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.