Preparation and Characterization of O-Acylated Fucosylated Chondroitin Sulfate from Sea Cucumber

Gao, Na; Wu, Mingyi; Shao, Lei; Wu, Lian; Li, Zi; Zhao, Jinhua

doi:10.3390/md10081647

Cited by 36 publications

(22 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NMR was also employed to investigate the structure of LMWCSs. LMWCSs from enzymatic methods showed additional chemical shifts at approximately 5.18, 3.78, 4.10 and 5.88 ppm for the H-1, H-2, H-3 and H-4 protons, respectively, indicating a non-reducing terminal Δ4,5-unsaturated uronic acid (ΔUA) residue, and the results were in accordance with references [19,20]. The major chemical shifts of LMWCSs from the remaining prepared methods were consistent with those of intact CS, which indicated that the non-reducing and reducing end were the same as intact CS.…”

Section: Resultssupporting

confidence: 90%

Preparation of Low Molecular Weight Chondroitin Sulfates, Screening of a High Anti-Complement Capacity of Low Molecular Weight Chondroitin Sulfate and Its Biological Activity Studies in Attenuating Osteoarthritis

Feng

et al. 2016

IJMS

View full text Add to dashboard Cite

Chondroitin sulfate (CS) plays important roles in the complement system. However, the CS structure is complicated due to different sources and the number and positions of sulfate groups. The objective of this study was to prepare different low molecular weight chondroitin sulfates (LMWCSs) and to investigate the biological activity in anti-complement capacity. A series of LMWCSs was prepared from different sources and characterized by ultraviolet-visible (UV) spectroscopy, high-performance liquid chromatography (HPLC), size exclusion chromatography-multiangle laser light scattering (SEC-MALLS) and nuclear magnetic resonance (NMR) spectroscopy. Hemolytic, anti-complement 3 deposition capacity and cell viability assays were carried out to investigate the biological activities in vitro. The results showed that LMWCS prepared from shark cartilage with the oxidative degradation method (LMWCS-S-O) had the best anti-complement capacity. LMWCS-S-O could inhibit the alternative pathway of the complement system and protect chondrocytes from cell death. The attenuating effect of LMWCS-S-O on Osteoarthritis (OA) was investigated by destabilization of the medial meniscus (DMM) model in vivo. Functional wind-up, histological and C5b-9 analyses were used to evaluate the treatment effect on the OA model. In vivo results showed that LMWCS-S-O could attenuate OA. LMWCS-S-O with a high content of ΔDi-2,6diS and ΔDi-6S could be used for attenuating OA through regulating the complement system.

show abstract

Section: Resultssupporting

confidence: 90%

Preparation of Low Molecular Weight Chondroitin Sulfates, Screening of a High Anti-Complement Capacity of Low Molecular Weight Chondroitin Sulfate and Its Biological Activity Studies in Attenuating Osteoarthritis

Feng

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…Additionally, the PT assays were also carried out but none of these polysaccharides showed any effects on PT at the concentrations tested (1–1000 μg/mL). The absence of PT activities of the sulfated polysaccharides is similar to that of other sulfated fucans and FuCSs [14,19,28]. …”

Section: Resultssupporting

confidence: 62%

“…Activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) clotting assays were carried out as described previously [14], using a coagulometer (TECO MC-4000, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Very recently, we have isolated a fucosylated chondroitin sulfate from the body wall of the sea cucumber T. ananas and elucidated its chemical structure and anticoagulant activity [10,13,14]. In order to examine the distribution of the sea cucumber polysaccharides and to compare their physicochemical characteristics and biological activities, we have now expanded our studies to include more species of sea cucumber, namely Holothuria edulis , Apostichopus japonicas and Holothuria nobilis .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of Physicochemical Characteristics and Anticoagulant Activities of Polysaccharides from Three Sea Cucumbers

et al. 2013

Marine Drugs

Self Cite

141

111

View full text Add to dashboard Cite

In order to search for sulfated polysaccharides in different invertebrate connective tissues and to examine their biological activities, we have isolated three types of polysaccharides from the body wall of the three sea cucumbers Holothuria edulis, Apostichopus japonicas and Holothuria nobilis. The physicochemical properties and anticoagulant activities of these polysaccharides were examined and compared. The chemical composition analysis and nuclear magnetic resonance (NMR) analysis indicate that two types of polysaccharides, sulfated fucan and fucosylated chondroitin sulfate (FuCS), were found in all of the three species and in addition a neutral glycan was observed in H. edulis. The neutral α-glucan was firstly obtained from sea cucumber. The same type of polysaccharides from different species of sea cucumbers have similar physicochemical properties and anticoagulant activities, but those of different types of glycans are significantly different, possibly due to their different monosaccharide compositions, electric charges and average molecular weights. The FuCSs have stronger anticoagulant activities than the sulfated fucans, although the molecular sizes of the FuCSs are lower than those of the sulfated fucans, whereas the neutral glucan has no activity, as expected from the absence of sulfate. Thus, anticoagulant activities of the different type of polysaccharides are likely to relate to monosaccharide composition and sulfate content. Preliminary analysis suggests that the sulfation patterns of the FuCSs may result in the difference in anticoagulant activities. Our data could help elucidate the structure-activity relationship of the sea cucumber polysaccharides.

show abstract

“…The APTT, PT, and TT of 1-8, LMWH, and dermatan sulfate (DS) were determined using assay kits on a coagulometer (TECO; MC-4000) as described previously (44). The inhibition of the intrinsic tenase was determined using the previously described method (31,45) with modifications and the reagents in the BIOPHEN FVIII:C Kit (HYPHEN BioMed).…”

Section: Methodsmentioning

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.

Self Cite

116

152

View full text Add to dashboard Cite

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...

show abstract

Preparation and Characterization of O-Acylated Fucosylated Chondroitin Sulfate from Sea Cucumber

Cited by 36 publications

References 21 publications

Preparation of Low Molecular Weight Chondroitin Sulfates, Screening of a High Anti-Complement Capacity of Low Molecular Weight Chondroitin Sulfate and Its Biological Activity Studies in Attenuating Osteoarthritis

Preparation of Low Molecular Weight Chondroitin Sulfates, Screening of a High Anti-Complement Capacity of Low Molecular Weight Chondroitin Sulfate and Its Biological Activity Studies in Attenuating Osteoarthritis

Comparison of Physicochemical Characteristics and Anticoagulant Activities of Polysaccharides from Three Sea Cucumbers

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

Contact Info

Product

Resources

About