Characterization and anticoagulant activity of a fucosylated chondroitin sulfate with unusually procoagulant effect from sea cucumber

Carbohydr Polym. 2017 Oct 15:174:760-771. doi: 10.1016/j.carbpol.2017.06.128. Epub 2017 Jul 3.

Abstract

The fucosylated chondroitin sulfate (FuCS) was isolated from the sea cucumber Holothuria polii body wall and then purified by anion exchange chromatography and the structure was characterized by FT-IR and NMR spectroscopy. Anticoagulant activity was measured in plasma by classical anticoagulation tests and the thrombin generation was assessed by calibrated automated thrombography. The results showed that the FuCS obtained at a yield of 4.66% possesses high sulfate content 43% and an average molecular mass of 45.8kDa. Structural analysis revealed the presence of alternating units of chondroitine sulfate branched at position 3 of the β-d-glucuronic acid by two types of fucose 2,4-O-di and 3,4-O-disulfated residues. The FuCS exhibited a high anticoagulant effect mediated essentially by heparin cofactor II and to lesser extent by antithrombin. Moreover, the CAT assay depicted a dual effect of FuCS with a procoagulant tendency for low doses and an anticoagulant effect at higher doses.

Keywords: Anticoagulant activity; Fucosylated chondroitin sulfate; Holothuria polii; Sea cucumber; Thrombin generation.

MeSH terms

  • Animals
  • Anticoagulants / pharmacology*
  • Chondroitin Sulfates / pharmacology*
  • Coagulants / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Platelet Aggregation / drug effects
  • Sea Cucumbers / chemistry*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Anticoagulants
  • Coagulants
  • fucosylated chondroitin sulfate
  • Chondroitin Sulfates