthetic totally sulfated octasaccharide (OS), related to fucoidans, were assessed on anticoagulant and antithrombotic activities in different in vitro experiments. The effects were shown to depend on the structural features of the compounds tested. Native fucoidan SL with a degree of sulfation (DS) of 1.3 was found to be the most active sample, fucoidan FV (DS 0.9) demonstrated moderate activity, while the polysaccharide CO (DS 0.4) was inactive in all performed experiments, even at high concentrations. Additional introduction of sulfate groups into fucoidan SL slightly decreased the anticoagulant effect of SL-S, while sulfation of CO, giving rise to the preparation CO-S, increased the activity dramatically. The high level of anticoagulant activity of polysaccharides SL, SL-S, and CO-S was explained by their ability to form ternary complexes with ATIII-Xa and ATIII-IIa, as well as to bind directly to thrombin. Synthetic per-O-sulfated octasaccharide OS showed moderate anticoagulant effect, determined mainly by the interaction of OS with the factor Xa in the presence of ATIII. Comparable tendencies were observed in the antithrombotic properties of the compounds tested.
Keywords: fucoidan; anticoagulant; hemostasis; heparin; thrombin; antithrombin; factor Xa
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Ustyuzhanina, N.E.; Ushakova, N.A.; Zyuzina, K.A.; Bilan, M.I.; Elizarova, A.L.; Somonova, O.V.; Madzhuga, A.V.; Krylov, V.B.; Preobrazhenskaya, M.E.; Usov, A.I.; Kiselevskiy, M.V.; Nifantiev, N.E. Influence of Fucoidans on Hemostatic System. Mar. Drugs 2013, 11, 2444-2458.
Ustyuzhanina NE, Ushakova NA, Zyuzina KA, Bilan MI, Elizarova AL, Somonova OV, Madzhuga AV, Krylov VB, Preobrazhenskaya ME, Usov AI, Kiselevskiy MV, Nifantiev NE. Influence of Fucoidans on Hemostatic System. Marine Drugs. 2013; 11(7):2444-2458.
Ustyuzhanina, Nadezhda E.; Ushakova, Natalia A.; Zyuzina, Ksenia A.; Bilan, Maria I.; Elizarova, Anna L.; Somonova, Oksana V.; Madzhuga, Albina V.; Krylov, Vadim B.; Preobrazhenskaya, Marina E.; Usov, Anatolii I.; Kiselevskiy, Mikhail V.; Nifantiev, Nikolay E. 2013. "Influence of Fucoidans on Hemostatic System." Mar. Drugs 11, no. 7: 2444-2458.