{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:32:35Z","timestamp":1792272755303,"version":"4.4.0"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T00:00:00Z","timestamp":1389225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Fucosylated chondroitin sulfate (FucCS) is a structurally distinct glycosaminoglycan found in sea cucumber species. It has the same backbone composition of alternating 4-linked glucuronic acid and 3-linked N-acetyl galactosamine residues within disaccharide repeating units as regularly found in mammalian chondroitin sulfates. However, FucCS has also sulfated fucosyl branching units 3-O-linked to the acid residues. The sulfation patterns of these branches vary accordingly with holothurian species and account for different biological actions and responses. FucCSs may exhibit anticoagulant, antithrombotic, anti-inflammatory, anticancer, antiviral, and pro-angiogenic activities, besides its beneficial effects in hemodialysis, cellular growth modulation, fibrosis and hyperglycemia. Through an historical overview, this document covers most of the science regarding the holothurian FucCS. Both structural and medical properties of this unique GAG, investigated during the last 25 years, are systematically discussed herein.<\/jats:p>","DOI":"10.3390\/md12010232","type":"journal-article","created":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T14:10:57Z","timestamp":1389276657000},"page":"232-254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":189,"title":["Holothurian Fucosylated Chondroitin Sulfate"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-8880","authenticated-orcid":false,"given":"Vitor","family":"Pomin","sequence":"first","affiliation":[{"name":"Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, and University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18176","DOI":"10.1016\/S0021-9258(19)81341-8","article-title":"Occurrence of a unique fucose-branched chondroitin sulfate in the body wall of a sea cucumber","volume":"263","author":"Vieira","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13530","DOI":"10.1016\/S0021-9258(18)92730-4","article-title":"Structure of a fucose-branched chondroitin sulfate from sea cucumber. Evidence for the presence of 3-O-sulfo-beta-d-glucuronosyl residues","volume":"266","author":"Vieira","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1021\/bi00060a018","article-title":"Extensive heterogeneity of proteoglycans bearing fucose-branched chondroitin sulfate extracted from the connective tissue of sea cucumber","volume":"32","author":"Vieira","year":"1993","journal-title":"Biochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0008-6215(94)84213-2","article-title":"Increased calcium affinity of a fucosylated chondroitin sulfate from sea cucumber","volume":"256","author":"Ruggiero","year":"1994","journal-title":"Carbohydr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"23973","DOI":"10.1074\/jbc.271.39.23973","article-title":"Structure and anticoagulant activity of a fucosylated chondroitin sulfate from echinoderm. Sulfated fucose branches on the polysaccharide account for its high anticoagulant action","volume":"271","author":"Pereira","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1046\/j.1365-2141.1998.00769.x","article-title":"Antithrombotic activity of a fucosylated chondroitin sulphate from echinoderm: Sulphated fucose branches on the polysaccharide account for its antithrombotic action","volume":"101","author":"Mulloy","year":"1998","journal-title":"Br. J. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1097\/00001721-200009000-00009","article-title":"Different antithrombotic mechanisms among glycosaminoglycans revealed with a new fucosylated chondroitin sulfate from an echinoderm","volume":"11","author":"Pacheco","year":"2000","journal-title":"Blood Coagul. Fibrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S1050-1738(00)00032-3","article-title":"Searching for alternatives to heparin: sulfated fucans from marine invertebrates","volume":"9","author":"Pereira","year":"1999","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0049-3848(01)00230-4","article-title":"Inactivation of thrombin by a fucosylated chondroitin sulfate from echinoderm","volume":"102","author":"Drouet","year":"2001","journal-title":"Thromb. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"967","DOI":"10.2174\/1381612043452730","article-title":"Use of sulfated fucans as anticoagulant and antithrombotic agents: Future perspectives","volume":"10","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/00001721-200401000-00008","article-title":"Venous and arterial thrombosis in rat models: dissociation of the antithrombotic effects of glycosaminoglycans","volume":"15","author":"Zancan","year":"2004","journal-title":"Blood Coagul. Fibrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1160\/TH06-06-0304","article-title":"Fucosylated chondroitin sulfate as a new oral antithrombotic agent","volume":"96","author":"Fonseca","year":"2006","journal-title":"Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1182\/blood-2009-02-203661","article-title":"Fucosylated chondroitin sulfate inhibits plasma thrombin generation via targeting of the factor IXa heparin-binding exosite","volume":"114","author":"Buyue","year":"2009","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1160\/TH08-11-0773","article-title":"Effects of polysaccharides enriched in 2,4-disulfated fucose units on coagulation, thrombosis and bleeding. Practical and conceptual implications","volume":"102","author":"Fonseca","year":"2009","journal-title":"Thromb. Haemost."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1160\/TH09-10-0734","article-title":"Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides","volume":"103","author":"Fonseca","year":"2010","journal-title":"Thromb. Haemost."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1016\/j.bbagen.2013.01.001","article-title":"Sulfation pattern of the fucose branch is important for the anticoagulant and antithrombotic activities of fucosylated chondroitin sulfates","volume":"1830","author":"Chen","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e56557","DOI":"10.1371\/journal.pone.0056557","article-title":"Holothurian glycosaminoglycan inhibits metastasis and thrombosis via targeting of nuclear factor-\u03baB\/tissue factor\/Factor Xa pathway in melanoma B16F10 cells","volume":"8","author":"Zhao","year":"2013","journal-title":"PLoS One"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0049-3848(98)00171-6","article-title":"Oral absorption and clearance of partially depolymerized fucosyl chondroitin sulfate from sea cucumber","volume":"93","author":"Imanari","year":"1999","journal-title":"Thromb. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0021-9673(99)00969-3","article-title":"Chiral resolution of basic drugs by capillary electrophoresis with new glycosaminoglycans","volume":"864","author":"Tsukamoto","year":"1999","journal-title":"J. Chromatogr. A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.carbpol.2010.08.040","article-title":"Comparison of structures and anticoagulant activities of fucosylated chondroitin sulfates from different sea cucumbers","volume":"83","author":"Chen","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.carbpol.2011.08.082","article-title":"Structure and effect of sulfated fucose branches on anticoagulant activity of the fucosylated chondroitin sulfate from sea cucumber Thelenata ananas","volume":"87","author":"Wu","year":"2012","journal-title":"Carbohydr. Polym."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.foodchem.2010.03.042","article-title":"Physicochemical characteristics and anticoagulant activities of low molecular weight fractions by free-radical depolymerization of a fucosylated chondroitin sulphate from sea cucumber Thelenata ananas","volume":"122","author":"Wu","year":"2010","journal-title":"Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1016\/S0040-4039(00)61245-5","article-title":"Structure of DHG, a depolymerized holothurian glycosaminoglycan from sea cucumber, Stichopus japonicus","volume":"33","author":"Yoshida","year":"1992","journal-title":"Tetrahedron lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"399","DOI":"10.3390\/md11020399","article-title":"Comparison of physicochemical characteristics and anticoagulant activities of polysaccharides from three sea cucumbers","volume":"11","author":"Luo","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/j.carbpol.2011.10.014","article-title":"Preparation and anticoagulant activity of a fucosylated polysaccharide sulfate from a sea cucumber Acaudina molpadioidea","volume":"87","author":"Ye","year":"2012","journal-title":"Carbohydr. Polym."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.carbpol.2012.01.052","article-title":"Vibrational spectrsocopy characterization and anticoagulant activity of a sulfated polysaccharide from sea cucumber Athyonidium chilensis","volume":"88","author":"Matsuhiro","year":"2012","journal-title":"Carbohydr. Polym."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1182\/blood.V85.6.1527.bloodjournal8561527","article-title":"Depolymerized holothurian glycosaminoglycan with novel anticoagulant actions: antithrombin III- and heparin cofactor II-independent inhibition of factor X activation by factor IXa-factor VIIIa complex and heparin cofactor II-dependent inhibition of thrombin","volume":"85","author":"Nagase","year":"1995","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1160\/TH08-04-0210","article-title":"Serpin-independent anticoagulant activity of a fucosylated chondroitin sulfate","volume":"100","author":"Glauser","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1055\/s-0038-1655975","article-title":"Antithrombin III-independent effect of depolymerized holothurian glycosaminoglycan (DHG) on acute thromboembolism in mice","volume":"77","author":"Nagase","year":"1997","journal-title":"Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.1182\/blood-2005-07-3043","article-title":"Depolymerized holothurian glycosaminoglycan and heparin inhibit the intrinsic tenase complex by a common antithrombin-independent mechanism","volume":"107","author":"Sheehan","year":"2006","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1093\/oxfordjournals.jbchem.a021217","article-title":"Effect of depolymerized holothurian glycosaminoglycan (DHG) on the activation of factor VIII and factor V by thrombin","volume":"119","author":"Nagase","year":"1996","journal-title":"J. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0049-3848(96)00166-1","article-title":"DHG, a new depolymerized holothurian glycosaminoglycan, exerts an antithrombotic effect with less bleeding than unfractionated or low molecular weight heparin, in rats","volume":"84","author":"Kitazato","year":"1996","journal-title":"Thromb. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0049-3848(96)00134-X","article-title":"Interaction of a new depolymerized holothurian glycosaminoglycan with proteins in human plasma","volume":"83","author":"Minamiguchi","year":"1996","journal-title":"Thromb. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.thromres.2003.10.005","article-title":"Prolonged bleeding time induced by anticoagulant glycosaminoglycans in dogs is associated with the inhibition of thrombin-induced platelet aggregation","volume":"112","author":"Kitazato","year":"2003","journal-title":"Thromb. Res."},{"key":"ref_35","first-page":"174","article-title":"Neutralization of DHG, a new depolymerized holothurian glycosaminoglycan, by protamine sulfate and platelet factor 4","volume":"27","author":"Sasaki","year":"1997","journal-title":"Haemostasis"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1248\/cpb.43.2182","article-title":"Determination of a depolymerized holothurian glycosaminoglycan in plasma after intravenous administration by postcolumn HPLC","volume":"43","author":"Huang","year":"1995","journal-title":"Chem. Pharm. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1055\/s-0038-1657643","article-title":"Effect of depolymerized holothurian glycosaminoglycan (DHG) on tissue factor pathway inhibitor: In vitro and in vivo studies","volume":"78","author":"Nagase","year":"1997","journal-title":"Thromb. Haemost."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.carbpol.2013.07.063","article-title":"Structure and anticoagulant activity of fucosylated glycosaminoglycan degraded by deaminative cleavage","volume":"98","author":"Zhao","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1055\/s-0038-1656128","article-title":"The anticoagulant and hemorrhagic effects of DHG, a new depolymerized holothurian glycosaminoglycan, on experimental hemodialysis in dogs","volume":"77","author":"Minamiguchi","year":"1997","journal-title":"Thromb. Haemost."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1046\/j.1523-1755.2003.00879.x","article-title":"Depolymerized holothurian glycosaminoglycan (DHG), a novel alternative anticoagulant for hemodialysis, is safe and effective in a dog renal failure model","volume":"63","author":"Minamiguchi","year":"2003","journal-title":"Kidney Intern."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0021-9150(96)05897-2","article-title":"High affinity of a fucosylated chondroitin sulfate for plasma low density lipoprotein","volume":"26","author":"Tovar","year":"1996","journal-title":"Atherosclerosis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0021-9150(96)06005-4","article-title":"Depolymerized holothurian glycosaminoglycan (DHG) prevents neointimal formation in balloon-injured rat carotid artery","volume":"129","author":"Igarashi","year":"1997","journal-title":"Atherosclerosis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1055\/s-0037-1614016","article-title":"Modulation of vascular human endothelial and rat smooth muscle cell growth by a fucosylated chondroitin sulfate from echinoderm","volume":"84","author":"Drouet","year":"2000","journal-title":"Thromb. Haemost."},{"key":"ref_44","first-page":"96","article-title":"A fucosylated chondroitin sulfate from echinoderm modulates in vitro fibroblast growth factor 2-dependent angiogenesis","volume":"1","author":"Chabut","year":"2002","journal-title":"Mol. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"F1299","DOI":"10.1152\/ajprenal.00217.2010","article-title":"Fucosylated chondroitin sulfate attenuates renal fibrosis in animals submitted to unilateral ureteral obstruction: A P-selectin-mediated event?","volume":"299","author":"Belmiro","year":"2010","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14984","DOI":"10.1074\/jbc.M610560200","article-title":"Selectin blocking activity of a fucosylated chondroitin sulfate glycosaminoglycan from sea cucumber. Effect on tumor metastasis and neutrophil recruitment","volume":"282","author":"Borsig","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1016\/j.bbagen.2013.06.003","article-title":"Anti-HIV-1 activity and structure-activity-relationship study of a fucosylated glycosaminoglycan from an echinoderm by targeting the conserved CD4 induced epitope","volume":"1830","author":"Lian","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.carres.2013.07.010","article-title":"The depolymerized fucosylated chondroitin sulfate from sea cucumber potently inhibits HIV replication via interfering with virus entry","volume":"380","author":"Huang","year":"2013","journal-title":"Carbohydr. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1039\/c3fo60247h","article-title":"Fucosylated chondroitin sulfate from Acaudina molpadioides improves hyperglycemia via activation of PKB\/GLUT4 signaling in skeletal muscle of insulin resistant mice","volume":"4","author":"Hu","year":"2013","journal-title":"Food Funct."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.3390\/md10081647","article-title":"Preparation and characterization of O-acylated fucosylated chondroitin sulfate from sea cucumber","volume":"10","author":"Gao","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.carbpol.2012.12.044","article-title":"Depolymerization of fucosylated chondroitin sulfate from sea cucumber, Pearsonothuria graeffei, via 60Co irradiation","volume":"93","author":"Wu","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_52","first-page":"1116","article-title":"Free-radical depolymerization of glycosaminoglycan from sea cucumber Thelenata ananas by hydrogen peroxide and copper ions","volume":"93","author":"Wu","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.1016\/j.tetlet.2013.05.064","article-title":"Synthesis of \u03b2-d-GalNAc(4,6-diS)(1\u20134)[\u03b1-l-Fuc(2,4-diS)(1\u20133)]-\u03b2-d-GlcA, a novel trisaccharide unit of chondroitin sulfate with a fucose branch","volume":"54","author":"Tamura","year":"2013","journal-title":"Tetrahedron lett."},{"key":"ref_54","first-page":"793","article-title":"Fucanomics and galactanomics: Marine distribution, medicinal impact, conceptions, and challenges","volume":"80","author":"Pomin","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/j.bbagen.2012.08.022","article-title":"Fucanomics and galactanomics: current status in drug discovery, mechanism of action and role of the well-defined chemical structure","volume":"1820","author":"Pomin","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1093\/glycob\/cwn085","article-title":"Structure, biology, evolution, and medical importance of sulfated fucans and galactans","volume":"18","author":"Pomin","year":"2008","journal-title":"Glycobiology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/bip.21200","article-title":"Review: An overview about the structure-function relationship of marine sulfated homopolysaccharides with regular chemical structures","volume":"91","author":"Pomin","year":"2009","journal-title":"Biopolymers"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/12\/1\/232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:07:15Z","timestamp":1760216835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/12\/1\/232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,9]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1]]}},"alternative-id":["md12010232"],"URL":"https:\/\/doi.org\/10.3390\/md12010232","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,9]]}}}