Fucans, but Not Fucomannoglucuronans, Determine the Biological Activities of Sulfated Polysaccharides from Laminaria saccharina Brown Seaweed

Sulfated polysaccharides from Laminaria saccharina (new name: Saccharina latissima) brown seaweed show promising activity for the treatment of inflammation, thrombosis, and cancer; yet the molecular mechanisms underlying these properties remain poorly understood. The aim of this work was to characterize, using in vitro and in vivo strategies, the anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-tumor activities of two main sulfated polysaccharide fractions obtained from L. saccharina: a) L.s.-1.0 fraction mainly consisting of O-sulfated mannoglucuronofucans and b) L.s.-1.25 fraction mainly composed of sulfated fucans. Both fractions inhibited leukocyte recruitment in a model of inflammation in rats, although L.s.-1.25 appeared to be more active than L.s.-1.0. Also, these fractions inhibited neutrophil adhesion to platelets under flow. Only fraction L.s.-1.25, but not L.s.-1.0, displayed anticoagulant activity as measured by the activated partial thromboplastin time. Investigation of these fractions in angiogenesis settings revealed that only L.s.-1.25 strongly inhibited fetal bovine serum (FBS) induced in vitro tubulogenesis. This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells. Furthermore, only parent sulfated polysaccharides from L. saccharina (L.s.-P) and its fraction L.s.-1.25 were powerful inhibitors of basic fibroblast growth factor (bFGF) induced pathways. Consistently, the L.s.-1.25 fraction as well as L.s.-P successfully interfered with fibroblast binding to human bFGF. The incorporation of L.s.-P or L.s.-1.25, but not L.s.-1.0 into Matrigel plugs containing melanoma cells induced a significant reduction in hemoglobin content as well in the frequency of tumor-associated blood vessels. Moreover, i.p. administrations of L.s.-1.25, as well as L.s.-P, but not L.s.-1.0, resulted in a significant reduction of tumor growth when inoculated into syngeneic mice. Finally, L.s.-1.25 markedly inhibited breast cancer cell adhesion to human platelet-coated surfaces. Thus, sulfated fucans are mainly responsible for the anti-inflammatory, anticoagulant, antiangiogenic, and antitumor activities of sulfated polysaccharides from L. saccharina brown seaweed

Fucoidans of Brown Algae: Comparison of Sulfated Polysaccharides from Fucus vesiculosus and Ascophyllum nodosum

Preparations of sulfated polysaccharides obtained from brown algae are known as fucoidans. These biopolymers have attracted considerable attention due to many biological activities which may find practical applications. Two Atlantic representatives of Phaeophyceae, namely, Fucus vesiculosus and Ascophyllum nodosum, belonging to the same order Fucales, are popular sources of commercial fucoidans, which often regarded as very similar in chemical composition and biological actions. Nevertheless, these two fucoidan preparations are polysaccharide mixtures which differ considerably in amount and chemical nature of components, and hence, this circumstance should be taken into account in the investigation of their biological properties and structure–activity relationships. In spite of these differences, fractions with carefully characterized structures prepared from both fucoidans may have valuable applications in drug development

Influence of Modified Fucoidan and Related Sulfated Oligosaccharides on Hematopoiesis in Cyclophosphamide-Induced Mice

Immunosuppression derived after cytostatics application in cancer chemotherapy is considered as an adverse side effect that leads to deterioration of quality of life and risk of infectious diseases. A linear sulfated (1→3)-α-l-fucan M-Fuc prepared by chemical modification of a fucoidan isolated from the brown seaweed Chordaria flagelliformis, along with two structurally related synthetic sulfated oligosaccharides, were studied as stimulators of hematopoiesis on a model of cyclophosphamide immunosuppression in mice. Recombinant granulocyte colony-stimulating factor (r G-CSF), which is currently applied in medicine to treat low blood neutrophils, was used as a reference. Polysaccharide M-Fuc and sulfated difucoside DS did not demonstrate significant effect, while sulfated octasaccharide OS showed higher activity than r G-CSF, causing pronounced neutropoiesis stimulation. In addition, production of erythrocytes and platelets was enhanced after the octasaccharide administration. The assessment of populations of cells in blood and bone marrow of mice revealed the difference in mechanisms of action of OS and r G-CSF

Fucosylated chondroitin sulfate from the sea cucumber Hemioedema spectabilis: Structure and influence on cell adhesion and tubulogenesis

Fucosylated chondroitin sulfate (FCS) HeSp was isolated from the Patagonian sea cucumber Hemioedema spectabilis. Ion-exchange chromatography was applied for purification of the FCS from the crude extract of sulfated polysaccharides. Analysis of monosaccharide and sulfate content of HeSp revealed the molar ratio of GlcA:GalNAc:Fuc:SO3Na as 1.15:1:1.1:3.9. Molecular weight of HeSp (44.1 kDa) was determined by GPC. According to the NMR spectral data, the main fragment of HeSp was the trisaccharide →3)-β-D-GalNAc-(1→4)-β-D-GlcA(3-O-α-L-Fuc)-(1→, where GalNAc units were sulfated either at O-4, at O-6 or both at O-4 and O-6. The fucosyl branches attached to O-3 of GlcA showed also different patterns of sulfation: Fucp2S4S, Fucp4S and Fucp3S4S were found in a ratio of 3.8:1.5:1. Besides, small amounts of the disaccharide fragment →3)-β-D-GalNAc-(1→4)-β-D-GlcA3S-(1→ were observed in a structure of HeSp. The polysaccharide was found to block cancer cells adhesion to platelet-coated surface and to inhibit tubulogenesis, thus demonstrating the potential antitumor activity.Fil: Ustyuzhanina, Nadezhda E.. Russian Academy of Sciences; RusiaFil: Bilan, Maria I.. Russian Academy of Sciences; RusiaFil: Dmitrenok, Andrey S.. Russian Academy of Sciences; RusiaFil: Shashkov, Alexander S.. Russian Academy of Sciences; RusiaFil: Ponce, Nora Marta Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Stortz, Carlos Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Nifantiev, Nikolay E.. Russian Academy of Sciences; RusiaFil: Usov, Anatolii I.. Russian Academy of Sciences; Rusi

Fucosylated Chondroitin Sulfates from the Sea Cucumbers Paracaudina chilensis and Holothuria hilla: Structures and Anticoagulant Activity

Fucosylated chondroitin sulfates (FCSs) PC and HH were isolated from the sea cucumbers Paracaudina chilensis and Holothuria hilla, respectively. The purification of the polysaccharides was carried out by anion-exchange chromatography on a DEAE-Sephacel column. The structural characterization of the polysaccharides was performed in terms of monosaccharide and sulfate content, as well as using a series of nondestructive NMR spectroscopic methods. Both polysaccharides were shown to contain a chondroitin core [→3)-β-d-GalNAc (N-acethyl galactosamine)-(1→4)-β-d-GlcA (glucuronic acid)-(1→]n, bearing sulfated fucosyl branches at O-3 of every GlcA residue in the chain. These fucosyl residues were different in their pattern of sulfation: PC contained Fuc2S4S and Fuc4S in a ratio of 2:1, whereas HH included Fuc2S4S, Fuc3S4S, and Fuc4S in a ratio of 1.5:1:1. Moreover, some GalNAc residues in HH were found to contain an unusual disaccharide branch Fuc4S-(1→2)-Fuc3S4S-(1→ at O-6. Sulfated GalNAc4S6S and GalNAc4S units were found in a ratio of 3:2 in PC and 2:1 in HH. Both polysaccharides demonstrated significant anticoagulant activity in a clotting time assay, which is connected with the ability of these FCSs to potentiate the inhibition of thrombin and factor Xa in the presence of anti-thrombin III (ATIII) and with the direct inhibition of thrombin in the absence of any cofactors

Structure and Anti-Inflammatory Activity of a New Unusual Fucosylated Chondroitin Sulfate from Cucumaria djakonovi

Fucosylated chondroitin sulfate CD was isolated from the sea cucumber Cucumaria djakonovi collected from the Avachinsky Gulf of the eastern coast of Kamchatka. Structural characterization of CD was performed using a series of non-destructive NMR spectroscopic procedures. The polysaccharide was shown to contain a chondroitin core [→3)-β-d-GalNAc-(1→4)-β-d-GlcA-(1→]n where about 60% of GlcA residues were 3-O-fucosylated, while another part of GlcA units did not contain any substituents. The presence of unsubstituted both at O-2 and O-3 glucuronic acid residues in a structure of holothurian chondroitin sulfate is unusual and has not been reported previously. Three different fucosyl branches Fucp2S4S, Fucp3S4S and Fucp4S were found in the ratio of 2:1:1. The GalNAc units were mono- or disulfated at positions 4 and 6. Anti-inflammatory activity of CD was assessed on a model of acute peritoneal inflammation in rats. About 45% inhibition was found for CD, while a structurally related linear chondroitin sulfate SS from cartilage of the fish Salmo salar demonstrated only 31% inhibition, indicating that the presence of sulfated fucosyl branches is essential for anti-inflammatory effect of chondroitin sulfates of marine origin

Glycosaminoglycans from the Starfish <i>Lethasterias fusca</i>: Structures and Influence on Hematopoiesis

Crude anionic polysaccharides extracted from the Pacific starfish Lethasterias fusca were purified by anion-exchange chromatography. The main fraction LF, having MW 14.5 kDa and dispersity 1.28 (data of gel-permeation chromatography), was solvolytically desulfated and giving rise to preparation LF-deS with a structure of dermatan core [→3)-β-d-GalNAc-(1→4)-α-l-IdoA-(1→]n, which was identified according to NMR spectroscopy data. Analysis of the NMR spectra of the parent fraction LF led to identification of the main component as dermatan sulfate LF-Derm →3)-β-d-GalNAc4R-(1→4)-α-l-IdoA2R3S-(1→ (where R was SO3 or H), bearing sulfate groups at O-3 or both at O-2 and O-3 of α-l-iduronic acid, as well as at O-4 of some N-acetyl-d-galactosamine residues. The minor signals in NMR spectra of LF were assigned as resonances of heparinoid LF-Hep composed of the fragments →4)-α-d-GlcNS3S6S-(1→4)-α-l-IdoA2S3S-(1→. The 3-O-sulfated and 2,3-di-O-sulfated iduronic acid residues are very unusual for natural glycosaminoglycans, and further studies are needed to elucidate their possible specific influence on the biological activity of the corresponding polysaccharides. To confirm the presence of these units in LF-Derm and LF-Hep, a series of variously sulfated model 3-aminopropyl iduronosides were synthesized and their NMR spectra were compared with those of the polysaccharides. Preparations LF and LF-deS were studied as stimulators of hematopoiesis in vitro. Surprisingly, it was found that both preparations were active in these tests, and hence, the high level of sulfation is not necessary for hematopoiesis stimulation in this particular case

Chemical structure and biological activity of a highly branched (1 → 3,1 → 6)- _-d-glucan from Isochrysis galbanaIrina.

International audiencetA highly branched (1 → 3,1 → 6)- -d-glucan was isolated from the microalga Isochrysis galbana Parke(Isochrysidales, Haptophyta). The polysaccharide structure was analyzed by methylation and Smithdegradation, as well as by ESI and MALDI TOF mass spectrometry and NMR spectroscopy. The glucanwas shown to contain a (1 → 6)-linked backbone, where every residue is substituted at position 3 byGlc, which in turn may be substituted at C-6 by a single Glc or by rather short (up to tetrasaccharide)oligosaccharide chains. All the 3-linked Glc residues are present in these side chains. In the biologicalactivity experiments it was demonstrated that the polysaccharide directly inhibits the proliferation ofU937 human leukemic monocyte lymphoma cells and therefore has potential anti-tumor activity