Anticoagulant activity of fucosylated chondroitin sulfate isolated from Cucumaria syracusana. (April 2020)

• Record Type: Journal Article
• Authors: Chahed, Latifa; Balti, Rafik; Elhiss, Sawsen; Bouchemal, Nadia; Ajzenberg, Nadine; Ollivier, Véronique; Chaubet, Frédéric; Maaroufi, Raoui Mounir; Mansour, Mohamed Ben
• Is Part Of: Process biochemistry. Volume 91(2020)
• Page Start: 149
• Page End: 157
• Publication Date: 2020-04
• Subjects: Fucosylated chondroitin sulfate -- Sea cucumber -- Cucumaria syracusana -- Anticoagulant activity -- Antithrombin; Biochemical engineering -- Periodicals; Biotechnology -- Periodicals; Biochemistry -- periodicals; Biotechnology -- periodicals; Chemical Engineering -- periodicals; Génie biochimique -- Périodiques; Biotechnologie -- Périodiques; Biochemical engineering; Biotechnology; Periodicals; 660.63
• DOI: 10.1016/j.procbio.2019.12.006
• Languages: English
• ISSNs: 1359-5113

Abstract

Graphical abstract: Highlights: FCScs structure was characterized using FT-IR, NMR and HPSEC-MALLS-dRI. Anticoagulant activity was investigated in comparison with FCS with different sulfation pattern. FCScs had high anticoagulant activity mediated by HCII and AT. Sulfation pattern affect antithrombin activity. Abstract: Fucosylated chondroitin sulfate (FCScs) isolated from sea cucumber Cucumaria syracusana was characterized by Fourier Transform InfraRed spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR) spectroscopy and high performance size exclusion chromatograph, a multi-angle laser light scattering detector, a viscometer and a differential refractive index (dRI) detector (HPSEC-MALLS-dRI). The anticoagulant activities of FCScs were studied by the classical clotting time assays and the purified systems containing thrombin and antithrombin or heparin cofactor II. The effect on thrombin generation was investigated using calibrated automated thrombography (CAT). The results obtained showed that the FCS with high sulfate content 31 % and relatively low average molecular weight of 36.3 kDa was isolated from C. syracusana in amount of ∼ 35.6 mg/g dry body wall. Structural analysis of this polysaccharide revealed the presence backbone structure of chondroitin sulfate chain branched by two types of fucose 2, 4-O-di and 3, 4-O-disulfated residues in respective ratios of 57.5 and 42.5 %. The FCScs exhibited a high anticoagulant activity mediated essentially by heparin cofactor II (HCII) and to lesser extent by antithrombin (AT) with IC50 values of 0.05 μg/mL and 0.09 μg/mL, respectively. Furthermore, the results of CAT assay showed that the velocity index decreases 3-times at 50 μg/mL in comparison with normal plasma. The overall results showed high anticoagulant activity attributed to the high sulfate content and abundance of disulfated fucose branches of FCScs which made it a promising candidate of anticoagulation drug.