Depolymerized glycosaminoglycan and its anticoagulant activities from sea cucumber Apostichopus japonicus

Yang, Jie; Wang, Yuanhong; Jiang, Tianyue; Lv, Lv; Zhang, Boyuan; Lv, Zhihua

doi:10.1016/j.ijbiomac.2014.09.025

Cited by 49 publications

(32 citation statements)

References 32 publications

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“…To date, there have been no reports on the acquisition of pure fragments of FG using known depolymerization methods such as free-radical depolymerization and photochemical depolymerization (20,25). Such depolymerization methods are nonselective and result in excess fragments that render further purification difficult.…”

Section: Resultsmentioning

confidence: 99%

Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan

Zhao

Xiao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

116

152

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Selective inhibition of the intrinsic coagulation pathway is a promising strategy for developing safer anticoagulants that do not cause serious bleeding. Intrinsic tenase, the final and rate-limiting enzyme complex in the intrinsic coagulation pathway, is an attractive but less explored target for anticoagulants due to the lack of a pure selective inhibitor. Fucosylated glycosaminoglycan (FG), which has a distinct but complicated and ill-defined structure, is a potent natural anticoagulant with nonselective and adverse activities. Herein we present a range of oligosaccharides prepared via the deacetylationdeaminative cleavage of FG. Analysis of these purified oligosaccharides reveals the precise structure of FG. Among these fragments, nonasaccharide is the minimum fragment that retains the potent selective inhibition of the intrinsic tenase while avoiding the adverse effects of native FG. In vivo, the nonasaccharide shows 97% inhibition of venous thrombus at a dose of 10 mg/kg in rats and has no obvious bleeding risk. This nonasaccharide may therefore serve as a novel promising anticoagulant.T hrombotic disease is seriously harmful to human health and is one of the major causes of death in modern society (1). Despite their long-term and widespread use as anticoagulants, heparin, low-molecular-weight heparin (LMWH), and coumarins still have a major unresolved issue: the risk of serious bleeding during therapy (1-3). It is generally recognized that the risk of bleeding associated with these agents is related to the nonselectivity of their anticoagulant activity. Therefore, selective inhibitors of human factor Xa (FXa) and thrombin (FIIa), such as dabigatran, rivaroxaban, and apixaban, which have predictable pharmacokinetics, have recently been developed; however, these agents have not effectively reduced the risk of bleeding in clinical applications (4-7).Components of the intrinsic coagulation pathway are promising targets for antithrombotic therapy because they are important for thrombosis but are not required for hemostasis (1,8). The development of new anticoagulant agents that inhibit components of the intrinsic pathway and that have a lower risk of causing bleeding has thus become a research focus (9-11). Factor IXa (FIXa), a serine protease, and factor VIIIa (FVIIIa), a protein cofactor, form a Ca 2+ -and phospholipid surface-dependent complex referred to as the intrinsic tenase complex, which efficiently converts zymogen factor X (FX) to FXa (1,12,13). Because the intrinsic tenase is the final and rate-limiting enzyme complex in the intrinsic pathway, the development of inhibitors of this enzyme complex is important for meeting clinical demands (1). However, limited progress has been achieved due to the unavailability of selective inhibitors with welldefined structures.Fucosylated glycosaminoglycan (FG; 1 in Fig. 1), which is a complex acidic polysaccharide isolated from sea cucumber, has recently attracted considerable attention because of its various bioactivities (14). Notably, FG has potent anticoagula...

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Section: Resultsmentioning

confidence: 99%

Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan

Zhao

Xiao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

116

152

View full text Add to dashboard Cite

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“…Hyaluronic acid (HA) is a nonsulfated glycosaminoglycan [16]. So far, the main method of production of hyaluronic acid has been its isolation from natural sources [17][18][19][20][21][22]. HA is biocompatible, biodegradable, non-toxic and it is viscoelastic due to the ability of water absorption [23].…”

Section: Introductionmentioning

confidence: 99%

3D composites based on the blends of chitosan and collagen with the addition of hyaluronic acid

Sionkowska

Kaczmarek

Lewandowska

et al. 2016

International Journal of Biological Macromolecules

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“…Therefore, there is a need to replace heparin with new safe anticoagulants. Yang et al (2015a) isolated a novel depolymerized fucosylated chondroitin sulfate from S. japonicus (DAHG) by Cu 2+ catalytic free-radical depolymerization and demonstrated its anticoagulant activities compared with low molecular weight heparin (LMWH; average molecular weight 3500 Da). The DAHG was fractionated into three different low molecular weight fractions such as DAHG-1 (41,149 Da), DAHG-2 (24,755 Da) and DAHG-3 (8871 Da).…”

Section: Anti-coagulationmentioning

confidence: 99%

“…The body wall of the sea cucumber is a major edible part and consists mainly of collagen and mucopolysaccharides (Duan et al 2010). In addition, the body wall with peptide, collagen, gelatin, polysaccharide, and saponin has several biological activities such as anticancer, anticoagulation, anti-oxidation, and anti-osteoclastogenesis (Kariya et al 2004;Lu et al 2010;Zhou et al 2012;Yang et al 2015a). Furthermore, sea cucumbers have high applications in the biomedical field because of their regenerative capacities as they can regenerate tissues and organs within a few months (Zohdi et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Biological activities and biomedical potential of sea cucumber (Stichopus japonicus): a review

Lee

et al. 2017

Fish Aquatic Sci

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Members of the phylum Echinodermata, commonly known as echinoderms, are exclusively marine invertebrates. Among the Echinodermata, sea cucumber belongs to the family Holothuroidea. The sea cucumber Stichopus (Apostichous) japonicus (Selenka) is an invertebrate animal inhabiting the coastal sea around Korean, Japan, China, and Russia. Sea cucumber has a significant commercial value, because it contains valuable nutrients such as vitamins and minerals. They possess a number of distinctive biologically and pharmacologically important compounds. In particular, the body wall of sea cucumber is a major edible part. It consists of peptide, collagen, gelatin, polysaccharide, and saponin, which possess several biological activities such as anti-cancer, anti-coagulation, anti-oxidation, and antiosteoclastogenesis. Furthermore, the regenerative capacity of sea cucumber makes it a medically important organism. This review presents the various biological activities and biomedical potential of sea cucumber S. japonicus.

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Depolymerized glycosaminoglycan and its anticoagulant activities from sea cucumber Apostichopus japonicus

Cited by 49 publications

References 32 publications

Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan

Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan

3D composites based on the blends of chitosan and collagen with the addition of hyaluronic acid

Biological activities and biomedical potential of sea cucumber (Stichopus japonicus): a review

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