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Sample records for sulfated polysaccharide inhibits

  1. Plant-derived polysaccharide supplements inhibit dextran sulfate sodium-induced colitis in the rat.

    PubMed

    Koetzner, Lee; Grover, Gary; Boulet, Jamie; Jacoby, Henry I

    2010-05-01

    Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term safety after 14 days of daily dosing. Rats were dosed daily orally with vehicle, Ambrotose or Advanced Ambrotose. On day six groups of rats received tap water or 5% Dextran Sulfate sodium. Ambrotose and Advanced Ambrotose significantly lowered the disease scores and partially prevented the shortening of colon length. An increase in monocyte count was induced by dextran sulfate sodium and inhibited by Ambrotose and Advanced Ambrotose. There were no observable adverse effects after 14-day daily doses. The mechanism of action of the formulations against DSS-induced colitis may be related to its effect on monocyte count.

  2. Plant-Derived Polysaccharide Supplements Inhibit Dextran Sulfate Sodium-Induced Colitis in the Rat

    PubMed Central

    Koetzner, Lee; Grover, Gary; Boulet, Jamie

    2009-01-01

    Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term safety after 14 days of daily dosing. Rats were dosed daily orally with vehicle, Ambrotose or Advanced Ambrotose. On day six groups of rats received tap water or 5% Dextran Sulfate sodium. Ambrotose and Advanced Ambrotose significantly lowered the disease scores and partially prevented the shortening of colon length. An increase in monocyte count was induced by dextran sulfate sodium and inhibited by Ambrotose and Advanced Ambrotose. There were no observable adverse effects after 14-day daily doses. The mechanism of action of the formulations against DSS-induced colitis may be related to its effect on monocyte count. PMID:19513840

  3. Inhibition of cultured bovine aortic endothelial cell proliferation by sodium spirulan, a new sulfated polysaccharide isolated from Spirulina platensis.

    PubMed

    Kaji, Toshiyuki; Fujiwara, Yasuyuki; Hamada, Chieko; Yamamoto, Chika; Shimada, Satomi; Lee, Jung-Bum; Hayashi, Toshimitsu

    2002-06-01

    Sodium spirulan (Na-SP) is a sulfated polysaccharide isolated from the blue-green alga Spirulina platensis, which consists of two types of disaccharide repeating units, O-hexuronosyl-rhamnose (aldobiuronic acid) and O-rhamnosyl-3-O-methylrhamnose (acofriose) with sulfate groups, other minor saccharides and sodium ion. Vascular endothelial cells are present on the inner surface of blood vessels in a monolayer and have anticoagulant properties. To address the question whether Na-SP influences the maintenance of endothelial cell monolayers, we investigated the proliferation of cultured bovine aortic endothelial cells treated with Na-SP. It was found that Na-SP has an inhibitory activity on endothelial cell proliferation accompanied with suppression of whole protein synthesis but without non-specific cell damage. The inhibitory activity of Na-SP was the strongest when compared to that of heparan sulfate, heparin, dextran sulfate, dermatan sulfate, chondroitin sulfate A/C and hyaluronan. Furthermore, it was shown that the inhibitory activity of Na-SP disappeared by either desulfation or depolymerization. The present data suggest that Na-SP is a unique sulfated polysaccharide that strongly inhibits vascular endothelial cell proliferation, and the inhibitory activity requires polymerization of sulfated O-rhamnosyl-acofriose repeating units.

  4. Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium

    PubMed Central

    Marques, Joana; Vilanova, Eduardo; Mourão, Paulo A. S.; Fernàndez-Busquets, Xavier

    2016-01-01

    The antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. Here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers Ludwigothurea grisea and Isostichopus badionotus, from the red alga Botryocladia occidentalis, and from the marine sponge Desmapsamma anchorata. In vitro experiments demonstrated for most compounds significant inhibition of Plasmodium falciparum growth at low-anticoagulant concentrations. This activity was found to operate through inhibition of erythrocyte invasion by Plasmodium, likely mediated by a coating of the parasite similar to that observed for heparin. In vivo four-day suppressive tests showed that several of the sulfated polysaccharides improved the survival of Plasmodium yoelii-infected mice. In one animal treated with I. badionotus fucan parasitemia was reduced from 10.4% to undetectable levels, and Western blot analysis revealed the presence of antibodies against P. yoelii antigens in its plasma. The retarded invasion mediated by sulfated polysaccharides, and the ensuing prolonged exposure of Plasmodium to the immune system, can be explored for the design of new therapeutic approaches against malaria where heparin-related polysaccharides of low anticoagulating activity could play a dual role as drugs and as potentiators of immune responses. PMID:27071342

  5. Sulfated polysaccharide from the marine algae Hypnea musciformis inhibits TNBS-induced intestinal damage in rats.

    PubMed

    V Brito, Tarcisio; Barros, Francisco C N; Silva, Renan O; Dias Júnior, Genilson J; C Júnior, José Simião; Franco, Álvaro X; Soares, Pedro M G; Chaves, Luciano S; Abreu, Clara M W S; de Paula, Regina C M; Souza, Marcellus H L P; Freitas, Ana Lúcia P; R Barbosa, André Luiz

    2016-10-20

    Sulfated polysaccharides extracted from seaweed have important pharmacological properties. Thus, the aim of this study was to characterize the sulfated polysaccharide (PLS) from the algae Hypnea musciformis and evaluate its protective effect in colitis induced by trinitrobenzene sulfonic acid in rats. The sulfated polysaccharide possess a high molecular mass (1.24×10(5)gmol(-1)) and is composed of a κ-carrageenan, as depicted by FT-IR and NMR spectroscopic data. PLS was administered orally (10, 30, and 60mg/kg, p.o.) for three days, starting before TNBS (trinitrobenzene sulfonic acid) instillation (day 1). The rats were killed on day three, the portion of distal colon (5cm) was excised and evaluated macroscopic scores and wet weight. Then, samples of the intestinal were used for histological evaluation and quantification of glutathione, malonyldialdehyde acid, myeloperoxidase, nitrate/nitrite and cytokines. Our results demonstrate that PLS reduced the colitis and all analyzed biochemical parameters. Thus, we concluded that the PLS extracted from the marine algae H. musciformis reduced the colitis in animal model and may have an important promising application in the inflammatory bowel diseases.

  6. Sulfated polysaccharides and immune response: promoter or inhibitor?

    PubMed

    Chen, D; Wu, X Z; Wen, Z Y

    2008-06-01

    Sulfated polysaccharides, which frequently connect to core protein, are expressed not only on cell surface but also throughout the extracellular matrix. Besides providing structural integrity of cells, sulfated polysaccharides interact with a variety of sulfated polysaccharides-binding proteins, such as growth factors, cytokines, chemokines and proteases. Sulfated polysaccharides play two-edged roles, inhibitor and promoter, in immune response. Some sulfated polysaccharides act as the immunosuppressor by blocking inflammatory signal transduction induced by proinflammatory cytokines, suppressing the activation of complement and inhibiting the process that leukocytes adhere to and pass through endothelium. On the contrary, the interaction between immune cells and sulfated polysaccharides produced by bacteria, endothelial cells and immune cells initiate the occurrence of immune response. It promotes the processes of recognizing and arresting antigen, migrating transendothelium, moving into and out of immune organ and enhancing the proliferation of lymphocyte. The structure of sulfated polysaccharides, such as molecular weight and sulfated sites heterogeneity, especially the degree of disaccharide sulfation, position of the sulfate moiety and organization of sulfated domains, may play critical role in their controversial effects. As a consequence, the interaction between sulfated polysaccharides and sulfated polysaccharide-binding proteins may be changed by modifying the structure of sulfated polysaccharides chains. The administration of drug targeting sulfated polysaccharide-protein interaction may be useful in treating inflammatory related diseases.

  7. A sulfated polysaccharide of Ecklonia cava inhibits the growth of colon cancer cells by inducing apoptosis

    PubMed Central

    Ahn, Ginnae; Lee, WonWon; Kim, Kil-Nam; Lee, Ji-Hyeok; Heo, Soo-Jin; Kang, Nalae; Lee, Seung-Hong; Ahn, Chang-Bum; Jeon, You-Jin

    2015-01-01

    We investigated anticancer effects of the crude polysaccharides (CPs) isolated from Ecklonia cava enzymatic extracts using AMG, Viscozyme, Protamex, and Alcalase enzyme against a colon cancer cell line, CT26 cells. Among them, the CP of Protamex extract (PCP) contained the highest fucose and sulfated group contents and showed the highest growth inhibitory effect against CT-26 cells. In addition, PCP dose-dependently increased the formation of apoptotic body and the percentage of Sub-G1 DNA contents. Also, PCP activated caspase 9 and PARP as regulating the expressions of Bax and Bcl-2. Moreover, PPP2, a fraction purified from PCP showed the highest growth inhibitory effect against CT 26 cells with the increased fucose and sulfated group contents. The results demonstrate that the isolated SP containing plentiful fucose and sulfated group contents has the anticancer effect on colon cancer cells via regulation of Bcl-2/Bax signal pathway. PMID:26417363

  8. Depolymerization of sulfated polysaccharides under hydrothermal conditions.

    PubMed

    Morimoto, Minoru; Takatori, Masaki; Hayashi, Tetsuya; Mori, Daiki; Takashima, Osamu; Yoshida, Shinichi; Sato, Kimihiko; Kawamoto, Hitoshi; Tamura, Jun-ichi; Izawa, Hironori; Ifuku, Shinsuke; Saimoto, Hiroyuki

    2014-01-30

    Fucoidan and chondroitin sulfate, which are well known sulfated polysaccharides, were depolymerized under hydrothermal conditions (120-180°C, 5-60min) as a method for the preparation of sulfated polysaccharides with controlled molecular weights. Fucoidan was easily depolymerized, and the change of the molecular weight values depended on the reaction temperature and time. The degree of sulfation and IR spectra of the depolymerized fucoidan did not change compared with those of untreated fucoidan at reaction temperatures below 140°C. However, fucoidan was partially degraded during depolymerization above 160°C. Nearly the same depolymerization was observed for chondroitin sulfate. These results indicate that hydrothermal treatment is applicable for the depolymerization of sulfated polysaccharides, and that low molecular weight products without desulfation and deformation of the initial glycan structures can be obtained under mild hydrothermal conditions.

  9. Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis.

    PubMed

    Mishima, T; Murata, J; Toyoshima, M; Fujii, H; Nakajima, M; Hayashi, T; Kato, T; Saiki, I

    1998-08-01

    We have investigated the effect of calcium spirulan (Ca-SP) isolated from a blue-green alga, Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose, on invasion of B16-BL6 melanoma, Colon 26 M3.1 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no effect on that to fibronectin. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel and laminin substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin, while the pretreatment of laminin substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contrast, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP. Seven intermittent i.v. injections of 100 microg of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung metastasis of B16-BL6 melanoma cells, by inhibiting the tumor invasion of basement membrane probably through the prevention of the adhesion and migration of tumor cells to laminin substrate and of the heparanase activity.

  10. Repair of wounded monolayers of cultured bovine aortic endothelial cells is inhibited by calcium spirulan, a novel sulfated polysaccharide isolated from Spirulina platensis.

    PubMed

    Kaji, Toshiyuki; Fujiwara, Yasuyuki; Inomata, Yuki; Hamada, Chieko; Yamamoto, Chika; Shimada, Satomi; Lee, Jung-Bum; Hayashi, Toshimitsu

    2002-03-08

    Calcium spirulan (Ca-SP) is a novel sulfated polysaccharide isolated from a blue-green alga Spirulina platensis. Ca-SP inhibits thrombin by activation of heparin cofactor II. Therefore, it could serve as an origin of anti-atherogenic medicines. Since maintenance of vascular endothelial cell monolayers is important for prevention of vascular lesions such as atherosclerosis, the effect of Ca-SP at 20 microg/ml or less on the repair of wounded bovine aortic endothelial cell monolayers in culture was investigated in the present study. When the monolayers were wounded and cultured in the presence of Ca-SP, the polysaccharide inhibited the appearance of the cells in the wounded area. The inhibition was also observed even when the repair was promoted by excess basic fibroblast growth factor, which is one of the autocrine growth factors that are involved in the endothelial cell monolayer maintenance. On the other hand, Ca-SP inhibited the cell growth and the incorporation of [3H]thymidine into the acid-insoluble fraction of proliferating endothelial cells, suggesting that Ca-SP inhibits endothelial cell proliferation. From these results, it is concluded that Ca-SP may retard the repair process of damaged vascular endothelium through inhibition of vascular endothelial cell proliferation by induction of a lower ability to respond to stimulation by endogenous basic fibroblast growth factor.

  11. Astragalus polysaccharides protect against dextran sulfate sodium-induced colitis by inhibiting NF-κВ activation.

    PubMed

    Lv, Jun; Zhang, Yahong; Tian, Zhiqiang; Liu, Fang; Shi, Ying; Liu, Yao; Xia, Peiyuan

    2017-05-01

    Astragalus polysaccharide (APS) is a bioactive extract of Astragalus membranaceus (AM), which possess a wide range of medicinal benefits, including anti-inflammatory, anti-oxidative, anti-tumor and anti-diabetic effects. The present work evaluated the therapeutic effect of APS and its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis. The APS treatment led to significant improvements in colitis disease activity index (DAI) and histological scores, as well as significantly increased weight and colon length in mice as compared to the control group. Mechanically, reduced NF-κВ DNA phosphorylation activity and downregulated TNF-α, IL-1β, IL-6, IL-17 expressions and myeloperoxidase (MPO) activity were associated with improvement in colitis observed in APS-treated mice. These findings suggest that APS may represent a natural therapeutic approach for treating inflammatory bowel disease, such as ulcerative colitis.

  12. Fucoidans — sulfated polysaccharides of brown algae

    NASA Astrophysics Data System (ADS)

    Usov, Anatolii I.; Bilan, M. I.

    2009-08-01

    The methods of isolation of fucoidans and determination of their chemical structures are reviewed. The fucoidans represent sulfated polysaccharides of brown algae, the composition of which varies from simple fucan sulfates to complex heteropolysaccharides. The currently known structures of such biopolymers are presented. A variety of the biological activities of fucoidans is briefly summarised.

  13. Anti-Food Allergic Activity of Sulfated Polysaccharide from Gracilaria lemaneiformis is Dependent on Immunosuppression and Inhibition of p38 MAPK.

    PubMed

    Liu, Qing-Mei; Yang, Yang; Maleki, Soheila J; Alcocer, Marcos; Xu, Sha-Sha; Shi, Chao-Lan; Cao, Min-Jie; Liu, Guang-Ming

    2016-06-08

    Polysaccharides from Gracilaria lemaneiformis in particular possess various bioactive functions, but their antiallergic activity remains incompletely defined. Sulfated polysaccharide from Gracilaria lemaneiformis (GLSP) was obtained by water extraction and ethanol precipitation followed by column chromatography. BALB/c mice, RBL-2H3, and KU812 cells were used for verifying the anti food allergic activity of GLSP. According to the results of mice experiment, GLSP was able to alleviate allergy symptoms, to reduce TM-specific IgE and IgG1, to suppress Th2 cell polarization, and to promote the function of regulatory T (Treg) cells. In addition, GLSP had the ability to inhibit the function of RBL-2H3 cells. Furthermore, GLSP inhibited the activation of KU812 via suppression of p38 mitogen-activated protein kinase (MAPK). In conclusion, immunosuppression as well as the reduction in the level of p38 MAPK may contribute to GLSP's putative activity against food allergy. GLSP may be used as a functional food component for allergic patients.

  14. Rising from the sea: correlations between sulfated polysaccharides and salinity in plants.

    PubMed

    Aquino, Rafael S; Grativol, Clicia; Mourão, Paulo A S

    2011-04-28

    High salinity soils inhibit crop production worldwide and represent a serious agricultural problem. To meet our ever-increasing demand for food, it is essential to understand and engineer salt-resistant crops. In this study, we evaluated the occurrence and function of sulfated polysaccharides in plants. Although ubiquitously present in marine algae, the presence of sulfated polysaccharides among the species tested was restricted to halophytes, suggesting a possible correlation with salt stress or resistance. To test this hypothesis, sulfated polysaccharides from plants artificially and naturally exposed to different salinities were analyzed. Our results revealed that the sulfated polysaccharide concentration, as well as the degree to which these compounds were sulfated in halophytic species, were positively correlated with salinity. We found that sulfated polysaccharides produced by Ruppia maritima Loisel disappeared when the plant was cultivated in the absence of salt. However, subjecting the glycophyte Oryza sativa Linnaeus to salt stress did not induce the biosynthesis of sulfated polysaccharides but increased the concentration of the carboxylated polysaccharides; this finding suggests that negatively charged cell wall polysaccharides might play a role in coping with salt stress. These data suggest that the presence of sulfated polysaccharides in plants is an adaptation to high salt environments, which may have been conserved during plant evolution from marine green algae. Our results address a practical biological concept; additionally, we suggest future strategies that may be beneficial when engineering salt-resistant crops.

  15. Solomonseal Polysaccharide and Sulfated Codonopsis pilosula Polysaccharide Synergistically Resist Newcastle Disease Virus

    PubMed Central

    Liu, Cui; Chen, Jin; Li, Entao; Fan, Qiang; Wang, Deyun; Zhang, Cunshuai; Li, Peng; Li, Xiuping; Chen, Xingying; Qiu, Shulei; Gao, Zhenzhen; Li, Hongquan; Hu, Yuanliang

    2015-01-01

    Five combinations of three ratios (PS9-sPS1, PS7-sPS3 and PS6-sPS4) were prepared with polysaccharide (PS) and sulfated polysaccharide (sPS). The antiviral activities of these compounds were subsequently compared in vitro using the MTT assay, observation of the virus structure and immunofluorescence. The results demonstrated that SP9-sCP1, CP7-sCA3, EP7-sAP3, CA9-sEP1 and EP7-sCA3 presented higher activities, and SP9-sCP1 displayed the highest virus inhibition rate and clearly killed the virus and inhibited viral antigen expression. In an in vivo test, 28-day-old chickens were challenged with Newcastle disease virus (NDV) and were administered the five drug combinations. On day 14 after the challenge, the morbidity, mortality and cure rate in each group were calculated. The results indicated that SP9-sCP1 presented the lowest morbidity and mortality and the highest cure rate. These results indicate that Solomonseal polysaccharide and sulfated Codonopsis pilosula polysaccharide synergistically resist NDV. Moreover, SP9-sCP1 had the highest efficacy and may be used as a new antiviral drug. PMID:25692886

  16. Sulfation of tea polysaccharides: synthesis, characterization and hypoglycemic activity.

    PubMed

    Wang, Yuanfeng; Peng, Yonghua; Wei, Xinlin; Yang, Zhiwei; Xiao, Jianbo; Jin, Zhengyu

    2010-03-01

    Neutral polysaccharides (NTPS) and acid polysaccharides (ATPS) from tea leaves were obtained on a D315 macroporous anion-exchange resin column chromatography. NTPS and ATPS were sulfated by the pyridine-sulfonic acid method to obtain NTPS-S and ATPS-S. It was found that NTPS was easier sulfated than ATPS. There are strong characteristic absorption peaks located in 1258 cm(-1), 1146 cm(-1), 832 cm(-1) and 617 cm(-1) in the FTIR spectra of sulfated polysaccharides. Sulfation of polysaccharides also affected the endothermic and exothermic peaks via the DSC scan analysis. The appearance of exothermic peaks in both NTPS-S and ATPS-S indicated that the redox reaction might happen. The comparative study of hypoglycemic effect on mice showed that the sulfation of polysaccharides significantly improved hypoglycemic activity.

  17. Sulfated polysaccharides from brown seaweeds Saccharina japonica and Undaria pinnatifida: isolation, structural characteristics, and antitumor activity.

    PubMed

    Vishchuk, Olesya S; Ermakova, Svetlana P; Zvyagintseva, Tatyana N

    2011-12-13

    During the last decade brown seaweeds attracted much attention as a source of polysaccharides, namely laminarans, alginic acids, and sulfated polysaccharides-fucoidans, with various structures and biological activities. In this study, sulfated polysaccharides were isolated from brown seaweeds Saccharina japonica (formerly named Laminaria) and Undaria pinnatifida and their antitumor activity was tested against human breast cancer T-47D and melanoma SK-MEL-28 cell lines. The sulfated polysaccharide form S. japonica was highly branched partially acetylated sulfated galactofucan, built up of (1→3)-α-L-fucose residues. The sulfated polysaccharide from U. pinnatifida was partially acetylated highly sulfated galactofucan consisting of (1→3)- or (1→3);(1→4)-α-L-fucose residues. Fucoidans from S. japonica and U. pinnatifida distinctly inhibited proliferation and colony formation in both breast cancer and melanoma cell lines in a dose-dependent manner. These results indicated that the use of sulfated polysaccharides from brown seaweeds S. japonica and U. pinnatifida might be a potential approach for cancer treatment.

  18. Ca2+-transport in sea urchin unfertilized eggs: regulation by endogenous sulfated polysaccharides and K+.

    PubMed

    Landeira-Fernandez, Ana M; Aquino, Rafael S; Mourão, Paulo A S; de Meis, Leopoldo

    2006-10-01

    Previous data from our laboratory showed that the reticulum of the sea cucumber smooth muscle body wall retains both a sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) and a sulfated polysaccharide. In this invertebrate, the transport of Ca(2+) by the SERCA is naturally inhibited by these endogenous sulfated polysaccharides. The inhibition is reverted by K(+) leading to an enhancement of the Ca(2+) transport rate. We now show that vesicles derived from the endoplasmic reticulum of unfertilized eggs from the sea urchin Arbacia lixula retain a SERCA that is able to transport Ca(2+) at the expense of ATP hydrolysis. As described for the sea cucumber SERCA isoform, the enzyme from the sea urchin is activated by K(+) but not by Li(+) and is inhibited by thapsigargin, a specific inhibitor of SERCA. A new sulfated polysaccharide was identified in the sea urchin eggs reticulum composed mainly by galactose, glucose, hexosamine and manose. After extraction and purification, this sulfated polysaccharide was able to inhibit the mammal SERCA isoform found in rabbit skeletal muscle and the inhibition is reversed by K(+). These data suggest that the regulation of the SERCA pump by K(+) and sulfated polysaccharides is not restricted to few marine invertebrates but is widespread.

  19. Sulfated polysaccharides extracted from sea algae as potential antiviral drugs.

    PubMed

    Witvrouw, M; De Clercq, E

    1997-10-01

    The inhibitory effects of polyanionic substances on the replication of herpes simplex virus (HSV) and other viruses were reported almost four decades ago. However, these observations did not generate much interest, because the antiviral action of the compounds was considered to be largely nonspecific. Shortly after the identification of human immunodeficiency virus (HIV) as the causative agent of the acquired immune deficiency syndrome (AIDS) in 1984, heparin and other sulfated polysaccharides were found to be potent and selective inhibitors of HIV-1 replication in cell culture. Since 1988, the activity spectrum of the sulfated polysaccharides has been shown to extend to various enveloped viruses, including viruses that emerge as opportunistic pathogens (e.g., herpes simplex virus [HSV] and cytomegalovirus [CMV]) in immunosuppressed (e.g., AIDS) patients. As potential anti-HIV drug candidates, sulfated polysaccharides offer a number of promising features. They are able to block HIV replication in cell culture at concentrations as low as 0.1 to 0.01 microgram ml-1 without toxicity to the host cells at concentrations up to 2.5 mg ml-1. We noted that some polysulfates show a differential inhibitory activity against different HIV strains, suggesting that marked differences exist in the target molecules with which polysulfates interact. They not only inhibit the cytopathic effect of HIV, but also prevent HIV-induced syncytium (giant cell) formation. Furthermore, experiments carried out with dextran sulfate samples of increasing molecular weight and with sulfated cyclodextrins of different degrees of sulfation have shown that antiviral activity increases with increasing molecular weight and degree of sulfation. A sugar backbone is not strictly needed for the anti-HIV activity of polysulfates because sulfated polymers composed of a carbon-carbon backbone have also proved to be highly efficient anti-HIV agents in vitro. Other, yet to be defined, structural features may

  20. Chemical Structures and Bioactivities of Sulfated Polysaccharides from Marine Algae

    PubMed Central

    Jiao, Guangling; Yu, Guangli; Zhang, Junzeng; Ewart, H. Stephen

    2011-01-01

    Sulfated polysaccharides and their lower molecular weight oligosaccharide derivatives from marine macroalgae have been shown to possess a variety of biological activities. The present paper will review the recent progress in research on the structural chemistry and the bioactivities of these marine algal biomaterials. In particular, it will provide an update on the structural chemistry of the major sulfated polysaccharides synthesized by seaweeds including the galactans (e.g., agarans and carrageenans), ulvans, and fucans. It will then review the recent findings on the anticoagulant/antithrombotic, antiviral, immuno-inflammatory, antilipidemic and antioxidant activities of sulfated polysaccharides and their potential for therapeutic application. PMID:21566795

  1. Fucose-containing sulfated polysaccharides from brown seaweeds inhibit proliferation of melanoma cells and induce apoptosis by activation of caspase-3 in vitro.

    PubMed

    Ale, Marcel Tutor; Maruyama, Hiroko; Tamauchi, Hidekazu; Mikkelsen, Jørn D; Meyer, Anne S

    2011-12-01

    Fucose-containing sulfated polysaccharides (FCSPs) extracted from seaweeds, especially brown macro-algae, are known to possess essential bioactive properties, notably growth inhibitory effects on tumor cells. In this work, we conducted a series of in vitro studies to examine the influence of FCSPs products from Sargassumhenslowianum C. Agardh (FSAR) and Fucus vesiculosus (FVES), respectively, on proliferation of melanoma B16 cells and to investigate the underlying apoptosis promoting mechanisms. Cell viability analysis showed that both FCSPs products, i.e., FSAR and FVES, decreased the proliferation of the melanoma cells in a dose-response fashion, with FSAR being more potent at lower dosages, and FVES being relatively more anti-proliferative than FSAR at higher dosages. Flow cytometric analysis by Annexin V staining of the melanoma cells exposed to the FCSPs products confirmed that both FSAR and FVES induced apoptosis. The FCSPs-induced apoptosis was evidenced by loss of plasma membrane asymmetry and translocation of the cell membrane phospholipids and was accompanied by the activation of caspase-3. The FCSPs bioactivity is proposed to be attributable to distinct structural features of the FCSPs, particularly the presence of sulfated galactofucans (notably in S.henslowianum) and sulfated fucans (notably in F. vesiculosus). This study thus indicates that unfractionated FCSPs may exert bioactive effects on skin cancer cells via induction of apoptosis through cascades of reactions that involve activation of caspase-3.

  2. Regioselective sulfation of Artemisia sphaerocephala polysaccharide: Characterization of chemical structure.

    PubMed

    Wang, Junlong; Yang, Wen; Wang, Jiancheng; Wang, Xia; Wu, Fang; Yao, Jian; Zhang, Ji; Lei, Ziqiang

    2015-11-20

    The biological activities of sulfated polysaccharides are related to the substitution positions of functional groups. In this study, regioselective sulfation of Artemisia sphaerocephala polysaccharides (SRSASP) was prepared by using triphenylchloromethane (TrCl) as protecting precursor. FT-IR spectra and X-ray photoelectron spectroscopy (XPS) showed that SO(3-) group (S(6+), high binding energy of 168.7eV) was widely present in sulfated polysaccharides. (13)C NMR spectroscopy showed that C-2 and C-3 substitution was occurred but not fully sulfation. Meanwhile, C-6 substituted signals near 65ppm were not observed. The degree of substitution varied from 0.44 to 0.63 in SRSASP which could be attributed to the low reactivity at secondary hydroxyl. Monosaccharide composition result showed a decrease in the ratio of mannose/glucose, indicating the change of chemical composition in sulfated polysaccharides. In size-exclusion chromatograph analysis, a decrease in molecular weight and broadening of molecular weight distribution of sulfated polysaccharides was also observed. It could be attributed to the hydrolysis of polysaccharide in the sulfated reaction.

  3. Catalytic synthesis of sulfated polysaccharides I: Characterization of chemical structure.

    PubMed

    Wang, Junlong; Yang, Wen; Yang, Ting; Zhang, Xiaonuo; Zuo, Yuan; Tian, Jia; Yao, Jian; Zhang, Ji; Lei, Ziqiang

    2015-03-01

    In the present study, sulfated derivatives of Artemisia sphaerocephala polysaccharide (SASP) with high degree of substitution (DS) were synthesized by using 4-dimethylaminopyridine (DMAP)/dimethylcyclohexylcarbodiimide (DCC) as catalyst in homogeneous conditions. It was found that DMAP/DCC showed marked improvement in DS of sulfated samples. Compared to sulfated derivatives without catalyst, the DS of SASP increased from 0.91 to 1.28 with an increment in dosage of DMAP from 0 to 10 mg. The influence of DMAP/DCC on the DS of sulfated derivatives was depended on the content of DMAP. The effect of DMAP might be due to its strong coordination to the hydroxy group. The results of FT-IR and X-ray photoelectron spectroscopy (XPS) indicated that SO3- group (S6+, binding energy of 172.3 eV) was widely present in sulfated polysaccharide molecules. 13C NMR results indicated that C-6 substitution was predominant for sulfated polysaccharide when compared with other positions. In the sulfation reaction, a sharp decrease in MW was observed. DMAP/DCC was an effective catalyst system in sulfated modification of polysaccharide.

  4. Sulfated polysaccharides from marine sponges (Porifera): an ancestor cell-cell adhesion event based on the carbohydrate-carbohydrate interaction.

    PubMed

    Vilanova, Eduardo; Coutinho, Cristiano C; Mourão, Paulo A S

    2009-08-01

    Marine sponges (Porifera) are ancient and simple eumetazoans. They constitute key organisms in the evolution from unicellular to multicellular animals. We now demonstrated that pure sulfated polysaccharides from marine sponges are responsible for the species-specific cell-cell interaction in these invertebrates. This conclusion was based on the following observations: (1) each species of marine sponge has a single population of sulfated polysaccharide, which differ among the species in their sugar composition and sulfate content; (2) sulfated polysaccharides from sponge interact with each other in a species-specific way, as indicated by an affinity chromatography assay, and this interaction requires calcium; (3) homologous, but not heterologous, sulfated polysaccharide inhibits aggregation of dissociated sponge cells; (4) we also observed a parallel between synthesis of the sulfated polysaccharide and formation of large aggregates of sponge cells, known as primmorphs. Once aggregation reached a plateau, the demand for the de novo synthesis of sulfated polysaccharides ceased. Heparin can mimic the homologous sulfated polysaccharide on the in vitro interaction and also as an inhibitor of aggregation of the dissociated sponge cells. However, this observation is not relevant for the biology of the sponge since heparin is not found in the invertebrate. In conclusion, marine sponges display an ancestor event of cell-cell adhesion, based on the calcium-dependent carbohydrate-carbohydrate interaction.

  5. Extraction, characterization and antimicrobial activity of sulfated polysaccharides from fish skins.

    PubMed

    Krichen, Fatma; Karoud, Wafa; Sila, Assaâd; Abdelmalek, Baha Eddine; Ghorbel, Raoudha; Ellouz-Chaabouni, Semia; Bougatef, Ali

    2015-04-01

    Sulfated polysaccharides were extracted from gray triggerfish (GTSP) and smooth hound (SHSP) skins. Their chemical and physical characteristics were determined using X-ray diffraction and Infrared spectroscopic analysis. The antibacterial activities of GTSP and SHSP against Listeria monocytogenes (ATCC 43251), Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25922), Salmonella enterica (ATCC 43972) and Enterobacter sp were evaluated by determining clear growth inhibition zone diameters and the minimum inhibitory concentration (MIC) values and by essays in liquid media. GTSP and SHSP were fractionated by a Diethylaminoethyl-cellulose chromatography. Fraction FGII, from GTSP, and fraction FSII, from SHSP, showed the most important inhibitory effects against the tested bacterial species. The sulfated polysaccharides from fish skins did not show hemolytic activity towards bovine erythrocytes. Overall, the results suggested that those polysaccharides could offer promising sources of polysaccharides for future application as dietary ingredients in the nutraceutical industry.

  6. Structure and anticoagulant property of a sulfated polysaccharide isolated from the green seaweed Monostroma angicava.

    PubMed

    Li, Na; Liu, Xue; He, Xiaoxi; Wang, Shuyao; Cao, Sujian; Xia, Zheng; Xian, Huali; Qin, Ling; Mao, Wenjun

    2017-03-01

    An anticoagulant-active polysaccharide PF2 was extracted with boiling water from the green seaweed Monostroma angicava, further purified by anion-exchange and size-exclusion chromatography. PF2 was a rhamnan-type sulfated polysaccharide with molecular weight of about 88.1kDa. Results of chemical and spectroscopic analyses demonstrated that PF2 consisted of→3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→residues, with partially branches at C-2 of→3)-α-l-Rhap-(1→residues. Sulfate groups were substituted at C-3 of →2)-α-l-Rhap-(1→ residues. The sulfated polysaccharide PF2 had a high anticoagulant action, and the mechanism of anticoagulant activity mediated by PF2 was mainly attributed to strong potentiation thrombin by heparin cofactor II. PF2 also exhibited weak effect on antithrombin-dependent thrombin or factor Xa inhibition. The fibrin(ogen)olytic activity and thrombolytic activity of PF2 were also evaluated. The investigation revealed that PF2 was a novel sulfated rhamnan differing from previously described sulfated polysaccharides from green seaweed and could be a potential anticoagulant polysaccharide.

  7. Sulfation of extracellular polysaccharides of red microalgae: preparation, characterization and properties.

    PubMed

    Geresh, Shimona; Mamontov, Anna; Weinstein, Jacob

    2002-01-04

    Polysaccharides are natural polymers with a variety of properties that may be translated into significant commercial applications. A program of chemical modifications of the extracellular polysaccharides of red microalgae, such as Porphyridium sp. and Rhodella reticulata, has been undertaken by our group in order to tailor new properties and hence to broaden the spectrum of potential applications. These algal biopolymers are anionic in nature due to the presence of uronic acids (about 10%) and sulfate half esters (about 7%). In the current study, the sulfate content of these biopolymers was increased to 35-40% by means of sulfation agents such as pyridine SO(3), DMF.SO(3) and ClSO(3)H. Reaction conditions were optimized in a model system based on potato starch as the model polysaccharide (type of reagent, temperature and time of reaction). After work-up procedures, the highest sulfate content was obtained by sulfation of the polysaccharide of Porphyridium sp. with a mixture of ClSO(3)H and pyridine at 70 degrees C for 1 h. The sulfated products were characterized by chemical and rheological analyses, IR spectroscopy, and GPC-HPLC chromatography. "Oversulfated" polymers (having sulfate contents exceeding 20%) with high molecular weights were found to inhibit mammalian cell growth when used at certain concentrations; for example, over 80% inhibition was obtained when oversulfated polymers at a concentration of 200 microg/ml were tested on T-cell lymphoma line 24-1. These preliminary results indicate that the modified polysaccharides do indeed exhibit potential therapeutic properties.

  8. Effect of sulfated modification on the molecular characteristics and biological activities of polysaccharides from Hypsizigus marmoreus.

    PubMed

    Bao, HongHui; Choi, Won-Seok; You, SangGuan

    2010-01-01

    The effect of sulfated modification on polysaccharides from Hypsizigus marmoreus was examined by determining their molecular structures and bioactivities. The sulfation, which was implemented by using an orthogonal array design, produced polysaccharides with varying degrees of substitution (DS) ranging from 0.11 to 1.06. The sulfated polysaccharides exhibited a lower average molecular weight (M(w)) and considerably higher radius of gyration (R(g)) than those of native polysaccharide, suggesting that the conformation of the sulfated polysaccharides had been changed towards a more extended type. The inhibitory activity toward cancer cell growth was enhanced by treating with the sulfated polysaccharides by up to 34%, as compared to the native polysaccharide. In addition, treating with the sulfated polysaccharides increased the nitric oxide (NO) and cytokine (IL-1beta and TNF-alpha) release to levels comparable to those detected in the positive control, lipopolysaccharide (LPS), suggesting that the sulfated polysaccharides might have strong immunomodulatory activity.

  9. Sulfation patterns determine cellular internalization of heparin-like polysaccharides

    PubMed Central

    Raman, Karthik; Mencio, Caitlin; Desai, Umesh R.; Kuberan, Balagurunathan

    2013-01-01

    Heparin is a highly sulfated polysaccharide which serves biologically relevant roles as an anticoagulant and anti-cancer agent. While it is well known that modification of heparin’s sulfation pattern can drastically influence its ability to bind growth factors and other extracellular molecules, very little is known about the cellular uptake of heparin and the role sulfation patterns serve in affecting its internalization. In this study, we chemically synthesized several fluorescently-labeled heparins consisting of a variety of sulfation patterns. These polysaccharides were thoroughly characterized using anion exchange chromatography and size exclusion chromatography. Subsequently, we utilized flow cytometry and confocal imaging to show that sulfation patterns differentially affect the amount of heparin uptake in multiple cell types. This study provides the first comprehensive analysis of the effect of sulfation pattern on the cellular internalization of heparin or heparan sulfate like polysaccharides. The results of this study expand current knowledge regarding heparin internalization and provide insights into developing more effective heparin-based drug conjugates for applications in intracellular drug delivery. PMID:23398560

  10. Sulfation patterns determine cellular internalization of heparin-like polysaccharides.

    PubMed

    Raman, Karthik; Mencio, Caitlin; Desai, Umesh R; Kuberan, Balagurunathan

    2013-04-01

    Heparin is a highly sulfated polysaccharide that serves biologically relevant roles as an anticoagulant and anticancer agent. While it is well-known that modification of heparin's sulfation pattern can drastically influence its ability to bind growth factors and other extracellular molecules, very little is known about the cellular uptake of heparin and the role sulfation patterns serve in affecting its internalization. In this study, we chemically synthesized several fluorescently labeled heparins consisting of a variety of sulfation patterns. These polysaccharides were thoroughly characterized using anion exchange chromatography and size exclusion chromatography. Subsequently, we utilized flow cytometry and confocal imaging to show that sulfation patterns differentially affect the amount of heparin uptake in multiple cell types. This study provides the first comprehensive analysis of the effect of sulfation pattern on the cellular internalization of heparin or heparan sulfate like polysaccharides. The results of this study expand current knowledge regarding heparin internalization and provide insights into developing more effective heparin-based drug conjugates for applications in intracellular drug delivery.

  11. Sulfated polysaccharides from Loligo vulgaris skin: potential biological activities and partial purification.

    PubMed

    Abdelmalek, Baha Eddine; Sila, Assaâd; Krichen, Fatma; Karoud, Wafa; Martinez-Alvarez, Oscar; Ellouz-Chaabouni, Semia; Ayadi, Mohamed Ali; Bougatef, Ali

    2015-01-01

    The characteristics, biological properties, and purification of sulfated polysaccharides extracted from squid (Loligo vulgaris) skin were investigated. Their chemical and physical characteristics were determined using X-ray diffraction and infrared spectroscopic analysis. Sulfated polysaccharides from squid skin (SPSS) contained 85.06% sugar, 2.54% protein, 1.87% ash, 8.07% sulfate, and 1.72% uronic acid. The antioxidant properties of SPSS were investigated based on DPPH radical-scavenging capacity (IC50 = 19.42 mg mL(-1)), hydrogen peroxide-scavenging activity (IC50 = 0.91 mg mL(-1)), and β-carotene bleaching inhibition (IC50 = 2.79 mg mL(-1)) assays. ACE-inhibitory activity of SPSS was also investigated (IC50 = 0.14 mg mL(-1)). Further antimicrobial activity assays indicated that SPSS exhibited marked inhibitory activity against the bacterial and fungal strains tested. Those polysaccharides did not display hemolytic activity towards bovine erythrocytes. Fractionation by DEAE-cellulose column chromatography showed three major absorbance peaks. Results of this study suggest that sulfated polysaccharides from squid skin are attractive sources of polysaccharides and promising candidates for future application as dietary ingredients.

  12. Structure-function relationship of anticoagulant and antithrombotic well-defined sulfated polysaccharides from marine invertebrates.

    PubMed

    Pomin, Vitor H

    2012-01-01

    Marine sulfated polysaccharides (MSPs), such as sulfated fucans (SFs), sulfated galactans (SGs), and glycosaminoglycans (GAGs) isolated from invertebrate animals, are highly anionic polysaccharides capable of interacting with certain cationic proteins, such as (co)-factors of the coagulation cascade during clotting-inhibition process. Primarily, these molecular complexes between MSPs and coagulation-related proteins seem to be driven mostly by electrostatic interactions. However, through a systematic comparison using several novel well-defined sulfated polysaccharides composed of repetitive oligosaccharides with clear sulfation patterns, it was proved that those molecular interactions are essentially regulated by the stereochemistry of the glycans (which depends on a conjunction of anomeric configurations, sugar types, conformational preferences, glycosylation, and sulfation sites), rather than just a mere consequence of the electronegative density charges (mainly from number of sulfate groups). Here, we present an overview about the structure-function relationship of the invertebrate MSPs with regular structures as potential anticoagulant and antithrombotic agents, as pathologies related to the cardiovascular system are one of the major causes of mortality in the world.

  13. Sulfated polysaccharides from Cyclocarya paliurus reduce H2O2-induced oxidative stress in RAW264.7 cells.

    PubMed

    Wang, Zhi-Jun; Xie, Jian-Hua; Kan, Li-Jiao; Wang, Jun-Qiao; Shen, Ming-Yue; Li, Wen-Juan; Nie, Shao-Ping; Xie, Ming-Yong

    2015-09-01

    In this study, two sulfated polysaccharides (S-CP1-4 and S-CP1-8) from Cyclocarya paliurus were produced by chlorosulfonic acid-pyridine method. Hydrogen peroxide (H2O2) was used to develop an oxidative stress model in the mouse macrophage cell line RAW264.7. Effects of the two sulfated polysaccharides on H2O2-induced oxidative stress were investigated. The results showed that S-CP(1-8) improved the viability of the H2O2-induced stressed RAW264.7 cells, as well as inhibited the lipid oxidation as determined by the level of malondialdehyde (MDA). Meanwhile, treatment with S-CP(1-4) increased superoxide dismutase (SOD) activity in these cells. The sulfated polysaccharides were found to have a better protective effect against H2O2-induced oxidative stress as compared to the native polysaccharide. Scanning electron microscopy also showed a significant change in the surface morphology of sulfated polysaccharides, but the degradation of main chain of polysaccharides was unconspicuous according to the results of monosaccharide composition. In addition, the sulfated polysaccharides had noticeable DPPH radical scavenging activity. In summary, our results demonstrated that H2O2 was able to induce oxidative stress in RAW264.7 cells, and sulfated group might play an important role in resistance to H2O2-induced oxidative damage.

  14. Sulfation of a polysaccharide produced by a marine filamentous fungus Phoma herbarum YS4108 alters its antioxidant properties in vitro.

    PubMed

    Yang, X B; Gao, X D; Han, F; Tan, R X

    2005-08-30

    Free radicals and other reactive oxygen species (ROS) are generated by all aerobic cells and are widely believed to play a significant role in aging as well as a number of degenerative or pathological diseases. This study compared the free radical-scavenging properties and antioxidant activity of YCP, a polysaccharide from the mycelium of a marine filamentous fungus Phoma herbarum YS 4108 and its two chemically sulfated derivatives YCP-S1 and YCP-S2. Sulfation, which masks hydroxyl groups of YCP polysaccharide molecule, could introduce new antioxidant activity, such as superoxide and hydroxyl radicals scavenging activity, metal chelating action, lipid peroxidation and linoleic acid oxidation inhibition capability. Furthermore, sulfated YCP was more potent than YCP at protecting erythrocytes against oxidative damage hemolysis. The current data suggest for the first time that sulfation of polysaccharide significantly increases its antioxidant activity and the chemical modification of polysaccharides may allow the preparation of derivatives with new properties and a variety of applications.

  15. Chemical characteristic and anticoagulant activity of the sulfated polysaccharide isolated from Monostroma latissimum (Chlorophyta).

    PubMed

    Mao, Wenjun; Li, Hongyan; Li, Yi; Zhang, Huijuan; Qi, Xiaohui; Sun, Haihong; Chen, Yin; Guo, Shoudong

    2009-01-01

    A polysaccharide was isolated from marine green algae Monostroma latissimum, and its chemical characteristic and anticoagulant activity were investigated. The results demonstrated that the polysaccharide was high rhamnose-containing sulfated polysaccharide, and was mainly composed of 1,2-linked l-rhamnose residues with sulfate groups substituted at positions C-3 and/or C-4. The sulfated polysaccharide exhibited high anticoagulant activities by assays of the activated partial thromboplastin time (APTT) and thrombin time (TT). The anticoagulant property of the sulfated polysaccharide was mainly attributed to powerful potentiation thrombin by heparin cofactor II.

  16. Sulfated Seaweed Polysaccharides as Multifunctional Materials in Drug Delivery Applications

    PubMed Central

    Cunha, Ludmylla; Grenha, Ana

    2016-01-01

    In the last decades, the discovery of metabolites from marine resources showing biological activity has increased significantly. Among marine resources, seaweed is a valuable source of structurally diverse bioactive compounds. The cell walls of marine algae are rich in sulfated polysaccharides, including carrageenan in red algae, ulvan in green algae and fucoidan in brown algae. Sulfated polysaccharides have been increasingly studied over the years in the pharmaceutical field, given their potential usefulness in applications such as the design of drug delivery systems. The purpose of this review is to discuss potential applications of these polymers in drug delivery systems, with a focus on carrageenan, ulvan and fucoidan. General information regarding structure, extraction process and physicochemical properties is presented, along with a brief reference to reported biological activities. For each material, specific applications under the scope of drug delivery are described, addressing in privileged manner particulate carriers, as well as hydrogels and beads. A final section approaches the application of sulfated polysaccharides in targeted drug delivery, focusing with particular interest the capacity for macrophage targeting. PMID:26927134

  17. Sulfated Seaweed Polysaccharides as Multifunctional Materials in Drug Delivery Applications.

    PubMed

    Cunha, Ludmylla; Grenha, Ana

    2016-02-25

    In the last decades, the discovery of metabolites from marine resources showing biological activity has increased significantly. Among marine resources, seaweed is a valuable source of structurally diverse bioactive compounds. The cell walls of marine algae are rich in sulfated polysaccharides, including carrageenan in red algae, ulvan in green algae and fucoidan in brown algae. Sulfated polysaccharides have been increasingly studied over the years in the pharmaceutical field, given their potential usefulness in applications such as the design of drug delivery systems. The purpose of this review is to discuss potential applications of these polymers in drug delivery systems, with a focus on carrageenan, ulvan and fucoidan. General information regarding structure, extraction process and physicochemical properties is presented, along with a brief reference to reported biological activities. For each material, specific applications under the scope of drug delivery are described, addressing in privileged manner particulate carriers, as well as hydrogels and beads. A final section approaches the application of sulfated polysaccharides in targeted drug delivery, focusing with particular interest the capacity for macrophage targeting.

  18. Antiviral activities of sulfated polysaccharides isolated from Sphaerococcus coronopifolius (Rhodophytha, Gigartinales) and Boergeseniella thuyoides (Rhodophyta, Ceramiales).

    PubMed

    Bouhlal, Rhimou; Haslin, Camille; Chermann, Jean-Claude; Colliec-Jouault, Sylvia; Sinquin, Corinne; Simon, Gaelle; Cerantola, Stephane; Riadi, Hassane; Bourgougnon, Nathalie

    2011-01-01

    Water-soluble sulfated polysaccharides isolated from two red algae Sphaerococcus coronopifolius (Gigartinales, Sphaerococcaceae) and Boergeseniella thuyoides (Ceramiales, Rhodomelaceae) collected on the coast of Morocco inhibited in vitro replication of the Human Immunodeficiency Virus (HIV) at 12.5 μg/mL. In addition, polysaccharides were capable of inhibiting the in vitro replication of Herpes simplex virus type 1 (HSV-1) on Vero cells values of EC₅₀ of 4.1 and 17.2 μg/mL, respectively. The adsorption step of HSV-1 to the host cell seems to be the specific target for polysaccharide action. While for HIV-1, these results suggest a direct inhibitory effect on HIV-1 replication by controlling the appearance of the new generations of virus and potential virucidal effect. The polysaccharides from S. coronopifolius (PSC) and B. thuyoides (PBT) were composed of galactose, 3,6-anhydrogalactose, uronics acids, sulfate in ratios of 33.1, 11.0, 7.7 and 24.0% (w/w) and 25.4, 16.0, 3.2, 7.6% (w/w), respectively.

  19. Antiviral Activities of Sulfated Polysaccharides Isolated from Sphaerococcus coronopifolius (Rhodophytha, Gigartinales) and Boergeseniella thuyoides (Rhodophyta, Ceramiales)

    PubMed Central

    Bouhlal, Rhimou; Haslin, Camille; Chermann, Jean-Claude; Colliec-Jouault, Sylvia; Sinquin, Corinne; Simon, Gaelle; Cerantola, Stephane; Riadi, Hassane; Bourgougnon, Nathalie

    2011-01-01

    Water-soluble sulfated polysaccharides isolated from two red algae Sphaerococcus coronopifolius (Gigartinales, Sphaerococcaceae) and Boergeseniella thuyoides (Ceramiales, Rhodomelaceae) collected on the coast of Morocco inhibited in vitro replication of the Human Immunodeficiency Virus (HIV) at 12.5 μg/mL. In addition, polysaccharides were capable of inhibiting the in vitro replication of Herpes simplex virus type 1 (HSV-1) on Vero cells values of EC50 of 4.1 and 17.2 μg/mL, respectively. The adsorption step of HSV-1 to the host cell seems to be the specific target for polysaccharide action. While for HIV-1, these results suggest a direct inhibitory effect on HIV-1 replication by controlling the appearance of the new generations of virus and potential virucidal effect. The polysaccharides from S. coronopifolius (PSC) and B. thuyoides (PBT) were composed of galactose, 3,6-anhydrogalactose, uronics acids, sulfate in ratios of 33.1, 11.0, 7.7 and 24.0% (w/w) and 25.4, 16.0, 3.2, 7.6% (w/w), respectively. PMID:21822410

  20. Fucans, but not fucomannoglucuronans, determine the biological activities of sulfated polysaccharides from Laminaria saccharina brown seaweed.

    PubMed

    Croci, Diego O; Cumashi, Albana; Ushakova, Natalia A; Preobrazhenskaya, Marina E; Piccoli, Antonio; Totani, Licia; Ustyuzhanina, Nadezhda E; Bilan, Maria I; Usov, Anatolii I; Grachev, Alexey A; Morozevich, Galina E; Berman, Albert E; Sanderson, Craig J; Kelly, Maeve; Di Gregorio, Patrizia; Rossi, Cosmo; Tinari, Nicola; Iacobelli, Stefano; Rabinovich, Gabriel A; Nifantiev, Nikolay E

    2011-02-28

    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

  1. In Vitro Antioxidant Activities of Sulfated Derivatives of Polysaccharides Extracted from Auricularia auricular

    PubMed Central

    Zhang, Hua; Wang, Zhen-Yu; Yang, Lin; Yang, Xin; Wang, Xue; Zhang, Zhi

    2011-01-01

    In this research, two types of sulfated polysaccharide derivatives were successfully synthesized. Their antioxidant activities were investigated by employing various established in vitro systems. In addition, the degree of sulfation was evaluated using ion-chromatography and IR spectra. The results verify that, when employing scavenging superoxide radical tests, both the sulfation of acid Auricularia auricular polysaccharides (SAAAP) and the sulfation of neutral Auricularia auricular polysaccharides (SNAAP) derivatives possessed considerable antioxidant activity and had a more powerful antioxidant competence than that of the native non-sulfated polysaccharides (AAAP and NAAP). On the other hand, AAAP and NAAP exhibited stronger activity on scavenging both the hydroxyl radical and lipid peroxidation. Available data obtained with in vitro measurements indicates that the sulfated groups of AAAP and NAAP played an important role on antioxidant activity. In sum, the research demonstrates that the antioxidant activity of sulfated polysaccharide derivatives in vitro has a potential significance for seeking new natural antioxidant protective agents. PMID:21686185

  2. In vitro antioxidant activities of sulfated derivatives of polysaccharides extracted from Auricularia auricular.

    PubMed

    Zhang, Hua; Wang, Zhen-Yu; Yang, Lin; Yang, Xin; Wang, Xue; Zhang, Zhi

    2011-01-01

    In this research, two types of sulfated polysaccharide derivatives were successfully synthesized. Their antioxidant activities were investigated by employing various established in vitro systems. In addition, the degree of sulfation was evaluated using ion-chromatography and IR spectra. The results verify that, when employing scavenging superoxide radical tests, both the sulfation of acid Auricularia auricular polysaccharides (SAAAP) and the sulfation of neutral Auricularia auricular polysaccharides (SNAAP) derivatives possessed considerable antioxidant activity and had a more powerful antioxidant competence than that of the native non-sulfated polysaccharides (AAAP and NAAP). On the other hand, AAAP and NAAP exhibited stronger activity on scavenging both the hydroxyl radical and lipid peroxidation. Available data obtained with in vitro measurements indicates that the sulfated groups of AAAP and NAAP played an important role on antioxidant activity. In sum, the research demonstrates that the antioxidant activity of sulfated polysaccharide derivatives in vitro has a potential significance for seeking new natural antioxidant protective agents.

  3. Physico-chemical characterization and pharmacological activities of sulfated polysaccharide from sea urchin, Paracentrotus lividus.

    PubMed

    Salem, Yosra Ben; Amri, Safa; Hammi, Khaoula Mkadmini; Abdelhamid, Amal; Cerf, Didier Le; Bouraoui, Abderrahman; Majdoub, Hatem

    2017-04-01

    Sulfated polysaccharide (SP) from the eggs of sea urchin Paracentrotus lividus, extracted by papain digestion, was characterized by size exclusion chromatography coupling on-line with light scattering and viscosity detectors (SEC/MALS/VD/DRI), gas chromatography coupled to mass spectrometer (GC-MS), and Fourier transform infrared spectroscopy (FTIR) analysis. The native molecular mass of the extracted polysaccharide is high (≥22 000 KDa) and it is composed mainly of arabinose, accompanied by other monosaccharides (mostly galactose, glucose and fucose), significant amounts of uronic acids (18.4%) and relatively high proportions of sulfate (22.4%). The pharmacological evaluation of SP showed a significant in vivo anti-inflammatory activity (p<0.001), 3h after injection, the edema inhibition was 75.8% at the dose of 100mg/Kg; a significant peripheral analgesic activity (p<0.001), with 64.9% of writhing inhibition, and a significant increase in the hot plate reaction time in mice indicating central analgesic activity. In addition, an interesting gastroprotective effect was observed with this polysaccharide; the gastric ulcer inhibition was 69.7%, at the dose of 100mg/Kg.

  4. Antitumor activities and immunomodulatory of rice bran polysaccharides and its sulfates in vitro.

    PubMed

    Wang, Li; Li, Yulin; Zhu, Lidan; Yin, Ran; Wang, Ren; Luo, Xiaohu; Li, Yongfu; Li, Yanan; Chen, Zhengxing

    2016-07-01

    Polysaccharides purified from rice bran show antitumor activity against tumor cells, yet the mechanism of this action remains poorly understood. To address this issue, our study evaluated the effect of rice bran polysaccharides on mouse melanoma cell line B16, and Raw264.7 macrophages. Rice bran polysaccharides (RBP) failed to inhibit B16 cell growth in vitro. However, Raw264.7 macrophages treated by RBP enhancement of cytotoxic effects. The cytotoxicity was confirmed by the stimulation of nitric oxide (NO) production and tumor necrosis factor-α (TNF-α) secretion on Raw264.7 macrophages in a dose-dependent manner. RBP2, a fraction of RBP, notably enhanced the inhibition of B16 cells and boosted the immunepotentiation effect compared with RBP. To further enhance the inhibition of B16 cell growth, sulfated polysaccharides (SRBP) was derived using the chlorosulfonic acid-pyridine method. SRBP2 was found to suppress B16 cell growth, reduce B16 cell survival and stimulate NO and TNF-α production. However, SRBP2 displayed a cytotoxic effect on Raw264.7 macrophages. These results suggest that the antitumor activity of RBP and RBP2 is mediated mainly through the activation of macrophages. SRBP2 exerts its antitumor activity by inducing apoptosis in tumor cells and the secretion of NO and TNF-α.

  5. Chemical characterization and antiherpes activity of sulfated polysaccharides from Lithothamnion muelleri.

    PubMed

    Malagoli, Bruna G; Cardozo, Francielle T G S; Gomes, Jose Hugo S; Ferraz, Vany P; Simões, Cláudia M O; Braga, Fernão C

    2014-05-01

    We report herein the chemical characterization and antiherpes activity of polysaccharides from the red alga Lithothamnion muelleri (Hapalidiaceae). The polysaccharide-rich fractions B1 and B2 were obtained by extraction with Na2CO3 and were purified by size exclusion chromatography to afford Fra-B1 and Fra-B2. The polysaccharides were characterized by FT-IR and chemical analysis (total contents of carbohydrates, proteins, sulfate and uronic acid), whereas their average molecular weights were estimated by high performance gel permeation chromatography. The monosaccharide analysis detected galactose, glucose, xylose, mannose, rhamnose and arabinose in the four polysaccharide samples. Antiherpetic in vitro assays showed that B1 and B2 inhibited Herpes Simplex Virus types 1 and 2 (HSV-1 and HSV-2) when added simultaneously to viral infection affording selectivity indices (SI=CC50/EC50) higher than 20. Investigation of the mechanism of action indicated that B1 and B2 act on the initial steps of HSV replication, mainly inhibiting viral adsorption but also viral penetration into the cells.

  6. Sulfation, anticoagulant and antioxidant activities of polysaccharide from green algae Enteromorpha linza.

    PubMed

    Wang, Xiaomei; Zhang, Zhongshan; Yao, Zhiyun; Zhao, Mingxing; Qi, Huimin

    2013-07-01

    Sulfated polysaccharides exerted potent biological property which was relative to degree of sulfation, molecular weight, substitution position and chain conformation. In present study, the polysaccharide with low molecular weight (LEP) from Enteromorpha linza was sulfated with chlorosulfuric acid in formamide. The obtained polysaccharide sulfate was selected to evaluate their antioxidant activities and the anticoagulant activity in the coagulation assays, activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT). The data obtained in vitro models indicated that high DS and moderate Mw showed the best anticoagulant and antioxidant activities.

  7. Structural characterization and biomedical properties of sulfated polysaccharide from the gladius of Sepioteuthis lessoniana (Lesson, 1831).

    PubMed

    Seedevi, Palaniappan; Moovendhan, Meivelu; Vairamani, Shanmugam; Shanmugam, Annian

    2016-04-01

    Sulfated polysaccharide was extracted from the internal shell (gladius) of Sepioteuthis lessoniana. The sulfated polysaccharide contained 61.3% of carbohydrate, 0.8% of protein, 28.2% of ash and 1.33% of moisture respectively. The elemental composition was analyzed using CHNS/O analyzer. The molecular weight of sulfated polysaccharide determined through PAGE was found to be as 66 kDa. Monosaccharides analysis revealed that sulfated polysaccharide was composed of rhamnose, galactose, xylose and glucose. The structural features of sulfated polysaccharide were analyzed by FT-IR and NMR spectroscopy. Further the sulfated polysaccharide was evaluated for its antibacterial activity against selected human clinical pathogens, namely Staphylococcus aureus, Klebsiella pneumoniae, Salmonella typhi, Vibrio cholerae, Klebsiella oxytoca, Escherichia coli, Salmonella paratyphi, Proteus mirabilis, Vibrio parahaemolyticus and Streptococcus pyogenes using agar well diffusion method. The polysaccharide has showed good antibacterial activity and MIC and MBC have also been evaluated. The anticancer activity was tested against HeLa cell line by MTT assay. The Cytotoxic Concentration (CC50) was observed as 700 μg/ml and the maximum anticancer activity of 62.89% was recorded at 200 μg/ml; whereas, the lowest of 9.87% was observed at 25 μg/ml. In conclusion, the sulfated polysaccharide is an alternate, non-toxic and cheap source of substance that showed good antibacterial and anticancer acitivity.

  8. Synthesis and catalytic activity of polysaccharide templated nanocrystalline sulfated zirconia

    SciTech Connect

    Sherly, K. B.; Rakesh, K.

    2014-01-28

    Nanoscaled materials are of great interest due to their unique enhanced optical, electrical and magnetic properties. Sulfate-promoted zirconia has been shown to exhibit super acidic behavior and high activity for acid catalyzed reactions. Nanocrystalline zirconia was prepared in the presence of polysaccharide template by interaction between ZrOCl{sub 2}⋅8H{sub 2}O and chitosan template. The interaction was carried out in aqueous phase, followed by the removal of templates by calcination at optimum temperature and sulfation. The structural and textural features were characterized by powder XRD, TG, SEM and TEM. XRD patterns showed the peaks of the diffractogram were in agreement with the theoretical data of zirconia with the catalytically active tetragonal phase and average crystalline size of the particles was found to be 9 nm, which was confirmed by TEM. TPD using ammonia as probe, FTIR and BET surface area analysis were used for analyzing surface features like acidity and porosity. The BET surface area analysis showed the sample had moderately high surface area. FTIR was used to find the type species attached to the surface of zirconia. UV-DRS found the band gap of the zirconia was found to be 2.8 eV. The benzylation of o-xylene was carried out batchwise in atmospheric pressure and 433K temperature using sulfated zirconia as catalyst.

  9. Synthesis and catalytic activity of polysaccharide templated nanocrystalline sulfated zirconia

    NASA Astrophysics Data System (ADS)

    Sherly, K. B.; Rakesh, K.

    2014-01-01

    Nanoscaled materials are of great interest due to their unique enhanced optical, electrical and magnetic properties. Sulfate-promoted zirconia has been shown to exhibit super acidic behavior and high activity for acid catalyzed reactions. Nanocrystalline zirconia was prepared in the presence of polysaccharide template by interaction between ZrOCl2ṡ8H2O and chitosan template. The interaction was carried out in aqueous phase, followed by the removal of templates by calcination at optimum temperature and sulfation. The structural and textural features were characterized by powder XRD, TG, SEM and TEM. XRD patterns showed the peaks of the diffractogram were in agreement with the theoretical data of zirconia with the catalytically active tetragonal phase and average crystalline size of the particles was found to be 9 nm, which was confirmed by TEM. TPD using ammonia as probe, FTIR and BET surface area analysis were used for analyzing surface features like acidity and porosity. The BET surface area analysis showed the sample had moderately high surface area. FTIR was used to find the type species attached to the surface of zirconia. UV-DRS found the band gap of the zirconia was found to be 2.8 eV. The benzylation of o-xylene was carried out batchwise in atmospheric pressure and 433K temperature using sulfated zirconia as catalyst.

  10. Synergistic Effects of Sulfated Polysaccharides from Mexican Seaweeds against Measles Virus

    PubMed Central

    Morán-Santibañez, Karla; Cruz-Suárez, Lucia Elizabeth; Ricque-Marie, Denis; Robledo, Daniel; Freile-Pelegrín, Yolanda; Peña-Hernández, Mario A.; Rodríguez-Padilla, Cristina

    2016-01-01

    Sulfated polysaccharides (SPs) extracted from five seaweed samples collected or cultivated in Mexico (Macrocystis pyrifera, Eisenia arborea, Pelvetia compressa, Ulva intestinalis, and Solieria filiformis) were tested in this study in order to evaluate their effect on measles virus in vitro. All polysaccharides showed antiviral activity (as measured by the reduction of syncytia formation) and low cytotoxicity (MTT assay) at inhibitory concentrations. SPs from Eisenia arborea and Solieria filiformis showed the highest antiviral activities (confirmed by qPCR) and were selected to determine their combined effect. Their synergistic effect was observed at low concentrations (0.0274 μg/mL and 0.011 μg/mL of E. arborea and S. filiformis SPs, resp.), which exhibited by far a higher inhibitory effect (96% syncytia reduction) in comparison to the individual SP effects (50% inhibition with 0.275 μg/mL and 0.985 μg/mL of E. arborea and S. filiformis, resp.). Time of addition experiments and viral penetration assays suggest that best activities of these SPs occur at different stages of infection. The synergistic effect would allow reducing the treatment dose and toxicity and minimizing or delaying the induction of antiviral resistance; sulfated polysaccharides of the tested seaweed species thus appear as promising candidates for the development of natural antiviral agents. PMID:27419139

  11. Sulfated polysaccharides as bioactive agents from marine algae.

    PubMed

    Ngo, Dai-Hung; Kim, Se-Kwon

    2013-11-01

    Recently, much attention has been paid by consumers toward natural bioactive compounds as functional ingredients in nutraceuticals. Marine algae are considered as valuable sources of structurally diverse bioactive compounds. Marine algae are rich in sulfated polysaccharides (SPs) such as carrageenans in red algae, fucoidans in brown algae and ulvans in green algae. These SPs exhibit many health beneficial nutraceutical effects such as antioxidant, anti-allergic, anti-human immunodeficiency virus, anticancer and anticoagulant activities. Therefore, marine algae derived SPs have great potential to be further developed as medicinal food products or nutraceuticals in the food industry. This contribution presents an overview of nutraceutical effects and potential health benefits of SPs derived from marine algae.

  12. Catalytic synthesis and antioxidant activity of sulfated polysaccharide from Momordica charantia L.

    PubMed

    Liu, Xin; Chen, Tong; Hu, Yan; Li, Kexin; Yan, Liushui

    2014-03-01

    Sulfated derivatives of polysaccharide from Momordica charantia L. (MCPS) with different degree of sulfation (DS) were synthesized by chlorosulfonic acid method with ionic liquids as solvent. Fourier transform infrared spectra and 13C nuclear magnetic resonance spectra indicated that C-6 substitution was predominant in MCPS compared with the C-2 position. Compared with the native polysaccharide from Momordica charantia L. (MCP), MCPS exhibited more excellent antioxidant activities in vitro, which indicated that sulfated modification could enhance antioxidant activities of MCP. Furthermore, high DS and moderate molecular weight could improve the antioxidant activities of polysaccharide.

  13. Influence of red algal sulfated polysaccharides on blood coagulation and platelets activation in vitro.

    PubMed

    Sokolova, Ekaterina V; Byankina, Anna O; Kalitnik, Alexandra A; Kim, Yong H; Bogdanovich, Larisa N; Solov'eva, Tamara F; Yermak, Irina M

    2014-05-01

    The influence of sulfated polysaccharides (λ-, κ-, and κ/β-carrageenan and porphyran) - on platelet activation was studied. Carrageenans were much weaker inhibitors of a coagulation process than heparin, while porphyran had not that effect. Results of the aPTT and PT assays suppose that carrageenans affected mostly intrinsic pathway of coagulation, while their effect on the extrinsic pathway is extremely low (λ and κ/β) or absent (κ, LMW derivative of κ-carrageenan). λ-Carrageenan was the most potent anticoagulant agent in TT, aPTT, PT, and anti-factor Xa activity. This sample was also the strongest inhibitor of collagen-induced platelet aggregation in PRP. Generally, the correlation of anticoagulant and antithrombotic action in PRP is preserved for carrageenans but not for heparin. Carrageenans and porphyran affected platelet adhesion to collagen by influencing glycoprotein VI. Low molecular weight κ-carrageenan had a similar effect on platelet adhesion mediated with both major collagen receptors: integrin α2 β1 and glycoprotein VI as native polysaccharide had. Carrageenans resulted in activation of platelets under platelet adhesion mediated by integrin αIIb β3 with less degree than heparin. The least sulfated κ/β-carrageenan that possessed an inhibiting effect on thrombin- and collagen-induced aggregation of washed platelets and on the PT test but it had no significant effect on TT was the weakest promoter of integrin αIIb β3 mediated platelet activation. In summary, our study showed that the polysaccharide action was complex, since it depended on its molecular mass, sulfation degree, and monosaccharide contents (3,6-anhydrogalactose).

  14. Sulfated Cyclocarya paliurus polysaccharides markedly attenuates inflammation and oxidative damage in lipopolysaccharide-treated macrophage cells and mice

    PubMed Central

    Wang, Zhijun; Xie, Jianhua; Yang, Yujiao; Zhang, Fan; Wang, Shengnan; Wu, Ting; Shen, Mingyue; Xie, Mingyong

    2017-01-01

    Natural polysaccharides and their modified derivatives are crucial supplements to the prevention of inflammation. This study aimed to evaluate the effect of sulfated modification on the anti-inflammatory and anti-oxidative activities of Cyclocarya paliurus polysaccharides (CP). A sulfated CP, S-CP1–4 was obtained using chlorosulfonic acid-pyridine method. The chemical components and FT-IR spectrum confirmed that sulfated group was synthesized to the polysaccharide chains successfully. S-CP1–4 was found to inhibit nitric oxide production, phagocytic activity and the release of interleukin (IL)-6 and IL-1β in lipopolysaccharide-treated macrophage cells, RAW 264.7. S-CP1–4 significantly decreased the secretion of IL-6 and TNF-α and the thymus and spleen indexes, and increased the production of IL-10 in lipopolysaccharide-treated mice. S-CP1–4 could better protect the liver by inhibiting the activities of alanine aminotransferase and aspartate aminotransferase, and malondialdehyde level while increasing the superoxide dismutase activity and total anti-oxidative capacity. These results suggested that S-CP1–4 may be an effective anti-inflammatory agent, and sulfated modification may be a reliable method for the development of food supplements. PMID:28094275

  15. In vitro and ex vivo studies of antioxidant activity of carrageenans, sulfated polysaccharides from red algae.

    PubMed

    Sokolova, E V; Barabanova, A O; Homenko, V A; Solov'eva, T F; Bogdanovich, R N; Yermak, I M

    2011-02-01

    Antioxidant properties of structurally different sulfated polysaccharides (carrageenans) were studied in vitro and ex vivo. Ferric reducing antioxidant activity of carrageenans and their inhibitory effects on hydroxyl radicals and superoxide anion radicals were demonstrated in vitro. Activity of carrageenans depends on the polysaccharide structure. Carrageenans stimulate catalytic activity of SOD from donor erythrocyte.

  16. Sulfated polysaccharides from the egg jelly layer are species-specific inducers of acrosomal reaction in sperms of sea urchins.

    PubMed

    Alves, A P; Mulloy, B; Diniz, J A; Mourão, P A

    1997-03-14

    We have characterized the fine structure of sulfated polysaccharides from the egg jelly layer of three species of sea urchins and tested the ability of these purified polysaccharides to induce the acrosome reaction in spermatozoa. The sea urchin Echinometra lucunter contains a homopolymer of 2-sulfated, 3-linked alpha-L-galactan. The species Arbacia lixula and Lytechinus variegatus contain linear sulfated alpha-L-fucans with regular tetrasaccharide repeating units. Each of these sulfated polysaccharides induces the acrosome reaction in conspecific but not in heterospecific spermatozoa. These results demonstrate that species specificity of fertilization in sea urchins depends in part on the fine structure of egg jelly sulfated polysaccharide.

  17. The structure-anticoagulant activity relationships of sulfated lacquer polysaccharide: effect of carboxyl group and position of sulfation.

    PubMed

    Yang, Jianhong; Du, Yumin; Huang, Ronghua; Wan, Yunyang; Wen, Yan

    2005-07-01

    Regiospecific oxidation of the primary hydroxyl groups in lacquer polysaccharide (LPL, Mw 6.85 x 10(4)) and its NaIO4 oxidation derivatives (LPLde) to C-6 carboxy groups was achieved with NaOCl in the presence of Tempo and NaBr. Sulfate groups were incorporated into the oxidated polysaccharides using Py.SO3 complex as a reagent. Reactivity of polysaccharide hydroxyl group was C-6 > C-2 > C-4. Sulfate groups were mainly linked to the second hydroxy at C-2 in the products. The results of APTT assay showed after incorporation of carboxyl groups into lacquer polysaccharides, the intrinsic coagulation pathway was promoted, and all sulfated polysaccharides had very weak anticoagulant activity within the scope of studied DS (0.39-1.11). These indicated that carboxyl groups and sulfate groups had the synergistic action. At the same time, the anticoagulant activity increased very slowly with the DS in the second hydroxy. This indicated that 6-O-SO3- in the side chains took an important role in the anticoagulant activity.

  18. Antioxidant and anticoagulant activity of sulfated polysaccharide from Gracilaria debilis (Forsskal).

    PubMed

    Sudharsan, Sadhasivam; Subhapradha, Namasivayam; Seedevi, Palaniappan; Shanmugam, Vairamani; Madeswaran, Perumal; Shanmugam, Annaian; Srinivasan, Alagiri

    2015-11-01

    Sulfated polysaccharide was isolated from Gracilaria debilis and purified through gel chromatography and their molecular weight was determined through AGE and PAGE. The total sugars in the crude, fractionated and purified polysaccharide were estimated as 52.65%, 59.70% and 67.60%, respectively. The ash and moisture content of crude and purified polysaccharide was found to be 14.2% and 23.5% and the polysaccharide was free from protein contamination. The sulfate and uronic acid contents in the crude, fractionated and purified were estimated as 14.08%, 15.33% and 16.01% and 10.12%, 13.56%, 16.70%. The elemental composition including carbon (crude - 23.12%, purified - 21.05%), hydrogen (crude - 3.4%, purified - 4.13%) and nitrogen (crude - 1.22%, purified - 0.56%) were also analyzed. The anticoagulant activity of the sulfated polysaccharide through APTT and PT was estimated at 14.11 and 8.23IU/mg. The purified polysaccharide with the molecular mass of 20kDa showed highest antioxidant activity (38.57%, 43.48% and 38.88%) in all the assays tested such as DPPH hydroxyl radical, superoxide radical, hydroxyl radical scavenging activities and the structural property was analyzed through FT-IR and (1)H NMR spectrum. The results together suggest that the isolated low molecular weight sulfated polysaccharide will demonstrate as a enormously available alternative natural source of antioxidant for industrial uses.

  19. Navicula sp. Sulfated Polysaccharide Gels Induced by Fe(III): Rheology and Microstructure

    PubMed Central

    Fimbres-Olivarría, Diana; López-Elías, José Antonio; Carvajal-Millán, Elizabeth; Márquez-Escalante, Jorge Alberto; Martínez-Córdova, Luis Rafael; Miranda-Baeza, Anselmo; Enríquez-Ocaña, Fernando; Valdéz-Holguín, José Eduardo; Brown-Bojórquez, Francisco

    2016-01-01

    A sulfated polysaccharide extracted from Navicula sp. presented a yield of 4.4 (% w/w dry biomass basis). Analysis of the polysaccharide using gas chromatography showed that this polysaccharide contained glucose (29%), galactose (21%), rhamnose (10%), xylose (5%) and mannose (4%). This polysaccharide presented an average molecular weight of 107 kDa. Scanning electron microscopy (SEM) micrographs showed that the lyophilized Navicula sp. polysaccharide is an amorphous solid with particles of irregular shapes and sharp angles. The polysaccharide at 1% (w/v) solution in water formed gels in the presence of 0.4% (w/v) FeCl3, showing elastic and viscous moduli of 1 and 0.7 Pa, respectively. SEM analysis performed on the lyophilized gel showed a compact pore structure, with a pore size of approximately 150 nm. Very few studies on the gelation of sulfated polysaccharides using trivalent ions exist in the literature, and, to the best of our knowledge, this study is the first to describe the gelation of sulfated polysaccharides extracted from Navicula sp. PMID:27483255

  20. Navicula sp. Sulfated Polysaccharide Gels Induced by Fe(III): Rheology and Microstructure.

    PubMed

    Fimbres-Olivarría, Diana; López-Elías, José Antonio; Carvajal-Millán, Elizabeth; Márquez-Escalante, Jorge Alberto; Martínez-Córdova, Luis Rafael; Miranda-Baeza, Anselmo; Enríquez-Ocaña, Fernando; Valdéz-Holguín, José Eduardo; Brown-Bojórquez, Francisco

    2016-07-30

    A sulfated polysaccharide extracted from Navicula sp. presented a yield of 4.4 (% w/w dry biomass basis). Analysis of the polysaccharide using gas chromatography showed that this polysaccharide contained glucose (29%), galactose (21%), rhamnose (10%), xylose (5%) and mannose (4%). This polysaccharide presented an average molecular weight of 107 kDa. Scanning electron microscopy (SEM) micrographs showed that the lyophilized Navicula sp. polysaccharide is an amorphous solid with particles of irregular shapes and sharp angles. The polysaccharide at 1% (w/v) solution in water formed gels in the presence of 0.4% (w/v) FeCl₃, showing elastic and viscous moduli of 1 and 0.7 Pa, respectively. SEM analysis performed on the lyophilized gel showed a compact pore structure, with a pore size of approximately 150 nm. Very few studies on the gelation of sulfated polysaccharides using trivalent ions exist in the literature, and, to the best of our knowledge, this study is the first to describe the gelation of sulfated polysaccharides extracted from Navicula sp.

  1. Bioactive potential and structural chracterization of sulfated polysaccharide from seaweed (Gracilaria corticata).

    PubMed

    Seedevi, Palaniappan; Moovendhan, Meivelu; Viramani, Shanmugam; Shanmugam, Annian

    2017-01-02

    The Sulfated polysaccharide was purified through anion-exchange and gel permeation column chromatography. The isolated sulfated polysaccharide from C. corticata contains 84% of carbohydrate, 0% of protein, 19.7% of ash and 29.4% of moisture was found. The carbon, hydrogen, nitrogen and sulfur content as 33.19%, 5.91%, 7.21% and 3.75%. The molecular weight of sulfated polysaccharide was found to be 43kDa. The sugar was composed of (90.11%), glucose (5.47%), xylose (2.30%) and mannose (2.12%). The structural feature of sulfated polysachharide was studied through FT-IR and (1)H NMR spectral analysis. Further the sulfated polysaccharide showed total antioxidant activity of 24.93%-75.21% at 50-250μg/ml, DPPH free radical scavenging activity of 23.12%-73.01% at 10-160μg/ml, ABTS scavenging activity of 15.8%-74.5% at 25-125μg/ml hydroxyl radical scavenging activity 12.87-69.19% at 25-125μg/ml and superoxide radical scavenging activity 28.10-78.11% at 50-250μg/ml respectively. The sulfated polysaccharide has shown good antibacterial activity against human pathogen.

  2. Sulfation effect on levan polysaccharide chains structure with molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Coskunkan, Binnaz; Turgut, Deniz; Rende, Deniz; Malta, Seyda; Baysal, Nihat; Ozisik, Rahmi; Toksoy-Oner, Ebru

    Diversity in conformations and structural heterogeneity make polysaccharides the most challenging biopolymer type for experimental and theoretical characterization studies. Levan is a biopolymer chain that consists of fructose rings with β(2-6) linkages. It is a glycan that has great potential as a functional biopolymer in foods, feeds, cosmetics, pharmaceutical and chemical industries. Sulfated polysaccharides are group of macromolecules with sulfated groups in their hydroxyl parts with a range of important biological properties. Sulfate groups and their positions have a major effect on anticoagulant activity. It is reported that sulfate modified levan has anticoagulant activity such as heparin. In the current study, the effect of sulfation on the structure and dynamics of unmodified and sulfate modified levan are investigated via fully atomistic Molecular Dynamics simulations in aqueous media and varying salt concentrations at 310 K. This material is based upon work supported by the National Science Foundation under Grant No. CMMI-1538730.

  3. Characterization of fungal sulfated polysaccharides and their synergistic anticancer effects with doxorubicin.

    PubMed

    Cheng, Jing-Jy; Chang, Chia-Chuan; Chao, Chi-Hsein; Lu, Mei-Kuang

    2012-09-01

    Sulfated polysaccharides (SPSs) from two edible fungal species, including two strains of Antrodia cinnamomea and Poria cocos, were isolated. Fucose, glucosamine, galactose, glucose, and mannose were the major sugars in the SPSs, and these SPSs had a high sulfate content. The area percentage of low-molecular-weight SPSs (1-100 kDa) covered almost half of the SPS mixture of the A. cinnamomea strains. In contrast, high-molecular-weight SPSs (>1000 kDa) of P. cocos covered a large proportion of the area at 30.06%. SPSs from A. cinnamomea B86 showed stronger inhibition of endothelial cell (EC) tube formation in an in vitro assay of angiogenesis, than did A. cinnamomea 35396 or P. cocos. The degree of sulfation paralleled their antiangiogenic activity. When tumor cells were concurrently exposed to doxorubicin (DOX) and fungal SPSs, SPSs synergistically increased the cytotoxicity of DOX to different degree up to 50-fold. Fungal SPSs may offer new applications for combinational-therapy drugs.

  4. Salt Effect on the Antioxidant Activity of Red Microalgal Sulfated Polysaccharides in Soy-Bean Formula.

    PubMed

    Burg, Ariela; Oshrat, Levy-Ontman

    2015-10-20

    Sulfated polysaccharides produced by microalgae, which are known to exhibit various biological activities, may potentially serve as natural antioxidant sources. To date, only a few studies have examined the antioxidant bioactivity of red microalgal polysaccharides. In this research, the effect of different salts on the antioxidant activities of two red microalgal sulfated polysaccharides derived from Porphyridium sp. and Porphyridium aerugineum were studied in a soy bean-based infant milk formula. Salt composition and concentration were both shown to affect the polysaccharides' antioxidant activity. It can be postulated that the salt ions intefer with the polysaccharide chains' interactions and alter their structure, leading to a new three-dimensional structure that better exposes antiooxidant sites in comparison to the polysaccharide without salt supplement. Among the cations that were studied, Ca(2+) had the strongest enhancement effect on antioxidant activities of both polysaccharides. Understanding the effect of salts on polysaccharides' stucture, in addition to furthering knowledge on polysaccharide bioactivities, may also shed light on the position of the antioxidant active sites.

  5. Microwave assisted extraction of sulfated polysaccharides (fucoidan) from Ascophyllum nodosum and its antioxidant activity.

    PubMed

    Yuan, Yuan; Macquarrie, Duncan

    2015-09-20

    Sulfated polysaccharides (fucoidan) from brown seaweed Ascophyllum nodosum were extracted by microwave assisted extraction (MAE) technology. Different conditions of temperature (90-150°C), extraction time (5-30 min) were evaluated and optimal fucoidan yield was 16.08%, obtained from 120°C for 15 min's extraction. Compositional analysis, GPC, HPAEC and IR analysis were employed for characterization of extracted sulfated polysaccharides. Fucose was the main monosaccharide of fucoidan extracted at 90°C while glucuronic acid was the main monosaccharide of fucoidan extracted at 150°C. Both the molecular weight and sulfate content of extracted fucoidan increased with decreasing extraction temperature. All fucoidans exhibited antioxidant activities as measured by DPPH scavenging and reducing power, among which fucoidan extracted at 90°C was highest. This study shows that MAE is an efficient technology to extract sulfated polysaccharides from seaweed and Ascophyllum nodosum could potentially be a resource for natural antioxidants.

  6. Structural characterization, sulfation and antitumor activity of a polysaccharide fraction from Cyclina sinensis.

    PubMed

    Jiang, Changxing; Xiong, Qingping; Li, Songlin; Zhao, Xirong; Zeng, Xiaoxiong

    2015-01-22

    In the present study, we investigated the preliminary structure, sulfation and antitumor activity of a polysaccharide fraction from Cyclina sinensis (CSPS-1). Results of structural characterization showed that the backbone chain of CSPS-1 was composed of glucose linked by α-(1→4) glycosidic bond, and the branch chain was attached to backbone chain by (1→6) glycosidic bond. CSPS-1 was sulfated by chlorosulfonic acid-pyridine method under different modification conditions according to the orthogonal test L9(3(4)), affording nine sulfated polysaccharides (CSPS-1-S). The optimal sulfation conditions for CSPS-1 were reaction temperature of 65°C, reaction time of 2h and chlorosulfonic acid-pyridine ratio of 1:4. Structural analysis revealed that sulfation had occurred at position of C-6 in CSPS-1. In addition, CSPS-1-S exhibited significantly higher inhibitory activity in vitro against human gastric cancer BGC-823 cells.

  7. Semi-synthesis of unusual chondroitin sulfate polysaccharides containing GlcA(3-O-sulfate) or GlcA(2,3-di-O-sulfate) units.

    PubMed

    Bedini, Emiliano; De Castro, Cristina; De Rosa, Mario; Di Nola, Annalida; Restaino, Odile F; Schiraldi, Chiara; Parrilli, Michelangelo

    2012-02-13

    The extraction from natural sources of Chondroitin sulfate (CS), a polysaccharide used for management of osteoarthritis, leads to very complex mixtures. The synthesis of CS by chemical modification of other polysaccharides has seldom been reported due to the intrinsic complexity that arises from fine chemical modifications of the polysaccharide structure. In view of the growing interest in expanding the application of CS to pharmacological fields other than osteoarthritis treatment, we launched a program to find new sources of known or even unprecedented CS polysaccharides. As part of this program, we report herein on an investigation of the use of a cyclic orthoester group to selectively protect the 4,6-diol of N-acetyl-galactosamine residues in chondroitin (obtained from a microbial source), thereby facilitating its transformation into CSs. In particular, three CS polysaccharides were obtained and demonstrated to possess rare or hitherto unprecedented sulfation patterns by 2D NMR spectroscopy characterization. Two of them contained disaccharide subunits characterized by glucuronic acid residues selectively sulfated at position 3 (GlcA(3S)), the biological functions of which are known but have yet to be fully investigated. This first semi-synthetic access to GlcA(3S)-containing CS could greatly expedite such studies, since it can easily furnish considerable amounts of these polysaccharides, which are usually isolated with difficulty and in very low quantity from natural sources.

  8. Antiviral Activity of Sulfated Polysaccharide of Adenanthera pavonina against Poliovirus in HEp-2 Cells

    PubMed Central

    de Godoi, Ananda Marques; Faccin-Galhardi, Lígia Carla; Lopes, Nayara; de Almeida, Raimundo Rafael; Ricardo, Nágila Maria Pontes Silva; Nozawa, Carlos; Linhares, Rosa Elisa Carvalho

    2014-01-01

    Adenanthera pavonina, popularly known as red-bead tree, carolina, pigeon's eye, and dragon's eye, is a plant traditionally used in Brazil for the treatment of several diseases. The present study aimed at evaluating the activity of sulfated polysaccharide from the Adenanthera pavonina (SPLSAp) seeds against poliovirus type 1 (PV-1) in HEp-2 cell cultures. The SPLSAp presented a cytotoxic concentration (CC50) of 500 μg/mL in HEp-2 cell cultures, evaluated by the dimethylthiazolyl-diphenyltetrazolium bromide method (MTT). The SPLSAp exhibited a significant antiviral activity, with a 50% inhibitory concentration (IC50) of 1.18 µg/mL, determined by plaque reduction assay and a high selectivity index (SI) of 423. The maximum inhibition (100%) of PV replication was found when the SPLSAp treatment was concomitant with viral infection (time 0 h), at all tested concentrations. The maximal inhibition was also found when the SPLSAp was used 1 h and 2 h postinfection, albeit at 50 μg/mL and 100 μg/mL. Therefore, we demonstrated that the SPLSAp inhibited PV growth. We also suggested that SPLSAp inhibited PV in more than one step of the replication, as the mechanism of antiviral action. We, therefore, selected the compound as a potential candidate for further development towards the control of the infection. PMID:25221609

  9. A Modular Approach to a Library of Semi-Synthetic Fucosylated Chondroitin Sulfate Polysaccharides with Different Sulfation and Fucosylation Patterns.

    PubMed

    Laezza, Antonio; Iadonisi, Alfonso; Pirozzi, Anna V A; Diana, Paola; De Rosa, Mario; Schiraldi, Chiara; Parrilli, Michelangelo; Bedini, Emiliano

    2016-12-12

    Fucosylated chondroitin sulfate (fCS)-a glycosaminoglycan (GAG) found in sea cucumbers-has recently attracted much attention owing to its biological properties. In particular, a low molecular mass fCS polysaccharide has very recently been suggested as a strong candidate for the development of an antithrombotic drug that would be safer and more effective than heparin. To avoid the use of animal sourced drugs, here we present the chemical transformation of a microbial sourced unsulfated chondroitin polysaccharide into a small library of fucosylated (and sulfated) derivatives thereof. To this aim, a modular approach based on the different combination of only five reactions was employed, with an almost unprecedented polysaccharide branching by O-glycosylation as the key step. The library was differentiated for sulfation patterns and/or positions of the fucose branches, as confirmed by detailed 2D NMR spectroscopic analysis. These semi-synthetic polysaccharides will allow a wider and more accurate structure-activity relationship study with respect to those reported in literature to date.

  10. In vitro fermentation of sulfated polysaccharides from E. prolifera and L. japonica by human fecal microbiota.

    PubMed

    Kong, Qing; Dong, Shiyuan; Gao, Jian; Jiang, Chaoyu

    2016-10-01

    In vitro fermentation of the sulfated polysaccharides from seaweeds Enteromorpha prolifera and Laminaria japonica and their prebiotic effects on human fecal microbiota were investigated in this study. The sulfated polysaccharides were fermented in vitro for 48h by human fecal cultures. When 0.8g MWCOL (polysaccharides MWCO<30kD) from L. japonica was fermented, the pH in fecal cultures decreased from 6.5 to 5.1 and the levels of short chain fatty acids, such as acetic, butyric and lactic acids all significantly increased. After 48h fermentation, 0.8g MWCOL showed good effect on modulating the gut microflora balance, because the beneficial strains (Lactobacillus and Bifidobacterium) were both significantly higher than those in control group (p<0.05). As far as we know, this is the first report that consumption of sulfated polysaccharides from E. prolifera and L. japonica is beneficial to the ecosystem of the intestinal tract by increasing the populations of probiotics and short chain fatty acids. Furthermore, our reports indicated that molecular weight of sulfated polysaccharide from marine algae is related to its prebiotic effects.

  11. Salt Effect on the Antioxidant Activity of Red Microalgal Sulfated Polysaccharides in Soy-Bean Formula

    PubMed Central

    Burg, Ariela; Oshrat, Levy-Ontman

    2015-01-01

    Sulfated polysaccharides produced by microalgae, which are known to exhibit various biological activities, may potentially serve as natural antioxidant sources. To date, only a few studies have examined the antioxidant bioactivity of red microalgal polysaccharides. In this research, the effect of different salts on the antioxidant activities of two red microalgal sulfated polysaccharides derived from Porphyridium sp. and Porphyridium aerugineum were studied in a soy bean-based infant milk formula. Salt composition and concentration were both shown to affect the polysaccharides’ antioxidant activity. It can be postulated that the salt ions intefer with the polysaccharide chains’ interactions and alter their structure, leading to a new three-dimensional structure that better exposes antiooxidant sites in comparison to the polysaccharide without salt supplement. Among the cations that were studied, Ca2+ had the strongest enhancement effect on antioxidant activities of both polysaccharides. Understanding the effect of salts on polysaccharides’ stucture, in addition to furthering knowledge on polysaccharide bioactivities, may also shed light on the position of the antioxidant active sites. PMID:26492255

  12. A Direct Sulfation Process of a Marine Polysaccharide in Ionic Liquid.

    PubMed

    Chopin, Nathalie; Sinquin, Corinne; Ratiskol, Jacqueline; Zykwinska, Agata; Weiss, Pierre; Cérantola, Stéphane; Le Bideau, Jean; Colliec-Jouault, Sylvia

    2015-01-01

    GY785 is an exopolysaccharide produced by a mesophilic bacterial strain Alteromonas infernus discovered in the deep-sea hydrothermal vents. GY785 highly sulfated derivative (GY785 DRS) was previously demonstrated to be a promising molecule driving the efficient mesenchymal stem cell chondrogenesis for cartilage repair. This glycosaminoglycan- (GAG-) like compound was modified in a classical solvent (N,N'-dimethylformamide). However, the use of classical solvents limits the polysaccharide solubility and causes the backbone degradation. In the present study, a one-step efficient sulfation process devoid of side effects (e.g., polysaccharide depolymerization and/or degradation) was developed to produce GAG-like derivatives. The sulfation of GY785 derivative (GY785 DR) was carried out using ionic liquid as a reaction medium. The successful sulfation of this anionic and highly branched heteropolysaccharide performed in ionic liquid would facilitate the production of new molecules of high specificity for biological targets such as tissue engineering or regenerative medicine.

  13. Comparison of the anti-duck hepatitis A virus activities of phosphorylated and sulfated Astragalus polysaccharides.

    PubMed

    Wang, Yixuan; Chen, Yun; Du, Hongxu; Yang, Jingjing; Ming, Ke; Song, Meiyun; Liu, Jiaguo

    2017-02-01

    Duck hepatitis A virus (DHAV) (Picornaviridae) causes an infectious disease in ducks which results in severe losses in duck industry. However, the proper antiviral supportive drugs for this disease have not been discovered. Polysaccharide is the main ingredient of Astragalus that has been demonstrated to directly and indirectly inhibit RNA of viruses replication. In this study, the antiviral activities of Astragalus polysaccharide (APS) and its derivatives against DHAV were evaluated and compared. APS was modified via the sodium trimetaphosphate and sodium tripolyphosphate (STMP-STPP) method and chlorosulfonic acid-pyridine method to obtain its phosphate (pAPS) and sulfate (sAPS), respectively. The infrared structures of APS, pAPS, and sAPS were analyzed with the potassium bromide disc method. Additionally, the antiviral activities were evaluated with the MTT ((4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) method in vitro and the artificial inoculation method in vivo. The clinical therapy effects were evaluated by mortality rate, liver function-related biochemical indicators, and visual changes in pathological anatomy. The anti-DHAV proliferation effects of APS, pAPS, and sAPS on the viral multiplication process in cell and blood were observed with the reverse transcription-polymerase chain reaction method. The results revealed that pAPS inhibited DHAV proliferation more efficiently in the entire process of viral multiplication than APS and sAPS. Moreover, only pAPS significantly improved the survival rate to 33.5% and reduced the DHAV particle titer in the blood as well as liver lesions in clinical trials. The results indicated that pAPS exhibited greater anti-DHAV activity than APS and sAPS both in vitro and in vivo.

  14. The structure of sulfated polysaccharides ensures a carbohydrate-based mechanism for species recognition during sea urchin fertilization.

    PubMed

    Vilela-Silva, Ana-Cristina E S; Hirohashi, Noritaka; Mourão, Paulo A S

    2008-01-01

    The evolution of barriers to inter-specific hybridization is a crucial step in the fertilization of free spawning marine invertebrates. In sea urchins, molecular recognition between sperm and egg ensures species recognition. Here we review the sulfated polysaccharide-based mechanism of sperm-egg recognition in this model organism. The jelly surrounding sea urchin eggs is not a simple accessory structure; it is molecularly complex and intimately involved in gamete recognition. It contains sulfated polysaccharides, sialoglycans and peptides. The sulfated polysaccharides have unique structures, composed of repetitive units of alpha-L-fucose or alpha-L-galactose, which differ among species in the sulfation pattern and/or the position of the glycosidic linkage. The egg jelly sulfated polysaccharides show species-specificity in inducing the sperm acrosome reaction, which is regulated by the structure of the saccharide chain and its sulfation pattern. Other components of the egg jelly do not possess acrosome reaction inducing activity, but sialoglycans act in synergy with the sulfated polysaccharide, potentiating its activity. The system we describe establishes a new view of cell-cell interaction in the sea urchin model system. Here, structural changes in egg jelly polysaccharides modulate cell-cell recognition and species-specificity leading to exocytosis of the acrosome. Therefore, sulfated polysaccharides, in addition to their known functions as growth factors, coagulation factors and selectin binding partners, also function in fertilization. The differentiation of these molecules may play a role in sea urchin speciation.

  15. Structural characterization and anticoagulant activity of a sulfated polysaccharide from the green alga Codium divaricatum.

    PubMed

    Li, Na; Mao, Wenjun; Yan, Mengxia; Liu, Xue; Xia, Zheng; Wang, Shuyao; Xiao, Bo; Chen, Chenglong; Zhang, Lifang; Cao, Sujian

    2015-05-05

    A sulfated polysaccharide, designated CP2-1, was isolated from the green alga Codium divaricatum by water extraction and purified by anion-exchange and size-exclusion chromatography. CP2-1 is a galactan which is highly sulfated and substituted with pyruvic acid ketals. On the basis of chemical and spectroscopic analyses, the backbone of CP2-1 was mainly composed of (1→3)-β-d-galactopyranose residues, branched by single (1→)-β-d-galactopyranose units attached to the main chain at C-4 positions. The degree of branching was estimated to be about 12.2%. Sulfate groups were at C-4 of (1→3)-β-d-galactopyranose and C-6 of non-reducing terminal galactose residues. In addition, the ketals of pyruvic acid were found at 3,4- of non-reducing terminal galactose residues forming a five-membered ring. CP2-1 possessed a high anticoagulant activity as assessed by the activated partial thromboplastin time and thrombin time assays. The investigation demonstrated that CP2-1 was an anticoagulant-active sulfated polysaccharide distinguishing from other sulfated polysaccharides from marine green algae.

  16. Effects of sulfate group in red seaweed polysaccharides on anticoagulant activity and cytotoxicity.

    PubMed

    Liang, Wanai; Mao, Xuan; Peng, Xiaohui; Tang, Shunqing

    2014-01-30

    In this paper, the structural effects of two main red seaweed polysaccharides (agarose and carrageenan) and their sulfated derivatives on the anticoagulant activity and cytotoxicity were investigated. The substitution position rather than the substitution degree of sulfate groups shows the biggest impact on both the anticoagulant activity and the cell proliferation. Among them, C-2 of 3,6-anhydro-α-d-Galp is the most favorable position for substitution, whereas C-6 of β-d-Galp is the most disadvantageous. Moreover, the secondary structures of glycans also play a key role in biological activities. These demonstrations warrant that the red seaweed polysaccharides should be seriously considered in biomedical applications after carefully tailoring the sulfate groups.

  17. In vitro and in vivo immunomodulatory activity of sulfated polysaccharides from red seaweed Nemalion helminthoides.

    PubMed

    Pérez-Recalde, Mercedes; Matulewicz, María C; Pujol, Carlos A; Carlucci, María J

    2014-02-01

    Water-soluble sulfated polysaccharides from the red seaweed Nemalion helminthoides: two xylomannan fractions (N3 and N4) and a mannan fraction (N6) were investigated to determine their in vitro and in vivo immunomodulatory activities. N3 and N4 induced in vitro proliferation of macrophages of the murine cell line RAW 264.7 and significantly stimulated the production of nitric oxide (NO) and cytokines (IL-6 and TNF-α) in the same cells, whereas this response was not observed with the mannan N6. The cytokine production was also stimulated by sulfated xylomannans in vivo in BALB/c mice inoculated intravenously with these polysaccharides. Remarkably, when mice were treated with N3 and N4 for 1 h before being infected with Herpes simplex virus type 2, they remained asymptomatic with no signs of disease. The in vitro and in vivo results suggest that sulfated xylomannans could be strong immunomodulators.

  18. Inhibition of hydrogen peroxide induced injuring on human skin fibroblast by Ulva prolifera polysaccharide.

    PubMed

    Cai, Chuner; Guo, Ziye; Yang, Yayun; Geng, Zhonglei; Tang, Langlang; Zhao, Minglin; Qiu, Yuyan; Chen, Yifan; He, Peimin

    2016-10-01

    Ulva prolifera can protect human skin fibroblast from being injured by hydrogen peroxide. This work studied the composition of Ulva prolifera polysaccharide and identified its physicochemical properties. The results showed that the cell proliferation of 0.5mg/mL crude polysaccharide was 154.4% of that in negative control group. Moreover, ROS detection indices, including DCFH-DA, GSH-PX, MDA and CAT, indicated that crude polysaccharide could improve cellular ability to scavenge free radical and decrease the injury on human skin fibroblast by hydrogen peroxide. In purified polysaccharide, the activity of fraction P1-1 was the highest, with 174.6% of that in negative control group. The average molecular weight of P1-1 was 137kD with 18.0% of sulfate content. This work showed the inhibition of hydrogen peroxide induced injuries on human skin fibroblast by Ulva prolifera polysaccharide, which may further evaluate the application of U. prolifera on cosmetics.

  19. Characterization and cytotoxic activity of sulfated derivatives of polysaccharides from Agaricus brasiliensis

    PubMed Central

    Cardozo, F. T. G. S.; Camelini, C. M.; Cordeiro, M. N. S.; Mascarello, A.; Malagoli, B. G.; Larsen, I.; Rossi, M. J.; Nunes, R. J.; Braga, F. C.; Brandt, C.R.; Simões, C. M. O.

    2014-01-01

    Agaricus brasiliensis cell-wall polysaccharides isolated from fruiting body (FR) and mycelium (MI) and their respective sulfated derivatives (FR-S and MI-S) were chemically characterized using elemental analysis, TLC, FT-IR, NMR, HPLC, and thermal analysis. Cytotoxic activity was evaluated against A549 tumor cells by MTT and sulforhodamine assays. The average molecular weight (Mw) of FR and MI was estimated to be 609 and 310 kDa, respectively. FR-S (127 kDa) and MI-S (86 kDa) had lower Mw, probably due to hydrolysis occurred during the sulfation reaction. FR-S and MI-S presented ~14 % sulfur content in elemental analysis. Sulfation of samples was characterized by the appearance of two new absorption bands at 1253 and 810 cm−1 in the infrared spectra, related to S=O and C-S-O sulfate groups, respectively. Through 1H and 13C NMR analysis FR-S was characterized as a (1→6)-(1→3)-β-D-glucan fully sulfated at C-4 and C-6 terminal and partially sulfated at C-6 of (1→3)-β-D-glucan moiety. MI-S was shown to be a (1→3)-β-D-gluco-(1→2)-β-D-mannan, partially sulfated at C-2, C-3, C-4, and C-6, and fully sulfated at C-6 of the terminal residues. The combination of high degree of sulfation and low molecular weight was correlated with the increased cytotoxic activity (48 h of treatment) of both FR-S (EC50=605.6 μg/mL) and MI-S (EC50=342.1 μg/mL) compared to the non-sulfated polysaccharides FR and MI (EC50>1500 μg/mL). PMID:23511057

  20. Characterization and cytotoxic activity of sulfated derivatives of polysaccharides from Agaricus brasiliensis.

    PubMed

    Cardozo, F T G S; Camelini, C M; Cordeiro, M N S; Mascarello, A; Malagoli, B G; Larsen, I V; Rossi, M J; Nunes, R J; Braga, F C; Brandt, C R; Simões, C M O

    2013-06-01

    Agaricus brasiliensis cell-wall polysaccharides isolated from fruiting body (FR) and mycelium (MI) and their respective sulfated derivatives (FR-S and MI-S) were chemically characterized using elemental analysis, TLC, FT-IR, NMR, HPLC, and thermal analysis. Cytotoxic activity was evaluated against A549 tumor cells by MTT and sulforhodamine assays. The average molecular weight (Mw) of FR and MI was estimated to be 609 and 310 kDa, respectively. FR-S (127 kDa) and MI-S (86 kDa) had lower Mw, probably due to hydrolysis occurring during the sulfation reaction. FR-S and MI-S presented ~14% sulfur content in elemental analysis. Sulfation of samples was characterized by the appearance of two new absorption bands at 1253 and 810 cm(-1) in the infrared spectra, related to S=O and C-S-O sulfate groups, respectively. Through (1)H and (13)C NMR analysis FR-S was characterized as a (1→6)-(1→3)-β-D-glucan fully sulfated at C-4 and C-6 terminal and partially sulfated at C-6 of (1→3)-β-D-glucan moiety. MI-S was shown to be a (1→3)-β-D-gluco-(1→2)-β-D-mannan, partially sulfated at C-2, C-3, C-4, and C-6, and fully sulfated at C-6 of the terminal residues. The combination of high degree of sulfation and low molecular weight was correlated with the increased cytotoxic activity (48 h of treatment) of both FR-S (EC₅₀=605.6 μg/mL) and MI-S (EC₅₀=342.1 μg/mL) compared to the non-sulfated polysaccharides FR and MI (EC₅₀>1500 μg/mL).

  1. High molecular weight polysaccharide that binds and inhibits virus

    DOEpatents

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  2. Purification, partial characterization and bioactivity of sulfated polysaccharides from Grateloupia livida.

    PubMed

    Tang, Liu; Chen, Yicun; Jiang, Zebin; Zhong, Shuping; Chen, Weizhou; Zheng, Fuchun; Shi, Ganggang

    2017-01-01

    Purification, preliminary characterization and bioactivity of polysaccharides from Grateloupia livida (GL) were investigated. Three water-soluble sulfated polysaccharide fractions (GLP-1, GLP-2 and GLP-3) were isolated and purified from the edible and medicinal red seaweed, Grateloupia livida (Harv.) Yamada by DEAE Sepharose CL-6B and Sephadex G-100 column chromatography, and chemical characterization was performed by HPGPC, GC-MS, FT-IR and SEM. In addition, anticoagulant activities were determined by activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) using normal human plasma in vitro. The antioxidant activities against DPPH and ABTS(+) radicals were evaluated and compared. The molecular weights of GLP-1, GLP-2 and GLP-3 were 39.5, 60.4 and 3.36kDa, respectively. Monosaccharide analysis revealed that three polysaccharide fractions were homopolysaccharides and comprised of galactose only. Anticoagulant assays indicated that crude GLP, and purified GLP-1 and GLP-2 effectively prolonged APTT and TT, but not PT. All polysaccharide fractions exhibited significant in vitro antioxidant activities in a dose-dependent manner. GLP-2 showed consistently better anticoagulant and antioxidant activities compared with GLP, GLP-1 and GLP-3. These results demonstrate that sulfated polysaccharides isolated from Grateloupia livida can serve as readily available alternative natural sources of anticoagulant and antioxidant agents.

  3. Regioselective sulfation of Artemisia sphaerocephala polysaccharide: Solution conformation and antioxidant activities in vitro.

    PubMed

    Wang, Junlong; Yang, Wen; Tang, YinYing; Xu, Qing; Huang, Shengli; Yao, Jian; Zhang, Ji; Lei, Ziqiang

    2016-01-20

    Regioselective modification is an effective approach to synthesize polysaccharides with different structure features and improved properties. In this study, regioselective sulfation of Artemisia sphaerocephala polysaccharide (SRSASP) was prepared by using triphenylchloromethane (TrCl) as protecting precursor. The decrease in fractal dimension (df) values (1.56-2.04) of SRSASP was observed in size-exclusion chromatography combined with multi angle laser light scattering (SEC-MALLS) analysis. Compared to sample substituted at C-6, SRSASP showed a more expanded conformation of random coil, which was attributed to the breakup of hydrogen bonds and elastic contributions. Circular dichroism (CD), methylene blue (MB) and congo red (CR) spectrophotometric method and atomic force microscopy (AFM) results confirmed the conformational transition and stiffness of the chains after sulfation. SRSASP exhibited enhanced antioxidant activities in the DPPH, superoxide and hydroxyl radical scavenging assay. Sulfation at C-2 or C-3 was favorable for the chelation which might prevent the generation of hydroxyl radicals. It concluded that the degree of substitution and substitution position were the factors influencing biological activities of sulfated polysaccharides.

  4. Sulfated modification of the polysaccharides obtained from defatted rice bran and their antitumor activities.

    PubMed

    Wang, Li; Li, Xiaoxuan; Chen, Zhengxing

    2009-03-01

    Nine sulfated defatted rice bran polysaccharides (sRBPS), with various degrees of sulfation (DS) and carbohydrate content, were prepared by chlorosulfonic acid-pyridine (CSA-Pyr) method according to orthogonal test. Nine sulfated derivatives sRBPS were obtained and their antitumor activities were compared by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results showed that when DS within the scope of 0.81-1.29, carbohydrate content in the range of 41.41-78.56%, sulfated derivatives exhibit relatively strong antitumor activity in vitro. The optimum modification conditions were reaction temperature of 70 degrees C, the ratio of chlorosulfonic acid to pyridine of 1:4 and the reaction time of 2h.

  5. Biochemical characteristics and antioxidant activity of crude and purified sulfated polysaccharides from Gracilaria fisheri.

    PubMed

    Imjongjairak, Siriluck; Ratanakhanokchai, Khanok; Laohakunjit, Natta; Tachaapaikoon, Chakrit; Pason, Patthra; Waeonukul, Rattiya

    2016-01-01

    Sulfated polysaccharides (SPs) from Gracilaria fisheri of Thailand, which were extracted in low-temperature (25 °C) water showed the highest content of phenolic compounds compared with those extracted at high temperature (55 °C). Crude SP antioxidant activity was evaluated by measuring the DPPH free radical scavenging effect which is directly related to the level of phenolic compounds. The sulfate content, total sugar, and SPs yield were also directly related to the extraction temperature. All extracts contained galactose as a major monosaccharide. High antioxidant activity of crude SP, positively correlated with the phenolic compound contents (R(2) = 0.996) contributed by the existence of sulfate groups and phenolic compounds. In purified SP, F1 fraction exhibited strong radical scavenging ability, but it was not significantly different compared to crude SP extracted at 25 °C. This indicated that the appropriate density and distribution of sulfate groups in the SP extract showed the best antioxidant activity.

  6. Chemical characteristics and anticoagulant activities of two sulfated polysaccharides from Enteromorpha linza (Chlorophyta)

    NASA Astrophysics Data System (ADS)

    Qi, Xiaohui; Mao, Wenjun; Chen, Yin; Chen, Yanli; Zhao, Chunqi; Li, Na; Wang, Chunyan

    2013-03-01

    Two sulfated polysaccharides, designated MP and SP, were extracted from the marine green alga Enteromorpha linza using hot water and then purified using ion-exchange and size-exclusion chromatography. The anticoagulant activities of MP and SP were examined by determination of their activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) using human plasma. Results showed that MP and SP were composed of abundant rhamnose with small amounts of xylose and glucuronic acid, whereas SP also contained a small amount of galactose. Approximate molecular weights of MP and SP were 535 and 502 kDa, respectively. As compared with SP, MP had higher contents of sulfate ester (19.0%) and uronic acid (14.9%). The MP mainly consisted of (1→4)-linked rhamnose residues with partially sulfated groups at the C-3 position, and small amounts of (1→3, 4)-linked rhamnose, (1→2, 4)-linked rhamnose, (1→4)-linked glucuronic acid and (1→4)-linked xylose residues. The SP contained abundant (1→4)-linked rhamnose with minor amounts of (1→3)-linked rhamnose, (1→3, 4)-linked rhamnose, (1→2, 4)-linked rhamnose, (1→4)-linked glucuronic acid, (1→4)-linked xylose, and (1→3)-linked galactose residues. The sulfate groups were mainly located at C-3 of (1→4)-linked rhamnose residues. Both MP and SP, in particular the former, effectively prolonged APTT and TT. This work demonstrates that MP and SP have unique structural characteristics distinct from those of other sulfated polysaccharides from Enteromorpha. The MP is a potential source of anticoagulant, and the difference in anticoagulant activities of the two sulfated polysaccharides is directly linked to the discrepancy of their chemical features.

  7. Effect of Chuanminshen violaceum polysaccharides and its sulfated derivatives on immunosuppression induced by cyclophosphamide in mice

    PubMed Central

    Zhao, Xinghong; Zhang, Yuetian; Song, Xu; Yin, Zhongqiong; Jia, Renyong; Zhao, Xingfang; Lai, Xin; Wang, Guangxi; Liang, Xiaoxia; He, Changliang; Yin, Lizi; Lv, Cheng; Zhao, Ling; Shu, Gang; Ye, Gang; Shi, Fei

    2015-01-01

    One hundred mice were randomly divided into five groups. The mice in one group were injected with physiological saline as the normal control group. The mice in the other four groups were injected with physiological saline, sulfated Chuanminshen violaceum polysaccharides (SCVP), Chuanminshen violaceum polysaccharide (CVP) and astragalus polysaccharide (AP) once daily for 7 d and then with cyclophosphamide (CY) in the last 3 d. The serum cytokine level, apoptosis protein expressions, spleen lymphocyte proliferation, changes in peripheral blood T-cell subsets, and immune organ index were then measured. Results showed that SCVP and CVP can overcome CY-induced immunosuppression by promoting spleen lymphocyte proliferation, raising serum IFN-γ and IL-2 levels, enlarging immune organ indexes, and decreasing excessive apoptosis. Moreover, SCVP and CVP showed the potential to treat autoimmune diseases based on CD4+/CD8+ ratios. Results suggested that SCVP and CVP exhibited the potential to treat autoimmune and immunosuppression diseases. PMID:25785030

  8. Sulfated modification promotes the immunomodulatory bioactivities of Lyciumbarbarum polysaccharides in vitro

    PubMed Central

    Wang, Junmin; Ge, Beilei; Du, Chunyan; Xue, Jingli; Zhuang, Yuwei; Xue, Kun

    2015-01-01

    Three kinds of purified Lyciumbarbarum polysaccharides (LBPSs), LBPS30, LBPS70 and total LBPS (LBPSt), were modified using chlorosulfonic acid-pyridine method based on the previous experiment, forming three sulfated LBPS (sLBPS), sLBPSt, sLBPS30 and sLBPS70 respectively. They were characterized by ultrasonic-acidic barium chromate spectrophotometry, infrared (FT-IR) and high performance gel permeation chromatography (HPGPC). The immunomodulatory activity of each kind of LBPSs and sLBPSs was further examined to determine the relationship between the structure and bioactivity, and the sLBPS with the highest activity was selected. The results showed that sulfate contents were 390.67, 542.75 and 291.71 mg/g respectively, with different molecular masses. The appearance of two new characteristic absorption bands at near 1230 and 855, 853 or 808 cm-1 in FT-IR spectra revealed the success of sulfation. sLBPSt with high molecular weight and moderate sulfate content exhibited the best immunomodulatory activity by promoting lymphopoiesis and T lymphocyte differentiation as well as increasing IL-2, IL-6, IFN-γ and TFN-α production in vitro compared with the inartificial polysaccharides. These results indicated that sulfated modification could be considered as an effective way to enhance immune activity of LBPSs. Furthermore, sLBPSt showed the best performances and would be expected as a new source of immunopotentiator. PMID:26884954

  9. Marine algae sulfated polysaccharides for tissue engineering and drug delivery approaches

    PubMed Central

    Silva, Tiago H.; Alves, Anabela; Popa, Elena G.; Reys, Lara L.; Gomes, Manuela E.; Sousa, Rui A.; Silva, Simone S.; Mano, João F.; Reis, Rui L.

    2012-01-01

    Biomedical field is constantly requesting for new biomaterials, with innovative properties. Natural polymers appear as materials of election for this goal due to their biocompatibility and biodegradability. In particular, materials found in marine environment are of great interest since the chemical and biological diversity found in this environment is almost uncountable and continuously growing with the research in deeper waters. Moreover, there is also a slower risk of these materials to pose illnesses to humans. In particular, sulfated polysaccharides can be found in marine environment, in different algae species. These polysaccharides don’t have equivalent in the terrestrial plants and resembles the chemical and biological properties of mammalian glycosaminoglycans. In this perspective, are receiving growing interest for application on health-related fields. On this review, we will focus on the biomedical applications of marine algae sulfated polymers, in particular on the development of innovative systems for tissue engineering and drug delivery approaches. PMID:23507892

  10. Freshwater Plants Synthesize Sulfated Polysaccharides: Heterogalactans from Water Hyacinth (Eicchornia crassipes)

    PubMed Central

    Dantas-Santos, Nednaldo; Gomes, Dayanne Lopes; Costa, Leandro Silva; Cordeiro, Sara Lima; Costa, Mariana Santos Santana Pereira; Trindade, Edvaldo Silva; Franco, Célia Regina Chavichiolo; Scortecci, Kátia Castanho; Leite, Edda Lisboa; Rocha, Hugo Alexandre Oliveira

    2012-01-01

    Sulfated polysaccharides (SP) are found mainly in seaweeds and animals. To date, they have only been found in six plants and all inhabit saline environments. Furthermore, there are no reports of SP in freshwater or terrestrial plants. As such, this study investigated the presence of SP in freshwaters Eichhornia crassipes, Egeria densa, Egeria naja, Cabomba caroliniana, Hydrocotyle bonariensis and Nymphaea ampla. Chemical analysis identified sulfate in N. ampla, H. bonariensis and, more specifically, E. crassipes. In addition, chemical analysis, FT-IR spectroscopy, histological analysis, scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA), as well as agarose gel electrophoresis detected SP in all parts of E. crassipes, primarily in the root (epidermis and vascular bundle). Galactose, glucose and arabinose are the main monosaccharides found in the sulfated polysaccharides from E. crassipes. In activated partial thromboplastin time (APTT) test, to evaluate the intrinsic coagulation pathway, SP from the root and rhizome prolonged the coagulation time to double the baseline value, with 0.1 mg/mL and 0.15 mg/mL, respectively. However, SP from the leaf and petiole showed no anticoagulant activity. Eichornia SP demonstrated promising anticoagulant potential and have been selected for further studies on bioguided fractionation; isolation and characterization of pure polysaccharides from this species. Additionally in vivo experiments are needed and are already underway. PMID:22312297

  11. Freshwater plants synthesize sulfated polysaccharides: heterogalactans from Water Hyacinth (Eicchornia crassipes).

    PubMed

    Dantas-Santos, Nednaldo; Gomes, Dayanne Lopes; Costa, Leandro Silva; Cordeiro, Sara Lima; Costa, Mariana Santos Santana Pereira; Trindade, Edvaldo Silva; Franco, Célia Regina Chavichiolo; Scortecci, Kátia Castanho; Leite, Edda Lisboa; Rocha, Hugo Alexandre Oliveira

    2012-01-01

    Sulfated polysaccharides (SP) are found mainly in seaweeds and animals. To date, they have only been found in six plants and all inhabit saline environments. Furthermore, there are no reports of SP in freshwater or terrestrial plants. As such, this study investigated the presence of SP in freshwaters Eichhornia crassipes, Egeria densa, Egeria naja, Cabomba caroliniana, Hydrocotyle bonariensis and Nymphaea ampla. Chemical analysis identified sulfate in N. ampla, H. bonariensis and, more specifically, E. crassipes. In addition, chemical analysis, FT-IR spectroscopy, histological analysis, scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA), as well as agarose gel electrophoresis detected SP in all parts of E. crassipes, primarily in the root (epidermis and vascular bundle). Galactose, glucose and arabinose are the main monosaccharides found in the sulfated polysaccharides from E. crassipes. In activated partial thromboplastin time (APTT) test, to evaluate the intrinsic coagulation pathway, SP from the root and rhizome prolonged the coagulation time to double the baseline value, with 0.1 mg/mL and 0.15 mg/mL, respectively. However, SP from the leaf and petiole showed no anticoagulant activity. Eichornia SP demonstrated promising anticoagulant potential and have been selected for further studies on bioguided fractionation; isolation and characterization of pure polysaccharides from this species. Additionally in vivo experiments are needed and are already underway.

  12. A Direct Sulfation Process of a Marine Polysaccharide in Ionic Liquid

    PubMed Central

    Sinquin, Corinne; Ratiskol, Jacqueline; Weiss, Pierre; Cérantola, Stéphane; Le Bideau, Jean

    2015-01-01

    GY785 is an exopolysaccharide produced by a mesophilic bacterial strain Alteromonas infernus discovered in the deep-sea hydrothermal vents. GY785 highly sulfated derivative (GY785 DRS) was previously demonstrated to be a promising molecule driving the efficient mesenchymal stem cell chondrogenesis for cartilage repair. This glycosaminoglycan- (GAG-) like compound was modified in a classical solvent (N,N′-dimethylformamide). However, the use of classical solvents limits the polysaccharide solubility and causes the backbone degradation. In the present study, a one-step efficient sulfation process devoid of side effects (e.g., polysaccharide depolymerization and/or degradation) was developed to produce GAG-like derivatives. The sulfation of GY785 derivative (GY785 DR) was carried out using ionic liquid as a reaction medium. The successful sulfation of this anionic and highly branched heteropolysaccharide performed in ionic liquid would facilitate the production of new molecules of high specificity for biological targets such as tissue engineering or regenerative medicine. PMID:26090416

  13. Antinociceptive and anti-inflammatory effect of sulfated polysaccharide fractions from Sargassum wightii and Halophila ovalis in male Wistar rats

    PubMed Central

    Neelakandan, Yuvaraj; Venkatesan, Arul

    2016-01-01

    Aim: The aim of this objective is to evaluate the antinociceptive and anti-inflammatory potential of sulfated polysaccharide purified fractions isolated from brown seaweed Sargassum wightii and seagrass Halophila ovalis in male Wistar rats. Subjects and Methods: Crude sulfated polysaccharide from S. wightii and H. ovalis was subjected to anion exchange chromatography, and the chemical composition was investigated. The antinociceptive activity of purified fractions was investigated using formalin and hot plate test. Carrageenan-induced paw edema, peritonitis model, and Freund's Complete Adjuvant-induced arthritis model were employed to determine the anti-inflammatory activity. Results: In the formalin test, there was a significant reduction in licking time in both phases of the test at a dose of 10 mg/kg. In the hot plate test, the antinociceptive effect was observed only in animals treated with 5, 10 mg/kg suggesting that the analgesic effect occurs through a central action mechanism. Sw FrIV and Ho FrIV significantly inhibited paw edema induced by carrageenan, especially at 3 h after treatment and potentially decreased neutrophil migration at 10 mg/kg, respectively. In Freund's adjuvant-induced arthritic rats, a significant reduction in paw volume was observed in Sw FrIV and Ho FrIV-treated groups (10 mg/kg). Conclusion: Purified components from S. wightii and H. ovalis have strong antinociceptive and anti-inflammatory effect on animal model. However, to determine the molecular mechanism, it is necessary to investigate the effect of purified fractions on inhibition of nitric oxide synthase expression mediated by inhibiting the phosphorylation of various signal proteins in lipopolysaccharide-stimulated RAW264.7 cells. PMID:27721544

  14. The sulfated polysaccharide from a marine red microalga as a platform for the incorporation of zinc ions.

    PubMed

    Netanel Liberman, Gal; Ochbaum, Guy; Malis Arad, Shoshana; Bitton, Ronit

    2016-11-05

    The cell-wall sulfated polysaccharide of the marine red microalga Porphyridium sp. is a high molecular weight biopolymer that has potential for use as a platform for metal complexation for various applications. This paper describes the structural and rheological characterization and antibacterial activity of the polysaccharide in combination with Zn(2+) (Zn-PS). SAXS and rheology studies indicate that with the addition of ZnCl2 to the sulfated polysaccharide the only change was the increase in viscosity in the entangled regime. The antibacterial activity of Zn-PS solutions was more potent than that of the native polysaccharide against Gram-negative and Gram-positive bacteria. The synergy between the bioactivities of Zn(2+) (which is a key player in wound healing and is active against variety of pathogens) and the unique bioactivities of the polysaccharide (e.g., anti-inflammatory) indicates promising potential for the development of novel products for the pharmaceutical and cosmetics industries.

  15. Antiinflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction extracted from the marine red algae Gracilaria caudata.

    PubMed

    Chaves, Luciano de Sousa; Nicolau, Lucas Antonio Duarte; Silva, Renan Oliveira; Barros, Francisco Clark Nogueira; Freitas, Ana Lúcia Ponte; Aragão, Karoline Sabóia; Ribeiro, Ronaldo de Albuquerque; Souza, Marcellus Henrique Loiola Ponte; Barbosa, André Luiz dos Reis; Medeiros, Jand-Venes Rolim

    2013-02-01

    Many algal species contain relatively high concentrations of polysaccharide substances, a number of which have been shown to have anti-inflammatory and/or immunomodulatory activity. In this study, we evaluated the anti-inflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction (PLS) extracted from the algae Gracilaria caudata. The antiinflammatory activity of PLS was evaluated using several inflammatory agents (carrageenan, dextran, bradykinin, and histamine) to induce paw edema and peritonitis in Swiss mice. Samples of the paw tissue and peritoneal fluid were removed to determine myeloperoxidase (MPO) activity or TNF-α and IL-1β levels, respectively. Mechanical hypernociception was induced by subcutaneous injection of carrageenan into the plantar surface of the paw. Pretreatment of mice by intraperitoneal administration of PLS (2.5, 5, and 10 mg/kg) significantly and dose-dependently reduced carrageenan-induced paw edema (p < 0.05) compared to vehicle-treated mice. Similarly, PLS 10 mg/kg effectively inhibited edema induced by dextran and histamine; however, edema induced by bradykinin was unaffected by PLS. PLS 10 mg/kg inhibited total and differential peritoneal leukocyte counts following carrageenan-induced peritonitis. Furthermore, PLS reduced carrageenan-increased MPO activity in paws and reduced cytokine levels in the peritoneal cavity. Finally PLS pretreatment also reduced hypernociception 3-4 h after carrageenan. We conclude that PLS reduces the inflammatory response and hypernociception in mice by reducing neutrophil migration and cytokines concentration.

  16. Optimization, characterization, sulfation and antitumor activity of neutral polysaccharides from the fruit of Borojoa sorbilis cuter.

    PubMed

    Xu, Fangfang; Liao, Kangsheng; Wu, Yunshan; Pan, Qi; Wu, Lilan; Jiao, Hong; Guo, Dean; Li, Ben; Liu, Bo

    2016-10-20

    Extraction optimization, purification, characterization, sulfation and antitumor activity of polysaccharides from the fruit body of Borojoa sorbilis cuter were investigated in present study. The optimal Ultrahigh Pressure extraction condition was determined as: extraction once with the solid-liquid ratio of 1:10 in 30°C and 1500Mpa for crude polysaccharide (BP) and experimental yield was 8.28%. Four water-soluble polysaccharides named as BP1-1, BP1-2, BP1-3 and BP1-4, with molecular weight of 35.8, 32.4, 30.1 and 27.7kDa, were purified by DEAE Sepharose and Superdex 200 chromatography. On the basis of chemical and spectroscopic analyses, BP1-1-BP1-4 were found to be neutral β-d-galactan containing a (1→4)-linked backbone. S-BP1s with the DSS of 1.18, was sulfated by chloro-sulfonic acid-pyridine method. Furthermore, S-BP1s exhibited significant in vitro antitumor activity against liver cancer HepG2 and lung cancer A549 cells in a dose-dependent manner. The results indicated that S-BP1s could be potentially developed as functional antitumor drug.

  17. Sulfation modification and anticoagulant activity of the polysaccharides obtained from persimmon (Diospyros kaki L.) fruits.

    PubMed

    Lu, Xiaoyun; Mo, Xiaoyan; Guo, Hui; Zhang, Yali

    2012-12-01

    The optimal conditions for sulfation of polysaccharides from persimmon fruits (PFP) with chlorosulfonic acid-pyridine (CSA-Pyr) method were determined by response surface methodology. Box-Behnken design was applied to evaluate the effects of three independent variables (volume ratio of Pyr to CSA, volume ratio of PFP to SO(3)Pyr and reaction time) on the degree of substitution (DS), molecular weight (MW) and activated partial thromboplastin time (APTT) of sulfated polysaccharides (PFP-S). The APTT activity of PFP-S could be improved by application of various volume ratio of Pyr to CSA, volume ratio of PFP to SO(3)Pyr and reaction time, which was possible due to the degradation of polysaccharides to different extent and increasing of DS. The optimal conditions to obtain the strongest APTT of PFP-S were the volume ratio of CSA to Pyr of 1:8, the volume ratio of SO(3)Pyr to PFP of 1:3.6 and the reaction time of 3 h, respectively.

  18. Characterization, antioxidant and cytotoxic activity of sulfated derivatives of a water-insoluble polysaccharides from Dictyophora indusiata.

    PubMed

    Deng, Chao; Xu, Jingjing; Fu, Haitian; Chen, Jinghua; Xu, Xin

    2015-04-01

    The present study described the characterization and biological properties of water‑soluble sulfated polysaccharides prepared from water‑insoluble polysaccharide (DIP), which were extracted from Dictyophora indusiata. The sulfation of DIP was performed using the chlorosulfonic acid‑pyridine method. The water solubilities of the sulfated derivatives were measured at room temperature according to the Chinese Pharmacopoeia. The scavenging activity of hydroxyl radicals and 1,1‑diphenyl‑2‑picrylhydrazyl (DPPH) as determined, together with the reduction ability of the sulfated polysaccharides. The cytotoxic and antiproliferative effects of DIP and the sulfated derivatives on MCF‑7 and B16 cells were then determined using an MTT assay. The substitution degrees of the sulfated polysaccharides were 0.584 (S1‑DIP), 0.989 (S2‑DIP) and 1.549 (S3‑DIP) according to barium chloride‑gelatin nephelometry. Infrared spectroscopy and 13C‑nuclear magnetic resonance indicated that the substitution of S‑DIP occurred mainly at the C‑6 position, followed by the C‑4 and C‑2 positions. A significant increase was noted in the antioxidant activity of the sulfated derivatives compared with that of DIP. In addition, the S‑DIPs exhibited a more marked reducing capacity and clearing activity of hydroxyl radicals and DPPH. This indicated that the antioxidant capacity of the polysaccharides was significantly higher following sulfation. Furthermore, in in vitro cell investigations, DIP exhibited no inhibitory effects on the growth of the B16 or MCF‑7 tumor cells. However, the sulfated derivatives exerted marked inhibitory effects on these cell lines. Sulfate modification may therefore contribute to an improvement in water solubility and in the antioxidant and antitumor activities of natural DIP.

  19. Structural characterization and functional properties of antihypertensive Cymodocea nodosa sulfated polysaccharide.

    PubMed

    Kolsi, Rihab Ben Abdallah; Fakhfakh, Jawhar; Krichen, Fatma; Jribi, Imed; Chiarore, Antonia; Patti, Francesco Paolo; Blecker, Christophe; Allouche, Noureddine; Belghith, Hafedh; Belghith, Karima

    2016-10-20

    A sulfated polysaccharide was successfully isolated from Cymodocea nodosa (CNSP). This is the first report that indicates the chemical composition, structural characterization, functional and antihypertensive properties of this polysaccharide. The CNSP consisted mainly of sulfate (23.17%), total sugars (54.90%), galactose (44.89%), mannose (17.30%), arabinose (12.05%), xylose (9.18%), maltose (1.07%) and uronic acid (11.03%) with low water activity (0.49). CNSP had an XRD pattern that was typical for a semi-crystalline polymer with homogeneous structure. It also displayed an important anti-hypertensive activity (IC50=0.43mgml) with a dose-dependent manner using a synthetic substrate, N-hippuryl-His-Leu hydrate salt (HHL). Overall, the results indicate that CNSP have attractive chemical, functional and biological properties, with a preliminary structural may have a backbone of branched 6-O-sulfated (1→4) galactosidic linkages, which can be considered in the future as alternative additive in various foods, cosmetic and pharmaceutical preparations.

  20. [Morphofunctional changes of dendritic cells induced by sulfated polysaccharides of brown algae].

    PubMed

    Makarenkova, I D; Akhmatova, N K; Ermakova, S P; Besednova, N N

    2017-01-01

    The effects of various sulfated polysaccharides of brown algae Fucus evanescens, Saccharina cichorioides and Saccharina japonica on the morphofunctional changes of dendritic cells have been investigated using flow cytometry and phase-contrast microscopy. The dendritic cells are characterized by larger sizes, vacuolated cytoplasm, eccentrically located nucleus, and also by the presence of numerous cytoplasmic pseudopodia of various shapes. They express surface markers, indicating their maturation (CD83, CD11c, HLA-DR, CD86). Increased production of immunoregulatory (IL-12) and proinflammatory TNF-a, IL-6) cytokines (by dendritic cells polarizes the development of the Th-1 type immune response.

  1. Polysaccharides from Gracilaria corticata: sulfation, chemical characterization and anti-HSV activities.

    PubMed

    Chattopadhyay, Kausik; Ghosh, Tuhin; Pujol, Carlos A; Carlucci, María J; Damonte, Elsa B; Ray, Bimalendu

    2008-11-01

    In this study, we have analyzed water-extracted polysaccharides of Gracilaria corticata. The water extract (WE), a galactan-containing sub-fraction (F3) and their hyper sulfated derivatives (WES1, WES2, F3S1 and F3S2) had anti-HSV activity with inhibitory concentration 50% (IC50) from 1.1 to 27.4 microg/ml. Sub-fraction F3, which has a molecular mass of 30 kDa, consists of a backbone of beta-(1-->3) and alpha-(1-->4)-linked-galactopyranosyl residues. This linear galactan contained Gal2Xyl1, Gal2AnGal2, Gal4 and Me-Gal3AnGal2 as oligomeric building subunits. Sulfate group was located at C-4 of (1-->3)-linked galactopyranosyl residues of the native galactan, and appeared to be very important for the anti-herpetic activity.

  2. Immunoglobulin-sulfated polysaccharide interactions. Binding of agaropectin and heparin by human IgG proteins

    PubMed Central

    1981-01-01

    The interaction of immunoglobulins with certain acidic polysaccharides was demonstrated by the binding of the sulfated glycans agaropectin and heparin by certain human IgG proteins. Heparin-binding IgG proteins can distinguish between the molecular forms of heparin derived from porcine intestine, bovine lung, and rat skin. The major specificity of these proteins is for native and certain high molecular weight subunit components of rat skin heparin. The interactions with multi-chain and single chain rat skin heparin are stable under physiological conditions and involve the Fab and, more specifically, the Fv region of the IgG molecule. These reactions occur as a result of an electrostatic interaction between cationic sites on certain IgG proteins and anionic sulfate resides of agaropectin or heparin. The characteristics of heparin-IgG interaction resemble those of heparin with other plasma proteins, the interactions of which have biological significance. PMID:7252414

  3. METHOD OF INHIBITING CORROSION IN URANYL SULFATE SOLUTIONS

    DOEpatents

    Bohlmann, E.G.; Griess, J.C. Jr.

    1960-08-23

    A method is given for treating a uranyl sulfate solution to inhibit the corrosiveness of the solution and elevate the phase separation temperature of the solution. Lithium sulfate is added to the solution in an amount ranging from 0.25 to 1.3 times the uranyl sulfate concentration. The corrosiveness of the solution with respect to stainless steel is substantially decreased by this means. This treatment also serves to raise the phase separation temperature of the solution (above 250 deg C), at which time the uranyl sulfate solution separates into two liquid phases of unequal uranium concentration and thus becomes unsuitable as nuclear reactor fuel.

  4. Chemoprevention of Diethylnitrosamine-Initiated and Phenobarbital-Promoted Hepatocarcinogenesis in Rats by Sulfated Polysaccharides and Aqueous Extract of Ulva lactuca.

    PubMed

    Hussein, Usama K; Mahmoud, Hamada M; Farrag, Asmaa G; Bishayee, Anupam

    2015-11-01

    -initiated hepatocarcinogenesis through inhibition of abnormal cell proliferation and induction of apoptosis. A modest inhibition rat liver carcinogenesis was observed with the aqueous extract. The sulfated polysaccharides altered serum parameters of hepatic damage and modulated various components of the hepatic enzymatic and nonenzymatic antioxidant defense systems. The sulfated polysaccharides from U. lactuca may have unique properties of providing protection against DENA-induced oxidative stress which could contribute to chemoprevention of experimental hepatocarcinogenesis. U. lactuca sulfated polysaccharides could be developed as chemopreventive and therapeutic drug against human HCC.

  5. Sulfated modification of the polysaccharides from Ganoderma atrum and their antioxidant and immunomodulating activities.

    PubMed

    Chen, Yi; Zhang, Hui; Wang, Yuanxing; Nie, Shaoping; Li, Chang; Xie, Mingyong

    2015-11-01

    In this study, three chemically sulfated polysaccharides (S-PSG) with different degree of sulfate substitution (DS) were derived from Ganoderma atrum. FT-IR and (13)C NMR spectra indicated that the substitution was predominantly on C-6 position compared with the C-2 position. The antioxidant and immunomodulatory activities of S-PSG were further examined to determine the relationship between its structure and bioactivity. The results showed that compared with the native polysaccharide, the S-PSG-2 with moderate DS and molecular weight exhibited the highest immunomodulatory activity by increasing the macrophage phagocytosis capacity and TNF-α production. The DPPH radical scavenging activity was also greatly enhanced by S-PSG in all the groups compared with PSG. However, the reducing power and the antioxidant activities in β-carotene-linoleic acid assay were decreased. These results indicated that except for the DS, some other structural characteristics such as molecular weight, substitution position and chain conformation were also important factors affecting their bioactivities. And the S-PSG-2 we derived could be served as immunomodulator and free-radical inhibitors.

  6. The comparison of antioxidative and hepatoprotective activities of Codonopsis pilosula polysaccharide (CP) and sulfated CP.

    PubMed

    Liu, Cui; Chen, Jin; Li, Entao; Fan, Qiang; Wang, Deyun; Li, Peng; Li, Xiuping; Chen, Xingying; Qiu, Shulei; Gao, Zhenzhen; Li, Hongquan; Hu, Yuanliang

    2015-02-01

    Codonopsis pilosula polysaccharide (CP) was extracted, purified and modified by chlorosulfonic acid-pyridine method to obtain a sulfated CP (sCP). Their antioxidative activities in vitro were compared through the free radical-scavenging test. The results demonstrated that the scavenging capabilities of sCP were significantly stronger than those of CP. In vivo test, the mice hepatic injury model was prepared by BCG/LPS method, then administrated respectively with sCP and CP at three dosages, the biochemical indexes in serum, antioxidative indexes in liver homogenate and histopathological change in liver of the mice were compared. The results showed that in high (200mg/kg) and middle (150mg/kg) dosages of sCP groups, the contents of ALT, AST and TNF-α in serum and MDA in liver homogenate were significantly lower than those in the model group and numerically lower than those in the CP groups, the activities of SOD and GSH-Px in liver homogenate were significantly higher than those in the model group and numerically higher than those in the CP groups. In the model group there were obvious pathological changes in the liver, while in the sCP groups were near normal. These results indicate that sCP and CP possess antioxidative activity in vitro and in vivo, the activity of sCP is stronger than that of CP and sulfation modification can enhance the antioxidative and hepatoprotective activities of Codonopsis pilosula polysaccharide.

  7. Separation, characterization and anticancer activities of a sulfated polysaccharide from Undaria pinnatifida.

    PubMed

    Han, Yun; Wu, Jun; Liu, Tingting; Hu, Youdong; Zheng, Qiusheng; Wang, Binsheng; Lin, Haiyan; Li, Xia

    2016-02-01

    The purpose of this paper was to investigate separation, characterization and anticancer activities of a sulfated polysaccharide (SPUP) from Undaria pinnatifida. Firstly, polysaccharide from U. pinnatifida was separated by DEAE-52 cellulose and Sephacryl S-400 column chromatography. As results, SPUP was obtained with the yield of 19.42%. Then, SPUP was characterized using chemical analysis, gas chromatography, size-exclusion HPLC chromatography, UV-vis spectra and FT-IR spectrum. The content of total sugar, uronic acid, protein and sulfate radical were 80.48%, 3.21%, 7.12% and 29.14%, respectively. SPUP was a heteropolysaccharide composed of fucose, glucose and galactose in a molar percentage of 27.15:19.34:53.51 with molecular weight of 97.9 kDa. Finally, the strongly against breast cancer activity of SPUP was confirmed by DMBA-induced breast cancer rats model. AS results, SPUP can significantly restrain breast abnormal enlargement, prolong tumor latency and reduced tumor incidence. Immunomodulatory activity and regulating abnormal sex hormones level might contribute to its anticancer activities.

  8. Structure-activity relationship of sulfated hetero/galactofucan polysaccharides on dopaminergic neuron.

    PubMed

    Wang, Jing; Liu, Huaide; Jin, Weihua; Zhang, Hong; Zhang, Quanbin

    2016-01-01

    Parkinson's disease (PD) is associated with progressive loss of dopaminergic neurons and more-widespread neuronal changes that cause complex symptoms. The aim of this study was to investigate the structure-activity relationship of sulfated hetero-polysaccharides (DF1) and sulfated galactofucan polysaccharides (DF2) on dopaminergic neuron in vivo and in vitro. Treatment with samples significantly ameliorated the depletion of both DA and TH-, Bcl-2- and Bax-positive neurons in MPTP-induced PD mice, DF1 showed the highest activity. The in vitro results found that DF1 and DF2 could reverse the decreased mitochondrial activity and the increased LDL release induced by MPP(+) (P<0.01 or P<0.001) which provides further evidence that DF1 and DF2 also exerts a direct protection against the neuronal injury caused by MPP(+). Furthermore, the administration of samples effectively decreased lipid peroxidation and increased the level/activities of GSH, GSH-PX, MDA and CAT in MPTP mice. Thus, the neuron protective effect may be mediated, in part, through antioxidant activity and the prevention of cell apoptosis. The chemical composition of DF1, DF2 and DF differed markedly, the DF1 fraction had the most complex chemical composition and showed the highest neuron protective activity. These results suggest that diverse monosaccharides and uronic acid might contribute to neuron protective activity.

  9. A Sulfated-Polysaccharide Fraction from Seaweed Gracilaria birdiae Prevents Naproxen-Induced Gastrointestinal Damage in Rats

    PubMed Central

    Silva, Renan O.; Santana, Ana Paula M.; Carvalho, Nathalia S.; Bezerra, Talita S.; Oliveira, Camila B.; Damasceno, Samara R. B.; Chaves, Luciano S.; Freitas, Ana Lúcia P.; Soares, Pedro M. G.; Souza, Marcellus H. L. P.; Barbosa, André Luiz R.; Medeiros, Jand-Venes R.

    2012-01-01

    Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group—vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation. PMID:23342384

  10. A sulfated-polysaccharide fraction from seaweed Gracilaria birdiae prevents naproxen-induced gastrointestinal damage in rats.

    PubMed

    Silva, Renan O; Santana, Ana Paula M; Carvalho, Nathalia S; Bezerra, Talita S; Oliveira, Camila B; Damasceno, Samara R B; Chaves, Luciano S; Freitas, Ana Lúcia P; Soares, Pedro M G; Souza, Marcellus H L P; Barbosa, André Luiz R; Medeiros, Jand-Venes R

    2012-12-01

    Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group-vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation.

  11. Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

    NASA Astrophysics Data System (ADS)

    Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Rong'e.; Chen, Xiaolin; Li, Pengcheng

    2016-08-01

    Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuria fuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides (HfP) from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man: Rha: Glc A: Glc: Gal: Xyl: Fuc=0.083 6: 0.437: 0.134: 0: 1.182: 0.748: 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity EC 50 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that of heparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

  12. Sulfated modification can enhance antiglycation abilities of polysaccharides from Dendrobium huoshanense.

    PubMed

    Qian, Xing-Ping; Zha, Xue-Qiang; Xiao, Jing-Jing; Zhang, Hai-Ling; Pan, Li-Hua; Luo, Jian-Ping

    2014-01-30

    Dendrobium huoshanense is an important edible-medicinal plant with high nutritional values and health functions. A homogenous polysaccharide (DHPD1) with molecular weight of 3.2 × 10(3)Da was extracted from D. huoshanense, which was mainly composed of glucose, arabinose, galactose, mannose and xylose. Chlorosulfonic acid-pyridine (CSA-Pyr) method was performed to modify the structure of DHPD1. In order to get a high degree of substitution (DS), sulfated modification conditions were optimized by response surface methodology. The maximum DS of 1.473 was obtained when the reaction condition was fixed at reaction temperature 60°C, reaction time 160 min and volume ratio of Pyr to CSA 2:1. NMR spectra revealed that this sulfation occurred to C-2 and C-6 of glycosyl residues in DHPD1. After 28 days of incubation, the sulfated DHPD1 at 1.0mg/mL showed the inhibitory ability of 58.5%, which increased by 16.2% and 52.5% than that of aminoguanidine and DHPD1 at the same dosage.

  13. Occurrence of sulfated fucose branches in fucosylated chondroitin sulfate are essential for the polysaccharide effect preventing muscle damage induced by toxins and crude venom from Bothrops jararacussu snake.

    PubMed

    Monteiro-Machado, Marcos; Tomaz, Marcelo A; Fonseca, Roberto J C; Strauch, Marcelo A; Cons, Bruno L; Borges, Paula A; Patrão-Neto, Fernando C; Tavares-Henriques, Matheus S; Teixeira-Cruz, Jhonatha M; Calil-Elias, Sabrina; Cintra, Adélia C O; Martinez, Ana Maria B; Mourão, Paulo A S; Melo, Paulo A

    2015-05-01

    Snake envenoming is an important public health problem around the world, particularly in tropics. Beyond deaths, morbidity induced by snake venoms, such as myotoxicity, is of pivotal consequence to population. Bothrops jararacussu is the main venomous snake in southeast region of Brazil, and particularly presents strong myotoxic effect. The only available therapy, antibothropic antivenom, poorly affects venom-induced myotoxicity. The aim of this study is to assess the ability of fucosylated chondroitin sulfate (fucCS), a glycosaminoglycan with anticoagulant and antithrombotic properties, and its derivatives to inhibit toxic activities of B. jararacussu crude venom and its isolated toxins, named bothropstoxins (BthTX-I and BthTX-II). The in vitro myotoxic activities induced by crude venom, by BthTX-I alone and by toxins together were abolished by fucCS. Carboxyl reduction (fucCS-CR) kept this ability whereas defucosilation (defucCS) abrogates myoprotection. We observed the same pattern in the response of these polysaccharides in antagonizing the increase in plasma creatine kinase (CK) levels, the reduction of skeletal muscle CK content and the rise of myeloperoxidase (MPO) activity induced by crude venom and isolated toxins. FucCS inhibited edematogenic activity and partially prevented the reduction of total leukocytes in blood when pre-incubated with crude venom. Furthermore, the venom procoagulant effect was completely antagonized by increasing concentrations of fucCS, although this polyanion could stop neither the tail bleeding nor the skin hemorrhage induced by Bothrops jararaca venom. The B. jararacussu phospholipase, hyaluronidase, proteolytic and collagenase activities were inhibited in vitro. The results suggest that fucCS could be able to interact with both toxins, and it is able to inhibit BthTX-II phospholipase activity. Light microscopy of extensor digitorum longus muscle (EDL) muscle showed myoprotection by fucCS, once necrotic areas, edema and

  14. Assessment of zymosan-induced leukocyte influx in a rat model using sulfated polysaccharides.

    PubMed

    Cardoso, Maria Leila; Xavier, Caroline A; Bezerra, Maria B Emilia; Paiva, Almino O Afonso; Carvalho, Maria F Goretti; Benevides, Norma M B; Rocha, Francisco A C; Leite, Edda Lisboa

    2010-02-01

    Fucoidan, a sulfated polysaccharide from the brown algae Fucus vesiculosus, has diverse biological properties, including anti-inflammatory, anticoagulant and antithrombotic activity. This study analyzed the therapeutic activity of total fucoidan (TF) from F. vesiculosus and that of purified fractions (F1 and F2) on zymosan-induced arthritis. Arthritis was induced by injecting zymosan into the knee joint. Thus, three fucoidan fractions were obtained by acetone fractionation. Due to the yield obtained from F3, we used only fucoidans F1 and F2 in the induced inflammation tests. Chemical analyses and electrophoretic characterization of these fractions demonstrated that they contain polysaccharides, sulfate ester and very low protein levels. The fucoidans obtained from TF showed only an electrophoretic band in agarose gel with much lower polydispersion. The F2 fraction showed a migration between fucoidans F1 and F3. We administered TF (15, 30, 50 mg/kg I. P.), F1 or F2 (10, 25 and 50 mg/kg I. P.), diclofenac sodium (10 mg/kg I. P.), lumiracoxib (5 mg/kg O. A.) or L-NAME (30 mg/kg I. P.), 1 hour after induction of articular inflammation. We analyzed cell influx and nitrite levels in addition to performing histopathological analysis. TF (total fucoidan) at 15, 30, 50 mg/kg I. P. and its fractions (F1 and F2 at concentrations of 25 and 50 mg/kg I. P.) significantly reduced cellular influx and nitric oxide concentration. Moreover, the articular inflammation in zymosan-induced arthritis caused a progressive loss in glycosaminoglycan content. This loss decreased when TF (30 mg/kg) was administered. These data suggest that fucoidan exerts anti-inflammatory action in a zymosan-induced model of acute inflammation in rats. Taken together with the fact that these natural compounds have minimal toxicity, this may have important therapeutic implications.

  15. Microanalysis and preliminary pharmacokinetic studies of a sulfated polysaccharide from Laminaria japonica

    NASA Astrophysics Data System (ADS)

    Zhang, Wenjing; Sun, Delin; Zhao, Xia; Jin, Weihua; Wang, Jing; Zhang, Quanbin

    2016-01-01

    A rapid, sensitive and reproducible high performance liquid chromatography (HPLC) method with post-column fluorescence derivatization has been developed to determine the amount of low-molecular-weight sulfated polysaccharide (GFS) in vivo. The metabolism of GFS has been shown to fit a two component model following its administration by intravenous injection, and its pharmacokinetic parameters were determined to be as follows: half-time of distribution phase ( t 1/2α)=11.24±2.93 min, half-time of elimination phase ( t 1/2β)=98.20±25.78 min, maximum concentration ( C max)=110.53 μg/mL and peak time ( T max)=5 min. The pharmacokinetic behavior of GFS was also investigated following intragastric administration. However, the concentration of GFS found in serum was too low for detection, and GFS could only be detected for up to 2 h after intragastric administration (200 mg/kg body weight). Thus, the bioavailability of GFS was low following intragastric administration because of the metabolism of GFS. In conclusion, HPLC with postcolumn derivatization could be used for quantitative microanalysis and pharmacokinetic studies to determine the presence of polysaccharides in the serum following intravenous injection.

  16. Coptis chinensis Polysaccharides Inhibit Advanced Glycation End Product Formation.

    PubMed

    Yang, Ye; Li, Yun; Yin, Dengke; Chen, Song; Gao, Xiangdong

    2016-06-01

    Coptis chinensis Franch (Huanglian) is commonly used to treat diabetes in China. In this study, the effects of the C. chinensis Franch polysaccharides (CCP) on advanced glycation end product (AGE) formation in vitro and in streptozotocin-induced diabetic mice were investigated. CCP significantly inhibited all the three periods of nonenzymatic protein glycation in vitro, including Amadori product, dicarbonyl compound, and AGE formation (P < .01). In diabetic mice, the administration of CCP not only improved both bodyweight and serum insulin and decreased fasting blood glucose and glycated serum protein concentrations but also decreased the AGE accumulations and morphological abnormalities in pancreas and liver. The inhibitory effects of CCP on AGE formation afford a potential therapeutic use in the prevention and treatment of diabetes.

  17. Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection in Human Lung Cells and Airway Tissues

    PubMed Central

    Klimyte, Edita M.; Smith, Stacy E.; Oreste, Pasqua; Lembo, David

    2016-01-01

    ABSTRACT Human metapneumovirus (HMPV), a recently discovered paramyxovirus, infects nearly 100% of the world population and causes severe respiratory disease in infants, the elderly, and immunocompromised patients. We previously showed that HMPV binds heparan sulfate proteoglycans (HSPGs) and that HMPV binding requires only the viral fusion (F) protein. To characterize the features of this interaction critical for HMPV binding and the role of this interaction in infection in relevant models, we utilized sulfated polysaccharides, heparan sulfate mimetics, and occluding compounds. Iota-carrageenan demonstrated potent anti-HMPV activity by inhibiting binding to lung cells mediated by the F protein. Furthermore, analysis of a minilibrary of variably sulfated derivatives of Escherichia coli K5 polysaccharide mimicking the HS structure revealed that the highly O-sulfated K5 polysaccharides inhibited HMPV infection, identifying a potential feature of HS critical for HMPV binding. The peptide dendrimer SB105-A10, which binds HS, reduced binding and infection in an F-dependent manner, suggesting that occlusion of HS at the target cell surface is sufficient to prevent infection. HMPV infection was also inhibited by these compounds during apical infection of polarized airway tissues, suggesting that these interactions take place during HMPV infection in a physiologically relevant model. These results reveal key features of the interaction between HMPV and HS, supporting the hypothesis that apical HS in the airway serves as a binding factor during infection, and HS modulating compounds may serve as a platform for potential antiviral development. IMPORTANCE Human metapneumovirus (HMPV) is a paramyxovirus that causes respiratory disease worldwide. It has been previously shown that HMPV requires binding to heparan sulfate on the surfaces of target cells for attachment and infection. In this study, we characterize the key features of this binding interaction using heparan sulfate

  18. Characterization and Comparison of the Structural Features, Immune-Modulatory and Anti-Avian Influenza Virus Activities Conferred by Three Algal Sulfated Polysaccharides

    PubMed Central

    Song, Lin; Chen, Xiaolin; Liu, Xiaodong; Zhang, Fubo; Hu, Linfeng; Yue, Yang; Li, Kecheng; Li, Pengcheng

    2015-01-01

    Three marine macroalgae, i.e., Grateloupia filicina, Ulva pertusa and Sargassum qingdaoense, were selected as the deputies of Rhodophyta, Chlorophyta and Ochrophyta for comparative analysis of the molecular structures and biological activities of sulfated polysaccharides (SP). The ratio of water-soluble polysaccharides, the monosaccharide composition and the sulfated contents of three extracted SPs were determined, and their structures were characterized by Fourier transformation infrared spectroscopy. In addition, biological activity analysis showed that all three SPs had immune-modulatory activity both in vitro and in vivo, and SPs from S. qingdaoense had the best effect. Further bioassays showed that three SPs could not only enhance the immunity level stimulated by inactivated avian influenza virus (AIV) in vivo but also significantly inhibited the activity of activated AIV (H9N2 subtype) in vitro. G. filicina SP exhibited the strongest anti-AIV activity. These results revealed the variations in structural features and bioactivities among three SPs and indicated the potential adjuvants for immune-enhancement and anti-AIV. PMID:26729137

  19. Immunomodulatory of selenium nano-particles decorated by sulfated Ganoderma lucidum polysaccharides.

    PubMed

    Wang, Jianguo; Zhang, Yifeng; Yuan, Yahong; Yue, Tianli

    2014-06-01

    In this study, we employed a one-step method to prepare selenium nanoparticles (SeNPs) decorated by the water-soluble derivative of Ganoderma lucidum polysaccharides (SPS). The SeNPs-SPS complexes were stable, and the diameter of the SeNPs was homogeneous at around 25 nm. We investigated the anti-inflammatory activity of SeNPs-SPS against murine Raw 264.7 macrophage cells induced by LPS. SeNPs-SPS were found to significantly inhibit LPS-stimulated nitric oxide (NO) production against Raw 264.7 macrophages. RT-PCR results reveal the down-regulation of mRNA gene expressions for pro-inflammatory cytokines, including inducible NO synthase (iNOS), interleukin (IL)-1 and TNF-α in a dose-dependent manner. However, the anti-inflammation cytokine IL-10 was markedly increased. In the NF-κB signal pathway, SeNPs-SPS significantly inhibited the phosphorylation of Iκ-Bα. Similar results were observed for inhibition of the phosphorylation of JNK1/2 and p38 mitogen-activated protein kinase(MAPKs), whereas ERK1/2 MAPK was not apparently affected by SeNPs-SPS. All of these results suggest that SeNPs-SPS complexes have anti-inflammatory potential modulating pro-/anti-inflammation cytokine secretion profiles, and that the mechanism is partially due to inhibition of activations of NF-κB, JNK1/2 and p38 MAPKs.

  20. Inhibition of α-glucosidase by polysaccharides from the fruit hull of Camellia oleifera Abel.

    PubMed

    Zhang, Sheng; Li, Xiang-Zhou

    2015-01-22

    We isolated and purified polysaccharides from the Camellia oleifera Abel. fruit hull and studied its hypoglycemic potential. Our results revealed six polysaccharides (CFPA-1-5 & CFPB) from the aqueous extract from the defatted C. oleifera fruit hull. Purified polysaccharides (purity >90%) were investigated for the inhibition of α-glucosidase activity in vitro. Two polysaccharides, CFPB and CFPA-3 were present in high concentration in the fruit hull and showed a dose-dependent inhibition of α-glucosidase activity, with IC50 concentrations of 11.80 and 10.95 μg/mL, respectively. This result suggests that polysaccharides (CFP) extracted from the fruit hull of C. oleifera may have potential as functional foods with featuring a hypoglycemic effect.

  1. Antiviral effect of sulfated Chuanmingshen violaceum polysaccharide in chickens infected with virulent Newcastle disease virus.

    PubMed

    Song, Xu; Zhang, Yuetian; Yin, Zhongqiong; Zhao, Xinghong; Liang, Xiaoxia; He, Changliang; Yin, Lizi; Lv, Cheng; Zhao, Ling; Ye, Gang; Shi, Fei; Shu, Gang; Jia, Renyong

    2015-02-01

    Newcastle disease virus (NDV) belonging to the Paramyxovirinae subfamily is one of the most devastating pathogens in poultry. Although vaccines are widely applied to control the infection, outbreaks of Newcastle disease (ND) repeatedly happen. Currently, there are no alternative control measures available for ND. In the present study, we found that sulfated Chuanmingshen violaceum polysaccharide (sCVPS) were potent inhibitors of NDV in specific pathogen free chickens infected with a virulent strain. With sCVPS treatment, the survival rate increased by almost 20% and virus titers in test organs, including brain, lung, spleen and thymus, were significantly decreased. The sCVPS also exhibited the ability to prevent viral transmission by reducing the amount of virus shed in saliva and feces. Higher concentrations of interferon α and γ in serum were detected in chickens treated with sCVPS, indicating that one of the antiviral mechanisms may be attributed to the property of immunoenhancement. Histopathological examination showed that sCVPS could alleviate the tissue lesions caused by NDV infection. These results suggest that sCVPS are expected to be a new alternative control measure for NDV infection and further studies could be carried out to evaluate the antiviral activity of sCVPS against other paramyxoviruses.

  2. Influence of sulfation on anti-myocardial ischemic activity of Ophiopogon japonicus polysaccharide.

    PubMed

    Zheng, Qin; Feng, Yi; Xu, De-Sheng; Lin, Xiao; Chen, Yan-Zuo

    2009-01-01

    Ophiopogon japonicus polysaccharide (FOJ-5) from Radix ophiopogonis has shown anti-myocardial ischemic action in vitro and in vivo in our previous studies. In order to clarify the influence of chemical modifications on the action, a series of sulfated FOJ-5 (FOJ-5-S) with different substitution degrees were prepared and the anti-myocardial ischemic action of the natural FOJ-5 and the FOJ-5-S were studied in vitro and in vivo. Langendorff isolated rat hearts and acute myocardial ischemic rats induced by isoprenaline were employed as myocardial ischemic models in our experiments. The amplitude and frequency of cardiac contraction, coronary blood flow at different time points after ischemia/reperfusion were measured in vitro. The ST segment shift in electrocardiogram and lactate dehydrogenase level in blood plasma were observed on the in vivo model. The results indicated that FOJ-5 and FOJ-5-S had the anti-myocardial ischemic action compared with non-treated vehicle groups. Furthermore, it was found that FOJ-5-S had significant action on the in vivo model compared with FOJ-5 (P < 0.05). And the obtained results from the further study also indicated that only when the degree of substitution was in a certain range, the FOJ-5-S had excellent anti-myocardial ischemic activity.

  3. The sulfated polysaccharide fucoidan rescues senescence of endothelial colony-forming cells for ischemic repair.

    PubMed

    Lee, Jun Hee; Lee, Sang Hun; Choi, Sung Hyun; Asahara, Takayuki; Kwon, Sang-Mo

    2015-06-01

    The efficacy of cell therapy using endothelial colony-forming cells (ECFCs) in the treatment of ischemia is limited by the replicative senescence of isolated ECFCs in vitro. Such senescence must therefore be overcome in order for such cell therapies to be clinically applicable. This study aimed to investigate the potential of sulfated polysaccharide fucoidan to rescue ECFCs from cellular senescence and to improve in vivo vascular repair by ECFCs. Fucoidan-preconditioning of senescent ECFCs was shown by flow cytometry to restore the expression of functional ECFC surface markers (CD34, c-Kit, VEGFR2, and CXCR4) and stimulate the in vitro tube formation capacity of ECFCs. Fucoidan also promoted the expression of cell cycle-associated proteins (cyclin E, Cdk2, cyclin D1, and Cdk4) in senescent ECFCs, significantly reversed cellular senescence, and increased the proliferation of ECFCs via the FAK, Akt, and ERK signaling pathways. Fucoidan was found to enhance the survival, proliferation, incorporation, and endothelial differentiation of senescent ECFCs transplanted in ischemic tissues in a murine hind limb ischemia model. Moreover, ECFC-induced functional recovery and limb salvage were markedly improved by fucoidan pretreatment of ECFCs. To our knowledge, the findings of our study are the first to demonstrate that fucoidan enhances the neovasculogenic potential of ECFCs by rescuing them from replicative cellular senescence. Pretreatment of ECFCs with fucoidan may thus provide a novel strategy for the application of senescent stem cells to therapeutic neovascularization.

  4. Kinetics and mechanism of oxidation of chondroitin-4-sulfate polysaccharide by chromic acid in aqueous perchlorate solutions.

    PubMed

    Hassan, Refat; Ibrahim, Samia; Dahy, Abdel Rahman; Zaafarany, Ishaq; Tirkistani, Fahd; Takagi, Hideo

    2013-02-15

    The kinetics of chromic acid oxidation of chondroitin-4-sulfate polysaccharide as sulfated carbohydrates at a constant ionic strength of 4.0 mol dm(-3) has been investigated, spectrophotometrically. The reaction kinetics showed a first-order dependence in chromic acid and fractional-first-order kinetics with respect to the chondroitin-4-sulfate concentration. The influence of [H(+)] on the reaction rates showed that the oxidation process is acid-catalyzed. Added Mn(2+) ions indicated the formation of Cr(IV) as intermediate species. A kinetic evidence for formation of 1:1 intermediate complex was revealed. The kinetic parameters have been evaluated and a tentative reaction mechanism in good consistent with the kinetic results obtained is discussed.

  5. Effects of sulfation on the physicochemical and functional properties of a water-insoluble polysaccharide preparation from Ganoderma lucidum.

    PubMed

    Liu, Wei; Wang, Hengyu; Yao, Wenbing; Gao, Xiangdong; Yu, Liangli Lucy

    2010-03-24

    The sulfation of a water-insoluble Ganoderma lucidum polysaccharide (GLP) was successfully carried out with chlorosulfonic acid-pyridine in dimethyl formamide to prepare three sulfated GLP derivatives, named sGLP1, sGLP2, and sGLP3. The chemical structure of the sulfated GLP was confirmed by Fourier transform infrared and (13)C NMR analyses. The sGLPs were evaluated for their water solubility, degree of substitution (DS), antioxidant properties, and bile acid-binding capacities. The results showed that sulfation improved the water solubility of GLP and increased its scavenging capacities against hydroxyl and superoxide anion radicals, hydrogen peroxide-scavenging activity, Fe(II) chelating ability, reducing power, and bile acid-binding capacities. It was also observed that the DS may influence the physicochemical and functional properties of sGLPs. For instance, the sulfated GLP with the lowest DS had the greatest bile acid-binding capacity, and the sGLP that had the highest DS showed the lowest bile acid-binding ability under the experimental conditions. The results from this study suggested that sulfation is a possible approach to obtain novel water-soluble derivatives of GLP with improved physicochemical, functional, and biological properties for potential utilization in functional foods or supplemental products.

  6. Sulphation can enhance the antioxidant activity of polysaccharides produced by Enterobacter cloacae Z0206.

    PubMed

    Jin, Mingliang; Wang, Youming; Huang, Ming; Lu, Zeqing; Wang, Yizhen

    2014-01-01

    The protective effects of sulfated polysaccharide derivatives produced by Enterobacter cloacae Z0206 against H₂O₂-induced oxidative damage in RAW264.7 murine macrophages as well as the possible mechanisms governing the protective effects were studied. Sulfated polysaccharides protected RAW264.7 cells from oxidative damage and apoptosis induced by H₂O₂ by protecting the cellular structure; improving the activity of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px); and inhibiting caspase-3 activation and DNA fragmentation. In addition, the sulfated polysaccharides conferred higher levels of protection from H₂O₂-induced oxidative damage in RAW264.7 murine macrophages compared to the native polysaccharide lacking sulfation. These results indicated that sulfated modifications might be an effective approach to enhance the antioxidant activity of polysaccharides produced by E. cloacae Z0206, and the sulfated derivatives of these polysaccharides may act as potent antioxidant agents.

  7. Overview on Biological Activities and Molecular Characteristics of Sulfated Polysaccharides from Marine Green Algae in Recent Years

    PubMed Central

    Wang, Lingchong; Wang, Xiangyu; Wu, Hao; Liu, Rui

    2014-01-01

    Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits. PMID:25257786

  8. Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin

    PubMed Central

    Verespy III, Stephen; Mehta, Akul Y.; Afosah, Daniel; Al-Horani, Rami A.; Desai, Umesh R.

    2016-01-01

    Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (<500 nM) and high selectivity for thrombin (>150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80–100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding. PMID:27053426

  9. Inhibition of oxidative stress by low-molecular-weight polysaccharides with various functional groups in skin fibroblasts.

    PubMed

    Chen, Szu-Kai; Hsu, Chu-Hsi; Tsai, Min-Lang; Chen, Rong-Huei; Drummen, Gregor P C

    2013-09-25

    The aim of this study was to evaluate the in cellulo inhibition of hydrogen-peroxide-induced oxidative stress in skin fibroblasts using different low-molecular-weight polysaccharides (LMPS) prepared from agar (LMAG), chitosan (LMCH) and starch (LMST), which contain various different functional groups (i.e., sulfate, amine, and hydroxyl groups). The following parameters were evaluated: cell viability, intracellular oxidant production, lipid peroxidation, and DNA damage. Trolox was used as a positive control in order to allow comparison of the antioxidant efficacies of the various LMPS. The experimentally determined attenuation of oxidative stress by LMPS in skin fibroblasts was: LMCH > LMAG > LMST. The different protection levels of these LMPS may be due to the physic-chemical properties of the LMPS' functional groups, including electron transfer ability, metal ion chelating capacities, radical stabilizing capacity, and the hydrophobicity of the constituent sugars. The results suggest that LMCH might constitute a novel and potential dermal therapeutic and sun-protective agent.

  10. Sulfated and sulfonated polysaccharide as chiral stationary phases for capillary electrochromatography and capillary electrochromatography–mass spectrometry

    PubMed Central

    Zheng, Jie; Bragg, William; Hou, Jingguo; Lin, Na; Chandrasekaran, Sekar; Shamsi, Shahab A.

    2009-01-01

    The applications of polysaccharide phenyl carbamate derivatives as chiral stationary phases (CSPs) for capillary electrochromatography (CEC) are often hindered by longer retention times, especially using a normal-phase (NP) eluent due to very low electroosmotic flow (EOF). Therefore, in this study, we propose an approach for the aforementioned problems by introducing two new types of negatively charged sulfate and sulfonated groups for polysaccharide CSPs. These CSPs were utilized to pack CEC columns for enantioseparation with a NP eluent. Compared to conventional cellulose tris(3,5-dimethylphenyl carbamate) or CDMPC CSPs, the sulfated CDMPC CSP (sulfur content 4.25%, w/w) shortened the analysis time up to 50% but with a significant loss of enantiomeric resolution (~60%). On the other hand, the sulfonated CDMPC CSP (sulfur content 1.76%, w/w) not only provided fast throughput but also maintained excellent resolving power. In addition, its synthesis is much more straightforward than the sulfated one. Furthermore, we studied several stationary phase parameters (CSP loading and silica gel pore size) and mobile phase parameters (including type of mobile phase and its composition) to evaluate the throughput and enantioselectivity. Using the optimized conditions, a chiral pool containing 66 analytes was screened to evaluate the enantioselectivity under three different mobile phase modes (i.e., NP, polar organic phase (POP) and reversed-phase (RP) eluents). Among these mobile phase modes, the RP mode showed the highest success rate, whereas some degree of complementary enantioselectivity was observed with NP and POP. Finally, the feasibility of applying this CSP for CEC–MS enantioseparation using internal tapered column was evaluated with NP, POP and RP eluents. In particular, the NP-CEC–MS provided significantly enhanced sensitivity when methanol was replaced with isopropanol in the sheath liquid. Using aminog-lutethimide as model chiral analyte, all three modes of

  11. Inhibition of synthesis of heparan sulfate by selenate: Possible dependence on sulfation for chain polymerization

    SciTech Connect

    Dietrich, C.P.; Nader, H.B. ); Buonassisi, V.; Colburn, P. )

    1988-01-01

    Selenate, a sulfation inhibitor, blocks the synthesis of heparan sulfate and chondroitin sulfate by cultured endothelial cells. In contrast, selenate does not affect the production of hyaluronic acid, a nonsulfated glycosaminoglycan. No differences in molecular weight, ({sup 3}H)glucosamine/({sup 35}S)sulfuric acid ratios, or disaccharide composition were observed when the heparan sulfate synthesized by selenate-treated cells was compared with that of control cells. The absence of undersulfated chains in preparations from cultures exposed to selenate supports the concept that, in the intact cell, the polymerization of heparan sulfate might be dependent on the sulfation of the saccharide units added to the growing glycosaminoglycan chain.

  12. Colominic acid inhibits the proliferation of cultured bovine aortic endothelial cells and injures their monolayers: cell density-dependent effects prevented by sulfation.

    PubMed

    Yamamoto, Chika; Morita, Yuki; Yamaguchi, Shinya; Hayashi, Toshimitsu; Kaji, Toshiyuki

    2006-01-18

    Colominic acid (CA), produced by Escherichia coli K1, is a polymer of sialic acid linked through alpha (2-->8) glycosidic linkages. Although there are several studies on the biological activities of chemically sulfated CA, the activity of CA has been incompletely understood. In the present study, we investigated the effects of CA, prepared as an alpha2,8-linked homopolymer of N-acetylneuraminic acid, on the proliferation and monolayer maintenance of bovine aortic endothelial cells in culture. The results indicate that CA potently inhibits the proliferation of sparse endothelial cells without nonspecific cell damage. The inhibitory effect of CA was markedly stronger than those of sodium spirulan and calcium spirulan, known polysaccharides that inhibit endothelial cell proliferation. On the other hand, in dense endothelial cells, CA induced nonspecific cell damage and markedly injured the monolayer. These results indicate that CA has two distinct effects on vascular endothelial cells: one is the inhibition of proliferation when the cell density is low, and the other is the nonspecific cytotoxicity when the cell density is high. Interestingly, these cell density-dependent effects of CA could be prevented by sulfation of the CA chains. Therefore, it is concluded that CA not only inhibits the proliferation of sparse endothelial cells without nonspecific cell damage but also injures dense cells in a monolayer by nonspecific cytotoxicity, which can be prevented by sulfation of the polysaccharide.

  13. Polysaccharides from Korean Citrus hallabong peels inhibit angiogenesis and breast cancer cell migration.

    PubMed

    Park, J Y; Shin, M S; Kim, S N; Kim, H Y; Kim, K H; Shin, K S; Kang, K S

    2016-04-01

    Although the peel of the hallabong (Citrus sphaerocarpa) fruit is rich in polysaccharides, which are valuable dietary ingredients for human health, it is normally wasted. The present study aimed to utilize the peel waste and identify properties it may have against breast cancer metastasis. Hallabong peel extract containing crude polysaccharides was fractionated by gel permeation chromatography to produce four different polysaccharide fractions (HBE-I, -II, -III, and -IV). The HBE polysaccharides significantly blocked tube formation of human umbilical vein vascular endothelial cells (HUVECs), at a concentration of 12.5 or 25 μg/mL. Tube formation appeared to be more sensitive to HBE-II than to other HBE polysaccharides. HBE-II also inhibited breast cancer cell migration, through downregulation of matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 triple-negative breast cancer cells. Therefore, inhibition of tube formation and MMP-9-mediated migration observed in HUVEC and MDA-MB-231 cells, respectively, are likely to be important therapeutic targets in triple-negative breast cancer metastasis.

  14. Isolation, purification, and characterization of fucose-containing sulfated polysaccharides from the brown seaweed Ecklonia kurome and their blood-anticoagulant activities.

    PubMed

    Nishino, T; Yokoyama, G; Dobashi, K; Fujihara, M; Nagumo, T

    1989-02-15

    A sulfated polysaccharide fraction, obtained from the hot-water extract of the brown seaweed, Ecklonia kurome by removing laminaran and the major part of alginic acid, gave sulfated polysaccharides (B-I, B-II, C-I, and C-II) by both anion-exchange chromatography on a column of Ecteola-cellulose and by fractional precipitation with ethanol containing 0.3% calcium acetate, and then by gel-filtration chromatography on a Sepharose 4B column. B-I and B-II are composed of fucose, galactose, mannose, xylose, glucuronic acid, and ester sulfate in the approximate molar ratios of 1.00:0.36:0.48:1.08:1.85:2.35 and 1.00:0.81:0.18:0.45:0.61:2.00, respectively. C-I and C-II are composed of fucose, galactose, glucuronic acid, and ester sulfate in approximate molar ratios of 1.00:0.03:0.03:1.61 and 1.00:0.19:0.07:1.48, respectively. Blood-anticoagulant activities with respect to activated partial thromboplastin time (APTT) were approximately 24, 19, 81, and 85% of that of heparin for B-I, B-II, C-I, and C-II, respectively. All the polysaccharides showed slight antithrombin activity. No antifactor Xa activity was observed for any of the polysaccharides.

  15. Suppression of Th2 immune responses by the sulfated polysaccharide from Porphyra haitanensis in tropomyosin-sensitized mice.

    PubMed

    Shi, Chaolan; Pan, Tzuming; Cao, Minjie; Liu, Qingmei; Zhang, Lingjing; Liu, Guangming

    2015-02-01

    The sulfated polysaccharide from Porphyra was hypothesized to exhibit immunoregulatory, anti-tumor and anti-inflammatory activity, but its anti-allergic activity is not fully understood. Therefore, the aim of this study was to isolate sulfated polysaccharide from Porphyra haitanensis (PHPS) and investigate its anti-allergic potential using a tropomyosin (TM)-induced mouse allergy model. Intraperitoneal injection of PHPS suppressed the allergic reaction by modulating serum IgE, IgG1 and IgG2a levels in mice. In particular, when PHPS was injected prior to the first immunization with TM, the IgE level decreased by 34.2% compared with the control (PBS) group. Oral therapeutic administration of PHPS to TM-sensitized mice decreased histamine release and repaired the pathology in the jejunum of the small intestine. In vitro, the mRNA expressions of the TM-induced Th2 cytokines (interleukin-4 (IL-4), IL-5 and IL-13) in splenic lymphocytes were reduced by PHPS; however, the expression of Th1 and regulatory cytokines (interferon gamma (IFN-γ) and IL-10) were up-regulated in PHPS-treated splenic lymphocytes. In the splenic lymphocyte supernatant, the IL-4, IL-13 and IFN-γ levels were also regulated by PHPS. Moreover, PHPS induced IFN-γ secretion via the Jun N-terminal kinase (JNK) and Janus kinase 2 (JAK2) signaling pathways. Therefore, these results suggest that PHPS suppresses the TM-induced allergic reaction, possibly by modulating the imbalance of the Th1/Th2 immune response.

  16. Adrenal Androgen Dehydroepiandrosterone Sulfate Inhibits Vascular Remodeling Following Arterial Injury

    PubMed Central

    Ii, Masaaki; Hoshiga, Masaaki; Negoro, Nobuyuki; Fukui, Ryosuke; Nakakoji, Takahiro; Kohbayashi, Eiko; Shibata, Nobuhiko; Furutama, Daisuke; Ishihara, Tadashi; Hanafusa, Toshiaki; Losordo, Douglas W.; Ohsawa, Nakaaki

    2009-01-01

    Recent epidemiologic studies have suggested that serum dehydroepiandrosterone sulfate (DHEAS) levels have a significant inverse correlation with the incidence of cardiovascular diseases. However, direct evidence for the association with DHEAS and vascular disorders has not yet been explored. DHEAS significantly reduced neointima formation 28 days after surgery without altering other serum metabolite levels in a rabbit carotid balloon injury model. Immunohistochemical analyses revealed the reduction of proliferating cell nuclear antigen (PCNA) index and increase of TdT-mediated dUTP-biotin Nick End Labeling (TUNEL) index, expressing differentiated vascular smooth muscle cell (VSMC) markers in the media 7 days after surgery. In vitro, DHEAS exhibited inhibitory effects on VSMC proliferation and migration activities, inducing G1 cell cycle arrest with upregulation of one of the cyclin dependent kinase (CDK) inhibitors p16INK4a and apoptosis with activating peroxisome proliferator-activated receptor (PPAR)-α in VSMCs. DHEAS inhibits vascular remodeling reducing neointima formation after vascular injury via its effects on VSMC phenotypic modulation, functions and apoptosis upregulating p16INK4a/activating PPARα. DHEAS may play a pathophysiological role for vascular remodeling in cardiovascular disease. PMID:19298964

  17. The effect of sulfated polysaccharides on the crystallization of calcite superstructures

    NASA Astrophysics Data System (ADS)

    Fried, Ruth; Mastai, Yitzhak

    2012-01-01

    Calcite with unique morphology and uniform size has been successfully synthesized in the presence of classes of polysaccharides based on carrageenans. In the crystallization of calcite, the choice of different carrageenans, (iota, lambda and kappa), as additives concedes systematic study of the influence of different chemical structures and particularly molecular charge on the formation of CaCO 3 crystals. The uniform calcite superstructures are formed by assemblies and aggregation of calcite crystals. The mechanism for the formation of calcite superstructures was studied by a variety of techniques, SEM, TEM, XRD, time-resolved conductivity and light scattering measurements, focusing on the early stages of crystals' nucleation and aggregation.

  18. Rheology and characteristics of sulfated polysaccharides from chlorophytan seaweeds Ulva fasciata.

    PubMed

    Shao, Ping; Qin, Minpu; Han, Longfei; Sun, Peilong

    2014-11-26

    The rheological characteristics of polysaccharides which were extracted and separated from Ulva fasciata (UFP) were investigated in aqueous solutions under conditions of concentration, temperature, solution pH and salt concentrations. It was described by the power-law model with a consistency index (k) and a flow behavior index (n). The rheology results showed UFP exhibited as a shear-thickening fluid and a possible mechanism was proposed to explain this phenomenon that might be the collapse of UFP necklace-type structures. UFP characteristics were evaluated by determining the chemical analysis and zeta potential. The findings indicated UFP may consist of partially ulvan, as the results were in accordance with the ulvan structure. Additionally, a rod-climbing effect and cold-set gelation were observed in the UFP semidilute solution. Therefore, the cold-set gelling properties and unique shear-thickening fluid properties in this work could be valuable for the exploration of U. fasciata as a new source of water-soluble gelling polysaccharides.

  19. Sulfated polysaccharide, curdlan sulfate, efficiently prevents entry/fusion and restricts antibody-dependent enhancement of dengue virus infection in vitro: a possible candidate for clinical application.

    PubMed

    Ichiyama, Koji; Gopala Reddy, Sindhoora Bhargavi; Zhang, Li Feng; Chin, Wei Xin; Muschin, Tegshi; Heinig, Lars; Suzuki, Youichi; Nanjundappa, Haraprasad; Yoshinaka, Yoshiyuki; Ryo, Akihide; Nomura, Nobuo; Ooi, Eng Eong; Vasudevan, Subhash G; Yoshida, Takashi; Yamamoto, Naoki

    2013-01-01

    Curdlan sulfate (CRDS), a sulfated 1→3-β-D glucan, previously shown to be a potent HIV entry inhibitor, is characterized in this study as a potent inhibitor of the Dengue virus (DENV). CRDS was identified by in silico blind docking studies to exhibit binding potential to the envelope (E) protein of the DENV. CRDS was shown to inhibit the DENV replication very efficiently in different cells in vitro. Minimal effective concentration of CRDS was as low as 0.1 µg/mL in LLC-MK2 cells, and toxicity was observed only at concentrations over 10 mg/mL. CRDS can also inhibit DENV-1, 3, and 4 efficiently. CRDS did not inhibit the replication of DENV subgenomic replicon. Time of addition experiments demonstrated that the compound not only inhibited viral infection at the host cell binding step, but also at an early post-attachment step of entry (membrane fusion). The direct binding of CRDS to DENV was suggested by an evident reduction in the viral titers after interaction of the virus with CRDS following an ultrafiltration device separation, as well as after virus adsorption to an alkyl CRDS-coated membrane filter. The electron microscopic features also showed that CRDS interacted directly with the viral envelope, and caused changes to the viral surface. CRDS also potently inhibited DENV infection in DC-SIGN expressing cells as well as the antibody-dependent enhancement of DENV-2 infection. Based on these data, a probable binding model of CRDS to DENV E protein was constructed by a flexible receptor and ligand docking study. The binding site of CRDS was predicted to be at the interface between domains II and III of E protein dimer, which is unique to this compound, and is apparently different from the β-OG binding site. Since CRDS has already been tested in humans without serious side effects, its clinical application can be considered.

  20. Strong cellulase inhibition by Mannan polysaccharides in cellulose conversion to sugars.

    PubMed

    Kumar, Rajeev; Wyman, Charles E

    2014-07-01

    Cellulase enzymes contribute a major fraction of the total cost for biological conversion of lignocellulosic biomass to fuels and chemicals. Although a several fold reduction in cellulase production costs and enhancement of cellulase activity and stability have been reported in recent years, sugar yields are still lower at low enzyme doses than desired commercially. We recently reported that hemicellulose xylan and its oligomers strongly inhibit cellulase and that supplementation of cellulase with xylanase and β-xylosidase would significantly reduce such inhibition. In this study, mannan polysaccharides and their enzymatically prepared hydrolyzates were discovered to be strongly inhibitory to fungal cellulase in cellulose conversion (>50% drop in % relative conversion), even at a small concentration of 0.1 g/L, and inhibition was much greater than experienced by other known inhibitors such as cellobiose, xylooligomers, and furfural. Furthermore, cellulase inhibition dramatically increased with heteromannan loading and mannan substitution with galactose side units. In general, enzymatically prepared hydrolyzates were less inhibitory than their respective mannan polysaccharides except highly substituted ones. Supplementation of cellulase with commercial accessory enzymes such as xylanase, pectinase, and β-glucosidase was effective in greatly relieving inhibition but only for less substituted heteromannans. However, cellulase supplementation with purified heteromannan specific enzymes relieved inhibition by these more substituted heteromannans as well, suggesting that commercial preparations need to have higher amounts of such activities to realize high sugar yields at the low enzyme protein loadings needed for low cost fuels production.

  1. Renoprotective effect of low-molecular-weight sulfated polysaccharide from the seaweed Laminaria japonica on glycerol-induced acute kidney injury in rats.

    PubMed

    Li, Xinpeng; Wang, Jing; Zhang, Hong; Zhang, Quanbin

    2017-02-01

    We investigated the renal protective effect of low-molecular-weight sulfated polysaccharide (LMWSP) fractions extracted from Laminaria japonica on glycerol-induced acute kidney injury (AKI) in rats. Glycerol treatment significantly increased serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Intraperitoneal injection of LMWSP fractions markedly decreased SCr and BUN levels and reduced renal swelling. The fraction of 1.0M NaCl displayed the best renal protective effect of all fractions in attenuating AKI and maintaining blood glucose.

  2. Vitamin C-sulfate inhibits mineralization in chondrocyte cultures: a caveat

    NASA Technical Reports Server (NTRS)

    Boskey, A. L.; Blank, R. D.; Doty, S. B.

    2001-01-01

    Differentiating chick limb-bud mesenchymal cell micro-mass cultures routinely mineralize in the presence of 10% fetal calf serum, antibiotics, 4 mM inorganic phosphate (or 2.5 mM beta-glycerophosphate), 0.3 mg/ml glutamine and either 25 microg/ml vitamin C or 5-12 microg/ml vitamin C-sulfate. The failure of these cultures to produce a mineralized matrix (assessed by electron microscopy, 45Ca uptake and Fourier transform infrared microscopy) led to the evaluation of each of these additives. We report here that the "stable" vitamin C-sulfate (ascorbic acid-2-sulfate) causes increased sulfate incorporation into the cartilage matrix. Furthermore, the release of sulfate from the vitamin C derivative appears to be responsible for the inhibition of mineral deposition, as demonstrated in cultures with equimolar amounts of vitamin C and sodium sulfate.

  3. Sulfated polysaccharide-protein complex sensitizes doxorubicin-induced apoptosis of breast cancer cells in vitro and in vivo

    PubMed Central

    Wang, Jie; Wu, Hua Jian; Zhou, Chao Zhu; Wang, Hao

    2016-01-01

    The present study aimed to investigate the effect of sulfated polysaccharide-protein complex (SPPC) on the antitumor effect of doxorubicin (Dox) on MDA-MB-231 breast cancer cells in vitro and in vivo. MTT and Annexin V/propidium iodide staining assays demonstrated that SPPC selectively sensitized MDA-MB-231 cells to Dox-induced cytotoxicity. The half maximal inhibitory concentration of Dox against MDA-MB-231 cells was decreased from 5.3 to 1.5 µM when it was used concomitantly with 5 µM SPPC. SPPC potentiated Dox-induced apoptosis in breast cancer cells via the mitochondrial apoptosis signaling pathway by activating caspase-3 and caspase-9. Notably, the caspase inhibitor Z-VAD-fmk diminished the effect of SPPC on Dox-mediated apoptosis. Furthermore, combination treatment with SPPC and Dox markedly reduced the growth of breast cancer xenografts in mice. The present study demonstrated that SPPC was able to enhance the antitumor effect of Dox on breast cancer cells, thus suggesting that SPCC may be used to reduce the cumulative dose of Dox and its associated toxicities in the chemotherapy of breast cancer and other types of cancer. PMID:27698706

  4. Sulfated-Polysaccharide Fraction from Red Algae Gracilaria caudata Protects Mice Gut Against Ethanol-Induced Damage

    PubMed Central

    Silva, Renan Oliveira; dos Santos, Geice Maria Pereira; Nicolau, Lucas Antonio Duarte; Lucetti, Larisse Tavares; Santana, Ana Paula Macedo; de Souza Chaves, Luciano; Barros, Francisco Clark Nogueira; Freitas, Ana Lúcia Ponte; Souza, Marcellus Henrique Loiola Ponte; Medeiros, Jand-Venes Rolim

    2011-01-01

    The aim of the present study was to investigate the gastroprotective activity of a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae Gracilaria caudata and the mechanism underlying the gastroprotective activity. Male Swiss mice were treated with PLS (3, 10, 30 and 90 mg·kg−1, p.o.), and after 30 min, they were administered 50% ethanol (0.5 mL/25 g−1, p.o.). One hour later, gastric damage was measured using a planimeter. Samples of the stomach tissue were also obtained for histopathological assessment and for assays of glutathione (GSH) and malondialdehyde (MDA). Other groups were pretreated with l-NAME (10 mg·kg−1, i.p.), dl-propargylglycine (PAG, 50 mg·kg−1, p.o.) or glibenclamide (5 mg·kg−1, i.p.). After 1 h, PLS (30 mg·kg−1, p.o.) was administered. After 30 min, ethanol 50% was administered (0.5 mL/25g−1, p.o.), followed by sacrifice after 60 min. PLS prevented-ethanol-induced macroscopic and microscopic gastric injury in a dose-dependent manner. However, treatment with l-NAME or glibenclamide reversed this gastroprotective effect. Administration of propargylglycine did not influence the effect of PLS. Our results suggest that PLS has a protective effect against ethanol-induced gastric damage in mice via activation of the NO/KATP pathway. PMID:22163181

  5. Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice.

    PubMed

    Taya, Sirinya; Kakehashi, Anna; Wongpoomchai, Rawiwan; Gi, Min; Ishii, Naomi; Wanibuchi, Hideki

    2016-01-01

    Ulcerative colitis (UC) results from colonic epithelial barrier defects and impaired mucosal immune responses. In this study, we aimed to investigate the modifying effects of a Spirogyra neglecta extract (SNE), a polysaccharide extract (PE) and a chloroform fraction (CF) on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the mechanisms. To induce colitis, ICR mice received 3% DSS in their drinking water for 7 days. Seven days preceding the DSS treatment, oral administration of SNE, PE and CF at doses of 50, 25 and 0.25 mg/kg body weight (low dose), 200, 100 and 1 mg/kg body weight (high dose) and vehicle was started and continued for 14 days. Histologic findings showed that DSS-induced damage of colonic epithelial structure and inflammation was attenuated in mice pre-treated with SNE, PE and CF. Furthermore, SNE and PE significantly protected colonic epithelial cells from DSS-induced cell cycle arrest, while SNE, PE and CF significantly diminished apoptosis. Proteome analysis demonstrated that SNE and PE might ameliorate DSS-induced colitis by inducing antioxidant enzymes, restoring impaired mitochondria function, and regulating inflammatory cytokines, proliferation and apoptosis. These results suggest that SNE and PE could prevent DSS-induced colitis in ICR mice by protection against and/or aiding recovery from damage to the colonic epithelium, reducing ROS and maintaining normal mitochondrial function and apoptosis.

  6. Structure-function relations of heparin-mimetic sulfated xylan oligosaccharides: inhibition of human immunodeficiency virus-1 infectivity in vitro.

    PubMed

    Stone, A L; Melton, D J; Lewis, M S

    1998-07-01

    Heparins/heparan sulfates modulate the function of proteins and cell membranes in numerous biological systems including normal and disease processes in humans. Heparin has been used for many years as an anticoagulant, and anticoagulant heparin-mimetics were developed several decades ago by chemical sulfation of non-mammalian polysaccharides, e.g., an antithrombotic sulfated xylan. This pharmaceutical, which comprises a mixture of sulfated oligoxylans, also mimics most other biological actions of natural heparins in vitro, including inhibition of the human immunodeficiency virus, but the molecular basis for these actions has been unclear. Here, numerous Components of the sulfated oligoxylan mixture were isolated and when bioassayed in the case of anti-HIV-1 infectivity revealed that a structural specificity underlines the capacity of sulfated xylan to inhibit HIV-1, rather than a non-specific mechanism. Components were isolated by chromatographic fractionation through Bio-Gel P10 in 0.5 M ammonium bicarbonate. This fractionation revealed an elution range associated with apparent molecular weights of approximately 22000 to <1500 relative to standard heparin and heparan sulfates and newly prepared sulfated oligosaccharide standards. Components were characterized by metachromatic absorption spectroscopy, ultracentrifugation, GlcA analysis, and potency against HIV-1 infectivity, both in the tetrazolium cytotoxicity assay and in syncytium-forming assays, in CD4-lymphocytes. Structural specificity was indicated by the differential potencies exhibited by the Components: Highest activity (cytotoxicity) was exhibited by Components in the chromatographic region > or = approximately 5500 in mass (50% effective (inhibitory) concentration = 0.5-0.7 microg ml(-1) in the first fractionation series, and 0.1-0.5 microg ml(-1) in a second series). The potency declined sharply below approximately 5400 in mass, but with an exception; a second structure exhibiting relatively high

  7. Inhibition of Streptococcus mutans polysaccharide synthesis by molecules targeting glycosyltransferase activity

    PubMed Central

    Ren, Zhi; Chen, Lulu; Li, Jiyao; Li, Yuqing

    2016-01-01

    Glycosyltransferase (Gtf) is one of the crucial virulence factors of Streptococcus mutans, a major etiological pathogen of dental caries. All the available evidence indicates that extracellular polysaccharide, particularly glucans produced by S. mutans Gtfs, contribute to the cariogenicity of dental biofilms. Therefore, inhibition of Gtf activity and the consequential polysaccharide synthesis may impair the virulence of cariogenic biofilms, which could be an alternative strategy to prevent the biofilm-related disease. Up to now, many Gtf inhibitors have been recognized in natural products, which remain the major and largely unexplored source of Gtf inhibitors. These include catechin-based polyphenols, flavonoids, proanthocyanidin oligomers, polymeric polyphenols, and some other plant-derived compounds. Metal ions, oxidizing agents, and some other synthetic compounds represent another source of Gtf inhibitors, with some novel molecules either discovered by structure-based virtual screening or synthesized based on key structures of known inhibitors as templates. Antibodies that inhibit one or more Gtfs have also been developed as topical agents. Although many agents have been shown to possess potent inhibitory activity against glucan synthesis by Gtfs, bacterial cell adherence, and caries development in animal models, much research remains to be performed to find out their mechanism of action, biological safety, cariostatic efficacies, and overall influence on the entire oral community. As a strategy to inhibit the virulence of cariogenic microbes rather than eradicate them from the microbial community, Gtf inhibition represents an approach of great potential to prevent dental caries. PMID:27105419

  8. Porcine epidemic diarrhea virus infection: inhibition by polysaccharide from Ginkgo biloba exocarp and mode of its action.

    PubMed

    Lee, Jung-Hee; Park, Jang-Soon; Lee, Seung-Woong; Hwang, Seock-Yeon; Young, Bae-Eun; Choi, Hwa-Jung

    2015-01-02

    Porcine epidemic diarrhea virus (PEDV) is the predominant cause of severe entero-pathogenic diarrhea in swine. Until now there is no recorded clinically effective antiviral chemotherapeutic agent for treatment of diseases caused by PEDV. This study aimed to investigate in vitro anti-PEDV effect of polysaccharide from Ginkgo biloba exocarp and mode of its action. The polysaccharide exhibited potent antiviral activity against PEDV reducing the formation of a visible CPE [a 50% inhibitory concentration (IC50)=1.7±1.3μg/mL], compared to positive control, ribavirin and it did not show cytotoxicity at 100μg/mL [a 50% cytotoxicity concentration (CC50)=100μg/mL]. Polysaccharide also showed effective inhibitory effects when added at the viral attachment and entry steps. Moreover, polysaccharide effectively inactivated PEDV infection in time-, dose- and temperature-dependent manners. Overall, this research revealed that polysaccharide could inhibit PEDV infection, and that polysaccharide may be involved in PEDV-Vero cell interactions, as the virus attachment and entry to the Vero cells was hindered by the polysaccharide. Therefore, polysaccharide possessing effective inhibitory effect on viral attachment and entry steps of PEDV life cycle is a good candidate for development of antivirals.

  9. Inhibition of sulfate-reducing bacteria by metal sulfide formation in bioremediation of acid mine drainage.

    PubMed

    Utgikar, Vivek P; Harmon, Stephen M; Chaudhary, Navendu; Tabak, Henry H; Govind, Rakesh; Haines, John R

    2002-02-01

    Acid mine drainage (AMD) containing high concentrations of sulfate and heavy metal ions can be treated by biological sulfate reduction. It has been reported that the effect of heavy metals on sulfate-reducing bacteria (SRB) can be stimulatory at lower concentrations and toxic/inhibitory at higher concentrations. The quantification of the toxic/inhibitory effect of dissolved heavy metals is critical for the design and operation of an effective AMD bioremediation process. Serum bottle and batch reactor studies on metal toxicity to SRB indicate that insoluble metal sulfides can inhibit the SRB activity as well. The mechanism of inhibition is postulated to be external to the bacterial cell. The experimental data indicate that the metal sulfides formed due to the reaction between the dissolved metal and biogenic sulfide act as barriers preventing the access of the reactants (sulfate, organic matter) to the necessary enzymes. Scanning electron micrographs of the SRB cultures exposed to copper and zinc provide supporting evidence for this hypothesis. The SRB cultures retained their ability to effect sulfate reduction indicating that the metal sulfides were not lethally toxic to the SRB. This phenomenon of metal sulfide inhibition of the SRB has to be taken into account while designing a sulfate-reducing bioreator, and subsequently an efficient biotreatment strategy for AMD. Any metal sulfide formed in the bioreactor needs to be removed immediately from the system to maintain the efficiency of the process of sulfate reduction.

  10. Glufosinate and Ammonium Sulfate Inhibits Atrazine Degradation in Adapted Soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The co-application of glufosinate with nitrogen fertilizers may alter atrazine co-metabolism, thereby extending the herbicide’s residual weed control in adapted soils. The objective of this study was to assess the effects of glufosinate, ammonium sulfate, and the combination of glufosinate and ammo...

  11. Asparagus polysaccharide and gum with hepatic artery embolization induces tumor growth and inhibits angiogenesis in an orthotopic hepatocellular carcinoma model.

    PubMed

    Weng, Ling-Ling; Xiang, Jian-Feng; Lin, Jin-Bo; Yi, Shang-Hui; Yang, Li-Tao; Li, Yi-Sheng; Zeng, Hao-Tao; Lin, Sheng-Ming; Xin, Dong-Wei; Zhao, Hai-Liang; Qiu, Shu-Qi; Chen, Tao; Zhang, Min-Guang

    2014-01-01

    Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy.

  12. Effect of ultrasonic treatment on the degradation and inhibition cancer cell lines of polysaccharides from Porphyra yezoensis.

    PubMed

    Yu, Xiaojie; Zhou, Cunshan; Yang, Hua; Huang, Xingyi; Ma, Haile; Qin, Xiaopei; Hu, Jiali

    2015-03-06

    The exposure of polysaccharides solutions to high-energy ultrasound produces a permanent reduction in viscosity and change in activity. However, the exact mechanism which occurs in the process is still not clear. In this work, degradation of polysaccharides from Porphyra yezoensis (PP) was indirectly and directly judged by intrinsic viscosity and high performance gel permeation chromatography. The degradation process was established with dynamics and affirmed by theoretical derivation. Inhibition of cancer cell lines (SGC-7901, 95D) was also investigated by assays of tetrazolium colorimetric. The intrinsic viscosity of the degraded PP decreased exponentially with increase in ultrasonic time, and theoretical derivation was established and confirmed well. The distribution and new fraction of degraded polysaccharides was found. Ultrasound degraded preferentially large PP molecules and cleavage took place roughly at the centre of the molecules. During ultrasound degradation the molecular weight distribution was narrowed. The inhibition activities of SGC7901 with ultrasound degraded polysaccharides were increased.

  13. Separation, purification, and α-glucosidase inhibition of polysaccharides from Coriolus versicolor LH1 mycelia.

    PubMed

    Hsu, Wen-kuang; Hsu, Tai-hao; Lin, Fang-yi; Cheng, Yuan-kai; Yang, John Po-wen

    2013-01-30

    Intracellular polysaccharides (iPs) were separated and purified from Coriolus versicolor LH1 mycelia and characterized for their α-glucosidase inhibitory properties. Three iP fractions (iPL-F5-2-1, iPL-F5-4-1, and iPL-F5-5-1) were extracted, separated, and purified from LH1 mycelia using microwave extraction technology, a DEAE-Sepharose CL-6B column, a Diaion HP20 macroporous adsorption column, and a Sephadex™ G-50 gel-permeation column. The principal constituents of iPL-F5-2-1, iPL-F5-4-1, and iPL-F5-5-1 were saponins and polyphenoic compound mixtures. The enzyme inhibition activity, IC(50) values, of these three fractions were 1.7, 1.8, and 0.8 mg/mL, respectively. The α-glucosidase inhibitory properties were related to the presence of α-(1,4) glycosidic linkages in the polysaccharide structure and the total relative percentage of d-glucose and d-galactose in the structure of polysaccharides, other than triterpenoids.

  14. A pure polysaccharide from Ephedra sinica treating on arthritis and inhibiting cytokines expression.

    PubMed

    Wang, Qiuhong; Shu, Zunpeng; Xing, Na; Xu, Bingqing; Wang, Changfu; Sun, Guibo; Sun, Xiaobo; Kuang, Haixue

    2016-05-01

    In our previous study, we found that the acidic polysaccharides of Ephedra sinica had immunosuppressive effect to treat rheumatoid arthritis and the pure polysaccharide ESP-B4 was the main composition of the acidic polysaccharides. At present, the exact molecular mechanism of ESP-B4 on treating arthritis is unclear. We are thus evaluating the properties of ESP-B4 on LPS-induced THP-1 pro-monocytic cells and adjuvant-induced arthritis in Wistar rats via TLR4. In vitro, ESP-B4 decreased the production of cytokines induced by LPS. In addition, ESP-B4 reduced the LPS-stimulated nuclear translocation of p65 subunit of NF-κB. Pretreatment with ESP-B4 significantly down-regulated the phosphorylation of MAPKs induced by LPS. Furthermore, in vivo, after 12 days of disease induced by adjuvant, rats were treated with ESP-B4 for 16 days. ESP-B4 significantly improved all parameters of inflammation. ESP-B4 reduced the release of inflammatory factors and cytokines by inhibiting the TLR4 signaling pathway to treat rheumatoid arthritis.

  15. Inhibition of Streptococcus mutans biofilm formation, extracellular polysaccharide production, and virulence by an oxazole derivative.

    PubMed

    Chen, Lulu; Ren, Zhi; Zhou, Xuedong; Zeng, Jumei; Zou, Jing; Li, Yuqing

    2016-01-01

    Dental caries, a biofilm-related oral disease, is a result of disruption of the microbial ecological balance in the oral environment. Streptococcus mutans, which is one of the primary cariogenic bacteria, produces glucosyltransferases (Gtfs) that synthesize extracellular polysaccharides (EPSs). The EPSs, especially water-insoluble glucans, contribute to the formation of dental plaque, biofilm stability, and structural integrity, by allowing bacteria to adhere to tooth surfaces and supplying the bacteria with protection against noxious stimuli and other environmental attacks. The identification of novel alternatives that selectively inhibit cariogenic organisms without suppressing oral microbial residents is required. The goal of the current study is to investigate the influence of an oxazole derivative on S. mutans biofilm formation and the development of dental caries in rats, given that oxazole and its derivatives often exhibit extensive and pharmacologically important biological activities. Our data shows that one particular oxazole derivative, named 5H6, inhibited the formation of S. mutans biofilms and prevented synthesis of extracellular polysaccharides by antagonizing Gtfs in vitro, without affecting the growth of the bacteria. In addition, topical applications with the inhibitor resulted in diminished incidence and severity of both smooth and sulcal surface caries in vivo with a lower percentage of S. mutans in the animals' dental plaque compared to the control group (P < 0.05). Our results showed that this oxazole derivative has the capacity to inhibit biofilm formation and cariogenicity of S. mutans.

  16. Baicalin inhibits colistin sulfate-induced apoptosis of PC12 cells.

    PubMed

    Jiang, Hong; Lv, Pengfei; Li, Jichang; Wang, Hongjun; Zhou, Tiezhong; Liu, Yingzi; Lin, Wei

    2013-10-05

    Baicalin, a type of flavonoid extracted from the dried root of Scutellaria baicalensis georgi, has been shown to effectively inhibit cell apoptosis. Therefore, we assumed that baicalin would suppress co-listin sulfate-induced neuronal apoptosis. PC12 cells exposed to colistin sulfate (62.5-500 μg/mL) for 24 hours resulted in PC12 cell apoptosis. In addition, caspase-3 activity, lactate dehydrogenase level and free radical content increased in a dose-dependent manner. Subsequently, PC12 cells were pretreated with baicalin (25, 50 and 100 μg/mL), and exposed to 125 μg/mL colistin sulfate. Cell morphology markedly changed, and cell viability increased. Moreover, caspase-3 activity, tate dehydrogenase level and free radical content decreased. Results indicated that baicalin inhi-bited colistin sulfate-induced PC12 cell apoptosis by suppressing free radical injury, and reducing caspase-3 activity and lactate dehydrogenase activity.

  17. Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions

    PubMed Central

    Barrey, Eric; Mucher, Elodie; Jeansoule, Nicolas; Larcher, Thibaut; Guigand, Lydie; Herszberg, Bérénice; Chaffaux, Stéphane; Guérin, Gérard; Mata, Xavier; Benech, Philippe; Canale, Marielle; Alibert, Olivier; Maltere, Péguy; Gidrol, Xavier

    2009-01-01

    Background Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype. Results Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA) and 5 heterozygous (GA) PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses. Gene expression analysis revealed 129 genes significantly modulated (p < 0.05). The following genes were up-regulated over 2 fold: IL18, CTSS, LUM, CD44, FN1, GST01. The most down-regulated genes were the following: mitochondrial tRNA, SLC2A2, PRKCα, VEGFα. Data mining analysis showed that protein synthesis, apoptosis, cellular movement, growth and proliferation were the main cellular functions significantly associated with the modulated genes (p < 0.05). Several up-regulated genes, especially IL18, revealed a severe muscular inflammation in PSSM muscles. The up-regulation of glycogen synthase kinase-3 (GSK3β) under its active form could be responsible for glycogen synthase (GYS1) inhibition and hypoxia-inducible factor

  18. Human Immunodeficiency Virus and Heparan Sulfate: From Attachment to Entry Inhibition

    PubMed Central

    Connell, Bridgette J.; Lortat-Jacob, Hugues

    2013-01-01

    By targeting cells that provide protection against infection, HIV-1 causes acquired immunodeficiency syndrome. Infection starts when gp120, the viral envelope glycoprotein, binds to CD4 and to a chemokine receptor usually CCR5 or CXCR4. As many microorganisms, HIV-1 also interacts with heparan sulfate (HS), a complex group of cell surface associated anionic polysaccharides. It has been thought that this binding, occurring at a step prior to CD4 recognition, increases infectivity by pre-concentrating the virion particles at the cell surface. Early work, dating from before the identification of CCR5 and CXCR4, showed that a variety of HS mimetics bind to the gp120 V3 loop through electrostatic interactions, compete with cell surface associated HS to bind the virus and consequently, neutralize the infectivity of a number of T-cell line-adapted HIV-1 strains. However, progress made to better understand HIV-1 attachment and entry, coupled with the recent identification of additional gp120 regions mediating HS recognition, have considerably modified this view. Firstly, the V3 loop from CXCR4-using viruses is much more positively charged compared to those using CCR5. HS inhibition of cell attachment is thus restricted to CXCR4-using viruses (such as T-cell line-adapted HIV-1). Secondly, studies aiming at characterizing the gp120/HS complex revealed that HS binding was far more complex than previously thought: in addition to the V3 loop of CXCR4 tropic gp120, HS interacts with several other cryptic areas of the protein, which can be induced upon CD4 binding, and are conserved amongst CCR5 and CXCR4 viruses. In view of these data, this review will detail the present knowledge on HS binding to HIV-1, with regards to attachment and entry processes. It will discuss the perspective of targeting the gp120 co-receptor binding site with HS mimetic compounds, a strategy that recently gave rise to entry inhibitors that work in the low nanomolar range, independently of co

  19. [Effect of sulfated polysaccharides from brown seaweed Laminaria japonica on the morfology of lymfoid organs and functional characteristics of immunocompetent cells].

    PubMed

    lebedynskaya, E A; Makarenkova, I D; Lebedynskaya, O V; Akhmatova, N K; Zvyagintseva, T N

    2014-01-01

    The effect of sulfated polysaccharide fucoidan from the brown alga Laminaria japonica on morphological characteristics of mouse lymphoid organs, subpopulations of spleen mononuclear leukocytes, cytokine production and cytotoxic activity of splenocytes has been investigated. Fucoidan promoted activation and proliferation of lymphoid hematopoietic cells in primary and secondary immunogenesis bodies, increased expression of markers CD19, NK, NKT, CD25, MHC II, TCR, TLR2 and TLR4, the cytotoxic activity of splenocytes and production of immunoregulatory and proinflammatory cytokines (IL- 2, IL-12, IFN-g, TNF-a, IL-6). This suggests activation of effector mechanisms of innate immunity and adaptive immune responses via the Th-1 type.

  20. Selenium inhibits sulfate-mediated methylmercury production in rice paddy soil.

    PubMed

    Wang, Yong-Jie; Dang, Fei; Zhao, Jia-Ting; Zhong, Huan

    2016-06-01

    There is increasing interest in understanding factors controlling methylmercury (MeHg) production in mercury-contaminated rice paddy soil. Sulfate has been reported to affect MeHg biogeochemistry under anoxic conditions, and recent studies revealed that selenium (Se) could evidently reduce MeHg production in paddy soil. However, the controls of sulfate and Se on net MeHg production in paddy soil under fluctuating redox conditions remain largely unknown. Microcosm experiments were conducted to explore the effects of sulfate and Se on net MeHg production in rice paddy soil. Soil was added with 0-960 mg/kg sulfate, in the presence or absence of 3.0 mg/kg selenium (selenite or selenate), and incubated under anoxic (40 days) or suboxic conditions (5 days), simulating fluctuating redox conditions in rice paddy field. Sulfate addition moderately affected soil MeHg concentrations under anoxic conditions, while reoxidation resulted in evidently higher (18-40%) MeHg levels in sulfate amended soils than the control. The observed changes in net MeHg production were related to dynamics of sulfate and iron. However, Se could inhibit sulfate-mediated MeHg production in the soils: Se addition largely reduced net MeHg production in the soils (23-86%, compared to the control), despite of sulfate addition. Similarly, results of the pot experiments (i.e., rice cultivation in amended soils) indicated that soil MeHg levels were rather comparable in Se-amended soils during rice growth period, irrespective of added sulfate doses. The more important role of Se than sulfate in controlling MeHg production was explained by the formation of HgSe nanoparticles irrespective of the presence of sulfate, confirmed by TEM-EDX and XANES analysis. Our findings regarding the effects of sulfate and Se on net MeHg production in rice paddy soil together with the mechanistic explanation of the processes advance our understanding of MeHg dynamics and risk in soil-rice systems.

  1. VANADYL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF ENOS

    EPA Science Inventory

    VANADYL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF eNOS.

    Zhuowei Li, Jacqueline D. Carter, Lisa A. Dailey, Joleen Soukup, Yuh-Chin T. Huang. CEMALB, University of North Carolina and NHEERL, US EPA, Chapel Hill, North Ca...

  2. VANADL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF ENOS

    EPA Science Inventory

    VANADYL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF eNOS. Zhuowei Li, Jacqueline D. Carter, Lisa A. Dailey, Joleen Soukup, Yuh-Chin T. Huang. CEMALB, University of North Carolina and ORD, US EPA, Chapel Hill, North Carolina
    V...

  3. Important determinants for fucoidan bioactivity: a critical review of structure-function relations and extraction methods for fucose-containing sulfated polysaccharides from brown seaweeds.

    PubMed

    Ale, Marcel Tutor; Mikkelsen, Jørn D; Meyer, Anne S

    2011-01-01

    Seaweeds--or marine macroalgae--notably brown seaweeds in the class Phaeophyceae, contain fucoidan. Fucoidan designates a group of certain fucose-containing sulfated polysaccharides (FCSPs) that have a backbone built of (1→3)-linked α-L-fucopyranosyl or of alternating (1→3)- and (1→4)-linked α-L-fucopyranosyl residues, but also include sulfated galactofucans with backbones built of (1→6)-β-D-galacto- and/or (1→2)-β-D-mannopyranosyl units with fucose or fuco-oligosaccharide branching, and/or glucuronic acid, xylose or glucose substitutions. These FCSPs offer several potentially beneficial bioactive functions for humans. The bioactive properties may vary depending on the source of seaweed, the compositional and structural traits, the content (charge density), distribution, and bonding of the sulfate substitutions, and the purity of the FCSP product. The preservation of the structural integrity of the FCSP molecules essentially depends on the extraction methodology which has a crucial, but partly overlooked, significance for obtaining the relevant structural features required for specific biological activities and for elucidating structure-function relations. The aim of this review is to provide information on the most recent developments in the chemistry of fucoidan/FCSPs emphasizing the significance of different extraction techniques for the structural composition and biological activity with particular focus on sulfate groups.

  4. Fractone-heparan sulfates mediate BMP-7 inhibition of cell proliferation in the adult subventricular zone.

    PubMed

    Douet, Vanessa; Arikawa-Hirasawa, Eri; Mercier, Frederic

    2012-10-24

    Bone morphogenetic protein-7 (BMP-7) is a heparin-binding growth factor that inhibits cell proliferation in the subventricular zone (SVZ) of the lateral ventricle, the primary neurogenic niche in the adult brain. However, the physiological mechanisms regulating the activity of BMP-7 in the SVZ are unknown. Here, we report the inhibitory effect of BMP-7 on cell proliferation through the anterior SVZ after intracerebroventricular injection in the adult mouse. To determine whether the inhibition of cell proliferation induced by BMP-7 is dependant on heparin-binding, heparitinase-1 was intracerebroventricularly injected to N-desulfate heparan sulfate proteoglycans before BMP-7 was injected. Heparatinase-1 drastically reduced the inhibitory effect of BMP-7 on cell proliferation in the SVZ. To determine where BMP-7 binds within the niche, we visualized biotinylated-BMP-7 after intracerebroventricular injection, using streptavidin Texas red on frozen brain sections. BMP-7 binding was seen as puncta in the SVZ at the location of fractones, the particulate specialized extracellular matrix of the SVZ, which have been identified primarily by N-sulfated heparan sulfate immunoreactivity (NS-HS+). BMP binding was also seen in NS-HS+ blood vessels of the SVZ. Injection of heparitinase-1 prior to biotinylated BMP-7 resulted in the absence of signal for biotinylated-BMP-7 in the fractones and blood vessels, indicating that the binding is heparan sulfate dependant. These results indicate that BMP-7 requires heparan sulfates to bind and inhibit cell proliferation in the SVZ neurogenic niche. Heparan sulfates concentrated in fractones and SVZ blood vessels emerge as a functional stem cell niche component involved in growth factor activity.

  5. Inhibition activities of polysaccharide (RG4-1) from Gentiana rigescens against RSV.

    PubMed

    Li, Xin; Zhou, Jing-Yu; Yang, Qing-Wei; Chen, Yang; Piao, Ying-Ai; Li, Hong-Yuan

    2011-06-01

    Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children. With the emergence of drug-resistant strains of RSV, new antiviral agents are needed urgently. Gentiana rigescens is a kind of Chinese herb, belonging to Gentianaceae, which has long been used as a folk medicine for curing inflammation, bacterial infection, viral infection, and so on. In this research, polysaccharide designated RG4-1 was isolated from G. rigescens by hot water extraction, ethanol precipitation, and macroreticular adsorbing resin column chromatography, and its antiviral activity, cytotoxicity, and possible antiviral mechanisms were assayed by cytopathogenic effect inhibition assay, 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and plaque reduction assay. RG4-1 was a fructose-binding lectin. In host cell cultures, RG4-1 was found to be an effective antiviral component against RSV. It showed good inhibitory effect against RSV when it was added 2 h after virus infection with 50% effective concentration of 12.86 μg/ml. RG4-1 also displayed its direct inactivation, attachment inhibition effect, and penetration inhibition effect against RSV. A time-dependent experiment was set up to confirm that RG4-1 blocked RSV infection at early stages of the infection. But RG4-1 seemed to be ineffective against intracellular virus and viral biosynthesis.

  6. Deciphering the Mode of Action of the Processive Polysaccharide Modifying Enzyme Dermatan Sulfate Epimerase 1 by Hydrogen–Deuterium Exchange Mass Spectrometry

    PubMed Central

    Tykesson, Emil; Mao, Yang; Maccarana, Marco; Pu, Yi; Gao, Jinshan; Lin, Cheng; Zaia, Joseph; Westergren-Thorsson, Gunilla; Ellervik, Ulf; Malmström, Lars; Malmström, Anders

    2015-01-01

    Distinct from template-directed biosynthesis of nucleic acids and proteins, the enzymatic synthesis of heterogeneous polysaccharides is a complex process that is difficult to study using common analytical tools. Therefore, the mode of action and processivity of those enzymes are largely unknown. Dermatan sulfate epimerase 1 (DS-epi1) is the predominant enzyme during the formation of iduronic acid residues in the glycosaminoglycan dermatan sulfate. Using recombinant DS-epi1 as a model enzyme, we describe a tandem mass spectrometry-based method to study the mode of action of polysaccharide processing enzymes. The enzyme action on the substrate was monitored by hydrogen-deuterium exchange mass spectrometry and the sequence information was then fed into mathematical models with two different assumptions of the mode of action for the enzyme: processive reducing end to non-reducing end, and processive non-reducing end to reducing end. Model data was scored by correlation to experimental data and it was found that DS-epi1 attacks its substrate on a random position, followed by a processive mode of modification towards the non-reducing end and that the substrate affinity of the enzyme is negatively affected by each additional epimerization event. It could also be shown that the smallest active substrate was the reducing end uronic acid in a tetrasaccharide and that octasaccharides and longer oligosaccharides were optimal substrates. The method of using tandem mass spectrometry to generate sequence information of the complex enzymatic products in combination with in silico modeling can be potentially applied to study the mode of action of other enzymes involved in polysaccharide biosynthesis. PMID:26900446

  7. The synergy of 6-O-sulfation and N- or 3-O-sulfation of chitosan is required for efficient inhibition of P-selectin-mediated human melanoma A375 cell adhesion.

    PubMed

    Wang, Ruifei; Huang, Jinfeng; Wei, Min; Zeng, Xianlu

    2010-01-01

    We prepared chitosan sulfated derivatives to address the common structural requirement of the sulfate pattern to block P-selectin-mediated tumor cell adhesion. Our results indicate that 6-O-sulfation of chitosan is indispensable for inhibition of P-selectin binding to human melanoma A375 cells. Furthermore, additional N-sulfation or 3-O-sulfation dramatically enhanced the inhibitory activity of 6-O-sulfated chitosan, suggesting that efficient anti-P-selectin adhesion activity of sulfated saccharides requires the synergy of 6-O-sulation and N- or 3-O-sulfation in glucosamine units.

  8. Astragalus polysaccharides attenuate PCV2 infection by inhibiting endoplasmic reticulum stress in vivo and in vitro

    PubMed Central

    Xue, Hongxia; Gan, Fang; Qian, Gang; Hu, Junfa; Hao, Shu; Xu, Jing; Chen, Xingxiang; Huang, Kehe

    2017-01-01

    This study explored the effects of Astragalus polysaccharide (APS) on porcine circovirus type 2 (PCV2) infections and its mechanism in vivo and vitro. First, fifty 2-week-old mice were randomly divided into five groups: a group without PCV2 infection and groups with PCV2 infections at 0, 100, 200 or 400 mg/kg APS treatments. The trial lasted for 28 days. The results showed that APS treatments at 200 and 400 mg/kg reduced the pathological injury of tissues, inhibited PCV2 infection and decreased glucose-regulated protein 78 (GRP78) and GADD153/CHOP gene mRNA and protein expression significantly (P < 0.05). Second, a study on endoplasmic reticulum stress mechanism was carried out in PK15 cells. APS treatments at 15 and 45 μg/mL significantly reduced PCV2 infection and GRP78 mRNA and protein expression (P < 0.05). Tunicamycin supplementation increased GRP78 mRNA and protein expression and significantly attenuated the APS-induced inhibition of PCV2 infection (P < 0.05). Tauroursodeoxycholic acid supplementation decreased GRP78 mRNA and protein expression and significantly inhibited PCV2 infection (P < 0.05). In addition, fifty 2-week-old mice were randomly divided into five groups: Con, PCV2, APS + PCV2, TM + PCV2 and TM + APS + PCV2. The results were similar to those in PK15 cells. Taken together, it could be concluded that APS suppresses PCV2 infection by inhibiting endoplasmic reticulum stress. PMID:28071725

  9. Inhibition of selectin-mediated cell adhesion and prevention of acute inflammation by nonanticoagulant sulfated saccharides. Studies with carboxyl-reduced and sulfated heparin and with trestatin a sulfate.

    PubMed

    Xie, X; Rivier, A S; Zakrzewicz, A; Bernimoulin, M; Zeng, X L; Wessel, H P; Schapira, M; Spertini, O

    2000-11-03

    Selectins play a major role in the inflammatory reaction by initiating neutrophil attachment to activated vascular endothelium. Some heparin preparations can interact with L- and P-selectin; however, the determinants required for inhibiting selectin-mediated cell adhesion have not yet been characterized. We now report that carboxyl-reduced and sulfated heparin (prepared by chemical modifications of porcine intestinal mucosal heparin leading to the replacement of carboxylates by O-sulfate groups) and trestatin A sulfate (obtained by sulfation of trestatin A, a non-uronic pseudo-nonasaccharide extracted from Streptomyces dimorphogenes) exhibit strong anti-P-selectin and anti-L-selectin activity while lacking antithrombin-mediated anticoagulant activity. In vitro experiments revealed that both compounds inhibited P-selectin- and L-selectin-mediated cell adhesion under laminar flow conditions. Moreover, carboxyl-reduced and sulfated heparin and trestatin A sulfate were also active in vivo, as assessed by experiments showing 1) that microinfusion of trestatin A sulfate reduced by 96% leukocyte rolling along rat mesenteric postcapillary venules and 2) that both compounds inhibited (by 58-81%) neutrophil migration into thioglycollate-inflamed peritoneum of BALB/c mice. These results indicate that nonanticoagulant sulfated saccharides targeted at P-selectin and L-selectin may have therapeutic potential in inflammatory disorders.

  10. A role for a lithium-inhibited Golgi nucleotidase in skeletal development and sulfation

    PubMed Central

    Frederick, Joshua P.; Tafari, A. Tsahai; Wu, Sheue-Mei; Megosh, Louis C.; Chiou, Shean-Tai; Irving, Ryan P.; York, John D.

    2008-01-01

    Sulfation is an important biological process that modulates the function of numerous molecules. It is directly mediated by cytosolic and Golgi sulfotransferases, which use 3′-phosphoadenosine 5′-phosphosulfate to produce sulfated acceptors and 3′-phosphoadenosine 5′-phosphate (PAP). Here, we identify a Golgi-resident PAP 3′-phosphatase (gPAPP) and demonstrate that its activity is potently inhibited by lithium in vitro. The inactivation of gPAPP in mice led to neonatal lethality, lung abnormalities resembling atelectasis, and dwarfism characterized by aberrant cartilage morphology. The phenotypic similarities of gPAPP mutant mice to chondrodysplastic models harboring mutations within components of the sulfation pathway lead to the discovery of undersulfated chondroitin in the absence of functional enzyme. Additionally, we observed loss of gPAPP leads to perturbations in the levels of heparan sulfate species in lung tissue and whole embryos. Our data are consistent with a model that clearance of the nucleotide product of sulfotransferases within the Golgi plays an important role in glycosaminoglycan sulfation, provide a unique genetic basis for chondrodysplasia, and define a function for gPAPP in the formation of skeletal elements derived through endochondral ossification. PMID:18695242

  11. Heparan sulfate inhibits hematopoietic stem and progenitor cell migration and engraftment in mucopolysaccharidosis I.

    PubMed

    Watson, H Angharad; Holley, Rebecca J; Langford-Smith, Kia J; Wilkinson, Fiona L; van Kuppevelt, Toin H; Wynn, Robert F; Wraith, J Edmond; Merry, Catherine L R; Bigger, Brian W

    2014-12-26

    Mucopolysaccharidosis I Hurler (MPSI-H) is a pediatric lysosomal storage disease caused by genetic deficiencies in IDUA, coding for α-l-iduronidase. Idua(-/-) mice share similar clinical pathology with patients, including the accumulation of the undegraded glycosaminoglycans (GAGs) heparan sulfate (HS), and dermatan sulfate (DS), progressive neurodegeneration, and dysostosis multiplex. Hematopoietic stem cell transplantation (HSCT) is the most effective treatment for Hurler patients, but reduced intensity conditioning is a risk factor in transplantation, suggesting an underlying defect in hematopoietic cell engraftment. HS is a co-receptor in the CXCL12/CXCR4 axis of hematopoietic stem and progenitor cell (HSPC) migration to the bone marrow (BM), but the effect of HS alterations on HSPC migration, or the functional role of HS in MPSI-H are unknown. We demonstrate defective WT HSPC engraftment and migration in Idua(-/-) recipient BM, particularly under reduced intensity conditioning. Both intra- but especially extracellular Idua(-/-) BM HS was significantly increased and abnormally sulfated. Soluble heparinase-sensitive GAGs from Idua(-/-) BM and specifically 2-O-sulfated HS, elevated in Idua(-/-) BM, both inhibited CXCL12-mediated WT HSPC transwell migration, while DS had no effect. Thus we have shown that excess overly sulfated extracellular HS binds, and sequesters CXCL12, limiting hematopoietic migration and providing a potential mechanism for the limited scope of HSCT in Hurler disease.

  12. Polysaccharides from Wolfberry Prevents Corticosterone-Induced Inhibition of Sexual Behavior and Increases Neurogenesis

    PubMed Central

    Lau, Benson Wui-Man; Lee, Jada Chia-Di; Li, Yue; Fung, Sophia Man-Yuk; Sang, Yan-Hua; Shen, Jiangang; Chang, Raymond Chuen-Chung; So, Kwok-Fai

    2012-01-01

    Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of infertility and sexual dysfunction. However, there is still a scarcity of experimental evidence to support the pro-sexual effect of wolfberry. The aim of this study is to determine the effect of Lycium barbarum polysaccharides (LBP) on male sexual behavior of rats. Here we report that oral feeding of LBP for 21 days significantly improved the male copulatory performance including increase of copulatory efficiency, increase of ejaculation frequency and shortening of ejaculation latency. Furthermore, sexual inhibition caused by chronic corticosterone was prevented by LBP. Simultaneously, corticosterone suppressed neurogenesis in subventricular zone and hippocampus in adult rats, which could be reversed by LBP. The neurogenic effect of LBP was also shown in vitro. Significant correlation was found between neurogenesis and sexual performance, suggesting that the newborn neurons are associated with reproductive successfulness. Blocking neurogenesis in male rats abolished the pro-sexual effect of LBP. Taken together, these results demonstrate the pro-sexual effect of LBP on normal and sexually-inhibited rats, and LBP may modulate sexual behavior by regulating neurogenesis. PMID:22523540

  13. Development of an opsonin inhibition assay for evaluation of complex polysaccharide protective epitopes.

    PubMed

    McNeely, Tessie; Luo, Shengyuan; Manger, Walt; Herber, Wayne; Schofield, Tim; Tan, Charles; Newman, Kathy; Sadoff, Jerald; Donnelly, John; Cross, Alan

    2006-03-10

    The induction of opsonic antibodies directed against capsular polysaccharides (Ps) is an important mechanism by which immunization protects against the development of invasive pneumococcal (Pn) infection. In preparing Pn vaccines, it is necessary to compare different manufacturing lots of capsular Ps, or to compare oligosaccharides used for conjugate vaccines with native capsular Ps, in order to insure that important epitopes of the Ps are maintained. We have developed an opsonic-antibody inhibition assay (OIA) to compare the functional epitopes of different capsular Ps preparations in vitro. Components of the OIA are primary neutrophils, rabbit complement (C'), and type-specific antibody (Ab). After conditions for optimal opsonic killing were determined for each Pn serotype, anti-Pn Ab was pre-incubated with different dilutions of purified capsular Ps, then added to the OIA mix. Plotting the % bacteria killed versus Ps concentration (log transformed) yielded a linear curve that was used to quantify the concentration of capsular Ps which inhibited the bacteria killing by 50% (IC50). The IC50 was determined for 8 Pn Ps types. These ranged between 6 ng/ml for type 6B and 1268 ng/ml for type 23F. Importantly OIA curves were statistically identical for two different manufacturing lots of capsular Ps for the 8 Pn Ps types. We conclude that differences among capsular Ps used for Pn vaccines could be detected with an OIA assay and these differences may predict the ability of Ps preparations to induce functionally active antibody when formulated into vaccines.

  14. Polysaccharides from wolfberry prevents corticosterone-induced inhibition of sexual behavior and increases neurogenesis.

    PubMed

    Lau, Benson Wui-Man; Lee, Jada Chia-Di; Li, Yue; Fung, Sophia Man-Yuk; Sang, Yan-Hua; Shen, Jiangang; Chang, Raymond Chuen-Chung; So, Kwok-Fai

    2012-01-01

    Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of infertility and sexual dysfunction. However, there is still a scarcity of experimental evidence to support the pro-sexual effect of wolfberry. The aim of this study is to determine the effect of Lycium barbarum polysaccharides (LBP) on male sexual behavior of rats. Here we report that oral feeding of LBP for 21 days significantly improved the male copulatory performance including increase of copulatory efficiency, increase of ejaculation frequency and shortening of ejaculation latency. Furthermore, sexual inhibition caused by chronic corticosterone was prevented by LBP. Simultaneously, corticosterone suppressed neurogenesis in subventricular zone and hippocampus in adult rats, which could be reversed by LBP. The neurogenic effect of LBP was also shown in vitro. Significant correlation was found between neurogenesis and sexual performance, suggesting that the newborn neurons are associated with reproductive successfulness. Blocking neurogenesis in male rats abolished the pro-sexual effect of LBP. Taken together, these results demonstrate the pro-sexual effect of LBP on normal and sexually-inhibited rats, and LBP may modulate sexual behavior by regulating neurogenesis.

  15. Optimized and standardized isolation and structural characterization of anti-inflammatory sulfated polysaccharides from the red alga Delesseria sanguinea (Hudson) Lamouroux (Ceramiales, Delesseriaceae).

    PubMed

    Grünewald, Niels; Alban, Susanne

    2009-11-09

    The red seaweed Delesseria sanguinea dominantly populates a large artificial reef in the southwestern Baltic Sea. It contains sulfated polysaccharides (SPs), which exhibit a pharmacological profile indicating anti-inflammatory and anti-skin aging potencies. To establish and optimize an extraction procedure for these SPs and to evaluate the influence of several parameters on their quality, 23 algae batches were harvested over the period of four years and extracted by different methods, resulting in 56 SP batches. Extraction with water at 85 degrees C proved to be superior and led to highly reproducible products with average yields of 11.6 +/- 3.9%, reaching 18% in spring. Their quality was independent of generation form and vitality of the algae. The SPs were identified as sulfated branched xylogalactans (degree of sulfation 0.50 +/- 0.08, mean M(r) 142000). The coextraction of floridean starch turned out to be the only parameter causing any seasonal variability. However, by using water, this concerns solely the yields of the isolated products. Compared to NaOH extracts, the antielastase activity of H(2)O extracted SPs was about twice as strong (IC(50) 0.204 +/- 0.024 microg/mL) and the batch to batch variability was much lower (CV 11.8 vs 28.6%). In conclusion, SPs from Delesseria sanguinea can be isolated in reproducibly high quality by using a specific extraction procedure. Thus, an important prerequisite for a potential economical utilization is fulfilled.

  16. Antibiofilm polysaccharides

    PubMed Central

    Rendueles, Olaya; Kaplan, Jeffrey B.; Ghigo, Jean-Marc

    2012-01-01

    Summary Bacterial extracellular polysaccharides have been shown to mediate many of the cell-to cell and cell-to-surface interactions that are required for the formation, cohesion and stabilization of bacterial biofilms. However, recent studies have identified several bacterial polysaccharides that inhibit biofilm formation by a wide-spectrum of bacteria and fungi both in vitro and in vivo. This review discusses the composition, modes of action, and potential biological roles of antibiofilm polysaccharides recently identified in bacteria and eukaria. Some of these molecules may have technological applications as antibiofilm agents in industry and medicine. PMID:22730907

  17. Sulfate- and sialic acid-containing glycolipids inhibit DNA polymerase alpha activity.

    PubMed

    Simbulan, C M; Taki, T; Tamiya-Koizumi, K; Suzuki, M; Savoysky, E; Shoji, M; Yoshida, S

    1994-03-16

    The effects of various glycolipids on the activity of immunoaffinity-purified calf thymus DNA polymerase alpha were studied in vitro. Preincubation with sialic acid-containing glycolipids, such as sialosylparagloboside (SPG), GM3, GM1, and GD1a, and sulfatide (cerebroside sulfate ester, CSE) dose-dependently inhibited the activity of DNA polymerase alpha, while other glycolipids, as well as free sphingosine and ceramide did not. About 50% inhibition was achieved by preincubating the enzyme with 2.5 microM of CSE, 50 microM of SPG or GM3, and 80 microM of GM1. Inhibition was noncompetitive with both the DNA template and the substrate dTTP, as well as with the other dNTPs. Since the inhibition was largely reversed by the addition of 0.05% Nonidet P40, these glycolipids may interact with the hydrophobic region of the enzyme protein. Apparently, the sulfate moiety in CSE and the sialic acid moiety in gangliosides were essential for the inhibition since neither neutral glycolipids (i.e., glucosylceramide, galactosylceramide, lactosylceramide) nor asialo-gangliosides (GA1 and GA2) showed any inhibitory effect. Furthermore, the ceramide backbone was also found to be necessary for maximal inhibition since the inhibition was largely abolished by substituting the lipid backbone with cholesterol. Increasing the number of sialic acid moieties per molecule further enhanced the inhibition, while elongating the sugar chain diminished it. It was clearly shown that the N-acetyl residue of the sialic acid moiety is particularly essential for inhibition by both SPG and GM3 because the loss of this residue or substitution with a glycolyl residue completely negated their inhibitory effect on DNA polymerase alpha activity.

  18. Polysaccharide enhances Radix Saposhnikoviae efficacy through inhibiting chromones decomposition in intestinal tract

    PubMed Central

    Yang, Jing-Ming; Jiang, Hua; Dai, Hong-Liang; Wang, Zi-Wei; Jia, Gui-Zhi; Meng, Xiang-Cai

    2016-01-01

    Vegetative but not reproductive stage of Saposhnikovia divaricate (Turxz.) schischk possesses pharmacological activities. However, our recent study showed that reproductive S. divaricate supplemented with polysaccharide showed evidently elevated pharmacological activities and increased cimifugin content in rat serum. The aims of present study were to assess the influence of polysaccharides on the chromones pharmacological activities in Radix Saposhnikoviae (RS), the dried root of vegetative stage of S. divaricate, and to explore the underlying mechanisms. Only cimifugin was detected in the plasma of chromone treated animals and RS polysaccharide significantly increased the plasma content of cimifugin. It was shown that neither cimifugin absorption nor glycoside components transformation in simulated digestive fluid was affected by RS polysaccharide. However, a significant promotion of transformation of cimifugin to more stable prime-O-glucosylcimifugin (PGCN) by RS polysaccharide, and a protective effect of polysaccharide on chromone components were observed in small intestine solutions. Meanwhile, RS polysaccharide produced a significant elevation of cimifugin and PGCN concentration in vivo. Based on these findings, we concluded that RS polysaccharide could greatly increase the content of cimifugin, which might be related to its degradation-proof effect on cimifugin, via transforming cimifugin to comparatively more stable PGCN and spatial structure protection. PMID:27595868

  19. Cordyceps sinensis polysaccharide inhibits PDGF-BB-induced inflammation and ROS production in human mesangial cells.

    PubMed

    Wang, Ying; Wang, Yan; Liu, Dan; Wang, Wang; Zhao, Huan; Wang, Min; Yin, Hongping

    2015-07-10

    CPS-F, a polysaccharide derived from Cordyceps sinensis, is a potential anti-inflammatory and anti-oxidative agent. We demonstrated that CPS-F not only inhibits platelet-derived growth factor BB (PDGF-BB)-induced intracellular reactive oxygen species (ROS) generation, and up-regulation of tumor necrosis factor-α (TNF-α), TNF-α receptor 1 (TNFR1), and monocyte chemotactic protein-1 (MCP-1), but also acts synergistically in combination with MAPK/ERK inhibitor U0126 and PI3K/Akt inhibitor LY294002. Additionally, up-regulation of pro-inflammatory factors was reversed by use of a combination of CPS-F and NADPH oxidase (NOX) inhibitor diphenyleneiodonium chloride (DPI) or silencing of NOX1. Furthermore, CPS-F prevents the PDGF receptor β (PDGFRβ) promoter activity induced by PDGF-BB in transfected cells and ameliorates increased levels of TNF-α, TNFR1, and MCP-1 when PDGFRβ is silenced, thereby suggesting that CPS-F possesses a bidirectional regulatory function. Our findings suggest CPS-F may exert its therapeutic effect for the treatment of glomerulonephritis related to human mesangial cells (HMCs) through the ERK1/2/Akt pathways.

  20. Preparation and inhibition on α-d-glucosidase of low molecular weight polysaccharide from Cordyceps militaris.

    PubMed

    Zhu, Zhen-Yuan; Guo, Ming-Zhu; Liu, Fei; Luo, You; Chen, Lu; Meng, Meng; Wang, Xiao-Ting; Zhang, Yong-Min

    2016-12-01

    The structural properties and the inhibition on α-d-glucosidase activity of the low molecular weight (LCMPs-II) obtained from the optimized acid hydrolysis of the Cordyceps militaris polysaccharides (CMPs) were investigated in this paper. The LCMPs-II with a molecular weight of 28 KDa mainly composed of rhamnose, xylose and glucose with the molar ratio of 1: 2.19: 6.73 was separated from LCMPs-I which was the acid hydrolysis product of CMPs by chromatography on Sephadex G-100 column. The solubility of LCMPs-II was tested to be 32.12±1.05g in 100mL distilled water under 25°C. Its solubility was almost as twice as that of CMPs. Afterward, the structural features of LCMPs-II was investigated by a combination of chemical and instrumental analysis such as the specific rotation determination, FT-IR, periodate oxidation-Smith degradation, Congo-red, GC, scanning electron microscope and NMR. The results showed that the optical rotation of LCMPs-II was +25° and it was 1,3-branched-rhamnoxyloglucan which had a linear backbone of (1→4)-linked α-d-glucopyranose (α-d-Glcp units).

  1. Divergent Synthesis of Chondroitin Sulfate Disaccharides and Identification of Sulfate Motifs that Inhibit Triple Negative Breast Cancer

    PubMed Central

    Wei Poh, Zhong; Heng Gan, Chin; Lee, Eric J.; Guo, Suxian; Yip, George W.; Lam, Yulin

    2015-01-01

    Glycosaminoglycans (GAGs) regulate many important physiological processes. A pertinent issue to address is whether GAGs encode important functional information via introduction of position specific sulfate groups in the GAG structure. However, procurement of pure, homogenous GAG motifs to probe the “sulfation code” is a challenging task due to isolation difficulty and structural complexity. To this end, we devised a versatile synthetic strategy to obtain all the 16 theoretically possible sulfation patterns in the chondroitin sulfate (CS) repeating unit; these include rare but potentially important sulfated motifs which have not been isolated earlier. Biological evaluation indicated that CS sulfation patterns had differing effects for different breast cancer cell types, and the greatest inhibitory effect was observed for the most aggressive, triple negative breast cancer cell line MDA-MB-231. PMID:26400608

  2. Divergent Synthesis of Chondroitin Sulfate Disaccharides and Identification of Sulfate Motifs that Inhibit Triple Negative Breast Cancer

    NASA Astrophysics Data System (ADS)

    Wei Poh, Zhong; Heng Gan, Chin; Lee, Eric J.; Guo, Suxian; Yip, George W.; Lam, Yulin

    2015-09-01

    Glycosaminoglycans (GAGs) regulate many important physiological processes. A pertinent issue to address is whether GAGs encode important functional information via introduction of position specific sulfate groups in the GAG structure. However, procurement of pure, homogenous GAG motifs to probe the “sulfation code” is a challenging task due to isolation difficulty and structural complexity. To this end, we devised a versatile synthetic strategy to obtain all the 16 theoretically possible sulfation patterns in the chondroitin sulfate (CS) repeating unit; these include rare but potentially important sulfated motifs which have not been isolated earlier. Biological evaluation indicated that CS sulfation patterns had differing effects for different breast cancer cell types, and the greatest inhibitory effect was observed for the most aggressive, triple negative breast cancer cell line MDA-MB-231.

  3. Inhibition of leukemia proliferation by a novel polysaccharide identified from Monascus-fermented dioscorea via inducing differentiation.

    PubMed

    Lee, Bao-Hong; Hsu, Wei-Hsuan; Liao, Te-Han; Pan, Tzu-Ming

    2012-07-01

    Monascus-fermented products offer valuable therapeutic benefits and have been extensively used in East Asia. However, the polysaccharide obtained from Monascus-fermented products has never been investigated. This study evaluated the effects of dioscorea polysaccharide (DPS) and red mold dioscorea polysaccharide (RMDPS) on differentiation of leukemic THP-1 cells. DPS and RMDPS inhibited THP-1 cells proliferation in dose- and time-dependent manners. The differentiation induction (macrophage-like cells) was observed when THP-1 cells were treated with DPS and RMDPS for 5 days. Superoxide anion production, phagocytic capacity, and cytokine secretion confirmed activity for differentiating THP-1 cells. Results indicated that RMDPS elevated reactive oxygen species production and immune activity, including phagocytosis, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) productions in THP-1 cells, which was greater than that seen with DPS. These results may be attributed to Monascus-fermentation altering the carbohydrate components and polysaccharide structure. RMDPS may serve as a novel material and functional ingredient to exert anticancer capacity.

  4. Inhibiting stromal cell heparan sulfate synthesis improves stem cell mobilization and enables engraftment without cytotoxic conditioning

    PubMed Central

    Saez, Borja; Ferraro, Francesca; Yusuf, Rushdia Z.; Cook, Colleen M.; Yu, Vionnie W. C.; Pardo-Saganta, Ana; Sykes, Stephen M.; Palchaudhuri, Rahul; Schajnovitz, Amir; Lotinun, Sutada; Lymperi, Stefania; Mendez-Ferrer, Simon; del Toro, Raquel; Day, Robyn; Vasic, Radovan; Acharya, Sanket S.; Baron, Roland; Lin, Charles P.; Yamaguchi, Yu; Wagers, Amy J.

    2014-01-01

    The glycosyltransferase gene, Ext1, is essential for heparan sulfate production. Induced deletion of Ext1 selectively in Mx1-expressing bone marrow (BM) stromal cells, a known population of skeletal stem/progenitor cells, in adult mice resulted in marked changes in hematopoietic stem and progenitor cell (HSPC) localization. HSPC egressed from BM to spleen after Ext1 deletion. This was associated with altered signaling in the stromal cells and with reduced vascular cell adhesion molecule 1 production by them. Further, pharmacologic inhibition of heparan sulfate mobilized qualitatively more potent and quantitatively more HSPC from the BM than granulocyte colony-stimulating factor alone, including in a setting of granulocyte colony-stimulating factor resistance. The reduced presence of endogenous HSPC after Ext1 deletion was associated with engraftment of transfused HSPC without any toxic conditioning of the host. Therefore, inhibiting heparan sulfate production may provide a means for avoiding the toxicities of radiation or chemotherapy in HSPC transplantation for nonmalignant conditions. PMID:25202142

  5. Polysaccharides of the red algae.

    PubMed

    Usov, Anatolii I

    2011-01-01

    Red algae (Rhodophyta) are known as the source of unique sulfated galactans, such as agar, agarose, and carrageenans. The wide practical uses of these polysaccharides are based on their ability to form strong gels in aqueous solutions. Gelling polysaccharides usually have molecules built up of repeating disaccharide units with a regular distribution of sulfate groups, but most of the red algal species contain more complex galactans devoid of gelling ability because of various deviations from the regular structure. Moreover, several red algae may contain sulfated mannans or neutral xylans instead of sulfated galactans as the main structural polysaccharides. This chapter is devoted to a description of the structural diversity of polysaccharides found in the red algae, with special emphasis on the methods of structural analysis of sulfated galactans. In addition to the structural information, some data on the possible use of red algal polysaccharides as biologically active polymers or as taxonomic markers are briefly discussed.

  6. The use of magnesium peroxide for the inhibition of sulfate-reducing bacteria under anoxic conditions.

    PubMed

    Chang, Yu-Jie; Chang, Yi-Tang; Hung, Chun-Hsiung

    2008-11-01

    Sulfate-reducing bacteria (SRB), which cause microbiologically influenced material corrosion under anoxic conditions, form one of the major groups of microorganisms responsible for the generation of hydrogen sulfide. In this study, which is aimed at reducing the presence of SRB, a novel alternative approach involving the addition of magnesium peroxide (MgO2) compounds involving the use of reagent-grade MgO2 and a commercial product (ORC) was evaluated as a means of inhibiting SRB in laboratory batch columns. Different concentrations of MgO2 were added in the columns when black sulfide sediment had appeared in the columns. The experimental results showed that MgO2 is able to inhibit biogenic sulfide. The number of SRB, the sulfide concentration and the sulfate reducing rate (SRR) were decreased. ORCtrade mark as an additive was able to decrease more effectively the concentration of sulfide in water and the SRB-control effect was maintained over a longer time period when ORCtrade mark was used. The level of oxidation-reduction potential (ORP), which has a linear relationship to the sulfide/sulfate ratio, is a good indicator of SRB activity. As determined by fluorescence in-situ hybridization (FISH), most SRB growth was inhibited under increasing amounts of added MgO2. The concentration of sulfide reflected the abundance of the SRB. Utilization of organic matter greater than the theoretical SRB utilization rate indicated that facultative heterotrophs became dominant after MgO2 was added. The results of this study could supply the useful information for further study on evaluating the solution to biocorrosion problems in practical situations.

  7. Inhibition of T cell receptor signaling by cholesterol sulfate, a naturally occurring derivative of membrane cholesterol

    PubMed Central

    Wang, Feng; Beck-García, Katharina; Zorzin, Carina; Schamel, Wolfgang W. A.; Davis, Mark M.

    2016-01-01

    Most adaptive immune responses require the activation of specific T cells through the T cell antigen receptor–CD3 complex (TCR). Here we show that cholesterol sulfate (CS), a naturally occurring analog of cholesterol, inhibits CD3 ITAM phosphorylation, a crucial first step in T cell activation. Biochemical studies show that CS disrupted TCR multimers, apparently by displacing cholesterol, known to bind TCRβ. Moreover, CS-deficient mice displayed a heightened sensitivity to a self-antigen, whereas increasing CS content by intrathymic injection inhibited thymic selection, indicating that this molecule is an intrinsic regulator of thymocyte development. These results reveal a regulatory role for CS in TCR signaling and thymic selection, highlighting the importance of the membrane microenvironment in modulating cell surface receptor activation. PMID:27213689

  8. Proteolysis, NaOH and ultrasound-enhanced extraction of anticoagulant and antioxidant sulfated polysaccharides from the edible seaweed, Gracilaria birdiae.

    PubMed

    Fidelis, Gabriel Pereira; Camara, Rafael Barros Gomes; Queiroz, Moacir Fernandes; Santos Pereira Costa, Mariana Santana; Santos, Pablo Castro; Rocha, Hugo Alexandre Oliveira; Costa, Leandro Silva

    2014-11-13

    The sulfated polysaccharides (SP) from the edible red seaweed, Gracilaria birdiae, were obtained using five different extraction conditions: Gracilaria birdiae 1 (GB1)-water; GB1s-water/sonication; GB1sp-water/sonication/proteolysis; GB2s-NaOH/sonication; and GB2sp-NaOH/sonication/proteolysis. The yield (g) increased in the following order: GB2sp>GB1sp>GB2s>GB1s>GB1. However, the amount of SP extracted increased in a different way: GB2sp>GB1>GB1sp>GB1s>GB2s. Infrared and electrophoresis analysis showed that all conditions extracted the same SP. In addition, monosaccharide composition showed that ultrasound promotes the extraction of polysaccharides other than SP. In the prothrombin time (PT) test, which evaluates the extrinsic coagulation pathway, none of the samples showed anticoagulant activity. While in the activated partial thromboplastin time (aPTT) test, which evaluates the intrinsic coagulation pathway, all samples showed anticoagulant activity, except GB2s. The aPTT activity decreased in the order of GB1sp>GB2sp>GB1>GB1s>GB2s. The total capacity antioxidant (TCA) of the SP was also affected by extraction condition, since GB2s and GB1 showed lower activity in comparison to the other conditions. In conclusion, the conditions of SP extraction influence their biological activities and chemical composition. The data revealed that NaOH/sonication/proteolysis was the best condition to extract anticoagulant and antioxidant SPs from Gracilaria birdiae.

  9. Taishan Pinus massoniana pollen polysaccharide inhibits subgroup J avian leucosis virus infection by directly blocking virus infection and improving immunity

    PubMed Central

    Yu, Cuilian; Wei, Kai; Liu, Liping; Yang, Shifa; Hu, Liping; Zhao, Peng; Meng, Xiuyan; Shao, Mingxu; Wang, Chuanwen; Zhu, Lijun; Zhang, Hao; Li, Yang; Zhu, Ruiliang

    2017-01-01

    Subgroup J avian leucosis virus (ALV-J) generally causes neoplastic diseases, immunosuppression and subsequently increases susceptibility to secondary infection in birds. The spread of ALV-J mainly depends on congenital infection and horizontal contact. Although ALV-J infection causes enormous losses yearly in the poultry industry worldwide, effective measures to control ALV-J remain lacking. In this study, we demonstrated that Taishan Pinus massoniana pollen polysaccharide (TPPPS), a natural polysaccharide extracted from Taishan Pinus massoniana pollen, can significantly inhibit ALV-J replication in vitro by blocking viral adsorption to host cells. Electron microscopy and blocking ELISA tests revealed that TPPPS possibly blocks viral adsorption to host cells by interacting with the glycoprotein 85 protein of ALV-J. Furthermore, we artificially established a congenitally ALV-J-infected chicken model to examine the anti-viral effects of TPPPS in vivo. TPPPS significantly inhibited viral shedding and viral loads in immune organs and largely eliminated the immunosuppression caused by congenital ALV-J infection. Additionally, pre-administration of TPPPS obviously reduced the size and delayed the occurrence of tumors induced by acute oncogenic ALV-J infection. This study revealed the prominent effects and feasible mechanisms of TPPPS in inhibiting ALV-J infection, thereby providing a novel prospect to control ALV-J spread. PMID:28287165

  10. Taishan Pinus massoniana pollen polysaccharide inhibits subgroup J avian leucosis virus infection by directly blocking virus infection and improving immunity.

    PubMed

    Yu, Cuilian; Wei, Kai; Liu, Liping; Yang, Shifa; Hu, Liping; Zhao, Peng; Meng, Xiuyan; Shao, Mingxu; Wang, Chuanwen; Zhu, Lijun; Zhang, Hao; Li, Yang; Zhu, Ruiliang

    2017-03-13

    Subgroup J avian leucosis virus (ALV-J) generally causes neoplastic diseases, immunosuppression and subsequently increases susceptibility to secondary infection in birds. The spread of ALV-J mainly depends on congenital infection and horizontal contact. Although ALV-J infection causes enormous losses yearly in the poultry industry worldwide, effective measures to control ALV-J remain lacking. In this study, we demonstrated that Taishan Pinus massoniana pollen polysaccharide (TPPPS), a natural polysaccharide extracted from Taishan Pinus massoniana pollen, can significantly inhibit ALV-J replication in vitro by blocking viral adsorption to host cells. Electron microscopy and blocking ELISA tests revealed that TPPPS possibly blocks viral adsorption to host cells by interacting with the glycoprotein 85 protein of ALV-J. Furthermore, we artificially established a congenitally ALV-J-infected chicken model to examine the anti-viral effects of TPPPS in vivo. TPPPS significantly inhibited viral shedding and viral loads in immune organs and largely eliminated the immunosuppression caused by congenital ALV-J infection. Additionally, pre-administration of TPPPS obviously reduced the size and delayed the occurrence of tumors induced by acute oncogenic ALV-J infection. This study revealed the prominent effects and feasible mechanisms of TPPPS in inhibiting ALV-J infection, thereby providing a novel prospect to control ALV-J spread.

  11. Inhibition of hyaluronan synthesis alters sulfated glycosaminoglycans deposition during chondrogenic differentiation in ATDC5 cells.

    PubMed

    Yoshioka, Yutaka; Kozawa, Eiji; Urakawa, Hiroshi; Arai, Eisuke; Futamura, Naohisa; Zhuo, Lisheng; Kimata, Koji; Ishiguro, Naoki; Nishida, Yoshihiro

    2015-08-01

    In chondrogenic differentiation, expression and collaboration of specific molecules, such as aggrecan and type II collagen, in extracellular matrix (ECM) are crucial. However, few studies have clarified the roles of hyaluronan (HA) in proteoglycan aggregation during chondrogenic differentiation. We assessed the roles of HA in sulfated glycosaminoglycans deposition during chondrogenic differentiation by means of 4-methylumbelliferone (4-MU), an HA synthase inhibitor, using ATDC5 cells. ATDC5 cells were treated with 0.5 mM 4-MU for 7 or 21 days after induction of chondrogenic differentiation with insulin. Depositions of sulfated glycosaminoglycans were evaluated with Alcian blue staining. mRNA expression of ECM molecules was determined using real-time RT-PCR. The deposition of aggrecan and versican was investigated with immunohistochemical staining using specific antibodies. Effects of 4-MU on HA concentrations were analyzed by HA binding assay. 4-MU suppressed the positivity of Alcian blue staining, although this delay was reversible. Interestingly, stronger positivity of Alcian blue staining was observed at day 21 in cultures with 4-MU discontinuation than in the control. 4-MU significantly increased the mRNA expression of aggrecan, versican, and type II collagen, which was consistent with increased deposition of aggrecan and versican. The HA concentration in ECM and cell-associated region was significantly suppressed with 4-MU treatment. We conclude that the inhibition of HA synthesis slows sulfated glycosaminoglycans deposition during chondrogenic differentiation despite the increased deposition of other ECM molecules. Transient starvation of HA with 4-MU accelerates chondrogenic ECM formation, suggesting its potential to stimulate chondrogenic differentiation with adequate use.

  12. Selenium-enriched polysaccharides from Pyracantha fortuneana (Se-PFPs) inhibit the growth and invasive potential of ovarian cancer cells through inhibiting β-catenin signaling

    PubMed Central

    Wang, Changdong; Sheng, Deqiao; Li, Zhihong; Huang, Debin; Yuan, Chengfu

    2016-01-01

    Polysaccharides from medicinal plants exert antitumor activity in many cancers. Our previous study demonstrated that polysaccharides extracted from the selenium-enriched Pyracantha fortuneana (Se-PFPs) showed antiproliferative effect in breast cancer cell line. This study aimed to investigate the antitumor effect of Se-PFPs in ovarian cancer cells in vitro and in vivo. Se-PFPs could decrease cell viability, induce apoptosis, and inhibit migratory and invasive potentials in HEY and SKOV3 cells. These findings are supported by reduced expression of cyclin D1, Bcl-2 and MMP-9, enhanced cleavage of PARP and caspase-3, elevated activity of caspase-3 and caspase-9, and EMT (epithelial to mesenchymal transition) inhibition (elevated expression of E-cadherin and cytokeratin 19, and reduced expression of N-cadherin, vimentin, ZEB1 and ZEB2). Moreover, Se-PFPs inhibited xenografted tumor growth through inhibiting cell proliferation and inducing cell apoptosis. More importantly, Se-PFPs significantly reduced cytoplasmic β-catenin particularly nuclear β-catenin expression but increased β-catenin phosphorylation in a GSK-3β-dependent mechanism. Furthermore, β-catenin knockdown exerted similar effects on cell proliferation and invasion as seen in Se-PFPs-treated cells, while β-catenin overexpression neutralized the inhibitory effects of Se-PFPs on cell proliferation and invasion. Take together,Se-PFPs exert antitumor activity through inhibiting cell proliferation, migration, invasion and EMT, and inducing cell apoptosis. These effects are achieved by the inhibition of β-catenin signaling. Thus Se-PFPs can be used as potential therapeutic agents in the prevention and treatment of ovarian cancer. PMID:27058760

  13. Sulfated Galactan from Palisada flagellifera Inhibits Toxic Effects of Lachesis muta Snake Venom

    PubMed Central

    da Silva, Ana Cláudia Rodrigues; Ferreira, Luciana Garcia; Duarte, Maria Eugênia Rabello; Noseda, Miguel Daniel; Sanchez, Eladio Flores; Fuly, André Lopes

    2015-01-01

    In Brazil, snakebites are a public health problem and accidents caused by Lachesis muta have the highest mortality index. Envenomation by L. muta is characterized by systemic (hypotension, bleeding and renal failure) and local effects (necrosis, pain and edema). The treatment to reverse the evolution of all the toxic effects is performed by injection of antivenom. However, such therapy does not effectively neutralize tissue damage or any other local effect, since in most cases victims delay seeking appropriate medical care. In this way, alternative therapies are in demand, and molecules from natural sources have been exhaustively tested. In this paper, we analyzed the inhibitory effect of a sulfated galactan obtained from the red seaweed Palisada flagellifera against some toxic activities of L. muta venom. Incubation of sulfated galactan with venom resulted in inhibition of hemolysis, coagulation, proteolysis, edema and hemorrhage. Neutralization of hemorrhage was also observed when the galactan was administered after or before the venom injection; thus mimicking a real in vivo situation. Moreover, the galactan blocked the edema caused by a phospholipase A2 isolated from the same venom. Therefore, the galactan from P. flagellifera may represent a promising tool to treat envenomation by L. muta as a coadjuvant for the conventional antivenom. PMID:26110897

  14. Targeted downregulation of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S6ST) significantly mitigates chondroitin sulfate proteoglycan (CSPG) mediated inhibition

    PubMed Central

    Karumbaiah, Lohitash; Anand, Sanjay; Thazhath, Rupal; Zhong, Yinghui; McKeon, Robert J.; Bellamkonda, Ravi V.

    2011-01-01

    Chondroitin Sulfate-4,6 (CS-E) glycosaminoglycan (GAG) upregulation in astroglial scars is a major contributor to CS proteoglycan (CSPG) mediated inhibition (Gilbert et al. 2005). However, the role of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S6ST) catalyzed sulfation of CS-E, and its contribution to CSPG mediated inhibition of CNS regeneration remains to be fully elucidated. Here, we used in situ hybridization to show localized upregulation of GalNAc4S6ST mRNA after CNS injury. Using in vitro spot assays with immobilized CS-E, we demonstrate dose dependent inhibition of rat embryonic day 18 (E18) cortical neurons. To determine whether selective downregulation of CS-E affected the overall inhibitory character of extracellular matrix produced by reactive astrocytes, single [against (chondroitin 4) sulfotransferase 11 (C4ST1) or GalNAc4S6ST mRNA) or double (against C4ST1 and GalNAc4S6ST mRNA] siRNA treatments were conducted and assayed using quantitative real-time PCR (qRT-PCR) and high performance liquid chromatography (HPLC) to confirm the specific downregulation of CS-4S GAG (CS-A) and CS-E. Spot and Bonhoeffer stripe assays using astrocyte conditioned media (ACM) from siRNA treated rat astrocytes showed a significant decrease in inhibition of neuronal attachment and neurite extensions when compared to untreated and TGFα treated astrocytes. These findings reveal that selective attenuation of CS-E via siRNA targeting of GalNAc4S6ST significantly mitigates CSPG mediated inhibition of neurons, potentially offering a novel intervention strategy for CNS injury. PMID:21456043

  15. Inhibition of bacterial oxidation of ferrous iron by lead nitrate in sulfate-rich systems

    USGS Publications Warehouse

    Wang, Hongmei; Gong, Linfeng; Cravotta, Charles A.; Yang, Xiaofen; Tuovinen, Olli H.; Dong, Hailiang; Fu, Xiang

    2013-01-01

    Inhibition of bacterial oxidation of ferrous iron (Fe(II)) by Pb(NO3)2 was investigated with a mixed culture of Acidithiobacillus ferrooxidans. The culture was incubated at 30 °C in ferrous-sulfate medium amended with 0–24.2 mM Pb(II) added as Pb(NO3)2. Anglesite (PbSO4) precipitated immediately upon Pb addition and was the only solid phase detected in the abiotic controls. Both anglesite and jarosite (KFe3(SO4)2(OH)6) were detected in inoculated cultures. Precipitation of anglesite maintained dissolved Pb concentrations at 16.9–17.6 μM regardless of the concentrations of Pb(NO3)2 added. Fe(II) oxidation was suppressed by 24.2 mM Pb(NO3)2 addition even when anglesite was removed before inoculation. Experiments with 0–48 mM KNO3 demonstrated that bacterial Fe(II) oxidation decreased as nitrate concentration increased. Therefore, inhibition of Fe(II) oxidation at 24.2 mM Pb(NO3)2 addition resulted from nitrate toxicity instead of Pb addition. Geochemical modeling that considered the initial precipitation of anglesite to equilibrium followed by progressive oxidation of Fe(II) and the precipitation of jarosite and an amorphous iron hydroxide phase, without allowing plumbojarosite to precipitate were consistent with the experimental time-series data on Fe(II) oxidation under biotic conditions. Anglesite precipitation in mine tailings and other sulfate-rich systems maintains dissolved Pb concentrations below the toxicity threshold of A. ferrooxidans.

  16. Inhibition of bacterial oxidation of ferrous iron by lead nitrate in sulfate-rich systems.

    PubMed

    Wang, Hongmei; Gong, Linfeng; Cravotta, Charles A; Yang, Xiaofen; Tuovinen, Olli H; Dong, Hailiang; Fu, Xiang

    2013-01-15

    Inhibition of bacterial oxidation of ferrous iron (Fe(II)) by Pb(NO(3))(2) was investigated with a mixed culture of Acidithiobacillus ferrooxidans. The culture was incubated at 30 °C in ferrous-sulfate medium amended with 0-24.2 mM Pb(II) added as Pb(NO(3))(2). Anglesite (PbSO(4)) precipitated immediately upon Pb addition and was the only solid phase detected in the abiotic controls. Both anglesite and jarosite (KFe(3)(SO(4))(2)(OH)(6)) were detected in inoculated cultures. Precipitation of anglesite maintained dissolved Pb concentrations at 16.9-17.6 μM regardless of the concentrations of Pb(NO(3))(2) added. Fe(II) oxidation was suppressed by 24.2 mM Pb(NO(3))(2) addition even when anglesite was removed before inoculation. Experiments with 0-48 mM KNO(3) demonstrated that bacterial Fe(II) oxidation decreased as nitrate concentration increased. Therefore, inhibition of Fe(II) oxidation at 24.2 mM Pb(NO(3))(2) addition resulted from nitrate toxicity instead of Pb addition. Geochemical modeling that considered the initial precipitation of anglesite to equilibrium followed by progressive oxidation of Fe(II) and the precipitation of jarosite and an amorphous iron hydroxide phase, without allowing plumbojarosite to precipitate were consistent with the experimental time-series data on Fe(II) oxidation under biotic conditions. Anglesite precipitation in mine tailings and other sulfate-rich systems maintains dissolved Pb concentrations below the toxicity threshold of A. ferrooxidans.

  17. Allosteric inhibition of factor XIa. Sulfated non-saccharide glycosaminoglycan mimetics as promising anticoagulants.

    PubMed

    Al-Horani, Rami A; Gailani, David; Desai, Umesh R

    2015-08-01

    Recent development of sulfated non-saccharide glycosaminoglycan mimetics, especially sulfated pentagalloyl glucopyranoside (SPGG), as potent inhibitors of factor XIa (FXIa) (J. Med. Chem. 2013; 56:867-878 and J. Med. Chem. 2014; 57:4805-4818) has led to a strong possibility of developing a new line of factor XIa-based anticoagulants. In fact, SPGG represents the first synthetic, small molecule inhibitor that appears to bind in site remote from the active site. Considering that allosteric inhibition of FXIa is a new mechanism for developing a distinct line of anticoagulants, we have studied SPGG's interaction with FXIa with a goal of evaluating its pre-clinical relevance. Comparative inhibition studies with several glycosaminoglycans revealed the importance of SPGG's non-saccharide backbone. SPGG did not affect the activity of plasma kallikrein, activated protein C and factor XIIIa suggesting that SPGG-based anticoagulation is unlikely to affect other pathways connected with coagulation factors. SPGG's effect on APTT of citrated human plasma was also not dependent on antithrombin or heparin cofactor II. Interestingly, SPGG's anticoagulant potential was diminished by serum albumin as well as factor XI, while it could be reversed by protamine or polybrene, which implies possible avenues for developing antidote strategy. Studies with FXIa mutants indicated that SPGG engages Lys529, Arg530 and Arg532, but not Arg250, Lys252, Lys253 and Lys255. Finally, SPGG competes with unfractionated heparin, but not with polyphosphates and/or glycoprotein Ibα, for binding to FXIa. These studies enhance understanding on the first allosteric inhibitor of FXIa and highlight its value as a promising anticoagulant.

  18. Specific sulfation and glycosylation-a structural combination for the anticoagulation of marine carbohydrates.

    PubMed

    Pomin, Vitor H; Mourão, Paulo A S

    2014-01-01

    Based on considered achievements of the last 25 years, specific combinations of sulfation patterns and glycosylation types have been proved to be key structural players for the anticoagulant activity of certain marine glycans. These conclusions were obtained from comparative and systematic analyses on the structure-anticoagulation relationships of chemically well-defined sulfated polysaccharides of marine invertebrates and red algae. These sulfated polysaccharides are known as sulfated fucans (SFs), sulfated galactans (SGs) and glycosaminoglycans (GAGs). The structural combinations necessary for the anticoagulant activities are the 2-sulfation in α-L-SGs, the 2,4-di-sulfation in α-L-fucopyranosyl units found as composing units of certain sea-urchin and sea-cucumber linear SFs, or as branching units of the fucosylated chondroitin sulfate, a unique GAG from sea-cucumbers. Another unique GAG type from marine organisms is the dermatan sulfate isolated from ascidians. The high levels of 4-sulfation at the galactosamine units combined with certain levels of 2-sulfation at the iduronic acid units is the anticoagulant structural requirements of these GAGs. When the backbones of red algal SGs are homogeneous, the anticoagulation is proportionally dependent of their sulfation content. Finally, 4-sulfation was observed to be the structural motif required to enhance the inhibition of thrombin via heparin cofactor-II by invertebrate SFs.

  19. Specific sulfation and glycosylation—a structural combination for the anticoagulation of marine carbohydrates

    PubMed Central

    Pomin, Vitor H.; Mourão, Paulo A. S.

    2014-01-01

    Based on considered achievements of the last 25 years, specific combinations of sulfation patterns and glycosylation types have been proved to be key structural players for the anticoagulant activity of certain marine glycans. These conclusions were obtained from comparative and systematic analyses on the structure-anticoagulation relationships of chemically well-defined sulfated polysaccharides of marine invertebrates and red algae. These sulfated polysaccharides are known as sulfated fucans (SFs), sulfated galactans (SGs) and glycosaminoglycans (GAGs). The structural combinations necessary for the anticoagulant activities are the 2-sulfation in α-L-SGs, the 2,4-di-sulfation in α-L-fucopyranosyl units found as composing units of certain sea-urchin and sea-cucumber linear SFs, or as branching units of the fucosylated chondroitin sulfate, a unique GAG from sea-cucumbers. Another unique GAG type from marine organisms is the dermatan sulfate isolated from ascidians. The high levels of 4-sulfation at the galactosamine units combined with certain levels of 2-sulfation at the iduronic acid units is the anticoagulant structural requirements of these GAGs. When the backbones of red algal SGs are homogeneous, the anticoagulation is proportionally dependent of their sulfation content. Finally, 4-sulfation was observed to be the structural motif required to enhance the inhibition of thrombin via heparin cofactor-II by invertebrate SFs. PMID:24639954

  20. Anti-tumor activity and the mechanism of SIP-S: A sulfated polysaccharide with anti-metastatic effect.

    PubMed

    Zong, Aizhen; Liu, Yuhong; Zhang, Yan; Song, Xinlei; Shi, Yikang; Cao, Hongzhi; Liu, Chunhui; Cheng, Yanna; Jiang, Wenjie; Du, Fangling; Wang, Fengshan

    2015-09-20

    Our previous studies demonstrated that SIP-S had anti-metastatic activity and inhibited the growth of metastatic foci. Here we report the anti-tumor and immunoregulatory potential of SIP-S. SIP-S could significantly inhibit tumor growth in S180-bearing mice, and the inhibition rates was 43.7% at 30 mg/kg d. Besides, SIP-S could improve the thymus and spleen indices of S180-bearing mice and the mice treated with CTX. The combination of SIP-S (15 mg/kg d) with CTX (12.5 mg/kg d) showed higher anti-tumor potency than CTX (25 mg/kg d) alone. These results indicated that SIP-S had immunoenhancing and anticancer activity, and the immunoenhancing activity might be one mechanism for its anti-tumor activity. Flow cytometry results showed that SIP-S could induce tumor cells apoptosis. Western blot analysis indicated that SIP-S could upregulate the expression of pro-apoptotic proteins, caspase-3, -8, -9 and Bax, and downregulate the expression of anti-apoptotic protein PARP-1 in tumor cells in a dose-dependent manner. In summary, SIP-S has anti-tumor activity, which may be associated with its immunostimulating and pro-apoptotic activity.

  1. Swallowing disorder and inhibition of cough reflex induced by atropine sulfate in conscious dogs.

    PubMed

    Tsubouchi, Tadashi; Tsujimoto, Shinji; Sugimoto, Shinichi; Katsura, Yasunori; Mino, Terumasa; Seki, Takaki

    2008-03-01

    In this study, the effects of atropine sulfate (atropine) on swallowing and cough reflex were evaluated in the two experimental models in conscious dogs. To evaluate the effects of atropine on swallowing, 1 mL of marker (contrast medium) was injected into the pharynx under X-ray exposure to induce swallowing. Baclofen, used as a positive control, caused marker congestion in the upper esophagus. In our experimental model, atropine (0.02 and 0.1 mg/kg, i.v.) dose-dependently increased not only the number of marker congestions but also that of the swallows. In addition, atropine significantly shortened the onset of first swallowing. In the evaluation of atropine effects on electrically evoked cough reflex induced by two electrodes implanted into the trachea, atropine strongly inhibited the number of coughs at 0.01 or 0.05 mg/kg accompanied with 0.01 or 0.05 mg/kg per hour (i.v.), respectively. These findings indicate that atropine has the potential of causing aspiration pneumonia through induction of swallowing disorder and inhibition of the cough reflex.

  2. Polygonatum sibiricum polysaccharide inhibits osteoporosis by promoting osteoblast formation and blocking osteoclastogenesis through Wnt/β-catenin signalling pathway

    PubMed Central

    Du, Li; Nong, Meng-Ni; Zhao, Jin-Min; Peng, Xiao-Ming; Zong, Shao-Hui; Zeng, Gao-Feng

    2016-01-01

    Bone homeostasis is maintained by a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoporosis occurs when osteoclast activity surpasses osteoblast activity. Our previous studies showed the plant-derived natural polysaccharide (Polygonatum sibiricum polysaccharide or PSP) had significant anti-ovariectomy (OVX)-induced osteoporosis effects in vivo, but the mechanisms of PSP’s anti-osteoporosis effect remains unclear. In this study, we assessed PSP’s effect on the generation of osteoblast and osteoclast in vitro. This study showed that PSP promoted the osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) without affecting BMPs signaling pathway. This effect was due to the increased nuclear accumulation of β-catenin, resulting in a higher expression of osteoblast-related genes. Furthermore, the study showed PSP could inhibit the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and exert prophylatic protection against LPS-induced osteolysis in vivo. This effect was also related to the increased nuclear accumulation of β-catenin, resulting in the decreased expression of osteoclast-related genes. In conclusion, our results showed that PSP effectively promoted the osteogenic differentiation of mouse BMSCs and suppressed osteoclastogenesis; therefore, it could be used to treat osteoporosis. PMID:27554324

  3. Bismuth Dimercaptopropanol (BisBAL) Inhibits the Expression of Extracellular Polysaccharides and Proteins by Brevundimonas diminuta: Implications for Membrane Microfiltration

    SciTech Connect

    Badireddy, Appala R.; Chellam, Shankararaman; Yanina, Svetlana; Gassman, Paul L.; Rosso, Kevin M.

    2008-02-15

    A 2:1 molar ratio preparation of bismuth with a lipophilic dithiol (3-dimercapto-1-propanol, BAL)significantly reduced extracellular polymeric substances (EPS) expression by Brevundimonas diminuta in suspended cultures at levels just below the minimum inhibitory concentration (MIC). Total polysaccharides and proteins secreted by B. diminuta decreased by approximately 95% over a 5-day period when exposed to the bismuth-BAL chelate (BisBAL) at near MIC (12 μM). Fourier-transform infrared spectroscopy (FTIR) suggested that a possible mechanism of biofilm disruption by BisBAL is the inhibition of carbohydrate Oacetylation. FTIR also revealed extensive homology between EPS samples with and without BisBAL treatment, with proteins, polysaccharides, and peptides varying predominantly only in the amount expressed. EPS secretion decreased following BisBAL treatment as verified by atomic force microscopy and scanning electron microscopy. Without BisBAL treatment, a slime-like EPS matrix secreted by B. diminuta resulted in biofouling and inefficient hydrodynamic backwashing of microfiltration membranes.

  4. Lycium barbarum polysaccharides inhibit proliferation and migration of bladder cancer cell lines BIU87 by suppressing Pi3K/AKT pathway

    PubMed Central

    Zhang, Xian-Jun; Yu, Hong-Yuan; Cai, Yong-jian; Ke, Mang

    2017-01-01

    The aim of this study was to verify whether Lycium barbarum polysaccharides inhibits proliferation and migration of BIU87 cells through Pi3K/AKT pathway. Different concentrations of Lycium barbarum polysaccharides were used to incubate with BIU87cells. LY-294002 and IGF-1 were used to inhibit and activate Pi3K/AKT pathway respectively. MTT were used to investigate the proliferation of BIU87cells. Transwell chambers and wound healing were used to test the migratory ability of BIU87cells. Western blotting were used to investigate the expressions of P21,P27,MMP-2, MMP-9, AKT and p-AKT in BIU87cells. Compared with the control group, the proliferation and migration of BIU87cells and the expression of p-AKT were significantly decreased in the study group; the inhibitory effect of the downregulation of p-AKT by LY-294002on the induction of BIU87cells proliferation and migration was identical to that of Lycium barbarum polysaccharides; upregulation of p-AKT by IGF-1 reversed the Lycium barbarum polysaccharides-induced inhibition of BIU87cells dedifferentiation. In conclusion, LBP inhibits the proliferation and migration of BIU87 cells by suppressing Pi3K/AKT signaling pathway. PMID:27992374

  5. Physicochemical properties and inhibition effect on iron deficiency anemia of a novel polysaccharide-iron complex (LPPC).

    PubMed

    Zhang, Zhong-Shan; Wang, Xiao-Mei; Han, Zhi-Ping; Yin, Li; Zhao, Ming-Xing; Yu, Shu-Chi

    2012-01-01

    Porphyran (P) was extracted from red algae Porphyra by boiling water. A novel polysaccharide-iron complex (LPPC) was prepared under the alkaline condition by adding a ferric chloride solution to the low molecular weight porphyran (LP) solution. Physicochemical properties and inhibition effect on iron deficiency anemia of this complex were studied. The content of iron(III) in the complex is 21.57% determined with iodometry. The results indicate that LPPC was product required. The complex can increase red blood cell count (RBC), hemoglobin (Hb), Serum iron (SI), spleen index, spleen mass and mass of mice with iron deficiency anemia (IDA). Although the structure and deeper mechanisms on hemolytic anemia of LPPC should be further studied, LPPC is hoped to be developed as a late-model iron supplement which has a synergism on anemia.

  6. Anti-inflammatory activity of a sulfated polysaccharide isolated from an enzymatic digest of brown seaweed Sargassum horneri in RAW 264.7 cells

    PubMed Central

    Sanjeewa, Kalu Kapuge Asanka; Fernando, Ilekkuttige Priyan Shanura; Kim, Eun-A; Jee, Youngheun

    2017-01-01

    BACKGROUND/OBJECTIVES Sargassum horneri is an edible brown alga that grows in the subtidal zone as an annual species along the coasts of South Korea, China, and Japan. Recently, an extreme amount of S. horneri moved into the coasts of Jeju Island from the east coast of China, which made huge economic and environmental loss to the Jeju Island. Thus, utilization of this biomass becomes a big issue with the local authorities. Therefore, the present study was performed to evaluate the anti-inflammatory potential of crude polysaccharides (CPs) extracted from S. horneri China strain in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. MATERIALS/METHODS CPs were precipitated from S. horneri digests prepared by enzyme assistant extraction using four food-grade enzymes (AMG, Celluclast, Viscozyme, and Alcalase). The production levels of nitric oxide (NO) and pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured by Griess assay and enzyme-linked immunosorbent assay, respectively. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPKs) were measured by using western blot. The IR spectrums of the CPs were recorded using a fourier transform infrared spectroscopy (FT-IR) spectrometer. RESULTS The polysaccharides from the Celluclast enzyme digest (CCP) showed the highest inhibition of NO production in LPS-stimulated RAW 264.7 cells (IC50 value: 95.7 µg/mL). Also, CCP dose-dependently down-regulated the protein expression levels of iNOS and COX-2 as well as the production of inflammatory cytokines, including TNF-α and IL-1β, compared to the only LPS-treated cells. In addition, CCP inhibited the activation of NF-κB p50 and p65 and the phosphorylation of MAPKs, including p38 and extracellular signal-regulated kinase, in LPS-stimulated RAW 264.7 cells. Furthermore, FT-IR analysis showed that the FT-IR spectrum of CCP is similar

  7. Panels of chemically-modified heparin polysaccharides and natural heparan sulfate saccharides both exhibit differences in binding to Slit and Robo, as well as variation between protein binding and cellular activity.

    PubMed

    Ahmed, Yassir A; Yates, Edwin A; Moss, Diana J; Loeven, Markus A; Hussain, Sadaf-Ahmahni; Hohenester, Erhard; Turnbull, Jeremy E; Powell, Andrew K

    2016-10-20

    Heparin/heparan sulfate (HS) glycosaminoglycans are required for Slit-Robo cellular responses. Evidence exists for interactions between each combination of Slit, Robo and heparin/HS and for formation of a ternary complex. Heparin/HS are complex mixtures displaying extensive structural diversity. The relevance of this diversity has been studied to a limited extent using a few select chemically-modified heparins as models of HS diversity. Here we extend these studies by parallel screening of structurally diverse panels of eight chemically-modified heparin polysaccharides and numerous natural HS oligosaccharide chromatographic fractions for binding to both Drosophila Slit and Robo N-terminal domains and for activation of a chick retina axon response to the Slit fragment. Both the polysaccharides and oligosaccharide fractions displayed variability in binding and cellular activity that could not be attributed solely to increasing sulfation, extending evidence for the importance of structural diversity to natural HS as well as model modified heparins. They also displayed differences in their interactions with Slit compared to Robo, with Robo preferring compounds with higher sulfation. Furthermore, the patterns of cellular activity across compounds were different to those for binding to each protein, suggesting that biological outcomes are selectively determined in a subtle manner that does not simply reflect the sum of the separate interactions of heparin/HS with Slit and Robo.

  8. Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host-cell interaction

    NASA Astrophysics Data System (ADS)

    Hu, Yu-Peng; Lin, Shu-Yi; Huang, Cheng-Yen; Zulueta, Medel Manuel L.; Liu, Jing-Yuan; Chang, Wen; Hung, Shang-Cheng

    2011-07-01

    Cell surface carbohydrates play significant roles in a number of biologically important processes. Heparan sulfate, for instance, is a ubiquitously distributed polysulfated polysaccharide that is involved, among other things, in the initial step of herpes simplex virus type 1 (HSV-1) infection. The virus interacts with cell-surface heparan sulfate to facilitate host-cell attachment and entry. 3-O-Sulfonated heparan sulfate has been found to function as an HSV-1 entry receptor. Achieving a complete understanding of these interactions requires the chemical synthesis of such oligosaccharides, but this remains challenging. Here, we present a convenient approach for the synthesis of two irregular 3-O-sulfonated heparan sulfate octasaccharides, making use of a key disaccharide intermediate to acquire different building blocks for the oligosaccharide chain assembly. Despite substantial structural differences, the prepared 3-O-sulfonated sugars blocked viral infection in a dosage-dependent manner with remarkable similarity to one another.

  9. Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

    PubMed Central

    Simpson, Hannah L.; Williams, Jonathan M.; Humphrey, Suzie; Salisbury, Anne-Marie; Watson, Alastair J. M.; Fry, Stephen C.; O'Brien, David; Roberts, Carol L.; O'Kennedy, Niamh; Keita, Åsa V.; Söderholm, Johan D.; Rhodes, Jonathan M.; Campbell, Barry J.

    2014-01-01

    Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well

  10. Dietary supplementation with soluble plantain non-starch polysaccharides inhibits intestinal invasion of Salmonella Typhimurium in the chicken.

    PubMed

    Parsons, Bryony N; Wigley, Paul; Simpson, Hannah L; Williams, Jonathan M; Humphrey, Suzie; Salisbury, Anne-Marie; Watson, Alastair J M; Fry, Stephen C; O'Brien, David; Roberts, Carol L; O'Kennedy, Niamh; Keita, Asa V; Söderholm, Johan D; Rhodes, Jonathan M; Campbell, Barry J

    2014-01-01

    Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1-99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5-10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64-81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75-90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well

  11. Heparin-like properties of sulfated alginates with defined sequences and sulfation degrees.

    PubMed

    Arlov, Øystein; Aachmann, Finn Lillelund; Sundan, Anders; Espevik, Terje; Skjåk-Bræk, Gudmund

    2014-07-14

    Sulfated glycosaminoglycans have a vast range of protein interactions relevant to the development of new biomaterials and pharmaceuticals, but their characterization and application is complicated mainly due to a high structural variability and the relative difficulty to isolate large quantities of structurally homogeneous samples. Functional and versatile analogues of heparin/heparan sulfate can potentially be created from sulfated alginates, which offer structure customizability through targeted enzymatic epimerization and precise tuning of the sulfation degree. Alginates are linear polysaccharides consisting of β-D-mannuronic acid (M) and α-L-guluronic acid (G), derived from brown algae and certain bacteria. The M/G ratio and distribution of blocks are critical parameters for the physical properties of alginates and can be modified in vitro using mannuronic-C5-epimerases to introduce sequence patterns not found in nature. Alginates with homogeneous sequences (poly-M, poly-MG, and poly-G) and similar molecular weights were chemically sulfated and structurally characterized by the use of NMR and elemental analysis. These sulfated alginates were shown to bind and displace HGF from the surface of myeloma cells in a manner similar to heparin. We observed dependence on the sulfation degree (DS) as well as variation in efficacy based on the alginate monosaccharide sequence, relating to relative flexibility and charge density in the polysaccharide chains. Co-incubation with human plasma showed complement compatibility of the alginates and lowering of soluble terminal complement complex levels by sulfated alginates. The sulfated polyalternating (poly-MG) alginate proved to be the most reproducible in terms of precise sulfation degrees and showed the greatest relative degree of complement inhibition and HGF interaction, maintaining high activity at low DS values.

  12. Pu-erh tea polysaccharides decrease blood sugar by inhibition of α-glucosidase activity in vitro and in mice.

    PubMed

    Deng, Yea-Tyz; Lin-Shiau, Shoei-Yn; Shyur, Lie-Fen; Lin, Jen-Kun

    2015-05-01

    Type 2 diabetes is mainly induced by environmental factors such as being overweight, decreased physical activity and inbalanced energy metabolism, such as pancreatic beta-cell dysfunction and peripheral insulin resistance. Acarbose, a microbial carbohydrate and an alpha-glucosidase inhibitor, is currently a useful agent for attenuating type 2 diabetes. However, it is usually accompanied by many side effects, such as abdominal distention, flatulence, diarrhea and meteorism. These side effects may be caused by its strong inhibition of alpha-amylase, leading to the accumulation of several undigested carbohydrates. The bacteria residing in the colon can further ferment the undigested carbohydrate to release gas. Finding a new alpha-glucosidase inhibitor with a low inhibitory effect on alpha-amylase is highly anticipated. In this report we describe a group of carbohydrates found in pu-erh tea polysaccharide (PTPS) that can inhibit alpha-glucosidase but have less of an inhibitory effect on alpha-amylase. The preliminary experiments on mice indicate that PTPS might be better than acarbose at suppressing blood glucose after oral administration of a carbohydrate diet; it is recommended that further clinical trials are required in type 2 diabetes in future studies.

  13. Inhibition of human gastric carcinoma cell growth in vitro by a polysaccharide from Aster tataricus.

    PubMed

    Zhang, Yunxin; Wang, Qiusheng; Wang, Tie; Zhang, Haikui; Tian, Ying; Luo, Hong; Yang, Shen; Wang, Yuan; Huang, Xun

    2012-11-01

    A water-soluble polysaccharide (WATP), with a molecular weight of 6.3 × 10⁴ Da, was isolated from Aster tataricus. According to gas chromatography (GC) analysis, WATP was composed of galactose, glucose, fucose, rhamnose, arabinose and mannose with molar ratios of 2.1:1.3:0.9:0.5:0.3:0.6. The effects of WATP on cell proliferation and apoptosis in human gastric cancer SGC-7901 cells were examined. MTT assay showed that WATP had a perfectly tumor growth inhibitory activity on SGC-7901 cells, but no cytotoxicity on SGC-7901 and primary human polymorphonuclear (PMN) cells analyzed using LDH assay. Flow cytometry analysis indicated that WATP could significantly induce apoptosis of SGC-7901 cells. Furthermore using Rh123 and Fluo-3 as fluorescent probes, respectively, it was found that mitochondrial transmembrane potential (ΔΨ(m)) of treatment groups was significantly lower than that in un-treatment group and the concentration of calcium in cells exposed to WATP for 24 h was increased in a dose dependent manner compared with unexposed group. These results suggest that WATP induces apoptosis of SGC-7901 cells through calcium- and ΔΨ(m)-dependent pathways, indicating that it is potentially useful as a natural anti-cancer agent.

  14. A polysaccharide from Agaricus blazei inhibits proliferation and promotes apoptosis of osteosarcoma cells.

    PubMed

    Wu, Bei; Cui, Juncheng; Zhang, Chaogui; Li, Zhihong

    2012-05-01

    Many reports have proved that traditional Chinese herbal medicines (TCM) have become popular used in disease prevention and as alternatives to cancer chemotherapy. In this study, we purified a polysaccharide (ABP-Ia) from the fruiting bodies of Agaricus blazei and identified its molecular weight to be 4.2×10(5)Da. ABP-Ia was a heteropolysaccharide fraction consisting of glucose, mannose, and galactose in a molar ratio of 1:1:1, along with trace of rhamnose. The effect of ABP-Ia at three concentrations of 100, 200 and 400 μg/mL on the cell growth and apoptosis was evaluated in osteosarcoma cell lines HOS and a normal human osteoblast cell line NHOst. ABP-Ia had a significant inhibitory effect against the growth of HOS cells, whereas a mild cytotoxicity to the HOS cells mediated by ABP-Ia was observed, which was in accordance with the results that ABP-Ia substantially induced apoptosis in a dose-dependent fashion in the HOS cells. However ABP-Ia had no or minor inhibitory and cytotoxic effects on the viability of NHOst cells even at the high concentration of 400 μg/mL. Base on all the observations, we could conclude that ABP-Ia had an evident inhibitory effect on the growth of HOS cells mainly through induction of apoptosis, with a minor toxicity to normal human osteoblast cell.

  15. Reducing phosphorus runoff and inhibiting ammonia loss from poultry manure with aluminum sulfate

    SciTech Connect

    Moore, P.A. Jr.; Daniel, T.C.; Edwards, D.R.

    2000-02-01

    Applications of aluminum sulfate (Al{sub 2}(SO{sub 4}){sub 3} {center_dot} 14H{sub 2}O), commonly referred to as alum, to poultry litter have been shown to decrease P runoff from lands fertilized with litter and to inhibit NH{sub 3} volatilization. The objectives of this study were to evaluate the effects of alum applications in commercial broiler houses on: (1) NH{sub 3} volatilization (in-house), (2) poultry production, (3) litter chemistry, and (4) P runoff following litter application. Two farms were used for this study: one had six poultry houses and the other had four. The litter in half of the houses at each farm was treated with alum; the other houses were controls. Alum was applied at a rate of 1,816 kg/house, which corresponded to 0.091 kg/bird. Each year the houses were cleaned in the spring and the litter was broadcast onto paired watersheds in tall fescue at each farm. Results from this study showed that alum applications lowered the litter pH, particularly during the first 3 to 4 wk of each growout. Reductions in litter pH resulted in less NH{sub 3} volatilization, which led to reductions in atmospheric NH{sub 3} in the alum-treated houses. Broilers grown on alum-treated litter were significantly heavier than controls (1.73 kg vs. 1.66 kg). Soluble reactive phosphorus (SRP) concentrations in runoff from pastures fertilized with alum-treated litter averaged 73% lower than that from normal litter throughout a 3-yr period. These results indicate that alum-treatment of poultry litter is a very effective best management practice that reduces nonpoint source pollution while it increases agricultural productivity.

  16. Vincristine sulfate-induced cell transformation, mitotic inhibition and aneuploidy in cultured Syrian hamster embryo cells

    SciTech Connect

    Tsutsui, T.; Suzuki, N.; Maizumi, H.; Barrett, J.C.

    1986-01-01

    Vincristine, a naturally occurring Vinca alkaloid and widely used anti-neoplastic agent, was examined for its ability to induce cell transformation, inhibition of growth and mitosis, and genetic effects in Syrian hamster embryo cells in culture. Treatment of the cells with doses of less than or equal to 1 ng/ml vincristine sulfate (VCR) had no effect on cell growth, while exposure to greater than or equal to 3 ng/ml reduced the growth rate and treatment with 30 ng/ml resulted in no detectable increase in cell number. At this latter dose the mitotic index of the cells increased significantly suggesting that VCR delayed completion of mitosis. Exposure of the cells to VCR at doses of 1-10 ng/ml for 48 h resulted in morphological transformation of the cells in a doserelated fashion. The vincristine-treated transformed colonies were morphologically indistinguishable from colonies transformed by benzo(a)pyrene or other chemical carcinogens. Morphological transformation was induced by VCR at non-toxic and slightly toxic doses as measured by a reduction in colony-forming ability of the treated cells. Over the dose range which resulted in cell transformation, VCR failed to induce either detectable gene mutations at two genetic loci, unscheduled DNA synthesis, or chromosome aberrations in the Syrian hamster embryo cells. However, a significant dose-dependent increase in aneuploid cells with a near-diploid chromosome number was induced by VCR. Both chromosome losses and gains were induced which is consistent with a non-disjunctional mechanism. These results further support our hypothesis that aneuploidy is one possible mechanism for induction of this early step in the neoplastic transformation of Syrian hamster embryo cells. Furthermore, these findings indicate that VCR may have some carcinogenic potential if exposure to rapidly dividing cells occurs.

  17. The inhibiting effect of the Coptis chinensis polysaccharide on the type II diabetic mice.

    PubMed

    Cui, Lijuan; Liu, Min; Chang, XiangYun; Sun, Kan

    2016-07-01

    In this paper, we investigated the effects of Coptis chinensis polysaccharide (CCP) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. CCP was prepared by extraction from Coptis chinensis and oral given to the mice. C57BL/6J mice in each of the 5 groups (eight mice per group) were given either the normal diet (ND) (D12450B, 10% kcal% fat; Research diet, New Brunswick, NJ, USA), HFD (D12451, 45% kcal% fat; Research diet, New Brunswick, NJ, USA), or HFD with CCP of differing hardness (500, 1000, and 2000ppm) for 20 weeks. Mice given an HFD with CCP showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that CCP improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that CCP recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with CCP. CCP increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. CCP stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that CCP has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake.

  18. Heparan sulfate structure: methods to study N-sulfation and NDST action.

    PubMed

    Dagälv, Anders; Lundequist, Anders; Filipek-Górniok, Beata; Dierker, Tabea; Eriksson, Inger; Kjellén, Lena

    2015-01-01

    Heparan sulfate proteoglycans are important modulators of cellular processes where the negatively charged polysaccharide chains interact with target proteins. The sulfation pattern of the heparan sulfate chains will determine the proteins that will bind and the affinity of the interactions. The N-deacetylase/N-sulfotransferase (NDST) enzymes are of key importance during heparan sulfate biosynthesis when the sulfation pattern is determined. In this chapter, metabolic labeling of heparan sulfate with [(35)S]sulfate or [(3)H]glucosamine in cell cultures is described, in addition to characterization of polysaccharide chain length and degree of N-sulfation. Methods to measure NDST enzyme activity are also presented.

  19. Apple Polysaccharide inhibits microbial dysbiosis and chronic inflammation and modulates gut permeability in HFD-fed rats.

    PubMed

    Wang, Sheng; Li, Qian; Zang, Yue; Zhao, Yang; Liu, Nan; Wang, Yifei; Xu, Xiaotao; Liu, Li; Mei, Qibing

    2017-02-24

    The saying "An apple a day keeps the doctor away" has been known for over 150 years, and numerous studies have shown that apple consumption is closely associated with reduced risks of chronic diseases. It has been well accepted that dysbiosis is the reflection of various chronic diseases. Therefore, this study investigates the effects of apple polysaccharides (AP) on gut dysbiosis. High-fat diet (HFD) fed rats were treated for 14 weeks with AP. The microbiota composition, microbiota-generated short chain fatty acids (SCFAs), gut permeability and chronic inflammation were analyzed. AP treatment showed higher abundance of Bacteroidetes and Lactobacillus while lower Firmicutes and Fusobacteium. AP significantly increased total SCFAs level that contributed by acetic acid and isobutyric acid. Moreover, AP dramatically alleviated dysbiosis-associated gut permeability and chronic inflammation with decreased plasma LBP, up-regulation of Occludin, down-regulation of tumor necrosis factor a (TNF-a), monocyte chemotactic protein 1 (MCP-1), chemokine ligand 1 (CXCL-1) and interleukin 1 beta (IL-1β). The potential mechanism is due to the fact that AP reduces gut permeability, which involves the induction of autophagy in goblet cells. Therefore, AP exerts health benefits through inhibiting gut dysbiosis and chronic inflammation and modulating gut permeability in HFD-induced dysbiosis rats.

  20. The virulence polysaccharide Vi released by Salmonella Typhi targets membrane prohibitin to inhibit T-cell activation.

    PubMed

    Santhanam, Srikanth K; Dutta, Debjani; Parween, Farhat; Qadri, Ayub

    2014-07-01

    T cells are critical to immunity against pathogenic Salmonella including Salmonella Typhi which causes systemic infection, typhoid, in humans. The strategies that this pathogen employs to keep T-cell mediated immune responses in check during establishment of systemic infection are not completely understood. Here, we show that the virulence polysaccharide Vi, which distinguishes S. Typhi from localized gastroenteritis-producing nontyphoidal Salmonella serovars, is a potent inhibitor of T-cell activation. Vi released by S. Typhi interacts with the membrane prohibitin complex and inhibits IL-2 secretion from T cells stimulated through the T-cell receptor (TCR) but does not affect PMA-activated interleukin 2 (IL-2) secretion. Treatment with Vi suppresses early activation events including TCR down-regulation, actin polymerization, and phosphorylation of ERK. Coadministration of Vi with anti-CD3 Ab reduces secretion of IL-2 and interferon γ in mice. Our findings reveal a mechanism by which S. Typhi may target T-cell immunity during establishment of typhoid.

  1. A polysaccharide from Lentinus edodes inhibits human colon cancer cell proliferation and suppresses tumor growth in athymic nude mice

    PubMed Central

    Wang, Jinglin; Li, Weiyong; Huang, Xiao; Liu, Ying; Li, Qiang; Zheng, Ziming; Wang, Kaiping

    2017-01-01

    The antitumor effect of Lentinan is thought rely on the activation of immune responses; however, little is known about whether Lentinan also directly attacks cancer cells. We therefore investigated the direct antitumor activity of SLNT (a water-extracted polysaccharide from Lentinus edodes) and its probable mechanism. We showed that SLNT significantly inhibited proliferation of HT-29 colon cancer cells and suppressed tumor growth in nude mice. Annxein V-FITC/PI, DAPI, AO/EB and H&E staining assays all showed that SLNT induced cell apoptosis both in vitro and in vivo. SLNT induced apoptosis by activating Caspase-3 via both intrinsic and extrinsic pathways, which presented as the activation of Caspases-9 and -8, upregulation of cytochrome c and the Bax/Bcl-2 ratio, downregulation of NF-κB, and overproduction of ROS and TNF-α in vitro and in vivo. Pretreatment with the caspase-3 inhibitor Ac-DEVD-CHO or antioxidant NAC blocked SLNT-induced apoptosis. These findings suggest that SLNT exerts direct antitumor effects by inducing cell apoptosis via ROS-mediated intrinsic and TNF-α-mediated extrinsic pathways. SLNT may thus represent a useful candidate for colon cancer prevention and treatment. PMID:27888812

  2. Mechanisms of direct inhibition of the respiratory sulfate-reduction pathway by (per)chlorate and nitrate

    PubMed Central

    Carlson, Hans K; Kuehl, Jennifer V; Hazra, Amrita B; Justice, Nicholas B; Stoeva, Magdalena K; Sczesnak, Andrew; Mullan, Mark R; Iavarone, Anthony T; Engelbrektson, Anna; Price, Morgan N; Deutschbauer, Adam M; Arkin, Adam P; Coates, John D

    2015-01-01

    We investigated perchlorate (ClO4−) and chlorate (ClO3−) (collectively (per)chlorate) in comparison with nitrate as potential inhibitors of sulfide (H2S) production by mesophilic sulfate-reducing microorganisms (SRMs). We demonstrate the specificity and potency of (per)chlorate as direct SRM inhibitors in both pure cultures and undefined sulfidogenic communities. We demonstrate that (per)chlorate and nitrate are antagonistic inhibitors and resistance is cross-inducible implying that these compounds share at least one common mechanism of resistance. Using tagged-transposon pools we identified genes responsible for sensitivity and resistance in Desulfovibrio alaskensis G20. We found that mutants in Dde_2702 (Rex), a repressor of the central sulfate-reduction pathway were resistant to both (per)chlorate and nitrate. In general, Rex derepresses its regulon in response to increasing intracellular NADH:NAD+ ratios. In cells in which respiratory sulfate reduction is inhibited, NADH:NAD+ ratios should increase leading to derepression of the sulfate-reduction pathway. In support of this, in (per)chlorate or nitrate-stressed wild-type G20 we observed higher NADH:NAD+ ratios, increased transcripts and increased peptide counts for genes in the core Rex regulon. We conclude that one mode of (per)chlorate and nitrate toxicity is as direct inhibitors of the central sulfate-reduction pathway. Our results demonstrate that (per)chlorate are more potent inhibitors than nitrate in both pure cultures and communities, implying that they represent an attractive alternative for controlling sulfidogenesis in industrial ecosystems. Of these, perchlorate offers better application logistics because of its inhibitory potency, solubility, relative chemical stability, low affinity for mineral cations and high mobility in environmental systems. PMID:25405978

  3. Direct detection of HSulf-1 and HSulf-2 activities on extracellular heparan sulfate and their inhibition by PI-88

    PubMed Central

    Hossain, Md Motarab; Hosono-Fukao, Tomomi; Tang, Renhong; Sugaya, Noriko; van Kuppevelt, Toin H; Jenniskens, Guido J; Kimata, Koji; Rosen, Steven D; Uchimura, Kenji

    2010-01-01

    Heparan sulfates (HS) bind a diversity of protein ligands on the cell surface and in the extracellular matrix and thus can modulate cell signaling. The state of sulfation in glucosamines and uronic acids within the chains strongly influences their binding. We have previously cloned and characterized two human extracellular endoglucosamine 6-sulfatases, HSulf-1 and HSulf-2, which selectively liberate the 6-O sulfate groups on glucosamines present in N, 6-O, and 2-O trisulfated disaccharides of intact HS and heparins. These enzymes serve important roles in development and are upregulated in a number of cancers. To determine whether the Sulfs act on the trisulfated disaccharides that exist on the cell surface, we expressed HSulfs in cultured cells and performed a flow cytometric analysis with the RB4CD12, an anti-HS antibody that recognizes N- and O-sulfated HS saccharides. The endogenously expressed level of the cell surface RB4CD12 epitope was greatly diminished in CHO, HEK293, and HeLa cells transfected with HSulf-1 or HSulf-2 cDNA. In correspondence with the RB4CD12 finding, the N, 6-O, and 2-O trisulfated disaccharides of the HS isolated from the cell surface/extracellular matrix were dramatically reduced in the Sulf-expressed HEK293 cells. We then developed an ELISA and confirmed that the RB4CD12 epitope in immobilized heparin was degraded by purified recombinant HSulf-1 and HSulf-2, and conditioned medium (CM) of MCF-7 breast carcinoma cells, which contain a native form of HSulf-2. Furthermore, HSulf-1 and HSulf-2 exerted activity against the epitope expressed on microvessels of mouse brains. Both HSulf activities were potently inhibited by PI-88, a sulfated heparin mimetic with anti-cancer activities. These findings provide new strategies for monitoring the extracellular remodeling of HS by Sulfs during normal and pathophysiological processes. PMID:19822709

  4. Mechanisms of direct inhibition of the respiratory sulfate-reduction pathway by (per)chlorate and nitrate.

    PubMed

    Carlson, Hans K; Kuehl, Jennifer V; Hazra, Amrita B; Justice, Nicholas B; Stoeva, Magdalena K; Sczesnak, Andrew; Mullan, Mark R; Iavarone, Anthony T; Engelbrektson, Anna; Price, Morgan N; Deutschbauer, Adam M; Arkin, Adam P; Coates, John D

    2015-06-01

    We investigated perchlorate (ClO(4)(-)) and chlorate (ClO(3)(-)) (collectively (per)chlorate) in comparison with nitrate as potential inhibitors of sulfide (H(2)S) production by mesophilic sulfate-reducing microorganisms (SRMs). We demonstrate the specificity and potency of (per)chlorate as direct SRM inhibitors in both pure cultures and undefined sulfidogenic communities. We demonstrate that (per)chlorate and nitrate are antagonistic inhibitors and resistance is cross-inducible implying that these compounds share at least one common mechanism of resistance. Using tagged-transposon pools we identified genes responsible for sensitivity and resistance in Desulfovibrio alaskensis G20. We found that mutants in Dde_2702 (Rex), a repressor of the central sulfate-reduction pathway were resistant to both (per)chlorate and nitrate. In general, Rex derepresses its regulon in response to increasing intracellular NADH:NAD(+) ratios. In cells in which respiratory sulfate reduction is inhibited, NADH:NAD(+) ratios should increase leading to derepression of the sulfate-reduction pathway. In support of this, in (per)chlorate or nitrate-stressed wild-type G20 we observed higher NADH:NAD(+) ratios, increased transcripts and increased peptide counts for genes in the core Rex regulon. We conclude that one mode of (per)chlorate and nitrate toxicity is as direct inhibitors of the central sulfate-reduction pathway. Our results demonstrate that (per)chlorate are more potent inhibitors than nitrate in both pure cultures and communities, implying that they represent an attractive alternative for controlling sulfidogenesis in industrial ecosystems. Of these, perchlorate offers better application logistics because of its inhibitory potency, solubility, relative chemical stability, low affinity for mineral cations and high mobility in environmental systems.

  5. [Inhibition of the activity of sulfate-reducing bacteria in produced water from oil reservoir by nitrate].

    PubMed

    Yang, De-Yu; Zhang, Ying; Shi, Rong-Jiu; Han, Si-Qin; Li, Guang-Zhe; Li, Guo-Qiao; Zhao, Jin-Yi

    2014-01-01

    Growth and metabolic activity of sulfate-reducing bacteria (SRB) can result in souring of oil reservoirs, leading to various problems in aspects of environmental pollution and corrosion. Nitrate addition and management of nitrate-reducing bacteria (NRB) offer potential solutions to controlling souring in oil reservoirs. In this paper, a facultive chemolithotrophic NRB, designated as DNB-8, was isolated from the produced fluid of a water-flooded oil reservoir at Daqing oilfield. Then the efficacies and mechanisms of various concentrations of nitrate in combination with DNB-8 in the inhibition of the activity of SRB enriched culture were compared. Results showed that 1.0 mmol x L(-1) of nitrate or 0.45 mmol x L(-1) of nitrite inhibited the sulfate-reducing activity of SRB enrichments; the competitive reduction of nitrate by DNB-8 and the nitrite produced were responsible for the suppression. Besides, the SRB enrichment cultures showed a metabolic pathway of dissimilatory nitrate reduction to ammonium (DNRA) via nitrite. The SRB cultures could possibly alleviate the nitrite inhibition by DNRA when they were subjected to high-strength nitrate.

  6. Inhibition of Helicobacter pylori adhesion to Kato III cells by intact and low molecular weight acharan sulfate.

    PubMed

    Sim, Joon-Soo; Hahn, Bum-Soo; Im, A-Rang; Park, Youmie; Shin, Ji-Eun; Bae, Eun-Ah; Kim, Dong-Hyun; Kim, Yeong Shik

    2011-08-01

    We investigated the inhibitory activity of glycosaminoglycans (GAGs) in terms of growth, adhesion, and VacA vacuolation of Helicobacter pylori. Intact acharan sulfate (AS, MW:114 kDa) potently inhibited H. pylori adhesion to Kato III cells with IC(50) value of 1.4 mg/mL, while other GAGs did not show any inhibitory activity except for heparin which is a well-known inhibitor of H. pylori adhesion. To investigate whether low molecular weight acharan sulfate (LMWAS) can inhibit H. pylori adhesion, we performed chemical depolymerization of AS by radical reactions to obtain LMWAS. Its physicochemical properties were characterized by high-performance size exclusion chromatography (HPSEC), agarose gel electrophoresis, disaccharide compositional analysis after digestion with heparinase II, and (1)H-NMR spectroscopy. The most potent molecular size of LMWAS was 3 kDa with IC(50) value of 32 μg/mL, which is 44-fold more potent than intact AS. These results suggest that AS as well as other GAGs can be chemically depolymerized by free radicals and LMWAS compared to intact AS can be applied as a pharmaceutical candidate in order to inhibit H. pylori adhesion to Kato III cells.

  7. Synergistic inhibition of Listeria monocytogenes in vitro through the combination of octanoic acid and acidic calcium sulfate.

    PubMed

    Brandt, Alex L; Castillo, Alejandro; Harris, Kerri B; Keeton, Jimmy T; Hardin, Margaret D; Taylor, T Matthew

    2011-01-01

    It has been hypothesized that inhibition of foodborne pathogens can be enhanced by using antimicrobials in combination. A broth dilution assay was devised to determine whether inhibition of Listeria monocytogenes exposed to the combination of the fatty acid octanoic acid (OCT) and the organic acid-containing antimicrobial acidic calcium sulfate (ACS) was enhanced compared with the inhibition of the pathogen exposed to either antimicrobial applied singly. MICs for OCT and ACS were 25.00 μg/g and 1.56 ml/liter, respectively, for all strains of the pathogen tested. Fractional inhibitory concentrations (FICs) from the combination exposures were calculated for use in characterizing the antimicrobial interaction as antagonistic, additive indifferent, or synergistic with respect to L. monocytogenes inhibition. Combining OCT and ACS resulted in observed synergistic inhibition of L. monocytogenes; isobolograms for all strains curved toward the origin, and FIC indices (FIC(I)s) were <1.0. Future investigations of the antimicrobial combination should focus on determining the mechanism of action of combined antimicrobials and the levels of antimicrobials required for pathogen inhibition on the surfaces of ready-to-eat meats.

  8. Pectic polysaccharide from corn (Zea mays L.) effectively inhibited multi-step mediated cancer cell growth and metastasis.

    PubMed

    Jayaram, Smitha; Kapoor, Sabeeta; Dharmesh, Shylaja M

    2015-06-25

    Corn pectic polysaccharide (COPP) inhibited galectin-3 mediated hemagglutination at Minimum Inhibitory Concentration (MIC) of 4.08 μg/mL as opposed to citrus pectin (25 μg/mL), a well known galectin-3 inhibitor and lactose (4.16 μg/mL)--sugar specific to galectin-3. COPP effectively (72%) inhibited invasion and metastasis in experimental animals. In vivo results were substantiated by modulation of cancer specific markers such as galectin-3, which is a key molecule for initiation of metastatic cascade, vascular endothelial growth factor (VEGF) that enhances angiogenesis, matrix metalloproteinases 2 and 9 that are required for invasion, NF-κB, a transcription factor for proliferative potency of tumor cells and a phosphoglucoisomerase (PGI), the activity of which favors cancer cell growth. Structural characterization studies indicate the active component (relatively less acidic, 0.05 M ammonium carbonate, 160 kDa fraction) which showed antimetastatic potency in vitro with MIC of 0.09 μg/mL, and ∼ 45 fold increase in the activity when compared to that of COPP. Gas liquid chromatographic analysis indicated the presence of rhamnose (1%), arabinose (20%), xylose (3%), mannose (4%), galactose (54%) and uronic acid (10%) in different proportions. However, correlative data attributed galectin-3 inhibitory activity to enhanced levels of arabinose and galactose. FTIR, HPLC and NMR spectroscopic analysis further highlights that COPP is an arabinogalactan with methyl/ethyl esters. It is therefore suggested that the blockade of galectin-3 mediated lung metastasis appears to be a result of an inhibition of mixed functions induced during metastasis. The data signifies the importance of dietary carbohydrate as cancer-preventive agent. Although pectin digestibility and absorption are issues of concern, promising in vivo data provides evidence for the cancer preventive property of corn. The present study reveals for the first time a new component of corn, i.e.,--corn pectin

  9. Hexavalent chromium reduction in Desulfovibrio vulgaris Hildenborough causes transitory inhibition of sulfate reduction and cell growth.

    PubMed

    Klonowska, A; Clark, M E; Thieman, S B; Giles, B J; Wall, J D; Fields, M W

    2008-04-01

    Desulfovibrio vulgaris Hildenborough is a well-studied sulfate reducer that can reduce heavy metals and radionuclides [e.g., Cr(VI) and U(VI)]. Cultures grown in a defined medium had a lag period of approximately 30 h when exposed to 0.05 mM Cr(VI). Substrate analyses revealed that although Cr(VI) was reduced within the first 5 h, growth was not observed for an additional 20 h. The growth lag could be explained by a decline in cell viability; however, during this time small amounts of lactate were still utilized without sulfate reduction or acetate formation. Approximately 40 h after Cr exposure (0.05 mM), sulfate reduction occurred concurrently with the accumulation of acetate. Similar amounts of hydrogen were produced by Cr-exposed cells compared to control cells, and lactate was not converted to glycogen during non-growth conditions. D. vulgaris cells treated with a reducing agent and then exposed to Cr(VI) still experienced a growth lag, but the addition of ascorbate at the time of Cr(VI) addition prevented the lag period. In addition, cells grown on pyruvate displayed more tolerance to Cr(VI) compared to lactate-grown cells. These results indicated that D. vulgaris utilized lactate during Cr(VI) exposure without the reduction of sulfate or production of acetate, and that ascorbate and pyruvate could protect D. vulgaris cells from Cr(VI)/Cr(III) toxicity.

  10. INHIBITION OF REDUCTIVE DECHLORINATION BY SULFATE REDUCTION IN MICROCOSMS (ABSTRACT ONLY)

    EPA Science Inventory

    High sulfate (>1,000 mg/L) concentrations are potentially problematic for field implementation of in situ bioremediation of chlorinated ethenes because its reduction competes for electron donor with reductive dechlorination. As a result of this competition, reductive dechl...

  11. Simulation of the inhibition of microbial sulfate reduction in a two-compartment upflow bioreactor subjected to molybdate injection.

    PubMed

    de Jesus, E B; de Andrade Lima, L R P

    2016-08-01

    Souring of oil fields during secondary oil recovery by water injection occurs mainly due to the action of sulfate-reducing bacteria (SRB) adhered to the rock surface in the vicinity of injection wells. Upflow packed-bed bioreactors have been used in petroleum microbiology because of its similarity to the oil field near the injection wells or production. However, these reactors do not realistically describe the regions near the injection wells, which are characterized by the presence of a saturated zone and a void region close to the well. In this study, the hydrodynamics of the two-compartment packing-free/packed-bed pilot bioreactor that mimics an oil reservoir was studied. The packed-free compartment was modeled using a continuous stirred tank model with mass exchange between active and stagnant zones, whereas the packed-bed compartment was modeled using a piston-dispersion-exchange model. The proposed model adequately represents the hydrodynamic of the packed-free/packed-bed bioreactor while the simulations provide important information about the characteristics of the residence time distribution (RTD) curves for different sets of model parameters. Simulations were performed to represent the control of the sulfate-reducing bacteria activity in the bioreactor with the use of molybdate in different scenarios. The simulations show that increased amounts of molybdate cause an effective inhibition of the souring sulfate-reducing bacteria activity.

  12. Polysaccharide-Modified Synthetic Polymeric Biomaterials

    PubMed Central

    Baldwin, Aaron D.; Kiick, Kristi L.

    2010-01-01

    This review presents an overview of polysaccharide-conjugated synthetic polymers and their use in tissue-engineered scaffolds and drug-delivery applications. This topic will be divided into four categories: (1) polymeric materials modified with non-mammalian polysaccharides such as alginate, chitin, and dextran; (2) polymers modified with mammalian polysaccharides such as hyaluronan, chondroitin sulfate, and heparin; (3) multi-polysaccharide-derivatized polymer conjugate systems; and (4) polymers containing polysaccharide-mimetic molecules. Each section will discuss relevant conjugation techniques, analysis, and the impact of these materials as micelles, particles, or hydrogels used in in-vitro and in-vivo biomaterial applications. PMID:20091875

  13. Inhibiting mild steel corrosion from sulfate-reducing and iron-oxidizing bacteria using gramicidin-S-producing biofilms.

    PubMed

    Zuo, Rongjun; Wood, Thomas K

    2004-11-01

    A gramicidin-S-producing Bacillus brevis 18-3 biofilm was shown to reduce corrosion rates of mild steel by inhibiting both the sulfate-reducing bacterium Desulfosporosinus orientis and the iron-oxidizing bacterium Leptothrix discophora SP-6. When L. discophora SP-6 was introduced along with D. orientis to a non-antimicrobial-producing biofilm control, Paenibacillus polymyxa ATCC 10401, a corrosive synergy was created and mild steel coupons underwent more severe corrosion than when only D. orientis was present, showing a 2.3-fold increase via electrochemical impedance spectroscopy (EIS) and a 1.8-fold difference via mass-loss measurements. However, when a gramicidin-S-producing, protective B. brevis 18-3 biofilm was established on mild steel, the metal coupons were protected against the simultaneous attack of D. orientis and L. discophora SP-6. EIS data showed that the protective B. brevis 18-3 biofilm decreased the corrosion rate about 20-fold compared with the non-gramicidin-producing P. polymyxa ATCC 10401 biofilm control. The mass loss for the protected mild steel coupons was also significantly lower than that for the unprotected ones (4-fold decrease). Scanning electron microscope images corroborated the corrosion inhibition by the gramicidin-S-producing B. brevis biofilm on mild steel by showing that the metal surface remained untarnished, i.e., the polishing grooves were still visible after exposure to the simultaneous attack of the sulfate-reducing bacterium and the iron-oxidizing bacterium.

  14. Sulfated gastrin stimulates ghrelin and growth hormone release but inhibits insulin secretion in cattle.

    PubMed

    Zhao, Hongqiong; Yannaing, Swe; Thanthan, Sint; Kuwayama, Hideto

    2011-11-01

    This study was designed to determine the effects of gastrin on the circulating levels of ghrelin, growth hormone (GH), insulin, glucagon and glucose in ruminants. Two experiments were done in eight Holstein steers. Animals were randomly assigned to receive intravenous bolus injections: (1) 0.1% bovine serum albumin in saline as vehicle, 0.8, 4.0 and 20.0 μg/kg body weight (BW) of bovine sulfated gastrin-34; (2) vehicle, 0.53 μg/kg BW of bovine sulfated gastrin-17 alone or combined with 20.0 μg/kg BW of [D-Lys(3)]-GHRP-6, the selective antagonist of GHS-R1a. Blood samples were collected from -10 to 150 min relative to injection time. Concentrations of acyl and total ghrelin in response to gastrin-34 injection were significantly increased in a dose-dependent manner. Concentrations of GH were also markedly elevated by gastrin-34 injection; however, the effect of 20.0 μg/kg was weaker than that of 4.0 μg/kg. The three doses of gastrin-34 equally decreased insulin levels within 15 min and maintained the level until the time of last sampling. Gastrin-34 had no effect (P > 0.05) on the levels of glucagon and glucose. Levels of acyl ghrelin increased after administration of gastrin-17 alone or combined with [D-Lys(3)]-GHRP-6; however, [D-Lys(3)]-GHRP-6 did not block the elevation of GH by gastrin-17. The present results indicate that sulfated gastrin stimulates both ghrelin and GH release, but the GHS-R1a may not contribute to the release of GH by gastrin. Moreover, sulfated gastrin seems to indirectly maintain the homeostasis of blood glucose through the down-regulation of insulin in ruminants.

  15. [NO3-/NO2- inhibits sulfate-reducing activity of the enrichment culture of sulfate-reducing prokaryotes from an off-shore oil reservoir at Bohai Bay, China].

    PubMed

    Liu, Hong-Yu; Shi, Rong-Jiu; Zhang, Ying; Shi, Zhen-Guo; Zhang, Ying-Yue; Yu, Liang; Zhang, Xiao-Bo; Tan, Tao

    2014-08-01

    Long-term injection of sulfate-rich water into oil reservoirs stimulates the proliferation of sulfate-reducing prokaryotes (SRP) therein and results in production of a great amount of H2S, leading to souring in oil reservoirs and related environmental problems. In this study, we first, using modified API RP 38 medium, enriched SRP present in production water from a producing well at Bohai Bay, China, and then examined the inhibitory effects of nitrate or nitrite on sulfate reduction activity of the SRP. Results showed that the enriched SRP culture exhibited a high sulfate reduction activity as indicated by a sulfate-reducing rate of 10.4 mmol SO4(2-) x d(-1) x g(-1) dry cell. In presence of 0.4, 0.8, 1.8, and 4.2 mmol x L(-1) nitrate, sulfate reduction was inhibited for 5, 9, 20, and over 35 days, respectively. With the addition of 0.6, 0.9, 1.4, 2.6 and 4.6 mmol x L(-1) of nitrite, the inhibitory period lasted 3, 12, 22, and over 39 days, respectively. The SRP enrichment culture could dissimilatorily reduce nitrate to ammonium. When sulfate, nitrate and nitrite coexisted, nitrate or nitrite was preferentially used over sulfate as electron acceptor by the enriched SRP. This competitive use of electron acceptor and the strong inhibitory effect of nitrite possibly accounted for the suppression of nitrate and nitrite on the sulfate-reducing activity of the enriched SRP cultures from offshore oil reservoir at Bohai Bay.

  16. Marine sulfated glycans with serpin-unrelated anticoagulant properties.

    PubMed

    Glauser, Bianca F; Mourão, Paulo A S; Pomin, Vitor H

    2013-01-01

    Marine organisms are a rich source of sulfated polysaccharides with unique structures. Fucosylated chondroitin sulfate (FucCS) from the sea cucumber Ludwigothurea grisea and sulfated galactan from the red alga Botryocladia occidentalis are one of these unusual molecules. Besides their uncommon structures, they also exhibit high anticoagulant and antithrombotic effects. Earlier, it was considered that the anticoagulant activities of these two marine glycans were driven mainly by a catalytic serpin-dependent mechanism likewise the mammalian heparins. Its serpin-dependent anticoagulant action relies on promoting thrombin and/or factor Xa inhibition by their specific natural inhibitors (the serpins antithrombin and heparin cofactor II). However, as opposed to heparins, these two previously mentioned marine glycans were proved still capable in promoting coagulation inhibition using serpin-free plasmas. This puzzle observation was further investigated and clearly demonstrated that the cucumber FucCS and the red algal sulfated galactan have an unusual serpin-independent anticoagulant effect by inhibiting the formation of factor Xa and/or thrombin through the procoagulants tenase and prothrombinase complexes, respectively. These marine polysaccharides with unusual anticoagulant effects open clearly new perspectives for the development of new antithrombotic drugs as well as push the glycomics project.

  17. Hexavalent chromium reduction in Desulfovibrio vulgarisHildenborough causes transitory inhibition of sulfate reduction and cellgrowth

    SciTech Connect

    Klonowska, A.; Clark, M.E.; Thieman, S.B.; Giles, B.J.; Wall,J.D.; Fields, M.W.

    2008-01-07

    Desulfovibrio vulgaris Hildenborough is a well-studiedsulfate reducer that can reduce heavy metals and radionuclides [e.g.,Cr(VI) and U(VI)]. Cultures grown in a defined medium had a lag period ofapproximately 30 h when exposed to 0.05 mM Cr(VI). Substrate analysesrevealed that although Cr(VI) was reduced within the first 5 h, growthwas not observed for an additional 20 h. The growth lag could beexplained by a decline in cell viability; however, during this time smallamounts of lactate were still utilized without sulfate reduction oracetate formation. Approximately 40 h after Cr exposure (0.05 mM),sulfate reduction occurred concurrently with the accumulation of acetate.Similar amounts of hydrogen were produced by Cr-exposed cells compared tocontrol cells, and lactate was not converted to glycogen duringnon-growth conditions. D. vulgaris cells treated with a reducing agentand then exposed to Cr(VI) still experienced a growth lag, but theaddition of ascorbate at the time of Cr(VI) addition prevented the lagperiod. In addition, cells grown on pyruvate displayed more tolerance toCr(VI) compared to lactate-grown cells. These results indicated that D.vulgaris utilized lactate during Cr(VI) exposure without the reduction ofsulfate or production of acetate, and that ascorbate and pyruvate couldprotect D. vulgaris cells from Cr(VI)/Cr(III) toxicity.

  18. Inhibition of microbial sulfate reduction in a flow-through column system by (per)chlorate treatment.

    PubMed

    Engelbrektson, Anna; Hubbard, Christopher G; Tom, Lauren M; Boussina, Aaron; Jin, Yong T; Wong, Hayden; Piceno, Yvette M; Carlson, Hans K; Conrad, Mark E; Anderson, Gary; Coates, John D

    2014-01-01

    Microbial sulfate reduction is a primary cause of oil reservoir souring. Here we show that amendment with chlorate or perchlorate [collectively (per)chlorate] potentially resolves this issue. Triplicate packed columns inoculated with marine sediment were flushed with coastal water amended with yeast extract and one of nitrate, chlorate, or perchlorate. Results showed that although sulfide production was dramatically reduced by all treatments, effluent sulfide was observed in the nitrate (10 mM) treatment after an initial inhibition period. In contrast, no effluent sulfide was observed with (per)chlorate (10 mM). Microbial community analyses indicated temporal community shifts and phylogenetic clustering by treatment. Nitrate addition stimulated Xanthomonadaceae and Rhizobiaceae growth, supporting their role in nitrate metabolism. (Per)chlorate showed distinct effects on microbial community structure compared with nitrate and resulted in a general suppression of the community relative to the untreated control combined with a significant decrease in sulfate reducing species abundance indicating specific toxicity. Furthermore, chlorate stimulated Pseudomonadaceae and Pseudoalteromonadaceae, members of which are known chlorate respirers, suggesting that chlorate may also control sulfidogenesis by biocompetitive exclusion of sulfate-reduction. Perchlorate addition stimulated Desulfobulbaceae and Desulfomonadaceae, which contain sulfide oxidizing and elemental sulfur-reducing species respectively, suggesting that effluent sulfide concentrations may be controlled through sulfur redox cycling in addition to toxicity and biocompetitive exclusion. Sulfur isotope analyses further support sulfur cycling in the columns, even when sulfide is not detected. This study indicates that (per)chlorate show great promise as inhibitors of sulfidogenesis in natural communities and provides insight into which organisms and respiratory processes are involved.

  19. Inhibition of microbial sulfate reduction in a flow-through column system by (per)chlorate treatment

    PubMed Central

    Engelbrektson, Anna; Hubbard, Christopher G.; Tom, Lauren M.; Boussina, Aaron; Jin, Yong T.; Wong, Hayden; Piceno, Yvette M.; Carlson, Hans K.; Conrad, Mark E.; Anderson, Gary; Coates, John D.

    2014-01-01

    Microbial sulfate reduction is a primary cause of oil reservoir souring. Here we show that amendment with chlorate or perchlorate [collectively (per)chlorate] potentially resolves this issue. Triplicate packed columns inoculated with marine sediment were flushed with coastal water amended with yeast extract and one of nitrate, chlorate, or perchlorate. Results showed that although sulfide production was dramatically reduced by all treatments, effluent sulfide was observed in the nitrate (10 mM) treatment after an initial inhibition period. In contrast, no effluent sulfide was observed with (per)chlorate (10 mM). Microbial community analyses indicated temporal community shifts and phylogenetic clustering by treatment. Nitrate addition stimulated Xanthomonadaceae and Rhizobiaceae growth, supporting their role in nitrate metabolism. (Per)chlorate showed distinct effects on microbial community structure compared with nitrate and resulted in a general suppression of the community relative to the untreated control combined with a significant decrease in sulfate reducing species abundance indicating specific toxicity. Furthermore, chlorate stimulated Pseudomonadaceae and Pseudoalteromonadaceae, members of which are known chlorate respirers, suggesting that chlorate may also control sulfidogenesis by biocompetitive exclusion of sulfate-reduction. Perchlorate addition stimulated Desulfobulbaceae and Desulfomonadaceae, which contain sulfide oxidizing and elemental sulfur-reducing species respectively, suggesting that effluent sulfide concentrations may be controlled through sulfur redox cycling in addition to toxicity and biocompetitive exclusion. Sulfur isotope analyses further support sulfur cycling in the columns, even when sulfide is not detected. This study indicates that (per)chlorate show great promise as inhibitors of sulfidogenesis in natural communities and provides insight into which organisms and respiratory processes are involved. PMID:25071731

  20. LL202 protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting MAPK/AP-1 signaling

    PubMed Central

    Zhao, Yue; Hu, Yang; Li, Zhiyu; Guo, Qinglong; Zhao, Kai; Lu, Na

    2016-01-01

    LL202, a newly-synthesized flavonoid derivative, has been reported to inhibit inflammatory-induced angiogenesis. However, the exact role of LL202 in inflammation along with its mechanism has not been explored. In this study, we investigated the anti-inflammatory effect of LL202 on intestinal inflammation by establishing dextran sulfate sodium (DSS)-induced experimental colitis. LL202 attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. The inflammatory cells infiltration, myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities were decreased by LL202 in a dose-dependent manner. LL202 reduced the production of pro-inflammatory cytokines in serum and colon of DSS-induced mice as well. Mechanically, LL202 could decrease the expression and nuclear translation of AP-1 to protect against DSS-induced colitis. In lipopolysaccharide (LPS)-induced THP-1 cells, LL202 markedly decreased the secretion, mRNA level and protein expression of IL-1β, IL-6 and TNF-α via inhibiting ERK/JNK/p38 MAPK pathways and the nuclear translocation of AP-1. Furthermore, these findings were confirmed in LPS-induced bone marrow derived macrophages (BMDM). In conclusion, our study demonstrated that LL202 could exert its anti-inflammatory effect via inhibiting MAPK/AP-1 signaling, which suggested that LL202 might be a potential effective drug for the treatment of inflammatory bowel diseases. PMID:27590510

  1. Inhibitory effect of sulfated galactans from the marine alga Bostrychia montagnei on herpes simplex virus replication in vitro.

    PubMed

    Duarte, M E; Noseda, D G; Noseda, M D; Tulio, S; Pujol, C A; Damonte, E B

    2001-01-01

    Sulfated polysaccharides exhibit many biological properties such as antiviral and anticoagulant activities. Herein, we report the antiviral activity of sulfated galactans extracted from the red sea-weed Bostrychia montagnei against herpes simplex virus types 1 (strain F and the thymidine kinase-deficient strains Field and B2006) and 2 (strain G). Two crude extracts obtained with cold and hot water as well as some fractions obtained by anion exchange chromatography, inhibited significantly the replication of the different strains of herpesviruses as determined by plaque reduction assays. The inhibitory effect of the compounds studied here took place only when they were added during the adsorption period. They were found to be highly selective antiviral substances, causing no impairment of Vero cell viability. Furthermore, they had no direct inactivating effect on virions by incubation in a virucidal assay. The antiviral activity could be correlated with the molecular weight and sulfate content of the polysaccharides. Although sulfated polysaccharides are generally endowed with anticoagulant properties, the results of the activated partial thromboplastin time and the thrombine time assays indicated that the natural sulfated polysaccharides from Bostrychia montagnei have very low anticoagulant activity, confirming that there is no relation between the antiviral and anticoagulant properties.

  2. Characterization of uniformly and atom-specifically 13C-labeled heparin and heparan sulfate polysaccharide precursors using 13C NMR spectroscopy and ESI mass spectrometry

    PubMed Central

    Nguyen, Thao K. N.; Tran, Vy M.; Victor, Xylophone V.; Skalicky, Jack J.; Kuberan, Balagurunathan

    2010-01-01

    The biological actions of heparin and heparan sulfate, two structurally related glycosaminoglycans, depend on the organization of the complex heparanome. Due to the structural complexity of the heparanome, the sequence of variably sulfonated uronic acid and glucosamine residues is usually characterized by the analysis of smaller oligosaccharide and disaccharide fragments. Even characterization of smaller heparin/heparan sulfate oligosaccharide or disaccharide fragments using simple 1D 1H NMR spectroscopy is often complicated by the extensive signal overlap. 13C NMR signals, on the other hand, overlap less and therefore, 13C NMR spectroscopy can greatly facilitate the structural elucidation of the complex heparanome and provide finer insights into the structural basis for biological functions. This is the first report of the preparation of anomeric carbon-specific 13C-labeled heparin/heparan sulfate precursors from the Escherichia coli K5 strain. Uniformly 13C- and 15N-labeled precursors were also produced and characterized by 13C NMR spectroscopy. Mass spectrometric analysis of enzymatically fragmented disaccharides revealed that anomeric carbon-specific labeling efforts resulted in a minor loss/scrambling of 13C in the precursor backbone, whereas uniform labeling efforts resulted in greater than 95% 13C isotope enrichment in the precursor backbone. These labeled precursors provided high-resolution NMR signals with great sensitivity and set the stage for studying the heparanome–proteome interactions. PMID:20832774

  3. Polysaccharide from Sepia esculenta ink and cisplatin inhibit synergistically proliferation and metastasis of triple-negative breast cancer MDA-MB-231 cells

    PubMed Central

    Liu, Hua-Zhong; Xiao, Wei; Gu, Yi-Peng; Tao, Ye-Xing; Zhang, Da-Yan; Du, Hui; Shang, Jiang-Hua

    2016-01-01

    Objective(s): This paper aims to investigate synergistic inhibition of polysaccharide from Sepia esculenta ink (SIP), a newly isolated marine polysaccharide in our laboratory, on breast cancer MDA-MB-231 cells exposed to cisplatin. Materials and Methods: Cell viability of MDA-MB-231 cells was determined by CCK 8 assay. Median-effect concentration was analyzed using Chou-Talalay method that was also subjected to determine cell inhibition ratio and combined index, as well as interaction between SIP and cisplatin. Proliferation and migration abilities were detected with plate colony formation assay and cell wound scratch assay, respectively. Expression of MMP-2 and MMP-9 proteins was measured with Western blot assay. Results: Data showed that SIP not only suppressed proliferation and migration of MDA-MB-231 cells, and expression of MMP-2 and MMP-9 proteins, also promoted inhibition of cisplatin on proliferation, migration and MMPs expression of MDA-MB-231 cells, which indicates synergy inhibition of drug combination of SIP and cisplatin on breast cancer cells. The median-effect concentrations of cisplatin and SIP were 4.9 and 1659.6 μg/ml, respectively. Whereas the concentration of combination drug was 158.5 μg/ml. The data indicated that drug combination can decrease dosages of the two single agents, especially the usual dosage of cisplatin. Conclusion: This research demonstrated that SIP repressed proliferation and metastasis of MDA-MB-231 cells and promoted anticancer effect of cisplatin on the breast cancer cells. The data suggested that SIP is a potential natural drug that can be used as an auxiliary medicine alongside chemotherapy in treating breast cancer. PMID:28096961

  4. A Heparan Sulfate-Binding Cell Penetrating Peptide for Tumor Targeting and Migration Inhibition

    PubMed Central

    Kuo, Ping-Hsueh; Chang, Pei-Lin; Wang, Wen-Ching; Chuang, Yung-Jen; Chang, Margaret Dah-Tsyr

    2015-01-01

    As heparan sulfate proteoglycans (HSPGs) are known as co-receptors to interact with numerous growth factors and then modulate downstream biological activities, overexpression of HS/HSPG on cell surface acts as an increasingly reliable prognostic factor in tumor progression. Cell penetrating peptides (CPPs) are short-chain peptides developed as functionalized vectors for delivery approaches of impermeable agents. On cell surface negatively charged HS provides the initial attachment of basic CPPs by electrostatic interaction, leading to multiple cellular effects. Here a functional peptide (CPPecp) has been identified from critical HS binding region in hRNase3, a unique RNase family member with in vitro antitumor activity. In this study we analyze a set of HS-binding CPPs derived from natural proteins including CPPecp. In addition to cellular binding and internalization, CPPecp demonstrated multiple functions including strong binding activity to tumor cell surface with higher HS expression, significant inhibitory effects on cancer cell migration, and suppression of angiogenesis in vitro and in vivo. Moreover, different from conventional highly basic CPPs, CPPecp facilitated magnetic nanoparticle to selectively target tumor site in vivo. Therefore, CPPecp could engage its capacity to be developed as biomaterials for diagnostic imaging agent, therapeutic supplement, or functionalized vector for drug delivery. PMID:26064887

  5. Synergistic effects between sodium tripolyphosphate and zinc sulfate in corrosion inhibition for copper in neutral tap water

    SciTech Connect

    Feng, Y.; Siow, K.S.; Teo, W.K.; Tan, K.L.; Hsieh, A.K.

    1997-07-01

    The corrosion inhibition behavior of sodium tripolyphosphate (Na{sub 5}P{sub 3}O{sub 10}, or TPP) and zinc sulfate and the synergistic effects between them were studied for copper in neutral simulated tap water using electrochemical methods, x-ray photoelectron spectroscopy, and scanning electron microscopy. Zn{sup 2+} alone showed few inhibiting effects on copper corrosion. The film formed in the presence of Zn{sup 2+} was porous and composed mainly of cuprous oxide, which was similar in morphology and composition to films formed in the absence of the inhibitor. In the presence of TPP, a smooth and compact film, believed to be of Cu(II)-TPP compounds, formed on the copper surface. More protective films were formed in solutions containing TPP and Zn{sup 2+} as a blend. High zinc content (15% to 19%) was detected by XPS. Synergistic effects of TPP and Zn{sup 2+} were believed to result from formation of Zn(II)-TPP compounds that incorporated in the films, with Cu(II)-TPP in the upper layer and Cu{sub 2}O in the inner layer. The zinc compounds increased the anodic diffusion resistance of copper ions in the films and enhanced polarization of the cathodic reduction of dissolved oxygen.

  6. Ferrous iron oxidation by Thiobacillus ferrooxidans: inhibition with benzoic acid, sorbic acid and sodium lauryl sulfate

    SciTech Connect

    Onysko, S.J.

    1984-07-01

    Acid mine drainage is formed by the weathering or oxidation of pyritic material exposed during coal mining. The rate of pyritic material oxidation can be greatly accelerated by certain acidophilic bacteria such as Thiobacillus ferrooxidans which catalyse the oxidation of ferrous to ferric iron. A number of organic compounds, under laboratory conditions, can apparently inhibit both the oxidation of ferrous to ferric iron by T. ferrooxidans and the weathering of pyritic material by mixed cultures of acid mine drainage micro-organisms. Sodium lauryl sulphate (SLS), an anionic surfactant has proved effective in this respect. Benzoic acid, sorbic acid and SLS at low concentrations, each effectively inhibited bacterial oxidation of ferrous iron in batch cultures of T. ferrooxidans. The rate of chemical oxidation of ferrous iron in low pH, sterile, batch reactors was not substantially affected at the tested concentrations of any of the compounds.

  7. Regulation of inorganic sulfate activation in filamentous fungi. Allosteric inhibition of ATP sulfurylase by 3'-phosphoadenosine-5'-phosphosulfate.

    PubMed

    Renosto, F; Martin, R L; Wailes, L M; Daley, L A; Segel, I H

    1990-06-25

    ATP sulfurylases from Penicillium chrysogenum, Penicillium duponti, Aspergillus nidulans, and Neurospora crassa are strongly inhibited by 3'-phosphoadenosine-5'-phosphosulfate (PAPS), the product of the second (adenosine-5'-phosphosulfate kinase-catalyzed) reaction in the two-step activation of inorganic sulfate. The v versus [PAPS] plots are sigmoidal. At physiological concentrations of MgATP (0.17-3 mM) and SO4(2-) (0.4-10 mM), the [I]0.5 for PAPS inhibition of the P. chrysogenum enzyme is 35-200 microM; [I]0.9 is 68-310 microM. In the presence of PAPS, the [S]0.5 values for both substrates are increased and the v versus [MgATP] and v versus [SO4(2-)] or [MoO4(2-)] plots are sigmoidal. Fluorosulfonate (FSO3-) and thiosulfate (S2O3(2-] (non-reactive sulfate analogs) inhibit the enzyme at subsaturating substrate concentrations in the absence of PAPS, but low concentrations of the analogs activate the enzyme when PAPS is present. Thus, PAPS behaves as an allosteric inhibitor of ATP sulfurylase. In contrast, adenosine-5'-phosphosulfate (APS = product Q), the immediate product of the SO4(2-)-dependent reaction, is a linear inhibitor of the P. chrysogenum enzyme, competitive with both MgATP and MoO4(2-) (Kiq = 36-73 nM). FSO3- or S2O3(2-) does not activate the enzyme in the presence of APS. The effect of PAPS on fungal ATP sulfurylase is very similar to that observed when a single highly reactive cysteinyl SH group/subunit (SH-1) is covalently modified (Renosto, F., Martin, R. L., and Segel, I. H. (1987) J. Biol. Chem. 262, 16279-16288). The results suggest that in vitro SH-1 modification induces a conformational change in the enzyme that mimics the change induced in vivo by the reversible binding of PAPS. No evidence was obtained to suggest that PAPS covalently modifies SH-1. ATP sulfurylases from rat liver (Yu, M., Martin, R. L., Jain, S., Chen, L. T., and Segel, I. H. (1989) Arch. Biochem. Biophys. 269, 156-174), spinach leaf, cabbage leaf, and Saccharomyces

  8. Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway.

    PubMed

    Gong, Juanjuan; Sun, Fumou; Li, Yihang; Zhou, Xiaoling; Duan, Zhenzhen; Duan, Fugang; Zhao, Lei; Chen, Hansen; Qi, Suhua; Shen, Jiangang

    2015-04-01

    Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury.

  9. Comparison of sodium acid sulfate to citric acid to inhibit browning of fresh-cut potatoes.

    PubMed

    Calder, Beth L; Kash, Emily A; Davis-Dentici, Katherine; Bushway, Alfred A

    2011-04-01

    Sodium acid sulfate (SAS) dip treatments were evaluated against a distilled water control and citric acid (CA) to compare its effectiveness in reducing enzymatic browning of raw, French-fry cut potatoes. Two separate studies were conducted with dip concentrations ranging from 0%, 1%, and 3% in experiment 1 to 0%, 2%, and 2.5% in experiment 2 to determine optimal dip concentrations. Russet Burbank potatoes were peeled, sliced, and dipped for 1 min and stored at 3 °C. Color, texture, fry surface pH, and microbiological analyses were conducted on days 0, 7, and 14. The 3% SAS- and CA-treated samples had significantly (p<0.0001) lower pH levels on fry surfaces than all other treatments. Both acidulants had significantly (p≤0.05) lower aerobic plate counts compared to controls in both studies by day 7. However, SAS appeared to be the most effective at the 3% level in maintaining a light fry color up to day 14 and had the highest L-values than all other treatments. The 3% SAS-treated fry slices appeared to have the least change in textural properties over storage time, having a significantly (p=0.0002) higher force value (kg force [kgf]) than the other treatments during experiment 1, without any signs of case-hardening that appeared in the control and CA-treated samples. SAS was just as comparable to CA in reducing surface fry pH and also lowering microbial counts over storage time. According to the results, SAS may be another viable acidulant to be utilized in the fresh-cut fruit and vegetable industry.

  10. Inhibition of Human Respiratory Syncytial Virus Infectivity by a Dendrimeric Heparan Sulfate-Binding Peptide

    PubMed Central

    Donalisio, Manuela; Rusnati, Marco; Cagno, Valeria; Civra, Andrea; Bugatti, Antonella; Giuliani, Andrea; Pirri, Giovanna; Volante, Marco; Papotti, Mauro; Landolfo, Santo

    2012-01-01

    Respiratory syncytial virus (RSV) interacts with cell surface heparan sulfate proteoglycans (HSPGs) to initiate infection. The interaction of RSV with HSPGs thus presents an attractive target for the development of novel inhibitors of RSV infection. In the present study, a minilibrary of linear, dimeric, and dendrimeric peptides containing clusters of basic amino acids was screened with the aim of identifying peptides able to bind HSPGs and thus block RSV attachment and infectivity. Of the compounds identified, the dendrimer SB105-A10 was the most potent inhibitor of RSV infectivity, with 50% inhibitory concentrations (IC50s) of 0.35 μM and 0.25 μM measured in Hep-2 and A549 cells, respectively. SB105-A10 was found to bind to both cell types via HSPGs, suggesting that its antiviral activity is indeed exerted by competing with RSV for binding to cell surface HSPGs. SB105-A10 prevented RSV infection when added before the viral inoculum, in line with its proposed HSPG-binding mechanism of action; moreover, antiviral activity was also exhibited when SB105-A10 was added postinfection, as it was able to reduce the cell-to-cell spread of the virus. The antiviral potential of SB105-A10 was further assessed using human-derived tracheal/bronchial epithelial cells cultured to form a pseudostratified, highly differentiated model of the epithelial tissue of the human respiratory tract. SB105-A10 strongly reduced RSV infectivity in this model and exhibited no signs of cytotoxicity or proinflammatory effects. Together, these features render SB105-A10 an attractive candidate for further development as a RSV inhibitor to be administered by aerosol delivery. PMID:22850525

  11. Protein-Bound Polysaccharide from Corbicula fluminea Inhibits Cell Growth in MCF-7 and MDA-MB-231 Human Breast Cancer Cells

    PubMed Central

    Liao, Ningbo; Zhong, Jianjun; Zhang, Ronghua; Ye, Xingqian; Zhang, Yanjun; Wang, Wenjun; Wang, Yuexia; Chen, Shiguo; Liu, Donghong; Liu, Ruihai

    2016-01-01

    A novel protein-bound polysaccharide, CFPS-1, isolated from Corbicula fluminea, is composed predominantly of mannose (Man) and glucose (Glc) in a molar ratio of 3.1:12.7. The polysaccharide, with an average molecular weight of about 283 kDa, also contains 10.8% protein. Atomic force microscopy, high-performance liquid chromatography, Fourier transform infrared spectroscopy, gas chromatography/mass spectrometry, and nuclear magnetic resonance spectroscopy analyses revealed that CFPS-1 has a backbone of 1,6-linked and 1,4,6-linked-α-D-Glc, which is terminated with a 1-linked-α-D-Man residue at the O-4 position of 1,4,6-linked-α-D-Glc, in a molar ratio of 3:1:1. Preliminary in vitro bioactivity tests revealed that CFPS-1 effectively and dose-dependently inhibits human breast cancer MCF-7 and MDA-MB-231 cell growth, with an IC50 of 243 ± 6.79 and 1142 ± 14.84 μg/mL, respectively. In MCF-7, CFPS-1 produced a significant up-regulation of p53, p21, Bax and cleaved caspase-7 and down-regulation of Cdk4, cyclin D1, Bcl-2 and caspase-7. These effects resulted in cell cycle blockade at the S-phase and apoptosis induction. In contrast, in MDA-MB-231, with limited degree of change in cell cycle distribution, CFPS-1 increases the proportion of cells in apoptotic sub-G1 phase executed by down-regulation of Bcl-2 and caspase-7 and up-regulation of Bax and cleaved caspase-7. This study extends our understanding of the anticancer mechanism of C. fluminea protein-bound polysaccharide. PMID:27959954

  12. Glucosamine sulfate

    MedlinePlus

    ... Glucosamine Sulphate KCl, Glucosamine-6-Phosphate, GS, Mono-Sulfated Saccharide, Poly-(1->3)-N-Acetyl-2-Amino- ... Sulfate de Glucosamine, Sulfate de Glucosamine 2KCl, SG, Sulfated Monosaccharide, Sulfated Saccharide, Sulfato de Glucosamina. Glucosamine Hydrochloride ...

  13. Soluble Epoxide Hydrolase Deficiency Inhibits Dextran Sulfate Sodium-induced Colitis and Carcinogenesis in Mice

    PubMed Central

    DONG, HUA; LIAO, JIE; HAMMOCK, BRUCE D.; YANG, GUANG-YU

    2014-01-01

    Soluble epoxide hydrolase (sEH) hydrolyses/inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs) to their corresponding diols, and targeting sEH leads to strong anti-inflammatory effects. In the present study, using a tissue microarray and immunohistochemical approach, a significant increase of sEH expression was identified in ulcerative colitis (UC)-associated dysplasia and adenocarcinoma. The effects of deficiency in the sEH gene were determined on dextran sulfate sodium (DSS) colitis-induced carcinogenesis. The effects of EETs on lipopolysaccharide (LPS)-activated macrophages were analyzed in vitro. With extensive histopathological and immunohistochemical analyses, compared to wild-type mice, sEH−/− mice exhibited a significant decrease in tumor incidence (13/20 vs. 6/19, p<0.05) and a markedly reduced average tumor size (59.62±20.91 mm3 vs. 22.42±11.22 mm3), and a significant number of pre-cancerous dysplasia (3±1.18 vs. 2±0.83, p<0.01). The inflammatory activity, as measured by the extent/proportion of erosion/ulceration/dense lymphoplasmacytosis (called active colitis index) in the colon, was significantly lower in sEH−/− mice (44.7%±24.9% vs. 20.2%±16.2%, p<0.01). The quantitative polymerase chain reaction (qPCR) assays demonstrated significantly low levels of cytokines/chemokines including monocyte chemoattractant protein (MCP-1), inducible nitric oxide synthase (iNOS), vasopressin-activated calcium-mobilizing (VCAM-1), interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). In vitro, LPS-activated macrophages treated with 14,15-EET showed a significant reduction of LPS-triggered IL-1β and TNF-α expression. Eicosanoic acid metabolic profiling revealed a significant increase of the ratios of EETs/dihydroeicosatrienoic acids (DHETs) and epoxyoctadecennoic acid/dihydroxyoctadecenoic acid (EpOMEs/DiHOMEs). These results indicate that sEH plays an important role in the development of colitis and in inducing carcinogenesis

  14. An HPLC method for microanalysis and pharmacokinetics of marine sulfated polysaccharide PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles in rat plasma.

    PubMed

    Li, Peng-Li; Li, Chun-Xia; Xue, Yi-Ting; Li, Hai-Hua; Liu, Hong-Bing; He, Xiao-Xi; Yu, Guang-Li; Guan, Hua-Shi

    2013-04-02

    This study was aimed at developing a sensitive and selective HPLC method with postcolumn fluorescence derivatization for the detection of propylene glycol alginate sodium sulfate (PSS) in rat plasma. Plasma samples were prepared by a simple and fast ultrafiltration method. PSS was extracted from rat plasma with D-glucuronic acid as internal standard. Isocratic chromatographic separation was performed on a TSKgel G2500 PWxL column with the mobile phase of 0.1 M sodium sulfate at a flow rate of 0.5 mL/min. Analyte detection was achieved by fluorescence detection (FLD) at 250 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as postcolumn derivatizing reagent in an alkaline medium at 120 °C. The calibration curve was linear over a concentration range of 1-500 μg/mL, and the lower limit of detection (LLOD) was found to be 250 ng/mL. This validated method was applied successfully to the pharmacokinetic study of PSS and PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (PSS-NP) in rat plasma after a single intravenous (PSS only) and oral administration (PSS and PSS-NP). Significant differences in the main pharmacokinetic parameters of PSS and PSS-NP were observed. The relative bioavailability of PSS-NP was 190.10% compared with PSS which shows that PSS-NP can improve oral bioavailability.

  15. An HPLC Method for Microanalysis and Pharmacokinetics of Marine Sulfated Polysaccharide PSS-Loaded Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles in Rat Plasma

    PubMed Central

    Li, Peng-Li; Li, Chun-Xia; Xue, Yi-Ting; Li, Hai-Hua; Liu, Hong-Bing; He, Xiao-Xi; Yu, Guang-Li; Guan, Hua-Shi

    2013-01-01

    This study was aimed at developing a sensitive and selective HPLC method with postcolumn fluorescence derivatization for the detection of propylene glycol alginate sodium sulfate (PSS) in rat plasma. Plasma samples were prepared by a simple and fast ultrafiltration method. PSS was extracted from rat plasma with d-glucuronic acid as internal standard. Isocratic chromatographic separation was performed on a TSKgel G2500 PWxL column with the mobile phase of 0.1 M sodium sulfate at a flow rate of 0.5 mL/min. Analyte detection was achieved by fluorescence detection (FLD) at 250 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as postcolumn derivatizing reagent in an alkaline medium at 120 °C. The calibration curve was linear over a concentration range of 1–500 μg/mL, and the lower limit of detection (LLOD) was found to be 250 ng/mL. This validated method was applied successfully to the pharmacokinetic study of PSS and PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (PSS-NP) in rat plasma after a single intravenous (PSS only) and oral administration (PSS and PSS-NP). Significant differences in the main pharmacokinetic parameters of PSS and PSS-NP were observed. The relative bioavailability of PSS-NP was 190.10% compared with PSS which shows that PSS-NP can improve oral bioavailability. PMID:23549283

  16. Purified polysaccharides of Geoffroea spinosa barks have anticoagulant and antithrombotic activities devoid of hemorrhagic risks.

    PubMed

    Souza, Racquel O S; Assreuy, Ana M S; Madeira, Juliana C; Chagas, Francisco D S; Parreiras, Luane A; Santos, Gustavo R C; Mourão, Paulo A S; Pereira, Maria G

    2015-06-25

    Polysaccharides were extracted from the barks of Geoffroea spinosa, purified using anion exchange chromatography and characterized by chemical and methylation analysis, complemented by infrared and NMR spectroscopies. These polysaccharides were tested for their anticoagulant, antithrombotic and antiplatelet activities and also for their effects on bleeding. Unfractionated polysaccharide contains low levels of protein and high levels of carbohydrate (including hexuronic acid). The purified polysaccharides (fractions FII and FIII) are composed of arabinose (Ara), rhamnose (Rha), hexuronic acid, small amounts of galactose, but no sulfate ester. They have highly complex structure, which was partially characterized. NMR and methylation analysis indicate that the polysaccharides have a core of α-Rhap and branches of 5-linked α-Araf. Residues of 4-linked α-GalpA are also found in the structure. The unfractionated (TPL) and fraction FIII, but not fractions FI and FII, prolonged the activated partial thromboplastin time (aPTT). TPL, FII and FIII inhibited the platelet aggregation induced by ADP. More significantly, both unfractionated and purified fractions exhibited potent antithrombotic effect (31-60%) and the fractions did not modify the bleeding tendency. These plant polysaccharides could be alternative source of new anticoagulant, antiplatelet and antithrombotic compounds devoid of the undesirable risk of hemorrhage.

  17. A RG-II Type Polysaccharide Purified from Aconitum coreanum Alleviates Lipopolysaccharide-Induced Inflammation by Inhibiting the NF-κB Signal Pathway

    PubMed Central

    Li, Xiaojun; Jiang, Jiaye; Shi, Songshan; Bligh, S. W. Annie; Li, Yuan; Jiang, Yongbo; Huang, Dan; Ke, Yan; Wang, Shunchun

    2014-01-01

    Korean mondshood root polysaccharides (KMPS) isolated from the root of Aconitum coreanum (Lévl.) Rapaics have shown anti-inflammatory activity, which is strongly influenced by their chemical structures and chain conformations. However, the mechanisms of the anti-inflammatory effect by these polysaccharides have yet to be elucidated. A RG-II polysaccharide (KMPS-2E, Mw 84.8 kDa) was isolated from KMPS and its chemical structure was characterized by FT-IR and NMR spectroscopy, gas chromatography–mass spectrometry and high-performance liquid chromatography. The backbone of KMPS-2E consisted of units of [→6) -β-D-Galp (1→3)-β-L-Rhap-(1→4)-β-D-GalpA-(1→3)-β-D-Galp-(1→] with the side chain →5)-β-D-Arap (1→3, 5)-β-D-Arap (1→ attached to the backbone through O-4 of (1→3,4)-L-Rhap. T-β-D-Galp is attached to the backbone through O-6 of (1→3,6)-β-D-Galp residues and T-β-D-Ara is connected to the end group of each chain. The anti-inflammatory effects of KMPS-2E and the underlying mechanisms using lipopolysaccharide (LPS) - stimulated RAW 264.7 macrophages and carrageenan-induced hind paw edema were investigated. KMPS-2E (50, 100 and 200 µg/mL) inhibits iNOS, TLR4, phospho-NF-κB–p65 expression, phosphor-IKK, phosphor-IκB-α expression as well as the degradation of IκB-α and the gene expression of inflammatory cytokines (TNF-α, IL-1β, iNOS and IL-6) mediated by the NF-κB signal pathways in macrophages. KMPS-2E also inhibited LPS-induced activation of NF-κB as assayed by electrophorectic mobility shift assay (EMSA) in a dose-dependent manner and it reduced NF-κB DNA binding affinity by 62.1% at 200µg/mL. In rats, KMPS-2E (200 mg/kg) can significantly inhibit carrageenan-induced paw edema as ibuprofen (200 mg/kg) within 3 h after a single oral dose. The results indicate that KMPS-2E is a promising herb-derived drug against acute inflammation. PMID:24927178

  18. Polysaccharide Isolated from Zizyphus jujuba (紅棗 Hóng Zǎo) Inhibits Interleukin-2 Production in Jurkat T Cells

    PubMed Central

    Hsu, Bo-Yang; Kuo, Yuh-Chi; Chen, Bing-Huei

    2014-01-01

    Zizyphus jujuba (紅棗 Hóng Zǎo), a traditional Chinese herb widely used in many Asian countries, has been shown to possess vital biological activities such as anti-cancer activity. The objective of this study was to evaluate the immunomodulatory effect of deproteinated polysaccharide (DP) isolated from Z. jujuba. The DP isolated from Z. jujuba consisted of two polysaccharide fractions and their molecular weights (MWs) were found to be 143,108 and 67,633 Da, respectively. The DP could significantly decrease interleukin (IL)-2 production in phytohemagglutinin (PHA)-activated Jurkat T cells in a dose-dependent manner after 48 h of incubation, with the inhibition being 47.5%, 61.2%, and 81.7% for DP concentrations of 0.75, 1.75, and 2.5 mg/ml, respectively. Thus, our study showed that DP isolated from Z. jujuba may possess anti-inflammatory activity as it could significantly reduce IL-2 production in activated Jurkat T cells. PMID:24860737

  19. Polysaccharide-capped silver Nanoparticles inhibit biofilm formation and eliminate multi-drug-resistant bacteria by disrupting bacterial cytoskeleton with reduced cytotoxicity towards mammalian cells

    PubMed Central

    Sanyasi, Sridhar; Majhi, Rakesh Kumar; Kumar, Satish; Mishra, Mitali; Ghosh, Arnab; Suar, Mrutyunjay; Satyam, Parlapalli Venkata; Mohapatra, Harapriya; Goswami, Chandan; Goswami, Luna

    2016-01-01

    Development of effective anti-microbial therapeutics has been hindered by the emergence of bacterial strains with multi-drug resistance and biofilm formation capabilities. In this article, we report an efficient green synthesis of silver nanoparticle (AgNP) by in situ reduction and capping with a semi-synthetic polysaccharide-based biopolymer (carboxymethyl tamarind polysaccharide). The CMT-capped AgNPs were characterized by UV, DLS, FE-SEM, EDX and HR-TEM. These AgNPs have average particle size of ~20–40 nm, and show long time stability, indicated by their unchanged SPR and Zeta-potential values. These AgNPs inhibit growth and biofilm formation of both Gram positive (B. subtilis) and Gram negative (E. coli and Salmonella typhimurium) bacterial strains even at concentrations much lower than the minimum inhibitory concentration (MIC) breakpoints of antibiotics, but show reduced or no cytotoxicity against mammalian cells. These AgNPs alter expression and positioning of bacterial cytoskeletal proteins FtsZ and FtsA. CMT-capped AgNPs can effectively block growth of several clinical isolates and MDR strains representing different genera and resistant towards multiple antibiotics belonging to different classes. We propose that the CMT-capped AgNPs can have potential bio-medical application against multi-drug-resistant microbes with minimal cytotoxicity towards mammalian cells. PMID:27125749

  20. Momordica charantia polysaccharides ameliorate oxidative stress, hyperlipidemia, inflammation, and apoptosis during myocardial infarction by inhibiting the NF-κB signaling pathway.

    PubMed

    Raish, Mohammad

    2017-04-01

    The polysaccharide extract of Momordica charantia has various biological activities; however, its effect on endothelial dysfunction in myocardial infarction remains unclear. To elucidate this, myocardial infarction was induced in rats using isoproterenol (ISP). Pretreatment with M. charantia polysaccharides (MCP; 150 or 300mg/kg) for 25days significantly inhibited increases in heart weight, the heart-weight-to-body-weight ratio, and infarction size, and ameliorated the increased serum levels of aspartate transaminase, creatine kinase, lactate dehydrogenase, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. In addition, MCP enhanced the activity of superoxide dismutase, catalase, and non-protein sulfhydryls, and decreased the level of lipid peroxidation. Moreover, MCP pretreatment downregulated the expression of proinflammatory cytokines (tumor necrosis factor alpha, interleukin (IL)-6, and IL-10), inflammatory markers (nitric oxide, myeloperoxidase, and inducible nitric oxide synthase), and apoptotic markers (caspase-3 and BAX), and upregulated Bcl-2 expression. Pretreatment with MCP reduced myonecrosis, edema, and inflammatory cell infiltration, and restored cardiomyocytes architecture. This myocardial protective effect could be related to the enhancement of the antioxidant defense system through the nuclear factor kappa B (NF-kB) pathways, and to anti-apoptosis through regulation of Bax, caspase-3, and Bcl-2.

  1. Polysaccharide-capped silver Nanoparticles inhibit biofilm formation and eliminate multi-drug-resistant bacteria by disrupting bacterial cytoskeleton with reduced cytotoxicity towards mammalian cells

    NASA Astrophysics Data System (ADS)

    Sanyasi, Sridhar; Majhi, Rakesh Kumar; Kumar, Satish; Mishra, Mitali; Ghosh, Arnab; Suar, Mrutyunjay; Satyam, Parlapalli Venkata; Mohapatra, Harapriya; Goswami, Chandan; Goswami, Luna

    2016-04-01

    Development of effective anti-microbial therapeutics has been hindered by the emergence of bacterial strains with multi-drug resistance and biofilm formation capabilities. In this article, we report an efficient green synthesis of silver nanoparticle (AgNP) by in situ reduction and capping with a semi-synthetic polysaccharide-based biopolymer (carboxymethyl tamarind polysaccharide). The CMT-capped AgNPs were characterized by UV, DLS, FE-SEM, EDX and HR-TEM. These AgNPs have average particle size of ~20–40 nm, and show long time stability, indicated by their unchanged SPR and Zeta-potential values. These AgNPs inhibit growth and biofilm formation of both Gram positive (B. subtilis) and Gram negative (E. coli and Salmonella typhimurium) bacterial strains even at concentrations much lower than the minimum inhibitory concentration (MIC) breakpoints of antibiotics, but show reduced or no cytotoxicity against mammalian cells. These AgNPs alter expression and positioning of bacterial cytoskeletal proteins FtsZ and FtsA. CMT-capped AgNPs can effectively block growth of several clinical isolates and MDR strains representing different genera and resistant towards multiple antibiotics belonging to different classes. We propose that the CMT-capped AgNPs can have potential bio-medical application against multi-drug-resistant microbes with minimal cytotoxicity towards mammalian cells.

  2. Chondroitinase C Selectively Degrades Chondroitin Sulfate Glycosaminoglycans that Inhibit Axonal Growth within the Endoneurium of Peripheral Nerve

    PubMed Central

    2016-01-01

    The success of peripheral nerve regeneration is highly dependent on the regrowth of axons within the endoneurial basal lamina tubes that promote target-oriented pathfinding and appropriate reinnervation. Restoration of nerve continuity at this structural level after nerve transection injury by direct repair and nerve grafting remains a major surgical challenge. Recently, biological approaches that alter the balance of growth inhibitors and promoters in nerve have shown promise to improve appropriate axonal regeneration and recovery of peripheral nerve function. Chondroitin sulfate proteoglycans (CSPGs) are known inhibitors of axonal growth. This growth inhibition is mainly associated with a CSPG's glycosaminoglycan chains. Enzymatic degradation of these chains with chondroitinase eliminates this inhibitory activity and, when applied in vivo, can improve the outcome of nerve repair. To date, these encouraging findings were obtained with chondroitinase ABC (a pan-specific chondroitinase). The aim of this study was to examine the distribution of CSPG subtypes in rodent, rabbit, and human peripheral nerve and to test more selective biological enzymatic approaches to improve appropriate axonal growth within the endoneurium and minimize aberrant growth. Here we provide evidence that the endoneurium, but not the surrounding epineurium, is rich in CSPGs that have glycosaminoglycan chains readily degraded by chondroitinase C. Biochemical studies indicate that chondroitinase C has degradation specificity for 6-sulfated glycosaminoglycans found in peripheral nerve. We found that chondroitinase C degrades and inactivates inhibitory CSPGs within the endoneurium but not so much in the surrounding nerve compartments. Cryoculture bioassays (neurons grown on tissue sections) show that chondroitinase C selectively and significantly enhanced neuritic growth associated with the endoneurial basal laminae without changing growth-inhibiting properties of the surrounding epineurium

  3. Strawberry phytochemicals inhibit azoxymethane/dextran sodium sulfate-induced colorectal carcinogenesis in Crj: CD-1 mice.

    PubMed

    Shi, Ni; Clinton, Steven K; Liu, Zhihua; Wang, Yongquan; Riedl, Kenneth M; Schwartz, Steven J; Zhang, Xiaoli; Pan, Zui; Chen, Tong

    2015-03-10

    Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory microenvironment. Pharmacologically driven chemopreventive agents and dietary variables are hypothesized to have future roles in the prevention of colon cancer by targeting these processes. The current study was designed to determine the ability of dietary lyophilized strawberries to inhibit inflammation-promoted colon carcinogenesis in a preclinical animal model. Mice were given a single i.p. injection of azoxymethane (10 mg kg-1 body weight). One week after injection, mice were administered 2% (w/v) dextran sodium sulfate in drinking water for seven days and then an experimental diet containing chemically characterized lyophilized strawberries for the duration of the bioassay. Mice fed control diet, or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05). The mechanistic studies demonstrate that strawberries reduced expression of proinflammatory mediators, suppressed nitrosative stress and decreased phosphorylation of phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and nuclear factor kappa B. In conclusion, strawberries target proinflammatory mediators and oncogenic signaling for the preventive efficacies against colon carcinogenesis in mice. This works supports future development of fully characterized and precisely controlled functional foods for testing in human clinical trials for this disease.

  4. Sulfation pattern of citrus pectin and its carboxy-reduced derivatives: influence on anticoagulant and antithrombotic effects.

    PubMed

    Maas, Nadiezda C; Gracher, Ana Helena P; Sassaki, Guilherme L; Gorin, Philip A J; Iacomini, Marcello; Cipriani, Thales R

    2012-08-01

    Citrus pectin (CP), a polysaccharide composed of [→4)-α-D-GalpA-(1→]n, was submitted to one or four carboxy-reduction cycles, resulting in CP-CR1 and CP-CR4, which had 40% and 2% of GalpA units, respectively. The polysaccharides were chemically sulfated and their anticoagulant and antithrombotic effects determined. Sulfated polysaccharides (CP-S, CP-CR1S and CP-CR4S) had different anticoagulant activities, doubling APTT at concentrations of 28.7, 13.2, and 4.9 μg/ml respectively. CP-CR1S and CP-CR4S also showed antithrombotic activity in vivo with ED50 of 3.01 and 1.70 mg/kg, respectively. Like heparin, they inhibited thrombin by a mechanism dependent on AT and HCII. Their hemorrhagic potential was also similar to that of heparin. According to methylation analysis, 91.1% and 50.2% of 6-O-position in CP-CR4S and CP-CR1S were sulfated, respectively. Therefore, substitution of carboxyl groups by sulfate esters in these polysaccharides increases the anticoagulant and antithrombotic effects.

  5. Epimedium polysaccharide and propolis flavone can synergistically inhibit the cellular infectivity of NDV and improve the curative effect of ND in chicken.

    PubMed

    Fan, Yunpeng; Liu, Jiaguo; Wang, Deyun; Hu, Yuanliang; Yang, Shujuan; Wang, Junmin; Guo, Liwei; Zhao, Xiaona; Wang, Huali; Jiang, Yu

    2011-04-01

    Four prescriptions, epimedium flavone plus propolis flavone (EF-PF), epimedium flavone plus propolis extracts (EF-PE), epimedium polysaccharide plus propolis flavone (EP-PF) and epimedium polysaccharide plus propolis extracts (EP-PE), were prepared and their antiviral effects were compared. In test in vitro, the four prescriptions within safety concentration scope and Newcastle disease virus (NDV) were added into cultured chick embryo fibroblast (CEF) in three modes, pre-, post-adding drug and simultaneous-adding drug and virus after being mixed, the cellular A(570) values were determined by MTT method and the highest virus inhibitory rates were calculated to compare the antiviral activity of four prescriptions. In test in vivo, three hundred 21-day-old chickens were randomly divided into 6 groups and challenged with NDV except for blank control group. After 24h the chickens in four prescription groups were injected with corresponding drugs respectively, in virus control and blank control groups, with physiological saline, once a day for three successive days. On days 3, 7 and 14 after challenge, the serum antibody titer was determined. On day 15 after challenge, the mortality, morbidity and cure rate in every group were counted. The results showed that the most of A(570) values in EP-PF group were numberly or significantly larger than those of the corresponding virus control group and the highest virus inhibitory rates of EP-PF at optimal concentration group were the highest among four prescription groups in three drug-adding modes, which confirmed that EP-PF could significantly inhibit the infectivity of NDV to CEF, its action was stronger than those of other three prescriptions; in EP-PF group, the antibody titers and cure rate were the highest and the mortality and morbidity were lowest presenting numberly or significantly differences in comparison with other three prescription groups. These results indicated that epimedium polysaccharide and propolis flavone

  6. Protein-bound Polysaccharide-K Inhibits Hedgehog Signaling Through Down-regulation of MAML3 and RBPJ Transcription Under Hypoxia, Suppressing the Malignant Phenotype in Pancreatic Cancer.

    PubMed

    Yamasaki, Akio; Onishi, Hideya; Imaizumi, Akira; Kawamoto, Makoto; Fujimura, Akiko; Oyama, Yasuhiro; Katano, Mitsuo

    2016-08-01

    Hedgehog signaling is activated in pancreatic cancer and could be a therapeutic target. We previously demonstrated that recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) contribute to the hypoxia-induced up-regulation of Smoothened (SMO) transcription. We have also shown that protein-bound polysaccharide-K (PSK) could be effective for refractory pancreatic cancer that down-regulates SMO transcription under hypoxia. In this study, we evaluated whether the anticancer mechanism of PSK involves inhibiting RBPJ and MAML3 expression under hypoxia. PSK reduced SMO, MAML3 and RBPJ expression in pancreatic cancer cells under hypoxia. PSK also blocked RBPJ-induced invasiveness under hypoxia by inhibiting matrix metalloproteinase expression. Lastly, we showed that PSK attenuated RBPJ-induced proliferation both in vitro and in vivo. These results suggest that PSK suppresses Hedgehog signaling through down-regulation of MAML3 and RBPJ transcription under hypoxia, inhibiting the induction of a malignant phenotype in pancreatic cancer. Our results may lead to development of new treatments for refractory pancreatic cancer using PSK as a Hedgehog inhibitor.

  7. Chemical structure and anticoagulant activity of highly pyruvylated sulfated galactans from tropical green seaweeds of the order Bryopsidales.

    PubMed

    Arata, Paula X; Quintana, Irene; Canelón, Dilsia J; Vera, Beatriz E; Compagnone, Reinaldo S; Ciancia, Marina

    2015-05-20

    Sulfated and pyruvylated galactans were isolated from three tropical species of the Bryopsidales, Penicillus capitatus, Udotea flabellum, and Halimeda opuntia. They represent the only important sulfated polysaccharides present in the cell walls of these highly calcified seaweeds of the suborder Halimedineae. Their structural features were studied by chemical analyses and NMR spectroscopy. Their backbone comprises 3-, 6-, and 3,6-linkages, constituted by major amounts of 3-linked 4,6-O-(1'-carboxy)ethylidene-d-galactopyranose units in part sulfated on C-2. Sulfation on C-2 was not found in galactans from other seaweeds of this order. In addition, a complex sulfation pattern, comprising also 4-, 6-, and 4,6-disulfated galactose units was found. A fraction from P. capitatus, F1, showed a moderate anticoagulant activity, evaluated by general coagulation tests and also kinetics of fibrin formation was assayed. Besides, preliminary results suggest that one of the possible mechanisms involved is direct thrombin inhibition.

  8. Ganoderma Lucidum polysaccharides protect against MPP+ and rotenone-induced apoptosis in primary dopaminergic cell cultures through inhibiting oxidative stress

    PubMed Central

    Guo, Shan-Shan; Cui, Xiao-Lan; Rausch, Wolf-Dieter

    2016-01-01

    Oxidative stress plays a pivotal role in the progressive neurodegeneration in Parkinson’s disease (PD) which is responsible for disabling motor abnormalities in more than 6.5 million people worldwide. Polysaccharides are the main active constituents from Ganoderma lucidum which is characterized with anti-oxidant, antitumor and immunostimulant properties. In the present study, primary dopaminergic cell cultures prepared from embryonic mouse mesencephala were used to investigate the neuroprotective effects and the potential mechanisms of Ganoderma lucidum polysaccharides (GLP) on the degeneration of dopaminergic neurons induced by the neurotoxins methyl-4-phenylpyridine (MPP+) and rotenone. Results revealed that GLP can protect dopamine neurons against MPP+ and rotenone at the concentrations of 100, 50 and 25 μg/ml in primary mesencephalic cultures in a dose-dependent manner. Interestingly, either with or without neurotoxin treatment, GLP treatment elevated the survival of THir neurons, and increased the length of neurites of dopaminergic neurons. The Trolox equivalent anti-oxidant capacity (TEAC) of GLP was determined to be 199.53 μmol Trolox/g extract, and the decrease of mitochondrial complex I activity induced by MPP+ and rotenone was elevated by GLP treatment (100, 50, 25 and 12.5 μg/ml) in a dose dependent manner. Furthermore, GLP dramatically decreased the relative number of apoptotic cells and increased the declining mitochondrial membrane potential (ΔΨm) induced by MPP+ and rotenone in a dose-dependent manner. In addition, GLP treatment reduced the ROS formation induced by MPP+ and rotenone at the concentrations of 100, 50 and 25 μg/ml in a dose-dependent manner. Our study indicates that GLP possesses neuroprotective properties against MPP+ and rotenone neurotoxicity through suppressing oxidative stress in primary mesencephalic dopaminergic cell culture owning to its antioxidant activities. PMID:27335703

  9. Açaí Berries Inhibit Colon Tumorigenesis in Azoxymethane/Dextran Sulfate Sodium-Treated Mice

    PubMed Central

    Choi, Yoon Jin; Choi, Yoon Jeong; Kim, Nayoung; Nam, Ryoung Hee; Lee, Seonmin; Lee, Hye Seung; Lee, Ha-Na; Surh, Young-Joon; Lee, Dong Ho

    2017-01-01

    Background/Aims The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer development. Methods The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting. Results Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells. Conclusions Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer. PMID:27965474

  10. Dicliptera Chinensis polysaccharides target TGF-β/Smad pathway and inhibit stellate cells activation in rats with dimethylnitrosamine-induced hepatic fibrosis.

    PubMed

    Zhang, X; Zhang, J; Jia, L; Xiao, S

    2016-01-27

    This study aims to study impact of Dicliptera chinensis polysaccharide (DCP) on hepatic fibrosis (HF) and activation of hepatic stellate cells (HSCs). Liver fibrosis model was induced by intraperitoneal injection of dimethyl nitrosamines (DMN) in rat. Rats in treatment group were administrated with different concentrations of DCP (0, 100, 300 mg/kg) by intraperitoneal injection. Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to assess histo-pathological change. α-SMA, TGF-β1 and pSmad 2/3 were assayed by immuno-histochemistry. HSC-T6 cells were stimulated by recombined rat TGF-β1 (1 ng/mL) to simulate an activating model in vitro and then interfered with DCP (concentration of 0, 25, 50, 100, 200, 400 µg/ml). MTT assay was used to determine cell proliferation and western blotting was used to detect α-SMA and pSmad 2/3 expression. Results demonstrated that DCP alleviated DMN-induced liver fibrosis in rat and significantly down-regulated TGF-β1 expression, pSmad2/3 and α-SMA in liver tissue in a dose-dependent way. DCP inhibited proliferation and activation of TGF-β1-stimulated HSC-T6 in vitro and significantly down-regulated α-SMA and pSmad2/3 expression. In conclusion, this study revealed that DCP attenuates progression of liver fibrosis through suppressing TGF-β/Smad pathway. DCP is a potential botanical polysaccharide to management liver fibrosis.

  11. Polysaccharide peptides from Coriolus versicolor competitively inhibit tolbutamide 4-hydroxylation in specific human CYP2C9 isoform and pooled human liver microsomes.

    PubMed

    Yeung, John H K; Or, Penelope M Y

    2011-10-15

    Polysaccharide peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy in China. Previous studies have shown that PSP decreased antipyrine clearance and inhibited CYP2C11-mediated tolbutamide 4-hydroxylation in the rat both in vitro and in vivo. In this study, the effects of water extractable fraction of PSP on tolbutamide 4-hydroxylation was investigated in pooled human liver microsomes and in specific human CYP2C9 isoform. PSP (2.5-20μM) dose-dependently decreased the biotransformation of tolbutamide to 4-hydroxy-tolbutamide. Enzyme kinetics studies showed inhibition of tolbutamide 4-hydroxylase activity was competitive and concentration-dependent. In pooled human liver microsomes, PSP had a K(i) value of 14.2μM compared to sulfaphenazole, a human CYP2C9 inhibitor, showed a K(i) value of 0.32μM. In human CYP2C9 isoform, the K(i) value of PSP was 29.5μM and the K(i) value of sulfaphenazole was 0.04μM. This study demonstrated that PSP can competitively inhibit tolbutamide 4-hydroxylation in both pooled human liver microsomes and specific human CYP2C9 in vitro. This study compliments previous findings in the rat that PSP can inhibit human tolbutamide 4-hydroxylase, but the relatively high K(i) values in human CYP2C9 would suggest a low potential for PSP to cause herb-drug interaction.

  12. Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/β-catenin in SW480 human colon cancer cells

    PubMed Central

    2011-01-01

    Background Polysaccharides extracted from the Phellinus linteus (PL) mushroom are known to possess anti-tumor effects. However, the molecular mechanisms responsible for the anti-tumor properties of PL remain to be explored. Experiments were carried out to unravel the anticancer effects of PL. Methods The anti-cancer effects of PL were examined in SW480 colon cancer cells by evaluating cell proliferation, invasion and matrix metallo-proteinase (MMP) activity. The anti-angiogenic effects of PL were examined by assessing human umbilical vein endothelial cell (HUVEC) proliferation and capillary tube formation. The in vivo effect of PL was evaluated in an athymic nude mouse SW480 tumor engraft model. Results PL (125-1000 μg/mL) significantly inhibited cell proliferation and decreased β-catenin expression in SW480 cells. Expression of cyclin D1, one of the downstream-regulated genes of β-catenin, and T-cell factor/lymphocyte enhancer binding factor (TCF/LEF) transcription activity were also significantly reduced by PL treatment. PL inhibited in vitro invasion and motility as well as the activity of MMP-9. In addition, PL treatment inhibited HUVEC proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice was significantly decreased as a consequence of PL treatment, and tumor tissues from treated animals showed an increase in the apoptotic index and a decrease in β-catenin expression. Moreover, the proliferation index and microvessel density were significantly decreased. Conclusions These data suggest that PL suppresses tumor growth, invasion, and angiogenesis through the inhibition of Wnt/β-catenin signaling in certain colon cancer cells. PMID:21781302

  13. Chondroitin Sulfate Is Indispensable for Pluripotency and Differentiation of Mouse Embryonic Stem Cells

    PubMed Central

    Izumikawa, Tomomi; Sato, Ban; Kitagawa, Hiroshi

    2014-01-01

    Chondroitin sulfate (CS) proteoglycans are present on the surfaces of virtually all cells and in the extracellular matrix and are required for cytokinesis at early developmental stages. Studies have shown that heparan sulfate (HS) is essential for maintaining mouse embryonic stem cells (ESCs) that are primed for differentiation, whereas the function of CS has not yet been elucidated. To clarify the role of CS, we generated glucuronyltransferase-I-knockout ESCs lacking CS. We found that CS was required to maintain the pluripotency of ESCs and promoted initial ESC commitment to differentiation compared with HS. In addition, CS-A and CS-E polysaccharides, but not CS-C polysaccharides, bound to E-cadherin and enhanced ESC differentiation. Multiple-lineage differentiation was inhibited in chondroitinase ABC-digested wild-type ESCs. Collectively, these results suggest that CS is a novel determinant in controlling the functional integrity of ESCs via binding to E-cadherin. PMID:24424429

  14. Polysaccharide structure of tetrasporic red seaweed Tichocarpus crinitus.

    PubMed

    Byankina Barabanova, A O; Sokolova, E V; Anastyuk, S D; Isakov, V V; Glazunov, V P; Volod'ko, A V; Yakovleva, I M; Solov'eva, T F; Yermak, I M

    2013-10-15

    Sulfated polysaccharide isolated from tetrasporic plants of Tichocarpus crinitus was investigated. The polysaccharide was isolated by two methods: with water extraction at 80 °C (HT) and with a mild alkaline extraction (AE). The extracted polysaccharides were presented by non-gelling ones only, while galactose and 3,6-AG were the main monosaccharides, at the same time amount of 3,6-AG in AE polysaccharides was the similar to that of HT. According to methods of spectroscopy and mass spectrometry, the polysaccharide from tetrasporic T. crinitus contains main blocks of 1,3-linked β-D-galactopyranosyl-2,4-disulfates and 1,4-linked 3,6-anhydro-α-D-galactopyranosyl while 6-sulfated 4-linked galactopyranosyl resudies are randomly distributed along the polysaccharide chain. The alkaline treatment of HT polysaccharide results in obtaining polysaccharide with regular structure that composed of alternating 1,3-linked β-D-galactopyranosyl-2,4-disulfates and 1,4-linked 3,6-anhydro-α-D-galactopyranosyl residues. Native polysaccharide (HT) possessed both high anticoagulant and antiplatelet activity measured by fibrin clotting and platelet aggregation induced by collagen. This activity could be connected with peculiar chemical structure of HT polysaccharide which has high sulfation degree and contains also 3,6-anhydrogalactose in the polymer chain.

  15. A polysaccharide from Glycyrrhiza inflata Licorice inhibits proliferation of human oral cancer cells by inducing apoptosis via mitochondrial pathway.

    PubMed

    Shen, Huan; Zeng, Guang; Sun, Bin; Cai, Xingwei; Bi, Lixia; Tang, Guo; Yang, Yongjin

    2015-06-01

    In the present study, we isolated and characterized a water-soluble polysaccharide (GIP1) from the roots of Glycyrrhiza inflata. The goal of this study was to investigate the anti-tumor effect of GIP1 on the human oral cancer SCC-25 cell line and to explore the possible mechanism. Our experimental result showed that GIP1 (50, 100, and 200 μg/mL) specifically decreased cell viability of SCC-25 cells in a concentration-dependent manner via the induction of apoptosis. Furthermore, Western blot analysis showed that exposure of SCC-25 cells to GIP1 led to down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, thus causing a loss of mitochondrial membrane potential and the release of cytochrome c to the cytosol. Moreover, we observed activation of the initiator caspaes-9, and the effector caspases-3, but not caspase-8. Concomitantly, GIP1-induced apoptosis can be blocked by caspase-3- or caspase-9-specific inhibitor, but not caspase-8 inhibitor. As well, the cleaved poly (ADP-ribose) polymerase, as a caspae-3 substrate, occurred in SCC-25 cells following GIP1 treatment at three concentrations. Collectively, our results showed that the GIP1 induced apoptosis in SCC-25 cells involving a caspase-dependent mitochondrial signaling pathway.

  16. The predominant molecular state of bound enzyme determines the strength and type of product inhibition in the hydrolysis of recalcitrant polysaccharides by processive enzymes.

    PubMed

    Kuusk, Silja; Sørlie, Morten; Väljamäe, Priit

    2015-05-01

    Processive enzymes are major components of the efficient enzyme systems that are responsible for the degradation of the recalcitrant polysaccharides cellulose and chitin. Despite intensive research, there is no consensus on which step is rate-limiting for these enzymes. Here, we performed a comparative study of two well characterized enzymes, the cellobiohydrolase Cel7A from Hypocrea jecorina and the chitinase ChiA from Serratia marcescens. Both enzymes were inhibited by their disaccharide product, namely chitobiose for ChiA and cellobiose for Cel7A. The products behaved as noncompetitive inhibitors according to studies using the (14)C-labeled crystalline polymeric substrates (14)C chitin nanowhiskers and (14)C-labeled bacterial microcrystalline cellulose for ChiA and Cel7A, respectively. The resulting observed Ki (obs) values were 0.45 ± 0.08 mm for ChiA and 0.17 ± 0.02 mm for Cel7A. However, in contrast to ChiA, the Ki (obs) of Cel7A was an order of magnitude higher than the true Ki value governed by the thermodynamic stability of the enzyme-inhibitor complex. Theoretical analysis of product inhibition suggested that the inhibition strength and pattern can be accounted for by assuming different rate-limiting steps for ChiA and Cel7A. Measuring the population of enzymes whose active site was occupied by a polymer chain revealed that Cel7A was bound predominantly via its active site. Conversely, the active-site-mediated binding of ChiA was slow, and most ChiA exhibited a free active site, even when the substrate concentration was saturating for the activity. Collectively, our data suggest that complexation with the polymer chain is rate-limiting for ChiA, whereas Cel7A is limited by dissociation.

  17. Carbonic anhydrase inhibitors. Inhibition of isozymes I, II, IV, V, and IX with anions isosteric and isoelectronic with sulfate, nitrate, and carbonate.

    PubMed

    Innocenti, Alessio; Vullo, Daniela; Scozzafava, Andrea; Supuran, Claudiu T

    2005-02-01

    The inhibition of five human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes; the cytosolic hCA I and II, the membrane-bound hCA IV, the mitochondrial hCA V, and the tumor-associated, transmembrane hCA IX, with anions isosteric and isoelectronic with sulfate, nitrate, and carbonate; such as chlorate, perchlorate, bromate, iodate, periodate, silicate, bismuthate, vanadate, molybdate, and wolframate is reported. Apparently, the geometry of the inhibitor (tetrahedral or trigonal) does not influence its binding to the Zn(II) ion of the enzyme active site, but the nature of the central element is the most important factor influencing potency. Isozymes hCA I and II are best inhibited by chlorate, perchlorate, and silicate, together with the anions structurally related to sulfate, sulfamate, and sulfamidate, but sulfate itself is a weak inhibitor (inhibition constant of 74 mM against hCA I and 183 mM against hCA II). Molybdate is a very weak hCA I inhibitor (K(I) of 914 mM) but it interacts with hCA II (K(I) of 27.5mM). Isozyme IV is well inhibited by sulfate (K(I) of 9 mM), sulfamate, and sulfamidate (in the low micromolar range), but not by perchlorate (K(I) of 767 mM). The mitochondrial isozyme V has the lowest affinity for sulfate (K(I) of 680 mM) and carbonate (K(I) of 95 mM) among all the investigated isozymes, suggesting on one hand its possible participation in metabolon(s) with sulfate anion exchanger(s), and on the other hand an evolutionary adaptation to working at higher pH values (around 8.5 in mitochondria) where rather high amounts of carbonate in equilibrium with bicarbonate may be present. Metasilicate, isosteric to carbonate, is also about a 10 times weaker inhibitor of this isozyme as compared to other CAs investigated here (K(I) of 28.2 mM). Surprisingly, the tumor-associated isozyme IX is resistant to sulfate inhibition (K(I) of 154 mM) but has affinity in the low micromolar range for carbonate, sulfamate, and sulfamidate (K(I) in the range of 8

  18. Synthetic polymer nanoparticle-polysaccharide interactions: a systematic study.

    PubMed

    Zeng, Zhiyang; Patel, Jiten; Lee, Shih-Hui; McCallum, Monica; Tyagi, Anuradha; Yan, Mingdi; Shea, Kenneth J

    2012-02-08

    The interaction between synthetic polymer nanoparticles (NPs) and biomacromolecules (e.g., proteins, lipids, and polysaccharides) can profoundly influence the NPs fate and function. Polysaccharides (e.g., heparin/heparin sulfate) are a key component of cell surfaces and the extracelluar matrix and play critical roles in many biological processes. We report a systematic investigation of the interaction between synthetic polymer nanoparticles and polysaccharides by ITC, SPR, and an anticoagulant assay to provide guidelines to engineer nanoparticles for biomedical applications. The interaction between acrylamide nanoparticles (~30 nm) and heparin is mainly enthalpy driven with submicromolar affinity. Hydrogen bonding, ionic interactions, and dehydration of polar groups are identified to be key contributions to the affinity. It has been found that high charge density and cross-linking of the NP can contribute to high affinity. The affinity and binding capacity of heparin can be significantly diminished by an increase in salt concentration while only slightly decreased with an increase of temperature. A striking difference in binding thermodynamics has been observed when the main component of a polymer nanoparticle is changed from acrylamide (enthalpy driven) to N-isopropylacryalmide (entropy driven). This change in thermodynamics leads to different responses of these two types of polymer NPs to salt concentration and temperature. Select synthetic polymer nanoparticles have also been shown to inhibit protein-heparin interactions and thus offer the potential for therapeutic applications.

  19. In vivo immunomodulatory effects of Antrodia camphorata polysaccharides in a T1/T2 doubly transgenic mouse model for inhibiting infection of Schistosoma mansoni

    SciTech Connect

    Cheng, P.-C.; Hsu, C.-Y.; Chen, C.-C.; Lee, K.-M.

    2008-03-01

    Antrodia camphorata (A. camphorata) is a fungus commonly used for treatment of viral hepatitis and cancer in Chinese folk medicine. Extract of A. camphorate is reported to possess anti-inflammatory, antihepatitis B virus and anticancer activities. In this study, we tested the in vivo effects of polysaccharides derived from A. camphorata (AC-PS) on immune function by detection of cytokine expression and evaluation of the immune phenotype in a T1/T2 doubly transgenic mouse model. The protective effect of AC-PS in mice was tested by infection with Schistosoma mansoni. The induction of large amounts of IFN-{gamma}, IL-2 and TNF-a mRNA were detected after 2 and 4 weeks of oral AC-PS administration in BALB/c and C57BL/6 mice. In transgenic mice, 3 to 6 weeks of oral AC-PS administration increased the proportion of CD4{sup +} T cells and B cells within the spleen. More specifically, there was an increase of Th1 CD4{sup +} T cells and Be1 cells among spleen cells as observed by detection the of Type1/Type2 marker molecules. By using a disease model of parasitic infection, we found that AC-PS treatment inhibited infection with S. mansoni in BALB/C and C57BL/6 mice. AC-PS appears to influence the immune system of mice into developing Th1 responses and have potential for preventing infection with S. mansoni.

  20. A Polysaccharide from the Culinary-Medicinal Mushroom Pholiota nameko (Agaricomycetes) Inhibits the NF-κB Pathway in Dendritic Cells Through the TLR2 Receptor.

    PubMed

    Li, Haiping; Zhao, Pei; Wang, Fengling; Huai, Lihua; Zhu, Ruixuan; Li, Guoliang; Xu, Yufeng

    2016-01-01

    A polysaccharide purified from Pholiota nameko (PNPS-1) was found to have anticancer and anti-inflammatory activity. This study investigated the effect of PNPS-1 on the nuclear factor (NF)-κB signaling pathway of TLR2 small interfering RNA-silenced murine bone marrow-derived dendritic cells (BMDCs) and relevant mechanisms. The expression of messenger RNA of 4 NF-κB-related genes, including MyD88, IKBKB, RelA(p65), and CCL2, was determined by real-time polymerase chain reaction; the expression of the phenotype molecule intercellular adhesion molecule-1 (ICAM-1) by flow cytometry; the protein expression of IKKβ and p65 by Western blot; the production of p65 by enzyme-linked immunosorbent assay; and the expression of p65 by immunocytochemistry. The results showed that TLR2-specific small interfering RNA could effectively inhibit the decrease in the expression of MyD88, IKBKB, CCL2, p65, and ICAM-1 in BMDCs induced by PNPS-1, and thus the transcription inactivation of NF-κB, which obviously suggests that PNPS-1 could downregulate the NF-κB signaling pathway via the TLR2 receptor.

  1. Sulphated polysaccharides from Ulva clathrata and Cladosiphon okamuranus seaweeds both inhibit viral attachment/entry and cell-cell fusion, in NDV infection.

    PubMed

    Aguilar-Briseño, José Alberto; Cruz-Suarez, Lucia Elizabeth; Sassi, Jean-François; Ricque-Marie, Denis; Zapata-Benavides, Pablo; Mendoza-Gamboa, Edgar; Rodríguez-Padilla, Cristina; Trejo-Avila, Laura María

    2015-01-26

    Sulphated polysaccharides (SP) extracted from seaweeds have antiviral properties and are much less cytotoxic than conventional drugs, but little is known about their mode of action. Combination antiviral chemotherapy may offer advantages over single agent therapy, increasing efficiency, potency and delaying the emergence of resistant virus. The paramyxoviridae family includes pathogens causing morbidity and mortality worldwide in humans and animals, such as the Newcastle Disease Virus (NDV) in poultry. This study aims at determining the antiviral activity and mechanism of action in vitro of an ulvan (SP from the green seaweed Ulva clathrata), and of its mixture with a fucoidan (SP from Cladosiphon okamuranus), against La Sota NDV strain. The ulvan antiviral activity was tested using syncytia formation, exhibiting an IC50 of 0.1 μg/mL; ulvan had a better anti cell-cell spread effect than that previously shown for fucoidan, and inhibited cell-cell fusion via a direct effect on the F0 protein, but did not show any virucidal effect. The mixture of ulvan and fucoidan showed a greater anti-spread effect than SPs alone, but ulvan antagonizes the effect of fucoidan on the viral attachment/entry. Both SPs may be promising antivirals against paramyxovirus infection but their mixture has no clear synergistic advantage.

  2. Sulphated Polysaccharides from Ulva clathrata and Cladosiphon okamuranus Seaweeds both Inhibit Viral Attachment/Entry and Cell-Cell Fusion, in NDV Infection

    PubMed Central

    Aguilar-Briseño, José Alberto; Cruz-Suarez, Lucia Elizabeth; Sassi, Jean-François; Ricque-Marie, Denis; Zapata-Benavides, Pablo; Mendoza-Gamboa, Edgar; Rodríguez-Padilla, Cristina; Trejo-Avila, Laura María

    2015-01-01

    Sulphated polysaccharides (SP) extracted from seaweeds have antiviral properties and are much less cytotoxic than conventional drugs, but little is known about their mode of action. Combination antiviral chemotherapy may offer advantages over single agent therapy, increasing efficiency, potency and delaying the emergence of resistant virus. The paramyxoviridae family includes pathogens causing morbidity and mortality worldwide in humans and animals, such as the Newcastle Disease Virus (NDV) in poultry. This study aims at determining the antiviral activity and mechanism of action in vitro of an ulvan (SP from the green seaweed Ulva clathrata), and of its mixture with a fucoidan (SP from Cladosiphon okamuranus), against La Sota NDV strain. The ulvan antiviral activity was tested using syncytia formation, exhibiting an IC50 of 0.1 μg/mL; ulvan had a better anti cell-cell spread effect than that previously shown for fucoidan, and inhibited cell-cell fusion via a direct effect on the F0 protein, but did not show any virucidal effect. The mixture of ulvan and fucoidan showed a greater anti-spread effect than SPs alone, but ulvan antagonizes the effect of fucoidan on the viral attachment/entry. Both SPs may be promising antivirals against paramyxovirus infection but their mixture has no clear synergistic advantage. PMID:25629385

  3. Structure and biological activity of a fucosylated chondroitin sulfate from the sea cucumber Cucumaria japonica.

    PubMed

    Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Shashkov, Alexander S; Kusaykin, Mikhail I; Stonik, Valentin A; Nifantiev, Nikolay E; Usov, Anatolii I

    2016-05-01

    A fucosylated chondroitin sulfate (FCS) was isolated from the body wall of Pacific sea cucumber Cucumaria japonicaby extraction in the presence of papain followed by Cetavlon precipitation and anion-exchange chromatography. FCS was shown to contain D-GalNAc, D-GlcA, L-Fuc and sulfate in molar proportions of about 1:1:1:4.5. Structure of FCS was elucidated using NMR spectroscopy and methylation analysis of the native polysaccharide and products of its desulfation and carboxyl reduction. The polysaccharide was shown to contain a typical chondroitin core → 3)-β-D-GalNAc-(1 → 4)-β-D-GlcA-(1 →. Sulfate groups in this core occupy O-4 and the majority of O-6 of GalNAc. Fucosyl branches are represented by 3,4- and 2,4-disulfated units in a ratio of 4:1 and are linked to O-3 of GlcA. In addition, ∼ 33% of GlcA are 3-O-sulfated, and hence, the presence of short fucooligosaccharide chains side by side with monofucosyl branches cannot be excluded. FCS was shown to inhibit platelets aggregation in vitro mediated by collagen and ristocetin, but not adenosine diphosphate, and demonstrated significant anticoagulant activity, which is connected with its ability to enhance inhibition of thrombin and factor Xa by antithrombin III, as well as to influence von Willebrand factor activity. The latest property significantly distinguished FCS from low-molecular-weight heparin.

  4. Fungal polysaccharides.

    PubMed

    San-Blas, G; Suzuki, S; Hearn, V; Pinel, C; Kobayashi, H; Mendez, C; Niño, G; Nishikawa, A; San-Blas, F; Shibata, N

    1994-01-01

    Fungal polysaccharides are cell wall components which may act as antigens or as structural substrates. As antigens, the role of mannans in Saccharomyces cerevisiae and Candida albicans, and of glycoproteins in Aspergillus fumigatus are discussed. Analyses on beta-glucan synthetase in Paracoccidioides brasiliensis and the inhibitory effect of Hansenula mrakii killer toxin on beta-glucan biosynthesis are also considered.

  5. Epitope mapping by a Wnt-blocking antibody: evidence of the Wnt binding domain in heparan sulfate

    PubMed Central

    Gao, Wei; Xu, Yongmei; Liu, Jian; Ho, Mitchell

    2016-01-01

    Heparan sulfate (HS) is a polysaccharide known to modulate many important biological processes, including Wnt signaling. However, the biochemical interaction between HS and Wnt molecules is not well characterized largely due to the lack of suitable methods. To determine the Wnt binding domain in HS, we used a Wnt signaling-inhibitory antibody (HS20) and a panel of synthetic HS oligosaccharides with distinct lengths and sulfation modifications. We found that the binding of HS20 to heparan sulfate required sulfation at both the C2 position (2-O-sulfation) and C6 position (6-O-sulfation). The oligosaccharides with the greatest competitive effect for HS20 binding were between six and eight saccharide residues in length. Additionally, a four residue-long oligosaccharide could also be recognized by HS20 if an additional 3-O-sulfation modification was present. Furthermore, similar oligosaccharides with 2-O, 6-O and 3-O-sulfations showed inhibition for Wnt activation. These results have revealed that HS20 and Wnt recognize a HS structure containing IdoA2S and GlcNS6S, and that the 3-O-sulfation in GlcNS6S3S significantly enhances the binding of both HS20 and Wnt. This study provides the evidence for identifying the Wnt binding domain in HS and suggests a therapeutic approach to target the interaction of Wnt and HS in cancer and other diseases. PMID:27185050

  6. Lycium barbarum polysaccharides induce apoptosis in human prostate cancer cells and inhibits prostate cancer growth in a xenograft mouse model of human prostate cancer.

    PubMed

    Luo, Qiong; Li, Zhuoneng; Yan, Jun; Zhu, Fan; Xu, Ruo-Jun; Cai, Yi-Zhong

    2009-08-01

    Lycium barbarum polysaccharides (LBPs) are important functional constituents in red-colored fruits of L. barbarum (Guo Qi Zi, a well-known traditional Chinese medicinal plant commonly known as Goji berry or wolfberry). The influence of LBP on human prostate cancer cells was systematically investigated in vitro and in vivo. The in vitro effects of LBP on two cell lines (PC-3 and DU-145) were examined by using trypan blue exclusion staining, single-cell gel electrophoresis, flow cytometry, terminal dUTP nick-end labeling assay, and immunohistochemical assay (assessment of Bcl-2 and Bax expression). The in vivo effect of LBP on PC-3 cells was assessed in the nude mouse xenograft tumor model. The in vitro results showed that LBP can dose- and time-dependently inhibit the growth of both PC-3 and DU-145 cells. LBP caused the breakage of DNA strands of PC-3 and DU-145 cells; the tail frequency and tail length were significantly higher than that of control cells. LBP also markedly induced PC-3 and DU-145 cell apoptosis, with the highest apoptosis rates at 41.5% and 35.5%, respectively. The ratio of Bcl-2/Bax protein expression following LBP treatments decreased significantly with a dose-effect relationship, which suggested that LBP can regulate the expression of Bcl-2 and Bax to induce apoptosis of PC-3 and DU-145 cells. The in vivo experimental results indicate that LBP might significantly inhibit PC-3 tumor growth in nude mice. Both the tumor volume and weight of the LBP treatment group were significantly lower than those of the control group.

  7. The symbiotic bacterial surface factor polysaccharide A on Bacteroides fragilis inhibits IL-1β-induced inflammation in human fetal enterocytes via toll receptors 2 and 4

    PubMed Central

    Jiang, Fei; Meng, Di; Weng, Meiqian; Zhu, Weishu; Wu, Wenxue; Kasper, Dennis; Walker, W. Allan

    2017-01-01

    Colonizing bacteria interacting with the immature, unlike the mature, human intestine favors inflammation over immune homeostasis. As a result, ten percent of premature infants under 1500 grams weight develop an inflammatory necrosis of the intestine after birth, e.g., necrotizing enterocolitis (NEC). NEC is a major health problem in this population causing extensive morbidity and mortality and an enormous expenditure of health care dollars. NEC can be prevented by giving preterm infants their mother’s expressed breast milk or ingesting selective probiotic organisms. Vaginally delivered, breast fed newborns develop health promoting bacteria (“pioneer” bacteria) which preferentially stimulate intestinal host defense and anti-inflammation. One such “pioneer” organism is Bacteroides fragilis with a polysaccharide (PSA) on its capsule. B. fragilis has been shown developmentally in intestinal lymphocytes and dendritic cells to produce a balanced T-helper cell (TH1/TH2) response and to reduce intestinal inflammation by activity through the TLR2 receptor stimulating IL-10 which inhibits IL-17 causing inflammation. No studies have been done on the role of B. fragilis PSA on fetal enterocytes and its increased inflammation. Accordingly, using human and mouse fetal intestinal models, we have shown that B. fragilis with PSA and PSA alone inhibits IL-1β-induced IL-8 inflammation in fetal and NEC intestine. We have also begun to define the mechanism for this unique inflammation noted in fetal intestine. We have shown that B. fragilis PSA anti-inflammation requires both the TLR2 and TLR4 receptor and is in part mediated by the AP1 transcription factor (TLR2) which is developmentally regulated. These observations may help to devise future preventative treatments of premature infants against NEC. PMID:28278201

  8. Chondroitin sulfate

    MedlinePlus

    ... in combination with glucosamine sulfate, shark cartilage, and camphor. Some people also inject chondroitin sulfate into the ... in combination with glucosamine sulfate, shark cartilage, and camphor seems to reduce arthritis symptoms. However, any symptom ...

  9. Hydrogen sulfide from a NaHS source attenuates dextran sulfate sodium (DSS)-induced inflammation via inhibiting nuclear factor-κB.

    PubMed

    Chen, Xi; Liu, Xi-shuang

    2016-03-01

    This study investigated the alleviating effects of hydrogen sulfide (H2S), derived from sodium hydrosulfide (NaHS), on inflammation induced by dextran sulfate sodium (DSS) in both in vivo and in vitro models. We found that NaHS injection markedly decreased rectal bleeding, diarrhea, and histological injury in DSS-challenged mice. NaHS (20 μmol/L) reversed DSS-induced inhibition in cell viability in Caco-2 cells and alleviated pro-inflammation cytokine expression in vivo and in vitro, indicating an anti-inflammatory function for H2S. It was also found that H2S may regulate cytokine expression by inhibiting the nuclear factor-κB (NF-κB) signaling pathway. In conclusion, our results demonstrated that H2S alleviated DSS-induced inflammation in vivo and in vitro and that the signal mechanism might be associated with the NF-κB signaling pathway.

  10. Hydrogen sulfide from a NaHS source attenuates dextran sulfate sodium (DSS)-induced inflammation via inhibiting nuclear factor-κB

    PubMed Central

    Chen, Xi; Liu, Xi-shuang

    2016-01-01

    This study investigated the alleviating effects of hydrogen sulfide (H2S), derived from sodium hydrosulfide (NaHS), on inflammation induced by dextran sulfate sodium (DSS) in both in vivo and in vitro models. We found that NaHS injection markedly decreased rectal bleeding, diarrhea, and histological injury in DSS-challenged mice. NaHS (20 μmol/L) reversed DSS-induced inhibition in cell viability in Caco-2 cells and alleviated pro-inflammation cytokine expression in vivo and in vitro, indicating an anti-inflammatory function for H2S. It was also found that H2S may regulate cytokine expression by inhibiting the nuclear factor-κB (NF-κB) signaling pathway. In conclusion, our results demonstrated that H2S alleviated DSS-induced inflammation in vivo and in vitro and that the signal mechanism might be associated with the NF-κB signaling pathway. PMID:26984841

  11. Designing Allosteric Regulators of Thrombin. Exosite 2 Features Multiple Sub-Sites That Can Be Targeted By Sulfated Small Molecules for Inducing Inhibition

    PubMed Central

    Sidhu, Preetpal Singh; Abdel Aziz, May H.; Sarkar, Aurijit; Mehta, Akul Y.; Zhou, Qibing; Desai, Umesh R.

    2013-01-01

    We recently designed a group of novel exosite 2-directed, sulfated, small, allosteric inhibitors of thrombin. To develop more potent inhibitors, monosulfated benzofuran tri- and tetrameric homologs of the parent designed dimers were synthesized in 7–8 steps and found to exhibit a wide range of potencies. Among these, trimer 9a was found to be nearly 10-fold more potent than the first generation molecules. Michaelis-Menten studies indicated an allosteric mechanism of inhibition. Competitive studies using a hirudin peptide (exosite 1 ligand) and, unfractionated heparin, heparin octasaccharide and γ′-fibrinogen peptide (exosite 2 ligands), demonstrated exosite 2 recognition in a manner different from the parent dimers. Alanine scanning mutagenesis of 12 Arg/Lys residues of exosite 2 revealed a defect in 9a potency for Arg233Ala thrombin only confirming the major difference in site of recognition between the two structurally related sulfated benzofurans. The results suggest that multiple avenues are available within exosite 2 for inducing thrombin inhibition. PMID:23718540

  12. Polysaccharide Degradation

    NASA Astrophysics Data System (ADS)

    Stone, Bruce A.; Svensson, Birte; Collins, Michelle E.; Rastall, Robert A.

    An overview of current and potential enzymes used to degrade polysaccharides is presented. Such depolymerases are comprised of glycoside hydrolases, glycosyl transferases, phosphorylases and lyases, and their classification, active sites and action patterns are discussed. Additionally, the mechanisms that these enzymes use to cleave glycosidic linkages is reviewed as are inhibitors of depolymerase activity; reagents which react with amino acid residues, glycoside derivatives, transition state inhibitors and proteinaceous inhibitors. The characterization of various enzymes of microbial, animal or plant origin has led to their widespread use in the production of important oligosaccharides which can be incorporated into food stuffs. Sources of polysaccharides of particular interest in this chapter are those from plants and include inulin, dextran, xylan and pectin, as their hydrolysis products are purported to be functional foods in the context of gastrointestinal health. An alternative use of degraded polysaccharides is in the treatment of disease. The possibility exists to treat bacterial exopolysaccharide with lyases from bacteriophage to produce oligosaccharides exhibiting bioactive sequences. Although this area is currently in its infancy the knowledge is available to investigate further.

  13. Anti-Epileptic Effect of Ganoderma Lucidum Polysaccharides by Inhibition of Intracellular Calcium Accumulation and Stimulation of Expression of CaMKII α in Epileptic Hippocampal Neurons

    PubMed Central

    Wang, Shu-Qiu; Li, Xiao-Jie; Qiu, Hong-Bin; Jiang, Zhi-Mei; Simon, Maria; Ma, Xiao-Ru; Liu, Lei; Liu, Jun-Xing; Wang, Fang-Fang; Liang, Yan-Feng; Wu, Jia-Mei; Di, Wei-Hua; Zhou, Shaobo

    2014-01-01

    Purpose To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II α expression in a model of epileptic neurons were investigated. Method Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II α protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results The CaMK II α expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion GLP may inhibit calcium overload and promote CaMK II α expression to protect epileptic neurons. PMID:25010576

  14. Acanthopanax senticosus polysaccharides-induced intestinal tight junction injury alleviation via inhibition of NF-κB/MLCK pathway in a mouse endotoxemia model

    PubMed Central

    Han, Jie; Li, Ji-Hong; Bai, Guang; Shen, Guo-Shun; Chen, Jing; Liu, Jia-Nan; Wang, Shuo; Liu, Xian-Jun

    2017-01-01

    AIM To examine the effects of Acanthopanax senticosus polysaccharides (ASPS) on intestinal tight junction (TJ) disruption and nuclear factor-kappa B (NF-κB)/myosin light chain kinase (MLCK) activation in endotoxemia. METHODS BALB/C mice (6-8-weeks-old) received continuous intragastric gavage of ASPS for 7 d before injection of lipopolysaccharide (LPS), or received ASPS once after LPS injection. Blood and intestinal mucosal samples were collected 6 h after LPS challenge. Clinical symptoms, histological injury, intestinal permeability, TJ ultrastructure, and TJ protein expression were determined. RESULTS Compared with mice in the LPS group, pretreatment with ASPS improved clinical and histological scores by 390.9% (P < 0.05) and 57.89% (P < 0.05), respectively, and gut permeability change in endotoxemic mice was shown by a 61.93% reduction in reduced leakage of fluorescein isothiocyanate-dextran 6 h after LPS injection (P < 0.05). ASPS pretreatment also prevented LPS-induced TJ ultrastructure breakdown supported by increased electron dense materials between adjoining cells, sustained redistribution and expression of occludin (0.597 ± 0.027 vs 0.103 ± 0.009, P < 0.05) and zonula occludens-1 (0.507 ± 0.032 vs 0.125 ± 0.019, P < 0.05), and suppressed activation of the NF-κB/MLCK pathway indicated by reduced expression of NF-κB, phospho-inhibitor kappa B-alpha, MLCK and phospho-myosin light-chain-2 by 16.06% (P < 0.05), 54.31% (P < 0.05), 66.10% (P < 0.05) and 64.82% (P < 0.05), respectively. CONCLUSION ASPS pretreatment may be associated with inhibition of the NF-κB/MLCK pathway and concomitant amelioration of LPS-induced TJ dysfunction of intestinal epithelium in endotoxemia.

  15. A polysaccharide from Pinellia ternata inhibits cell proliferation and metastasis in human cholangiocarcinoma cells by targeting of Cdc42 and 67kDa Laminin Receptor (LR).

    PubMed

    Li, Yong; Li, Dajiang; Chen, Jian; Wang, Shuguang

    2016-12-01

    In this study, we isolated and purified a polysaccharide (PTPA) from the tubers of Pinellia ternate. We aimed to evaluate the cytotoxic effects of PTPA on human cholangiocarcinoma (CCA) cell lines and to identify the underlying molecular mechanism. PTPA at the dose from 25 to 200μg/mL showed significant inhibitory effect on the proliferation of four cancer cell lines (SNU-245, CL-6, Sk-ChA-1 and MZ-ChA-1), among which Sk-ChA-1 was a most sensitive cell line to PTPA treatment via induction of apoptosis. Interestingly, RNA interference of Sk-ChA-1 cells with 67LR or Cdc42-targeted shRNAs resulted a similar potency in decreasing cell viability and causing apoptotic death. Moreover, PTPA (100μg/mL) or 67LR or Cdc42 special shRNAs increased the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2, induced the activation of caspase-9 and caspase-3, but not caspsase-8, and inhibited the expression of 67LR or Cdc42 protein in Sk-ChA-1 cells. Taken together, the inhibitory effect of PTPA on the cell growth of Sk-ChA-1 cells was at least in part mediated via the activation of the intrinsic mitochondrial apoptotic pathway and the downregulation of 67LR or Cdc42 protein expression. Thus, PTPA may be developed as a promising candidate for chemopreventive agent in the prevention and treatment of human CCA.

  16. Comparison of physicochemical characteristics and anticoagulant activities of polysaccharides from three sea cucumbers.

    PubMed

    Luo, Lan; Wu, Mingyi; Xu, Li; Lian, Wu; Xiang, Jingying; Lu, Feng; Gao, Na; Xiao, Chuang; Wang, Shengmin; Zhao, Jinhua

    2013-02-05

    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.

  17. Polysaccharide peptides from COV-1 strain of Coriolus versicolor inhibit tolbutamide 4-hydroxylation in the rat in vitro and in vivo.

    PubMed

    Yeung, John H K; Chan, Siu-Lung; Or, Penelope M Y

    2006-08-01

    Polysaccharide peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy in China. In this study, the effects of whole PSP extract and water extract of PSP on 4-hydroxylation of tolbutamide were investigated in rat liver microsomes in vitro and in vivo in the rat. Both the whole PSP extract and the water soluble fraction (0.5-20 microM) decreased the metabolism of tolbutamide to 4-hydroxytolbutamide in vitro. Enzyme kinetics studies showed that PSP inhibited tolbutamide 4-hydroxylase activity in a competitive, concentration-dependent manner. The whole PSP extract had a Ki value of 12.6 microM and IC50 at 18.4 microM, while the water extract had a Ki value of 6.9 microM and IC50 at 9.8 microM. Sulphaphenazole, a specific human CYP2C9 inhibitor, showed a Ki value of 30.8 microM and IC50 at 44.0 microM in the test system. In the pharmacokinetic studies in vivo, acute PSP (4 micromol/kg, i.p.) treatment did not produce significant changes in tolbutamide clearance, but produced a decrease in the Cinitial (7.4%) and an increase in the Vd (7.4%). Sub-chronic pre-treatment of PSP (1-2 micromol/kg/day, i.p.) for three days did not affect the clearance and AUC of tolbutamide, but the Cinitial was decreased, together with increases in the T1/2, and Vd. The formation of 4-hydroxytolbutamide in vivo was decreased in both acute and sub-chronic studies. Taken together, this study demonstrated the PSP can inhibit tolbutamide 4-hydroxylation both in vitro and in vivo. Despite the fact that CYP isoforms that metabolise tolbutamide are different between rat and human liver due to different catalytic characteristics, and rat studies may not be directly extrapolatable to man, the concomitant use of PSP with other CYP2C substrates should be carefully monitored.

  18. Cloning and Characterization of a Novel Chondroitin Sulfate/Dermatan Sulfate 4-O-Endosulfatase from a Marine Bacterium*

    PubMed Central

    Wang, Wenshuang; Han, Wenjun; Cai, Xingya; Zheng, Xiaoyu; Sugahara, Kazuyuki; Li, Fuchuan

    2015-01-01

    Sulfatases are potentially useful tools for structure-function studies of glycosaminoglycans (GAGs). To date, various GAG exosulfatases have been identified in eukaryotes and prokaryotes. However, endosulfatases that act on GAGs have rarely been reported. Recently, a novel HA and CS lyase (HCLase) was identified for the first time from a marine bacterium (Han, W., Wang, W., Zhao, M., Sugahara, K., and Li, F. (2014) J. Biol. Chem. 289, 27886–27898). In this study, a putative sulfatase gene, closely linked to the hclase gene in the genome, was recombinantly expressed and characterized in detail. The recombinant protein showed a specific N-acetylgalactosamine-4-O-sulfatase activity that removes 4-O-sulfate from both disaccharides and polysaccharides of chondroitin sulfate (CS)/dermatan sulfate (DS), suggesting that this sulfatase represents a novel endosulfatase. The novel endosulfatase exhibited maximal reaction rate in a phosphate buffer (pH 8.0) at 30 °C and effectively removed 17–65% of 4-O-sulfates from various CS and DS and thus significantly inhibited the interactions of CS and DS with a positively supercharged fluorescent protein. Moreover, this endosulfatase significantly promoted the digestion of CS by HCLase, suggesting that it enhances the digestion of CS/DS by the bacterium. Therefore, this endosulfatase is a potential tool for use in CS/DS-related studies and applications. PMID:25648894

  19. Anticoagulant Activity of a Unique Sulfated Pyranosic (1→3)-β-l-Arabinan through Direct Interaction with Thrombin*

    PubMed Central

    Fernández, Paula V.; Quintana, Irene; Cerezo, Alberto S.; Caramelo, Julio J.; Pol-Fachin, Laercio; Verli, Hugo; Estevez, José M.; Ciancia, Marina

    2013-01-01

    A highly sulfated 3-linked β-arabinan (Ab1) with arabinose in the pyranose form was obtained from green seaweed Codium vermilara (Bryopsidales). It comprised major amounts of units sulfated on C-2 and C-4 and constitutes the first polysaccharide of this type isolated in the pure form and fully characterized. Ab1 showed anticoagulant activity by global coagulation tests. Less sulfated arabinans obtained from the same seaweed have less or no activity. Ab1 exerts its activity through direct and indirect (antithrombin- and heparin cofactor II-mediated) inhibition of thrombin. Direct thrombin inhibition was studied in detail. By native PAGE, it was possible to detect formation of a complex between Ab1 and human thrombin (HT). Ab1 binding to HT was measured by fluorescence spectroscopy. CD spectra of the Ab1 complex suggested that ligand binding induced a small conformational change on HT. Ab1-thrombin interactions were studied by molecular dynamic simulations using the persulfated octasaccharide as model compound. Most carbohydrate-protein contacts would occur by interaction of sulfate groups with basic amino acid residues on the surface of the enzyme, more than 60% of them being performed by the exosite 2-composing residues. In these interactions, the sulfate groups on C-2 were shown to interact more intensely with the thrombin structure. In contrast, the disulfated oligosaccharide does not promote major conformational modifications at the catalytic site when complexed to exosite 1. These results show that this novel pyranosic sulfated arabinan Ab1 exerts its anticoagulant activity by a mechanism different from those found previously for other sulfated polysaccharides and glycosaminoglycans. PMID:23161548

  20. Anticoagulant activity of a unique sulfated pyranosic (1->3)-β-L-arabinan through direct interaction with thrombin.

    PubMed

    Fernández, Paula V; Quintana, Irene; Cerezo, Alberto S; Caramelo, Julio J; Pol-Fachin, Laercio; Verli, Hugo; Estevez, José M; Ciancia, Marina

    2013-01-04

    A highly sulfated 3-linked β-arabinan (Ab1) with arabinose in the pyranose form was obtained from green seaweed Codium vermilara (Bryopsidales). It comprised major amounts of units sulfated on C-2 and C-4 and constitutes the first polysaccharide of this type isolated in the pure form and fully characterized. Ab1 showed anticoagulant activity by global coagulation tests. Less sulfated arabinans obtained from the same seaweed have less or no activity. Ab1 exerts its activity through direct and indirect (antithrombin- and heparin cofactor II-mediated) inhibition of thrombin. Direct thrombin inhibition was studied in detail. By native PAGE, it was possible to detect formation of a complex between Ab1 and human thrombin (HT). Ab1 binding to HT was measured by fluorescence spectroscopy. CD spectra of the Ab1 complex suggested that ligand binding induced a small conformational change on HT. Ab1-thrombin interactions were studied by molecular dynamic simulations using the persulfated octasaccharide as model compound. Most carbohydrate-protein contacts would occur by interaction of sulfate groups with basic amino acid residues on the surface of the enzyme, more than 60% of them being performed by the exosite 2-composing residues. In these interactions, the sulfate groups on C-2 were shown to interact more intensely with the thrombin structure. In contrast, the disulfated oligosaccharide does not promote major conformational modifications at the catalytic site when complexed to exosite 1. These results show that this novel pyranosic sulfated arabinan Ab1 exerts its anticoagulant activity by a mechanism different from those found previously for other sulfated polysaccharides and glycosaminoglycans.

  1. Sulfation and biological activities of konjac glucomannan.

    PubMed

    Bo, Surina; Muschin, Tegshi; Kanamoto, Taisei; Nakashima, Hideki; Yoshida, Takashi

    2013-05-15

    The sulfation of konjac glucomannan and its anti-HIV and blood anticoagulant activities were investigated. Konjac glucomannan is a polysaccharide occurring naturally in konjac plant tubers and has high molecular weights. Solubility in water is very low, and the aqueous solutions at low concentrations have high viscosity. Before sulfation, hydrolysis by diluted sulfuric acid was carried out to decrease the molecular weights of M¯n=19.2 × 10(4)-0.2 × 10(4). Sulfation with piperidine-N-sulfonic acid or SO3-pyridine complex gave sulfated konjac glucomannans with molecular weights of M¯n=1.0 × 10(4)-0.4 × 10(4) and degrees of sulfation (DS) of 1.3-1.4. It was found that the sulfated konjac glucomannans had potent anti-HIV activity at a 50% effective concentration, (EC50) of 1.2-1.3 μg/ml, which was almost as high as that of an AIDS drug, ddC, whose EC50=3.2 μg/ml, and moderate blood anticoagulant activity, AA=0.8-22.7 units/mg, compared to those of standard sulfated polysaccharides, curdlan (10 units/mg) and dextran (22.7 units/mg) sulfates. Structural analysis of sulfated konjac glucomannans with negatively charged sulfated groups was performed by high resolution NMR, and the interaction between poly-l-lysine with positively charged amino groups as a model compound of proteins and peptides was measured by surface plasmon resonance measurement, suggesting that the sulfated konjac glucomannans had a high binding stability on immobilized poly-l-lysine. The binding of sulfated konjac glucomannan was concentration-dependent, and the biological activity of the sulfated konjac glucomannans may be due to electrostatic interaction between the sulfate and amino groups.

  2. Glycyrrhiza polysaccharide induces apoptosis and inhibits proliferation of human hepatocellular carcinoma cells by blocking PI3K/AKT signal pathway.

    PubMed

    Chen, Jiayu; Jin, Xiaoyan; Chen, Jie; Liu, Chibo

    2013-06-01

    To study the antitumor effect of glycyrrhiza polysaccharide (GPS) on human hepatocellular carcinoma cells and its mechanism, GPS was extracted and identified with phenol-sulfuric acid assay, Limulus amebocytes lysate assay, gel permeation chromatography, and infrared spectroscopy analysis. To study its antitumor function, 4-5-week-old imprinting control region mice were subcutaneously implanted with H22 cells and intragastrically subjected to 1 ml GPS (25, 50, and 75 mg/kg/day), 150 mg/kg cyclophosphamide in a dose of 150 mg/kg, or equal volume of phosphate buffered saline as control. Tumor weights were detected 10 days later. Apoptosis of intraperitoneally cultured and GPS-treated H22 cells was identified by flow cytometry and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide. In vitro, the function of GPS on cell proliferation was applied on BEL7402 cells and confirmed by 4,6-diamidino-z-phenylindole staining. Assessment of the effect of GPS on P53 gene was analyzed by real-time PCR and Western blot, and the effects of GPS on phosphatidylinositol-3 kinase (PI3K), AKT, p-PI3K, and p-AKT were analyzed by Western blot. We extracted the GPS, and it dose-dependently inhibited the tumorigenicity of hepatocellular carcinoma cells in nude mice. GPS treatment resulted in a significant (P<0.05) dose-dependent increase in the number of apoptotic cells in vivo and a significant (P<0.05) dose-dependent decrease in hepatocellular carcinoma cell proliferation in vitro. GPS modified multiple key enzymes (p-PI3K, p-AKT, and P53) in P53/PI3K/AKT signaling pathways on DNA or protein levels. Taken together, we extracted the GPS successfully and our findings suggest that GPS functions as a tumor suppressor through influencing the P53/PI3K/AKT pathway in the carcinogenesis of hepatocellular carcinoma and may have therapeutic implications for the clinical management of hepatocellular carcinoma patients.

  3. Quorum Sensing and the Use of Quorum Quenchers as Natural Biocides to Inhibit Sulfate-Reducing Bacteria

    PubMed Central

    Scarascia, Giantommaso; Wang, Tiannyu; Hong, Pei-Ying

    2016-01-01

    Sulfate-reducing bacteria (SRB) are one of the main protagonist groups of biocorrosion in the seawater environment. Given their principal role in biocorrosion, it remains a crucial task to develop strategies to reduce the abundance of SRBs. Conventional approaches include the use of biocides and antibiotics, which can impose health, safety, and environmental concerns. This review examines an alternative approach to this problem. This is achieved by reviewing the role of quorum sensing (QS) in SRB populations and its impact on the biofilm formation process. Genome databases of SRBs are mined to look for putative QS systems and homologous protein sequences representative of autoinducer receptors or synthases. Subsequently, this review puts forward the potential use of quorum quenchers as natural biocides against SRBs and outlines the potential strategies for the implementation of this approach. PMID:27983678

  4. Bioengineered heparins and heparan sulfates.

    PubMed

    Fu, Li; Suflita, Matthew; Linhardt, Robert J

    2016-02-01

    Heparin and heparan sulfates are closely related linear anionic polysaccharides, called glycosaminoglycans, which exhibit a number of important biological and pharmacological activities. These polysaccharides, having complex structures and polydispersity, are biosynthesized in the Golgi of animal cells. While heparan sulfate is a widely distributed membrane and extracellular glycosaminoglycan, heparin is found primarily intracellularly in the granules of mast cells. While heparin has historically received most of the scientific attention for its anticoagulant activity, interest has steadily grown in the multi-faceted role heparan sulfate plays in normal and pathophysiology. The chemical synthesis of these glycosaminoglycans is largely precluded by their structural complexity. Today, we depend on livestock animal tissues for the isolation and the annual commercial production of hundred ton quantities of heparin used in the manufacture of anticoagulant drugs and medical device coatings. The variability of animal-sourced heparin and heparan sulfates, their inherent impurities, the limited availability of source tissues, the poor control of these source materials and their manufacturing processes, suggest a need for new approaches for their production. Over the past decade there have been major efforts in the biotechnological production of these glycosaminoglycans, driven by both therapeutic applications and as probes to study their natural functions. This review focuses on the complex biology of these glycosaminoglycans in human health and disease, and the use of recombinant technology in the chemoenzymatic synthesis and metabolic engineering of heparin and heparan sulfates.

  5. Heparin sequences in the heparan sulfate chains of an endothelial cell proteoglycan

    SciTech Connect

    Nader, H.B.; Dietrich, C.P.; Buonassisi, V.; Colburn, P.

    1987-06-01

    The structure of the glycosaminoglycan chain of a heparan sulfate proteoglycan isolated from the conditioned medium of an endothelial cell line has been analyzed by using various degradative enzymes (heparitinase I, heparitinase II, heparinase, glycuronidase, sulfatases) from Flavobacterium heparinum. (/sup 35/S)sulfuric acid and/or (/sup 3/H) glucosamine ucre used in preparing heparan sulfate proteoglycan. This proteoglycan inhibits the thromboplastin-activated pathway of coagulation; as a consequence, the catalytic conversion of prothrombin to thrombin is arrested. Heparitinase I, an enzyme with specificity restricted to the heparan sulfate portion of the polysaccharide, releases fragments with the electrophoretic mobility and the structure of heparin. Conversely, as assessment of the size and distribution of the heparan sulfate regions has been provided by the use of heparinase, which, by degrading the heparin sections of the chain, releases two segments that exhibit the structure of heparan sulfate. One of these segments is attached to the protein core. On the basis of these findings, the heparan sulfate chain can be defined as a copolymer containing heparin regions in its structure. The combined use of these enzymes has made it possible to establish the disaccharide sequence of parts of the glycosaminoglycan moiety of this proteoglycan.

  6. Optimization of chemical sulfation, structural characterization and anticoagulant activity of Agaricus bisporus fucogalactan.

    PubMed

    Román, Yony; Iacomini, Marcello; Sassaki, Guilherme L; Cipriani, Thales R

    2016-08-01

    A fucogalactan (E) was isolated from aqueous extract of Agaricus bisporus. The monosaccharide composition, methylation, and NMR analyses showed it is constituted by a (1→6)-linked α-d-Galp main-chain, partially methylated at O-3, and partially substituted at O-2 by non-reducing end-units of α-l-Fucp or α-d-Galp. HPSEC analysis showed it had Mw of 1.28×10(4)gmol(-1). The polysaccharide was sulfated modifying reaction time, molar ratio of sulfation agent to hydroxyl group on the polysaccharide (ηClSO3H/OH ratio), and ratio of total reaction volume to weight of sample (VT/w ratio; μLmg(-1)). The degree of substitution (DS) was evaluated for all sulfated derivatives. The sulfated fucogalactan with the highest DS value (2.83) had the best anticoagulant activity on Activated Partial Thromboplastin Time (APTT) and Protrombin Time (PT) assays. This sulfated fucogalactan, named E100, was obtained with the optimal conditions of ηClSO3H/OH ratio of 18, VT/w ratio of 100, in 6h of reaction. The results showed that E100 produces a linear increment of APTT for concentrations of 15-45μgmL(-1), whereas PT was almost constant between 20 and 400μgmL(-1), suggesting an anticoagulant activity via inhibition of the intrinsic pathway of blood coagulation. NMR and methylation analyses showed that α-d-Galp units of the main chain were greatly sulfated on 2-O-, 3-O-, and 4-O-positions.

  7. Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation.

    PubMed

    Wang, Xiaoping; Sun, Yang; Zhao, Yue; Ding, Youxiang; Zhang, Xiaobo; Kong, Lingyi; Li, Zhiyu; Guo, Qinglong; Zhao, Li

    2016-04-15

    Oroxyloside, as a metabolite of oroxylin A, may harbor various beneficial bioactivities which have rarely been reported in the previous studies. Here we established the dextran sulfate sodium (DSS)-induced experimental colitis and evaluated the anti-inflammatory effect of oroxyloside in vivo. As a result, oroxyloside attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. Furthermore, oroxyloside inhibited inflammatory cell infiltration and decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well. The production of pro-inflammatory cytokines in serum and colon was also significantly reduced by oroxyloside. We unraveled the underlying mechanisms that oroxyloside inhibited NF-κB pathway by activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) to attenuate DSS-induced colitis. Moreover, we investigated the anti-inflammatory effect and mechanisms of oroxyloside in the mouse macrophage cell line RAW264.7 and bone marrow derived macrophages (BMDM). Oroxyloside decreased several LPS-induced inflammatory cytokines, including IL-1β, IL-6 and TNF-α in RAW264.7 and BMDM. We also found that oroxyloside inhibited LPS-induced activation of NF-κB signaling pathway via activating PPARγ in RAW 264.7 and BMDM. Docking study showed that oroxyloside could bind with PPARγ. GW9662, the inhibitor of PPARγ, and PPARγ siRNA transfection blocked the effect of oroxyloside on PPARγ activation. Our study suggested that oroxyloside prevented DSS-induced colitis by inhibiting NF-κB pathway through PPARγ activation. Therefore, oroxyloside may be a promising and effective agent for inflammatory bowel disease (IBD).

  8. Ginsenoside Metabolite Compound K Promotes Recovery of Dextran Sulfate Sodium-Induced Colitis and Inhibits Inflammatory Responses by Suppressing NF-κB Activation

    PubMed Central

    Li, Juan; Zhong, Wei; Wang, Weiwei; Hu, Shaoping; Yuan, Jiahui; Zhang, Bing; Hu, Tianhui; Song, Gang

    2014-01-01

    Phytogenic compounds with anti-oxidant and anti-inflammatory properties, such as ginsenoside metabolite compound K (CK) or berberine (BBR), are currently discussed as promising complementary agents in the prevention and treatment of cancer and inflammation. The latest study showed that ginsenoside Rb1 and its metabolites could inhibit TNBS-induced colitis injury. However, the functional mechanisms of anti-inflammation effects of ginsenoside, particularly its metabolite CK are still not clear. Here, using dextran sulfate sodium (DSS)-induced colitis in mice, clinical parameters, intestinal integrity, pro-inflammatory cytokines production, and signaling pathways in colonic tissues were determined. In mild and sever colitis mice, CK and BBR (as a positive agent) alleviated colitis histopathology injury, ameliorated myeloperoxidase (MPO) activity, reduced pro-inflammatory cytokines production, such as, IL-6, IL-1β, TNF-α, and increased anti-inflammatory cytokine IL-10 production in both mice colon tissues and blood. Nevertheless, the results revealed that CK and BBR inhibited NF-κB p65 nuclear translocation, downregulated p-IκBα and upregulated IκBα, indicating that CK, as well as BBR, suppressed the activation of the NF-κB pathway in the progression of colitis with immunofluorescence, immunohistochemical and western blotting analysis. Furthermore, CK inhibited pro-inflammatory cytokines production in LPS-activated macrophages via down-regulation of NF-κB signaling pathway. Taken together, our results not only reveal that CK promotes the recovery of the progression of colitis and inhibits the inflammatory responses by suppressing NF-κB activation, but also suggest that CK downregulates intestinal inflammation through regulating the activation of macrophages and pro-inflammatory cytokines production. PMID:24504372

  9. Polysaccharides purified from wild Cordyceps activate FGF2/FGFR1c signaling

    NASA Astrophysics Data System (ADS)

    Zeng, Yangyang; Han, Zhangrun; Yu, Guangli; Hao, Jiejie; Zhang, Lijuan

    2015-02-01

    Land animals as well as all organisms in ocean synthesize sulfated polysaccharides. Fungi split from animals about 1.5 billion years ago. As fungi make the evolutionary journey from ocean to land, the biggest changes in their living environment may be a sharp decrease in salt concentration. It is established that sulfated polysaccharides interact with hundreds of signaling molecules and facilitate many signaling transduction pathways, including fibroblast growth factor (FGF) and FGF receptor signaling pathway. The disappearance of sulfated polysaccharides in fungi and plants on land might indicate that polysaccharides without sulfation might be sufficient in facilitating protein ligand/receptor interactions in low salinity land. Recently, it was reported that plants on land start to synthesize sulfated polysaccharides in high salt environment, suggesting that fungi might be able to do the same when exposed in such environment. Interestingly, Cordyceps, a fungus habituating inside caterpillar body, is the most valued traditional Chinese Medicine. One of the important pharmaceutical active ingredients in Cordyceps is polysaccharides. Therefore, we hypothesize that the salty environment inside caterpillar body might allow the fungi to synthesize sulfated polysaccharides. To test the hypothesis, we isolated polysaccharides from both lava and sporophore of wild Cordyceps and also from Cordyceps militaris cultured without or with added salts. We then measured the polysaccharide activity using a FGF2/FGFR1c signaling-dependent BaF3 cell proliferation assay and found that polysaccharides isolated from wild Cordyceps activated FGF2/FGFR signaling, indicating that the polysaccharides synthesized by wild Cordyceps are indeed different from those by the cultured mycelium.

  10. Simultaneous inhibition of sulfate-reducing bacteria, removal of H2S and production of rhamnolipid by recombinant Pseudomonas stutzeri Rhl: Applications for microbial enhanced oil recovery.

    PubMed

    Zhao, Feng; Zhou, Ji-Dong; Ma, Fang; Shi, Rong-Jiu; Han, Si-Qin; Zhang, Jie; Zhang, Ying

    2016-05-01

    Sulfate-reducing bacteria (SRB) are widely existed in oil production system, and its H2S product inhibits rhamnolipid producing bacteria. In-situ production of rhamnolipid is promising for microbial enhanced oil recovery. Inhibition of SRB, removal of H2S and production of rhamnolipid by recombinant Pseudomonas stutzeri Rhl were investigated. Strain Rhl can simultaneously remove S(2-) (>92%) and produce rhamnolipid (>136mg/l) under S(2-) stress below 33.3mg/l. Rhl reduced the SRB numbers from 10(9) to 10(5)cells/ml, and the production of H2S was delayed and decreased to below 2mg/l. Rhl also produced rhamnolipid and removed S(2-) under laboratory simulated oil reservoir conditions. High-throughput sequencing data demonstrated that addition of strain Rhl significantly changed the original microbial communities of oilfield production water and decreased the species and abundance of SRB. Bioaugmentation of strain Rhl in oilfield is promising for simultaneous control of SRB, removal of S(2-) and enhance oil recovery.

  11. Adding sodium dodecyl sulfate and Pseudomonas aeruginosa UG2 biosurfactants inhibits polycyclic aromatic hydrocarbon biodegradation in a weathered creosote-contaminated soil.

    PubMed

    Deschênes, L; Lafrance, P; Villeneuve, J P; Samson, R

    1996-12-01

    The effect of two anionic surfactants was assessed during biodegradation of 13 of the 16 USEPA priority polycyclic aromatic hydrocarbons (PAH) in a wood-preserving soil contaminated with creosote and pentacholorophenol for a period of at least 20 years. Sodium dodecyl sulfate (SDS) and biosurfactants from Pseudomonas aeruginosa UG2 were utilized at concentrations of 10, 100 and 500 micrograms/g soil. Because both surfactants are readily biodegradable, the microcosms received a fresh spike of surfactant every 2 weeks. Biodegradation of aged PAH residues was monitored by GC/MS for a period of 45 weeks. Results indicated that the biodegradation of the three-ring PAH was rapid and almost complete but was slowed by the addition of 100 micrograms/g and 500 micrograms/g chemical surfactant. Similarly, at the same concentrations, the two surfactants significantly decreased the biodegradation rate of the four-ring PAH. In this case, the inhibition was more pronounced with SDS. High-molecular-mass PAH (more than four rings) were not biodegraded under the test conditions. It was suggested that the preferential utilization of surfactants by PAH degraders was responsible for the inhibition observed in the biodegradation of the hydrocarbons. The high biodegradability and the inhibitory effect of these two surfactants would have a significant impact on the development of both above-ground and in situ site reclamation processes.

  12. Phosphatidylcholine nanovesicles coated with chitosan or chondroitin sulfate as novel devices for bacteriocin delivery

    NASA Astrophysics Data System (ADS)

    da Silva, Indjara Mallmann; Boelter, Juliana Ferreira; da Silveira, Nádya Pesce; Brandelli, Adriano

    2014-07-01

    There is increased interest on the use of natural antimicrobial peptides in biomedicine and food preservation technologies. In this study, the antimicrobial activity of nisin encapsulated into nanovesicles containing polyanionic polysaccharides was investigated. Nisin was encapsulated in phosphatidylcholine (PC) liposomes containing chitosan or chondroitin sulfate by the thin-film hydration method and tested for antimicrobial activity against Listeria spp. The mean particle size of PC liposomes was 145 nm and varied to 210 and 134 nm with the incorporation of chitosan and chondroitin sulfate, respectively. Nisin-containing nanovesicles with and without incorporation of polysaccharides had a zeta potential values around -20 mV, showing mostly spherical structures when observed by transmission electron microscopy. Encapsulated nisin had similar efficiency as free nisin in inhibiting Listeria spp. isolated from bovine carcass, and greater efficiency in inhibiting Listeria monocytogenes. The formulation containing chitosan was more stable and more efficient in inhibiting L. monocytogenes when compared to the other nanovesicles tested. After 24 h, the viable cell counts were 2 log lower as compared with the other treatments and 7 log comparing to controls.

  13. Panels of chemically-modified heparin polysaccharides and natural heparan sulfate saccharides both exhibit differences in binding to Slit and Robo, as well as variation between protein binding and cellular activity† †Electronic supplementary information (ESI) available: NMR chemical shift characterisation of modified heparins, protein sequence alignment methodology and data, protein binding and activity assay dose-response curves. See DOI: 10.1039/c6mb00432f Click here for additional data file.

    PubMed Central

    Ahmed, Yassir A.; Yates, Edwin A.; Moss, Diana J.; Loeven, Markus A.; Hussain, Sadaf-Ahmahni; Hohenester, Erhard; Turnbull, Jeremy E.

    2016-01-01

    Heparin/heparan sulfate (HS) glycosaminoglycans are required for Slit–Robo cellular responses. Evidence exists for interactions between each combination of Slit, Robo and heparin/HS and for formation of a ternary complex. Heparin/HS are complex mixtures displaying extensive structural diversity. The relevance of this diversity has been studied to a limited extent using a few select chemically-modified heparins as models of HS diversity. Here we extend these studies by parallel screening of structurally diverse panels of eight chemically-modified heparin polysaccharides and numerous natural HS oligosaccharide chromatographic fractions for binding to both Drosophila Slit and Robo N-terminal domains and for activation of a chick retina axon response to the Slit fragment. Both the polysaccharides and oligosaccharide fractions displayed variability in binding and cellular activity that could not be attributed solely to increasing sulfation, extending evidence for the importance of structural diversity to natural HS as well as model modified heparins. They also displayed differences in their interactions with Slit compared to Robo, with Robo preferring compounds with higher sulfation. Furthermore, the patterns of cellular activity across compounds were different to those for binding to each protein, suggesting that biological outcomes are selectively determined in a subtle manner that does not simply reflect the sum of the separate interactions of heparin/HS with Slit and Robo. PMID:27502551

  14. Solid substrate-room temperature phosphorimetry for the determination of trace terbutaline sulfate based on its inhibition oxidation of rhodamine 6G by sodium periodate.

    PubMed

    Liu, Jia-Ming; Gao, Fei; Gao, Wen-Yan; Zeng, Li-Qing; Huang, Xiao-Mei; Li, Zhi-Ming; Huang, Xiu-Chai; Lin, Wei-Nv; Wang, Fang-Mei; Nie, Chang-Ling

    2008-03-01

    When 1.00 mol l(-1) I(-) is used as ion perturber, rhodamine 6G (Rh 6G) can emit strong and stable room temperature phosphorescence (RTP) on filter paper substrate in KHC(8)H(4)O(4)-HCl buffer solution (pH = 3.50), heated at 70 degrees C for 10 min. NaIO(4) can oxidize Rh 6G, which makes the RTP signal quench. Terbutaline sulfate (TBS) can inhibit NaIO(4) from oxidizing Rh 6G, which makes the RTP signal of Rh 6G enhance sharply. The content of TBS is linear correlation to DeltaIp of the system. Based on the facts above, a new inhibition solid substrate-room temperature phosphorimetry (SS-RTP) for the determination of trace TBS has been established. The linear range of this method is 0.0104-2.08 pg spot(-1) (corresponding concentration: 0.026-5.2 ng ml(-1), with a sample volume of 0.4 microl) with a detection limit (L.D.) of 2.6 fg spot(-1) (corresponding concentration: 6.5 x 10(-12) g ml(-1)), and the regression equation of working curve is DeltaIp = 2.040 + 54.54 m(TBS) (pg spot(-1)), n = 6, correlation coefficient is 0.9994. For the samples containing 0.0104 pg spot(-1) and 2.08 pg spot(-1) TBS, the relative standard deviation (RSD) are 3.8% and 2.3% (n = 8), respectively, indicating good precision. This method has been applied to determination of trace TBS in the practical samples with satisfactory results. The reaction mechanism of NaIO(4) oxidizing Rh 6G to inhibit SS-RTP for the determination of trace TBS is also discussed.

  15. Selective sulfation of carrageenans and the influence of sulfate regiochemistry on anticoagulant properties.

    PubMed

    de Araújo, Cristiano A; Noseda, Miguel D; Cipriani, Thales R; Gonçalves, Alan G; Duarte, Maria Eugênia R; Ducatti, Diogo R B

    2013-01-16

    Sulfated polysaccharides are recognized for their broad range of biological activities, including anticoagulant properties. The positions occupied by the sulfate groups are often related to the level of the inherent biological activity. Herein the naturally sulfated galactans, kappa-, iota- and theta-carrageenan, were additionally sulfated by regioselective means. The anticoagulant activity of the resulting samples was then studied using the aPTT in vitro assay. The influence of sulfate regiochemistry on the anticoagulant activity was evaluated. From kappa-carrageenan three rare polysaccharides were synthesized, one of them involved a synthetic route with an amphiphilic polysaccharide intermediate containing pivaloyl groups. Iota- and theta-carrageenan were utilized in a selective C6 sulfation at β-D-Galp units to produce different structures comprising trisulfated diads. All the samples were characterized by NMR (1D and 2D). The resulting aPPT measurements suggested that sulfation at C2 of 3,6-anhydro-α-D-Galp and C6 of β-D-Galp increased the anticoagulant activity.

  16. Ulvans induce resistance against plant pathogenic fungi independently of their sulfation degree.

    PubMed

    de Freitas, Mateus B; Ferreira, Luciana G; Hawerroth, Caroline; Duarte, Maria Eugênia R; Noseda, Miguel D; Stadnik, Marciel J

    2015-11-20

    The present work aimed to evaluate the defense responses induced by chemically sulfated ulvans in Arabidopsis thaliana plants against the phytopathogenic fungi Alternaria brassicicola and Colletotrichum higginsianum. Derivatives with growing sulfate content (from 20.9 to 36.6%) were prepared with SO3-pyridine complex in formamide. NMR and FTIR spectroscopic analyses confirmed the increase of sulfate groups after the chemical sulfation process. The native sulfated polysaccharide (18.9% of sulfate) and its chemically sulfated derivatives similarly reduced the severity of both pathogenic fungi infections. Collectively, our results suggest that ulvans induce resistance against both fungal pathogens independently of its sulfation degree.

  17. Polysaccharides from Smilax glabra inhibit the pro-inflammatory mediators via ERK1/2 and JNK pathways in LPS-induced RAW264.7 cells.

    PubMed

    Lu, Chuan-li; Wei, Zhu; Min, Wang; Hu, Meng-mei; Chen, Wen-long; Xu, Xiao-jie; Lu, Chuan-jian

    2015-05-20

    The rhizomes of Smilax glabra have been used as both food and folk medicine in many countries for a long time. However, little research has been reported on polysaccharides of S. glabra. In the present study, two polysaccharide fractions, SGP-1 and SGP-2, were isolated from the rhizomes of S. glabra with the number average molecular weights of 1.72 × 10(2)kDa and 1.31 × 10(2)kDa, and the weight average molecular weights of 1.31 × 10(5)kDa and 1.18 × 10(5)kDa, respectively, and their mainly monosaccharide compositions were both galactose and rhamnose (2.5:1). Both SGP-1 and SGP-2 significantly suppressed the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from LPS-induced RAW 264.7 cells, as well as the mRNA expression of inducible nitric oxide synthase (iNOS), TNF-α and IL-6. Additionally, SGP-1 and SGP-2 repressed the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK). These findings strongly suggested polysaccharides were also the anti-inflammatory active ingredient for S. glabra, and the potential of SGP-1 and SGP-2 as the anti-inflammatory agents.

  18. Anticoagulant activity of native and partially degraded glycoglucuronomannan after chemical sulfation.

    PubMed

    de Oliveira Barddal, Helyn Priscila; Gracher, Ana Helena Pereira; Simas-Tosin, Fernanda Fogagnoli; Iacomini, Marcello; Cipriani, Thales Ricardo

    2015-09-01

    Heparin has great clinical importance as anticoagulant and antithrombotic agent. However, because of its risks of causing bleeding and contamination by animal pathogens, several studies aim to obtain alternatives to heparin. In the search for anticoagulant and antithrombotic agents from a non-animal source, a glycoglucuronomannan from the gum exudate of the plant Vochysia thyrsoidea was partially hydrolyzed, and both native and partially degraded polysaccharides were chemically sulfated, yielding VThS and Ph-VThS respectively. Methylation analysis indicated that sulfation occurred preferentially at the O-5 position of arabinose units in the VThS and at the O-6 position of mannose units in Ph-VThS. In vitro aPTT assay showed that VThS and Ph-VThS have anticoagulant activity, which could be controlled by protamine, and ex vivo aPTT assay demonstrated that Ph-VThS is absorbed by subcutaneous route. Like heparin, they were able to inhibit α-thrombin and factor Xa by a serpin-dependent mechanism. In vivo, VThS and Ph-VThS reduced thrombus formation by approximately 50% at a dose of 40 IU/kg, similarly to heparin. The results demonstrated that the chemically sulfated polysaccharides are promising anticoagulant and antithrombotic agents.

  19. Health benefits of algal polysaccharides in human nutrition.

    PubMed

    Mišurcová, Ladislava; Škrovánková, Soňa; Samek, Dušan; Ambrožová, Jarmila; Machů, Ludmila

    2012-01-01

    The interest in functional food, both freshwater and marine algal products with their possible promotional health effects, increases also in regions where algae are considered as rather exotic food. Increased attention about algae as an abundant source of many nutrients and dietary fiber from the nutrition point of view, as well as from the scientific approaches to explore new nutraceuticals and pharmaceuticals, is based on the presence of many bioactive compounds including polysaccharides extracted from algal matter. Diverse chemical composition of dietary fiber polysaccharides is responsible for their different physicochemical properties, such as their ability to be fermented by the human colonic microbiota resulted in health benefit effects. Fundamental seaweed polysaccharides are presented by alginates, agars, carrageenans, ulvanes, and fucoidans, which are widely used in the food and pharmaceutical industry and also in other branches of industry. Moreover, freshwater algae and seaweed polysaccharides have emerged as an important source of bioactive natural compounds which are responsible for their possible physiological effects. Especially, sulfate polysaccharides exhibit immunomodulatory, antitumor, antithrombotic, anticoagulant, anti-mutagenic, anti-inflammatory, antimicrobial, and antiviral activities including anti-HIV infection, herpes, and hepatitis viruses. Generally, biological activity of sulfate polysaccharides is related to their different composition and mainly to the extent of the sulfation of their molecules. Significant attention has been recently focused on the use of both freshwater algae and seaweed for developing functional food by reason of a great variety of nutrients that are essential for human health.

  20. Review on biomedical and bioengineering applications of cellulose sulfate.

    PubMed

    Zhang, Qilei; Lin, Dongqiang; Yao, Shanjing

    2015-11-05

    Polysaccharide sulfates are naturally existing chemicals that show important biological activities in living organisms. Cellulose sulfate is a semi-synthesized polysaccharide sulfate with a relatively simple chain structure and unique biological properties and its biological applications have been explored in research and clinical trials. With the advance of cellulose derivatization and characterization, cellulose sulfate molecules with tailored structures have been developed to fulfill individual requirements. This review aims to provide a summary of recent development of cellulose sulfate in biomedical applications. Its synthesis pathways were discussed with structure-property relationship elucidated. The application of cellulose sulfate in drug delivery and microbe/cell immobilization were summarized with emphasis given on its polyelectrolyte complex formation processes.

  1. [Biological activities of exogenous polysaccharides via controlling endogenous proteoglycan metabolism in vascular endothelial cells].

    PubMed

    Sato, Tomoko; Yamamoto, Chika; Fujiwara, Yasuyuki; Kaji, Toshiyuki

    2008-05-01

    Proteoglycan contains glycosmainoglycans, which are endogenous sulfated polysaccharides, in the molecule. The metabolism of proteoglycans regulates cell behavior and cellular events. It is possible that exogenous polysaccharide-related molecules exhibit their biological activities by two mechanisms. One is the interaction with cells and the other is the interaction with growth factors/cytokines that regulate proteoglycans. In this review, we describe sodium spirulan, a sulfated polysaccharide obtained from a hot-water extract of the blue-green alga Spirulina platensis, as an exogenous polysaccharide that stimulates the release of proteoglycans from vascular endothelial cells. Factors that regulate endothelial proteoglycan metabolism are also being described as possible target molecules of exogenous polysaccharides. Further research is required to obtain exogenous polysaccharide-related molecules that exhibit useful biological activities through controlling endothelial proteoglycan metabolism for protection against vascular lesions such as atheroslcerosis.

  2. The "in and out" of glucosamine 6-O-sulfation: the 6th sense of heparan sulfate.

    PubMed

    El Masri, Rana; Seffouh, Amal; Lortat-Jacob, Hugues; Vivès, Romain R

    2016-11-03

    The biological properties of Heparan sulfate (HS) polysaccharides essentially rely on their ability to bind and modulate a multitude of protein ligands. These interactions involve internal oligosaccharide sequences defined by their sulfation patterns. Amongst these, the 6-O-sulfation of HS contributes significantly to the polysaccharide structural diversity and is critically involved in the binding of many proteins. HS 6-O-sulfation is catalyzed by 6-O-sulfotransferases (6OSTs) during biosynthesis, and it is further modified by the post-synthetic action of 6-O-endosulfatases (Sulfs), two enzyme families that remain poorly characterized. The aim of the present review is to summarize the contribution of 6-O-sulfates in HS structure/function relationships and to discuss the present knowledge on the complex mechanisms regulating HS 6-O-sulfation.

  3. Enzymatic Modifications of Polysaccharides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polysaccharides are often modified chemically in order to improve its properties or to impart specific characteristics. Indeed quite a few commercial products are based on modified polysaccharides. In this talk, I shall describe a new set of modified polysaccharides based on enzymatic reactions. ...

  4. Biosensor analysis of the molecular interactions of pentosan polysulfate and of sulfated glycosaminoglycans with immobilized elastase, hyaluronidase and lysozyme using surface plasmon resonance (SPR) technology.

    PubMed

    Shen, Bojiang; Shimmon, Susan; Smith, Margaret M; Ghosh, Peter

    2003-02-05

    Pentosan polysulfate (NaPPS) and chondroitin sulfates (ChSs) have recently been shown to exhibit both symptom and disease modifying activities in osteoarthritis (OA), but their respective mechanisms of action are still the subject of conjecture. Excessive catabolism of joint articular cartilage is considered to be responsible for the initiation and progression of OA but the abilities of these drugs to mitigate this process has received only limited attention. Human neutrophil elastase (HNE) is a proteinase, which can degrade the collagens and proteoglycans (PGs) of the cartilage directly or indirectly by activating latent matrix metalloproteinases. Hyaluronidase (HAase) is an endoglycosidase, which degrades glycosaminoglycans including hyaluronan, which provides the aggregating component of the PG aggrecan complex. In the present study the molecular interactions between the NaPPS, ChSs and some other sulfated polysaccharides with immobilized HNE, HAase or lysozyme (a cationic protein implicated in PG metabolism) were studied using a SPR biosensor device-BIAcore2000. The above three enzymes were covalently immobilized to a biosensor chip CM5 separately using amine coupling. The binding affinity of each sulfated polysaccharide and the kinetics of NaPPS over the concentration range of 0.3-5.0 microg/ml were determined. The inhibition of HNE by the sulfated polysaccharides as determined using the synthetic substrate succinyl-Ala-Ala-Val-nitroanilide (SAAVNA) in a functional assay was compared with their respective binding affinities for this proteinase using the BIAcore system. The results obtained with the two independent techniques showed good correlation and indicated that the degree and ring positions of oligosaccharide sulfation were major determinants of enzyme inhibitory activity. The observed difference in order of binding affinities of the drugs to the immobilized HNE, HAase and lysozyme suggests a conformational relationship, in addition to the charge

  5. Selenium-Containing Phycocyanin from Se-Enriched Spirulina platensis Reduces Inflammation in Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Activation.

    PubMed

    Zhu, Chenghui; Ling, Qinjie; Cai, Zhihui; Wang, Yun; Zhang, Yibo; Hoffmann, Peter R; Zheng, Wenjie; Zhou, Tianhong; Huang, Zhi

    2016-06-22

    Selenium (Se) plays an important role in fine-tuning immune responses. Inflammatory bowel disease (IBD) involves hyperresponsive immunity of the digestive tract, and a low Se level might aggravate IBD progression; however, the beneficial effects of natural Se-enriched diets on IBD remain unknown. Previously, we developed high-yield Se-enriched Spirulina platensis (Se-SP) as an excellent organic nutritional Se source. Here we prepared Se-containing phycocyanin (Se-PC) from Se-SP and observed that Se-PC administration effectively reduced the extent of colitis in mouse induced by dextran sulfate sodium. Supplementation with Se-PC resulted in significant protective effects, including mitigation of body weight loss, bloody diarrhea, and colonic inflammatory damage. The anti-inflammatory effects of Se-PC supplementation were found to involve modulation of cytokines, including IL-6, TNF-α, MCP-1, and IL-10. Mechanistically, Se-PC inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which is involved in the transcription of these pro-inflammatory cytokines. These results together suggest potential benefits of Se-PC as a functional Se supplement to reduce the symptoms of IBD.

  6. Chemically engineered sulfated glucans from rice bran exert strong antiviral activity at the stage of viral entry.

    PubMed

    Ray, Bimalendu; Hutterer, Corina; Bandyopadhyay, Shruti S; Ghosh, Kanika; Chatterjee, Udipta R; Ray, Sayani; Zeitträger, Isabel; Wagner, Sabrina; Marschall, Manfred

    2013-12-27

    Attachment and entry of many viruses are mediated by their affinity for polysaccharides present on the surface of target cells. In this paper, we demonstrate that sulfated glucans isolated from rice (Oryza sativa) can be utilized as experimental drugs exerting strong antiviral activity. In particular, oleum-DMF-based extraction is described as a procedure for the generation of chemically engineered glucans from commercially available rice bran. The one-step procedure has the potential to provide a spectrum of related glucans with varying molecular masses and modifications, including sulfation. The sulfated glucans P444, P445, and P446 possess increased antiviral activity compared to a previously described glucan (S1G). P444, P445, and P446 were highly active against human cytomegalovirus (HCMV), moderately active against other members of the family Herpesviridae, while not active against unrelated viruses. Specific experimentation with HCMV-infected cells provided evidence that antiviral activity was based on inhibition of viral entry and that inhibition occurred in the absence of drug-induced cytotoxicity. These findings underline the high potential of sulfated glucans for antiviral research and drug development. In addition, the procedure described for the efficient transformation of glucan hydroxy groups to sulfate groups may be similarly beneficial for the chemical alteration of other natural products.

  7. Fucosylated Chondroitin Sulfates from the Body Wall of the Sea Cucumber Holothuria forskali

    PubMed Central

    Panagos, Charalampos G.; Thomson, Derek S.; Moss, Claire; Hughes, Adam D.; Kelly, Maeve S.; Liu, Yan; Chai, Wengang; Venkatasamy, Radhakrishnan; Spina, Domenico; Page, Clive P.; Hogwood, John; Woods, Robert J.; Mulloy, Barbara; Bavington, Charlie D.; Uhrín, Dušan

    2014-01-01

    Fucosylated chondroitin sulfate (fCS) extracted from the sea cucumber Holothuria forskali is composed of the following repeating trisaccharide unit: →3)GalNAcβ4,6S(1→4) [FucαX(1→3)]GlcAβ(1→, where X stands for different sulfation patterns of fucose (X = 3,4S (46%), 2,4S (39%), and 4S (15%)). As revealed by NMR and molecular dynamics simulations, the fCS repeating unit adopts a conformation similar to that of the Lex blood group determinant, bringing several sulfate groups into close proximity and creating large negative patches distributed along the helical skeleton of the CS backbone. This may explain the high affinity of fCS oligosaccharides for L- and P-selectins as determined by microarray binding of fCS oligosaccharides prepared by Cu2+-catalyzed Fenton-type and photochemical depolymerization. No binding to E-selectin was observed. fCS poly- and oligosaccharides display low cytotoxicity in vitro, inhibit human neutrophil elastase activity, and inhibit the migration of neutrophils through an endothelial cell layer in vitro. Although the polysaccharide showed some anti-coagulant activity, small oligosaccharide fCS fragments had much reduced anticoagulant properties, with activity mainly via heparin cofactor II. The fCS polysaccharides showed prekallikrein activation comparable with dextran sulfate, whereas the fCS oligosaccharides caused almost no effect. The H. forskali fCS oligosaccharides were also tested in a mouse peritoneal inflammation model, where they caused a reduction in neutrophil infiltration. Overall, the data presented support the action of fCS as an inhibitor of selectin interactions, which play vital roles in inflammation and metastasis progression. Future studies of fCS-selectin interaction using fCS fragments or their mimetics may open new avenues for therapeutic intervention. PMID:25147180

  8. Method for producing capsular polysaccharides

    NASA Technical Reports Server (NTRS)

    Kern, Roger G. (Inventor); Petersen, Gene R. (Inventor); Richards, Gil F. (Inventor)

    1994-01-01

    Structurally altered capsular polysaccharides are produced by mutant bacteria. These polysaccharides are isolated by selecting a wild type bacterial strain and a phage producing degradative enzymes that have substrate specificity for the capsular polysaccharides produced by the wild type bacteria. Phage-resistant mutants producing capsular polysaccharides are selected and the structurally altered capsular polysaccharide is isolated therefrom.

  9. Inhibition of dextran sulfate sodium (DSS)-induced intestinal inflammation via enhanced IL-10 and TGF-beta production by galectin-9 homologues isolated from intestinal parasites.

    PubMed

    Kim, Joo-Young; Cho, Min Kyoung; Choi, Seon Hee; Lee, Keun Hee; Ahn, Soon Cheol; Kim, Dong-Hee; Yu, Hak Sun

    2010-11-01

    We isolated a galectin-9 (Gal-9) homologue gene (Tl-gal) from an adult worm of the canine gastrointestinal nematode parasite, Toxascaris leonina, via random cDNA library sequencing. The deduced amino acid sequence of the Tl-gal genes evidenced an identity of 89% with the galectin of Dirofilaria immitis, 87% identity with the galectin of Brugia malayi, and 35% identity with the human GAL-9 gene. To evaluate immune modulate function of Tl-GAL in host inflammatory response, we constructed recombinant Tl-GAL (rTl-GAL) using an Escherichia coli expression vector system and treated to intestinal inflammation mice. Although the carbohydrate-binding ability of rTl-GAL was less than that of rat galectin, we confirmed that recombinant rTl-GAL has carbohydrate-binding activity. The clinical symptoms of dextran sulfate sodium (DSS)-treated mice after rTl-GAL pre-treatment were found to be minimized, or less profound, as compared to those of the rTl-GAL untreated group. Additionally, the DSS-treated mice exhibited a significant shortening of the colon, but the large intestines of the rTl-GAL pre-treated mice were longer than those of the control group (P<0.05). Additionally, the rTl-GAL treated group exhibited significantly increased the levels of TGF-beta and IL-10 (P<0.05). The production of these regulatory cytokines may ameliorate intestinal inflammation. These findings demonstrate that rTl-GAL could inhibit inflammation reactions via the inhibition of Th1 and Th2 cytokine production by increasing the production of TGF-beta and IL-10 cytokines. The rTl-GAL may induce TGF-beta expression, primarily via the activation of the p38 pathway. In conclusion, rTl-GAL may function like a host galectin, thus functioning as a regulatory molecule in the host immune system; rTl-GAL may prove useful in the design of novel therapeutic intervention strategies for the treatment of allergic and immune diseases.

  10. Chemical Modification of Polysaccharides

    PubMed Central

    Cumpstey, Ian

    2013-01-01

    This review covers methods for modifying the structures of polysaccharides. The introduction of hydrophobic, acidic, basic, or other functionality into polysaccharide structures can alter the properties of materials based on these substances. The development of chemical methods to achieve this aim is an ongoing area of research that is expected to become more important as the emphasis on using renewable starting materials and sustainable processes increases in the future. The methods covered in this review include ester and ether formation using saccharide oxygen nucleophiles, including enzymatic reactions and aspects of regioselectivity; the introduction of heteroatomic nucleophiles into polysaccharide chains; the oxidation of polysaccharides, including oxidative glycol cleavage, chemical oxidation of primary alcohols to carboxylic acids, and enzymatic oxidation of primary alcohols to aldehydes; reactions of uronic-acid-based polysaccharides; nucleophilic reactions of the amines of chitosan; and the formation of unsaturated polysaccharide derivatives. PMID:24151557

  11. Properties of polysaccharides in several seaweeds from Atlantic Canada and their potential anti-influenza viral activities

    NASA Astrophysics Data System (ADS)

    Jiao, Guangling; Yu, Guangli; Wang, Wei; Zhao, Xiaoliang; Zhang, Junzeng; Ewart, Stephen H.

    2012-06-01

    To explore the polysaccharides from selected seaweeds of Atlantic Canada and to evaluate their potential anti-influenza virus activities, polysaccharides were isolated from several Atlantic Canadian seaweeds, including three red algae ( Polysiphonia lanosa, Furcellaria lumbricalis, and Palmaria palmata), two brown algae ( Ascophyllum nodosum and Fucus vesiculosus), and one green alga ( Ulva lactuca) by sequential extraction with cold water, hot water, and alkali solutions. These polysaccharides were analyzed for monosaccharide composition and other general chemical properties, and they were evaluated for anti-influenza virus activities. Total sugar contents in these polysaccharides ranged from 15.4% (in U. lactuca) to 91.4% (in F. lumbricalis); sulfation level was as high as 17.6% in a polysaccharide from U. lactuca, whereas it could not be detected in an alikali-extract from P. palmaria. For polysaccharides from red seaweeds, the main sugar units were sulfated galactans (agar or carrageenan) for P. lanosa, F. lumbricalis, and xylans for P. palmata. In brown seaweeds, the polysaccharides largely contained sulfated fucans, whereas the polysaccharides in green seaweed were mainly composed of heteroglycuronans. Screening for antiviral activity against influenza A/PR/8/34 (H1N1) virus revealed that brown algal polysaccharides were particularly effective. Seaweeds from Atlantic Canada are a good source of marine polysaccharides with potential antiviral properties.

  12. Preparation of animal polysaccharides nanofibers by electrospinning and their potential biomedical applications.

    PubMed

    Zhao, Wen; Liu, Wenlong; Li, Jiaojiao; Lin, Xiao; Wang, Ying

    2015-02-01

    Animal polysaccharides belong to a class of biological macromolecules. They are natural biopolymers with numerous advantages for biomedical applications, such as biocompatibility, biodegradability, non-antigenicity and non-toxicity. Electrospinning is a versatile and facile technique which can produce continuous fibers with nanoscale from a wide range of natural and synthetic polymers. The review aims to provide an up-to-date overview of the preparation of animal polysaccharides nanofibers by electrospinning and their potential biomedical applications such as tissue engineering, wound healing, and drug delivery. Various animal polysaccharides including chitin and chitosan (CS), hyaluronic acid (HA), heparin and heparan sulfate (HS), and chondroitin sulfate (ChS), are discussed. The challenges and some useful strategies in electrospinning of animal polysaccharides also are summarized. In addition, future study of animal polysaccharides nanofibers by electrospinning is proposed.

  13. Chemical composition and moisture-absorption/retention ability of polysaccharides extracted from five algae.

    PubMed

    Wang, Jing; Jin, Weihua; Hou, Yun; Niu, Xizhen; Zhang, Hong; Zhang, Quanbin

    2013-06-01

    In this study, we prepared seven polysaccharides extracted from five algae including one brown alga Saccharina japonica, one red alga Porphyra haitanensis and three green algae Codium fragile, Enteromorpha linza and Bryopsis plumose. The chemical composition and capability of moisture-absorption and moisture-retention were investigated in comparison with those of hyaluronic acid (HA). The low molecular weight polysaccharides extracted from brown seaweed exhibited the highest moisture-absorption and moisture-retention abilities of all of the polysaccharides studied and performed better than HA. The relationships between chemical composition (including sulfated groups, monosaccharide, and molecular weight) and the functions of polysaccharides were also studied. We found the sulfated group was a main active site for moisture-absorption and moisture-retention abilities. These abilities were also related to molecular weight; with the exception of the low molecular weight polysaccharide extracted from red seaweed, lower molecular weight improved moisture-absorption and moisture-retention abilities.

  14. In vivo growth-inhibition of Sarcoma 180 by an alpha-(1-->4)-glucan-beta-(1-->6)-glucan-protein complex polysaccharide obtained from Agaricus blazei Murill.

    PubMed

    Gonzaga, Maria Leônia Costa; Bezerra, Daniel Pereira; Alves, Ana Paula Negreiros Nunes; de Alencar, Nylane Maria Nunes; Mesquita, Rodney de Oliveira; Lima, Michael Will; Soares, Sandra de Aguiar; Pessoa, Cláudia; de Moraes, Manoel Odorico; Costa-Lotufo, Letícia Veras

    2009-01-01

    Agaricus blazei Murrill, a native mushroom of Brazil, has been widely consumed in different parts of the world due to its anticancer potential. This effect is generally attributed to its polysaccharides; however, the precise structure of these has not been fully characterized. To better understand the relationship between polysaccharide structures and antitumor activity, we investigated the effect of the intraperitoneally (i.p.) or orally (p.o.) administered alpha-(1-->4)-glucan-beta-(1-->6)-glucan-protein complex polysaccharide from A. blazei alone or in association with 5-fluorouracil (5-FU) in tumor growth using Sarcoma 180 transplanted mice. Hematological, biochemical, and histopathological analyses were performed in order to evaluate the toxicological aspects of the polysaccharide treatment. The polysaccharide had no direct cytotoxic action on tumor cells in vitro. However, the polysaccharide showed strong in vivo antitumor effect. Thus, the tumor growth-inhibitory effect of the polysaccharide is apparently due to host-mediated mechanisms. The histopathological analysis suggests that the liver and the kidney were not affected by polysaccharide treatment. Neither enzymatic activity of transaminases (AST and ALT) nor urea levels were significantly altered. In hematological analysis, leucopeny was observed after 5-FU treatment, but this effect was prevented when the treatment was associated with the polysaccharide. In conclusion, this polysaccharide probably could explain the ethnopharmacological use of this mushroom in the treatment of cancer.

  15. TOP 1 and 2, polysaccharides from Taraxacum officinale, inhibit NFκB-mediated inflammation and accelerate Nrf2-induced antioxidative potential through the modulation of PI3K-Akt signaling pathway in RAW 264.7 cells.

    PubMed

    Park, Chung Mu; Cho, Chung Won; Song, Young Sun

    2014-04-01

    Anti-inflammatory and anti-oxidative activities of polysaccharides from Taraxacum officinale (TOP 1 and 2) were analyzed in RAW 264.7 cells. First, lipopolysaccharide (LPS) was applied to identify anti-inflammatory activity of TOPs, which reduced expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. TOPs treatment inhibited phosphorylation of inflammatory transcription factor, nuclear factor (NF)κB, and its upstream signaling molecule, PI3K/Akt. Second, cytoprotective potential of TOPs against oxidative stress was investigated via heme oxygenase (HO)-1 induction. HO-1, one of phase II enzymes shows antioxidative activity, was potently induced by TOPs treatment, which was in accordance with the nuclear translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). In addition, TOPs treatment phosphorylated PI3K/Akt with slight activation of c-Jun NH2-terminal kinase (JNK). TOPs-mediated HO-1 induction protected macrophage cells from oxidative stress-induced cell death, which was confirmed by SnPP and CoPP (HO-1 inhibitor and inducer, respectively). Consequently, TOPs potently inhibited NFκB-mediated inflammation and accelerated Nrf2-mediated antioxidative potential through the modulation of PI3K/Akt pathway, which would contribute to their promising strategy for novel anti-inflammatory and anti-oxidative agents.

  16. Primary mesenchyme cell migration requires a chondroitin sulfate/dermatan sulfate proteoglycan.

    PubMed

    Lane, M C; Solursh, M

    1991-02-01

    Primary mesenchyme cell migration in the sea urchin embryo is inhibited by sulfate deprivation and exposure to exogenous beta-D-xylosides, two treatments known to disrupt proteoglycan synthesis. We show that in the developing sea urchin, exogenous xyloside affects the synthesis by the primary mesenchyme cells of a very large, cell surface chondroitin sulfate/dermatan sulfate proteoglycan. This proteoglycan is present in a partially purified fraction that restores migratory ability to defective cells in vitro. The integrity of this chondroitin sulfate/dermatan sulfate proteoglycan appears essential for primary mesenchyme cell migration since treatment of actively migrating cells with chondroitinase ABC reversibly inhibited their migration in vitro.

  17. Polysaccharides from the green seaweed Codium decorticatum. Structure and cell wall distribution.

    PubMed

    Fernández, Paula Virginia; Raffo, María Paula; Alberghina, Josefina; Ciancia, Marina

    2015-03-06

    The cell wall polysaccharides from Codium decorticatum and their assembly were studied and these results were compared with those obtained previously for this genus. The water soluble polysaccharides are: (i) Pyruvylated and sulfated 3- and 6-linked β-D-galactans with sulfate mainly on C-4 and also on C-6. Pyruvate ketals are linked to O-3 and O-4 of terminal β-D-galactose or O-4 and O-6 of 3-linked β-D-galactose. (ii) Sulfated 3-linked β-L-arabinans substituted on C-2 or C-2 and C-4 predominantly with sulfate, but also with single stubs of arabinose, and (iii) 4-linked β-D-mannans with a low degree of sulfation on C-2. The whole polysaccharide system comprises 6.9% of sulfated polysaccharides and 32.9% of fibrillar polysaccharides, mostly insoluble mannans. By in situ localization it was possible to detect two similar fibrillar layers separated by a zone rich in charged polymers. Besides, arabinogalactan proteins co-localized with the fibrillar components.

  18. Species difference in the inhibitory potentials of non-steroidal anti-inflammatory drugs on the hepatic sulfation and glucuronidation of bioactive flavonoids: differential observations among common inhibition parameters.

    PubMed

    Fong, Sophia Yui Kau; Zuo, Zhong

    2014-05-01

    1. This study elucidated the species differences between rats and humans in the inhibitory potential of drugs against sulfation and glucuronidation, and whether such differences depend on the inhibition parameter adopted. 2. With 14 non-steroidal anti-inflammatory drugs (NSAIDs) as model inhibitors and three flavanoids baicalein, wogonin and oroxylin A as model substrates, three common inhibition parameters percentage of control, IC50 and Ki were determined in rat liver cytosols (RLCs), human liver cytosols (HLCs), rat liver microsomes (RLMs) and human liver microsomes (HLMs). The closeness of the inhibition parameters from rat liver preparations to that from human liver preparations was analyzed by geometric mean fold error (GMFE) and statistical comparisons. 3. The percentage of control in RLC/RLM was not significantly different from that in HLC/HLM, with a GMFE of 0.85 (RLC-HLC) and 1.03 (RLM-HLM); whereas the IC50 and Ki in RLC/RLM were significantly different from that in HLC/HLM. The trend of difference was consistent between IC50 and Ki, where these parameters in RLC and RLM underestimated (GMFE <0.5) and overestimated (GMFE >2) that in HLC and HLM, respectively. 4. In conclusion, the inhibitory potentials of NSAIDs against sulfation and glucuronidation in rats and humans were different and depended on the adopted inhibition parameters.

  19. Studies on the binding of amylopectin sulfate with gastric mucin.

    PubMed

    Kim, Y S; Bella, A; Whitehead, J S; Isaacs, R; Remer, L

    1975-07-01

    Amylopectin sulfate, a sulfated polysaccharide that has an antipeptic property, was examined for its ability to bind gastric mucins. After chemically cross-linking the amylopectin sulfate into an insoluble gel, its binding with mucins isolated from antral and fundic mucosa of canine stomachs was studied with chromatography. A component present in both mucin fractions bound to the amylopectin sulfate gel below pH 4.5. This binding was reversible, and the complex dissociated above pH 5. Similar binding properties were found with soluble amylopectin sulfate. The component of the mucine which bound to amylopectin sulfate differed from the one which did not bind in its electrophoretic mobility and in its higher proportion of basic amino acids and a lower hexosamine, serine, and threonine content. This study suggests that amylopectin sulfate may bind to gastric mucins only under conditions of low pH.

  20. Ganoderma lucidum polysaccharides counteract inhibition on CD71 and FasL expression by culture supernatant of B16F10 cells upon lymphocyte activation

    PubMed Central

    SUN, LI-XIN; LIN, ZHI-BIN; DUAN, XIN-SUO; LU, JIE; GE, ZHI-HUA; LI, MIN; XING, EN-HONG; LAN, TIAN-FEI; JIANG, MIAO-MIAO; YANG, NING; LI, WEI-DONG

    2013-01-01

    Immune responses to tumor-associated antigens are often detectable in tumor-bearing hosts, but they fail to eliminate malignant cells or prevent development of metastases. Tumor cells produce factors such as interleukin-10, transforming growth factor-β1 and vascular endothelial growth factor (VEGF) that suppress the function of immune cells or induce apoptosis of immune cells. Culture supernatant of tumor cells may contain these immunosuppressive factors which suppress lymphocyte activation. CD71 and FasL are two important molecules that are expressed upon lymphocyte activation. Counteraction against suppression CD71 and FasL expression upon lymphocyte activation may benefit tumor control. A potential component with this effect is Ganoderma lucidum polysaccharides (Gl-PS). In this study, Gl-PS was used on lymphocytes incubating with culture supernatant of B16F10 melanoma cells (B16F10-CS) in the presence of phytohemagglutinin. Following induction with phytohemagglutinin, B16F10-CS suppressed CD71 expression in lymphocytes (as detected by immunofluorescence and flow cytometry), proliferation in lymphocytes (as detected by MTT assay), and FasL expression in lymphocytes (as detected by immunocytochemistry and western blot analysis), while Gl-PS fully or partially counteracted these suppressions. Gl-PS showed counteractive effects against suppression induced by B16F10-CS on CD71 and FasL expression upon lymphocyte activation, suggesting the potential of Gl-PS to facilitate cancer immunotherapy. PMID:23596479

  1. Diethyl sulfate

    Integrated Risk Information System (IRIS)

    Diethyl sulfate ; CASRN 64 - 67 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  2. Barium Sulfate

    MedlinePlus

    ... uses a computer to put together x-ray images to create cross-sectional or three dimensional pictures of the inside of the body). Barium sulfate is in a class of medications called radiopaque contrast media. It works by coating the esophagus, stomach, or ...

  3. Dimethyl sulfate

    Integrated Risk Information System (IRIS)

    Dimethyl sulfate ; CASRN 77 - 78 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  4. Polysaccharide-Based Vaccines

    NASA Astrophysics Data System (ADS)

    Santana, Violeta Fernández; Balbin, Yury Valdés; Calderón, Janoi Chang; Icart, Luis Peña; Verez-Bencomo, Vicente

    Capsular polysaccharides (CPS) and lipopolysaccharides from bacteria are employed for the production of vaccines against human diseases. Initial development of CPS as a vaccine was followed by the development and introduction of conjugate polysaccharide-protein vaccines. The principles leading to both developments are reviewed.

  5. G1-4A, a Polysaccharide from Tinospora cordifolia Inhibits the Survival of Mycobacterium tuberculosis by Modulating Host Immune Responses in TLR4 Dependent Manner

    PubMed Central

    Gupta, Pramod Kumar; Chakraborty, Pampi; Kumar, Santosh; Singh, Prafull Kumar; Rajan, M. G. R.; Sainis, Krishna B.; Kulkarni, Savita

    2016-01-01

    Rapid emergence of drug resistance in Mycobacterium tuberculosis (MTB) is a major health concern and demands the development of novel adjunct immunotherapeutic agents capable of modulating the host immune responses in order to control the pathogen. In the present study, we sought to investigate the immunomodulatory effects of G1-4A, a polysaccharide derived from the Indian medicinal plant Tinospora cordifolia, in in-vitro and aerosol mouse models of MTB infection. G1-4A treatment of MTB infected RAW264.7 macrophages significantly induced the surface expression of MHC-II and CD-86 molecules, secretion of proinflammatory cytokines (TNF-α, IL-β, IL-6, IL-12, IFN-γ) and nitric oxide leading to reduced intracellular survival of both drug sensitive (H37Rv) as well as multi drug resistant strains (Beijing and LAM) of MTB, which was partially attributed to G1-4A induced NO production in TLR4-MyD88 dependent manner. Similarly, bacillary burden was significantly reduced in the lungs of MTB infected BALB/c mice treated with G1-4A, with simultaneous up-regulation of the expression of TNF-α, INF-γ and NOS2 in the mouse lung along with increased levels of Th1 cytokines like IFN-γ, IL-12 and decreased levels of Th2 cytokine like IL-4 in the serum. Furthermore, combination of G1-4A with Isoniazid (INH) exhibited better protection against MTB compared to that due to INH or G1-4A alone, suggesting its potential as adjunct therapy. Our results demonstrate that modulation of host immune responses by G1-4A might improve the therapeutic efficacy of existing anti-tubercular drugs and provide an attractive strategy for the development of alternative therapies to control tuberculosis. PMID:27148868

  6. Niches of two polysaccharide-degrading Polaribacter isolates from the North Sea during a spring diatom bloom

    PubMed Central

    Xing, Peng; Hahnke, Richard L; Unfried, Frank; Markert, Stephanie; Huang, Sixing; Barbeyron, Tristan; Harder, Jens; Becher, Dörte; Schweder, Thomas; Glöckner, Frank Oliver; Amann, Rudolf I; Teeling, Hanno

    2015-01-01

    Members of the flavobacterial genus Polaribacter thrive in response to North Sea spring phytoplankton blooms. We analyzed two respective Polaribacter species by whole genome sequencing, comparative genomics, substrate tests and proteomics. Both can degrade algal polysaccharides but occupy distinct niches. The liquid culture isolate Polaribacter sp. strain Hel1_33_49 has a 3.0-Mbp genome with an overall peptidase:CAZyme ratio of 1.37, four putative polysaccharide utilization loci (PULs) and features proteorhodopsin, whereas the agar plate isolate Polaribacter sp. strain Hel1_85 has a 3.9-Mbp genome with an even peptidase:CAZyme ratio, eight PULs, a mannitol dehydrogenase for decomposing algal mannitol-capped polysaccharides but no proteorhodopsin. Unlike other sequenced Polaribacter species, both isolates have larger sulfatase-rich PULs, supporting earlier assumptions that Polaribacter take part in the decomposition of sulfated polysaccharides. Both strains grow on algal laminarin and the sulfated polysaccharide chondroitin sulfate. For strain Hel1_33_49, we identified by proteomics (i) a laminarin-induced PUL, (ii) chondroitin sulfate-induced CAZymes and (iii) a chondroitin-induced operon that likely enables chondroitin sulfate recognition. These and other data suggest that strain Hel1_33_49 is a planktonic flavobacterium feeding on proteins and a small subset of algal polysaccharides, while the more versatile strain Hel1_85 can decompose a broader spectrum of polysaccharides and likely associates with algae. PMID:25478683

  7. Niches of two polysaccharide-degrading Polaribacter isolates from the North Sea during a spring diatom bloom.

    PubMed

    Xing, Peng; Hahnke, Richard L; Unfried, Frank; Markert, Stephanie; Huang, Sixing; Barbeyron, Tristan; Harder, Jens; Becher, Dörte; Schweder, Thomas; Glöckner, Frank Oliver; Amann, Rudolf I; Teeling, Hanno

    2015-06-01

    Members of the flavobacterial genus Polaribacter thrive in response to North Sea spring phytoplankton blooms. We analyzed two respective Polaribacter species by whole genome sequencing, comparative genomics, substrate tests and proteomics. Both can degrade algal polysaccharides but occupy distinct niches. The liquid culture isolate Polaribacter sp. strain Hel1_33_49 has a 3.0-Mbp genome with an overall peptidase:CAZyme ratio of 1.37, four putative polysaccharide utilization loci (PULs) and features proteorhodopsin, whereas the agar plate isolate Polaribacter sp. strain Hel1_85 has a 3.9-Mbp genome with an even peptidase:CAZyme ratio, eight PULs, a mannitol dehydrogenase for decomposing algal mannitol-capped polysaccharides but no proteorhodopsin. Unlike other sequenced Polaribacter species, both isolates have larger sulfatase-rich PULs, supporting earlier assumptions that Polaribacter take part in the decomposition of sulfated polysaccharides. Both strains grow on algal laminarin and the sulfated polysaccharide chondroitin sulfate. For strain Hel1_33_49, we identified by proteomics (i) a laminarin-induced PUL, (ii) chondroitin sulfate-induced CAZymes and (iii) a chondroitin-induced operon that likely enables chondroitin sulfate recognition. These and other data suggest that strain Hel1_33_49 is a planktonic flavobacterium feeding on proteins and a small subset of algal polysaccharides, while the more versatile strain Hel1_85 can decompose a broader spectrum of polysaccharides and likely associates with algae.

  8. Comparison of antioxidant and antiproliferation activities of polysaccharides from eight species of medicinal mushrooms.

    PubMed

    Chen, Peiying; Yong, Yangyang; Gu, Yifan; Wang, Zeliang; Zhang, Shizhu; Lu, Ling

    2015-01-01

    Polysaccharides from mushrooms including Pleurotus eryngii, P. ostreatus, P. nebrodensis, Lentinus edodes, Hypsizygus marmoreus, Flammulina velutipes, Ganoderma lucidum, and Hericium erinaceus were isolated by water extraction and alcohol precipitation. Our results suggest that all tested polysaccharides have the significant antioxidant capacities of scavenging free radicals (1,1-diphenyl-2-picrylhydrazyl and hydroxyl radicals). Among them, the H. erinaceus polysaccharide exhibits the highest 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity, whereas the L. edodes polysaccharide shows the strongest scavenging ability for hydroxyl radicals. Furthermore, using the MCF-7 breast cancer cell line and HeLa cells, all 8 selected polysaccharides are able to inhibit the proliferation of tumor cells, but the strength of inhibition varied depending on the mushroom species and the concentration used. Notably, G. lucidum polysaccharide shows the highest inhibition activity on MCF-7 cells. By comparison, H. erinaceus polysaccharide has the strongest inhibitory effect on HeLa cells. Moreover, high-performance liquid chromatography with a carbohydrate analysis column showed significant differences in polysaccharide components among these mushrooms. Thus our data suggest that the different species of mushrooms have the variable functions because of their own specific polysaccharide components. The 8 mushroom polysaccharides have the potential to be used as valuable functional food additives or sources of therapeutic agents for antioxidant and cancer treatments, especially polysaccharides from H. erinaceus, L. edodes, and G. lucidum.

  9. Inter vs. intraglycosidic acetal linkages control sulfation pattern in semi-synthetic chondroitin sulfate.

    PubMed

    Laezza, Antonio; De Castro, Cristina; Parrilli, Michelangelo; Bedini, Emiliano

    2014-11-04

    Microbial-sourced unsulfated chondroitin could be converted into chondroitin sulfate (CS) polysaccharide by a multi-step strategy relying upon benzylidenation and acetylation reactions as key-steps for its regioselective protection. By conducting the two reactions one- or two-pots, CSs with different sulfation patterns could be obtained at the end of the semi-synthesis. In particular, a CS polysaccharide possessing sulfate groups randomly distributed between positions 4 and 6 of N-acetyl-galactosamine (GalNAc) units could be obtained through the two-pots route, whereas the one-pot pathway allowed an additional sulfation at position 3 of some glucuronic acid (GlcA) units. This difference was ascribed to the stabilization of a labile interglycosidic benzylidene acetal involving positions O-3 and O-6 of some GlcA and GalNAc, respectively, when the benzylidene-acetylation reactions were conducted in a one-pot fashion. Isolation and characterization of a polysaccharide intermediate showing interglycosidic acetal moieties was accomplished.

  10. Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the Toll-like receptor 2 pathway.

    PubMed

    Liu, Yi; Zhang, Lingyun; Zhu, Xiangxiang; Wang, Yuehua; Liu, WenWei; Gong, Wei

    2015-11-01

    Gr-1(+) CD11b(+) myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing animals and play a critical negative role during tumor immunotherapy. Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy. Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti-cancer activity, but the underlying mechanism of this is poorly understood. Here, pAbM directly activated the purified MDSCs through inducing the expression of interleukin-6 (IL-6), IL-12, tumour necrosis factor and inducible nitric oxide synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer and T cells in the presence of Gr-1(+) CD11b(+) monocytic MDSCs. On further analysis, we demonstrated that pAbM could selectively block the Toll-like receptor 2 (TLR2) signal of Gr-1(+) CD11b(+) MDSCs and increased their M1-type macrophage characteristics, such as producing IL-12, lowering expression of Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr-1(+) CD11b(+) MDSCs by pAbM treatment had less ability to convert the CD4(+) CD25(-) cells into CD4(+) CD25(+) phenotype. Moreover, result from selective depletion of specific cell populations in xenograft mice model suggested that the anti-tumour effect of pAbM was dependent on Gr-1(+ ) CD11b(+) monocytes, nether CD8(+) T cells nor CD4(+) T cells. In addition to, pAbM did not inhibit tumour growth in TLR2(-/-) mice. All together, these results suggested that pAbM, a natural product commonly used for cancer treatment, was a specific TLR2 agonist and had potent anti-tumour effects through the opposite of the suppressive function of Gr-1(+) CD11b(+) MDSCs.

  11. Structure and properties of an under-sulfated heparan sulfate proteoglycan synthesized by a rat hepatoma cell line

    PubMed Central

    1984-01-01

    A rat hepatoma cell line was shown to synthesize heparan sulfate and chondroitin sulfate proteoglycans. Unlike cultured hepatocytes, the hepatoma cells did not deposit these proteoglycans into an extracellular matrix, and most of the newly synthesized heparan sulfate proteoglycans were secreted into the culture medium. Heparan sulfate proteoglycans were also found associated with the cell surface. These proteoglycans could be solubilized by mild trypsin or detergent treatment of the cells but could not be displaced from the cells by incubation with heparin. The detergent-solubilized heparan sulfate proteoglycan had a hydrophobic segment that enabled it to bind to octyl- Sepharose. This segment could conceivably anchor the molecule in the lipid interior of the plasma membrane. The size of the hepatoma heparan sulfate proteoglycans was similar to that of proteoglycans isolated from rat liver microsomes or from primary cultures of rat hepatocytes. Ion-exchange chromatography on DEAE-Sephacel indicated that the hepatoma heparan sulfate proteoglycans had a lower average charge density than the rat liver heparan sulfate proteoglycans. The lower charge density of the hepatoma heparan sulfate can be largely attributed to a reduced number of N-sulfated glucosamine units in the polysaccharide chain compared with that of rat liver heparan sulfate. Hepatoma heparan sulfate proteoglycans purified from the culture medium had a considerably lower affinity for fibronectin-Sepharose compared with that of rat liver heparan sulfate proteoglycans. Furthermore, the hepatoma proteoglycan did not bind to the neoplastic cells, whereas heparan sulfate from normal rat liver bound to the hepatoma cells in a time-dependent reaction. The possible consequences of the reduced sulfation of the heparan sulfate proteoglycan produced by the hepatoma cells are discussed in terms of the postulated roles of heparan sulfate in the regulation of cell growth and extracellular matrix formation. PMID

  12. Is N-sulfation just a gateway modification during heparan sulfate biosynthesis?

    PubMed

    Raman, Karthik; Nguyen, Thao Kim Nu; Kuberan, Balagurunathan

    2011-11-04

    Several biologically important growth factor-heparan sulfate (HS) interactions are regulated by HS sulfation patterns. However, the biogenesis of these combinatorial sulfation patterns is largely unknown. N-Deacetylase/N-sulfotrasferase (NDST) converts N-acetyl-d-glucosamine residues to N-sulfo-d-glucosamine residues. This enzyme is suggested to be a gateway enzyme because N-sulfation dictates the final HS sulfation pattern. It is known that O-sulfation blocks C5-epimerase, which acts immediately after NDST action. However, it is still unknown whether O-sulfation inhibits NDST action in a similar manner. In this article we radically change conventional assumptions regarding HS biosynthesis by providing in vitro evidence that N-sulfation is not necessarily just a gateway modification during HS biosynthesis.

  13. Polysaccharides from the green seaweeds Codium fragile and C. vermilara with controversial effects on hemostasis.

    PubMed

    Ciancia, Marina; Quintana, Irene; Vizcargüénaga, María Isabel; Kasulin, Luciana; de Dios, Agustina; Estevez, José Manuel; Cerezo, Alberto Saúl

    2007-12-01

    Codium fragile and Codium vermilara biosynthesize water-soluble sulfated arabinans and galactans (and/or sulfated arabinogalactans), alpha(1-->4)-D-glucans and beta(1-->4)-D-mannans. The former polysaccharides are composed by 3-linked beta-D-galactopyranose and beta-L-arabinopyranose residues, they are highly sulfated and substituted with pyruvic acid ketals. For both seaweeds, they have the same main structural units, but in different percentages. All the room-temperature water extracts from both seaweeds showed a dual haemostatic effect: they prevented coagulation, but they induced platelet aggregation. Anticoagulant activity and platelet aggregation were higher in the samples with polysaccharides richer in sulfate, mainly in those from C. vermilara, which have a higher degree of sulfation and arabinose content.

  14. Rat pro-opiomelanocortin contains sulfate

    SciTech Connect

    Hoshina, H.; Hortin, G.; Boime, I.

    1982-07-02

    Intermediate lobes isolated from rat pituitary glands incorporated (/sup 35/S)sulfate into pro-opiomelanocortin and other adrenocorticotropic hormone-containing peptides. Incubation of intermediate lobes in medium containing the arginine analog canavanine inhibited the cleavage of pro-opiomelanocortin into smaller products. Pro-opiomelanocortin that accumulated in the presence of canavanine was also sulfated.

  15. Uronic polysaccharide degrading enzymes.

    PubMed

    Garron, Marie-Line; Cygler, Miroslaw

    2014-10-01

    In the past several years progress has been made in the field of structure and function of polysaccharide lyases (PLs). The number of classified polysaccharide lyase families has increased to 23 and more detailed analysis has allowed the identification of more closely related subfamilies, leading to stronger correlation between each subfamily and a unique substrate. The number of as yet unclassified polysaccharide lyases has also increased and we expect that sequencing projects will allow many of these unclassified sequences to emerge as new families. The progress in structural analysis of PLs has led to having at least one representative structure for each of the families and for two unclassified enzymes. The newly determined structures have folds observed previously in other PL families and their catalytic mechanisms follow either metal-assisted or Tyr/His mechanisms characteristic for other PL enzymes. Comparison of PLs with glycoside hydrolases (GHs) shows several folds common to both classes but only for the β-helix fold is there strong indication of divergent evolution from a common ancestor. Analysis of bacterial genomes identified gene clusters containing multiple polysaccharide cleaving enzymes, the Polysaccharides Utilization Loci (PULs), and their gene complement suggests that they are organized to process completely a specific polysaccharide.

  16. Ca2+-mediated association of human serum amyloid P component with heparan sulfate and dermatan sulfate.

    PubMed

    Hamazaki, H

    1987-02-05

    The serum amyloid P component (SAP) is a precursor glycoprotein of amyloid P component found in all types of amyloid deposits. The binding of human SAP to heparan sulfate and dermatan sulfate was studied using Sepharose-immobilized SAP. The apparent dissociation constants of heparan sulfate and dermatan sulfate for immobilized-SAP were estimated to be approximately 2 X 10(-7) M in the presence of 2 mM CaCl2 at neutral pH and physiological ionic strength. Both the binding affinity of SAP for these glycosaminoglycans and the numbers of binding sites of SAP depended on calcium concentration. Cadmium partially substituted for calcium as an activator of glycosaminoglycan binding to SAP. No binding occurs in the absence of added metal, or in the presence of barium, copper, magnesium, manganese, and strontium. The calcium-dependent binding of [3H]heparan sulfate and [3H]dermatan sulfate to SAP was strongly inhibited by heparan sulfate, heparin, and dermatan sulfate. Chondroitin 6-sulfate was a moderate inhibitor, whereas hyaluronic acid, chondroitin 4-sulfate, and keratan sulfate were not potent inhibitors. The calcium-dependent binding of amyloid P component to heparan sulfate and/or dermatan sulfate may be a cause of the coexistence of the particular glycoprotein and these glycosaminoglycans in amyloid tissues.

  17. Isolation and antiviral activity of water-soluble Cynomorium songaricum Rupr. polysaccharides.

    PubMed

    Tuvaanjav, Suvdmaa; Shuqin, Han; Komata, Masashi; Ma, Chunjie; Kanamoto, Taisei; Nakashima, Hideki; Yoshida, Takashi

    2016-01-01

    The plant, Cynomorium songaricum Rupr., is used as a traditional medicine in China and Mongolia. In the present study, two new water-soluble polysaccharides isolated from C. songaricum Rupr. were purified by successive Sephadex G-75 and G-50 column chromatographies and then characterized by high resolution NMR and IR spectroscopies. The molecular weights of two polysaccharides were determined by an aqueous GPC to be [Formula: see text] = 3.7 × 10(4) and 1.0 × 10(4), respectively. In addition, it was found that the polysaccharide with the larger molecular weight was an acidic polysaccharide. It was found that the iodine-starch reaction of both isolated polysaccharides was negative and the methylation analysis gave 2, 4, 6-tri-O-methyl alditol acetate as a main product. NMR and IR measurements and sugar analysis revealed that both polysaccharides had a (1 → 3)-α-d-glucopyranosidic main chain with a small number of branches. After sulfation, the sulfated C. songaricum Rupr. polysaccharides were found to have a potent inhibitory effect on HIV infection of MT-4 cells at a 50% effective concentration of 0.3-0.4 μg/ml, a concentration that has almost the same high activity as standard dextran and curdlan sulfates, EC50 = 0.35 and 0.14 μg/ml, respectively. The 50% cytotoxic concentration was low, CC50>1000 μg/ml. In addition, the interaction between the sulfated polysaccharides and poly-l-lysine as a model protein compound was investigated by a surface plasmon resonance to reveal the anti-HIV mechanism.

  18. A synthetic heparan sulfate oligosaccharide library reveals the novel enzymatic action of d-glucosaminyl 3-O-sulfotransferase-3a†

    PubMed Central

    Nu Nguyen, Thao Kim; Arungundram, Sailaja; Tran, Vy My; Raman, Karthik; Al-Mafraji, Kanar; Venot, Andre; Boons, Geert-Jan; Kuberan, Balagurunathan

    2014-01-01

    Heparan sulfate (HS) glucosaminyl 3-O-sulfotranferases sulfate the C3-hydroxyl group of certain glucosamine residues on heparan sulfate. Six different 3-OST isoforms exist, each of which can sulfate very distinct glucosamine residues within the HS chain. Among these isoforms, 3-OST1 has been shown to play a role in generating ATIII-binding HS anticoagulants whereas 3-OST2, 3-OST3, 3-OST4 and 3OST-6 have been shown to play a vital role in generating gD-binding HS chains that permit the entry of herpes simplex virus type 1 into cells. 3-OST5 has been found to generate both ATIII- and gD-binding HS motifs. Previous studies have examined the substrate specificities of all the 3-OST isoforms using HS polysaccharides. However, very few studies have examined the contribution of the epimer configuration of neighboring uronic acid residues next to the target site to 3-OST action. In this study, we utilized a well-defined synthetic oligosaccharide library to examine the substrate specificity of 3-OST3a and compared it to 3-OST1. We found that both 3-OST1 and 3-OST3a preferentially sulfate the 6-O-sulfated, N-sulfoglucosamine when an adjacent iduronyl residue is located to its reducing side. On the other hand, 2-O-sulfation of this uronyl residue can inhibit the action of 3-OST3a on the target residue. The results reveal novel substrate sites for the enzyme actions of 3-OST3a. It is also evident that both these enzymes have promiscuous and overlapping actions that are differentially regulated by iduronyl 2-O-sulfation. PMID:22116385

  19. Layer-by-layer structured polysaccharides-based multilayers on cellulose acetate membrane: Towards better hemocompatibility, antibacterial and antioxidant activities

    NASA Astrophysics Data System (ADS)

    Peng, Lincai; Li, Hui; Meng, Yahong

    2017-04-01

    The development of multifunctional cellulose acetate (CA) membranes with enhanced hemocompatibility and antibacterial and antioxidant activities is extremely important for biomedical applications. In this work, significant improvements in hemocompatibility and antibacterial and antioxidant activities of cellulose acetate (CA) membranes were achieved via layer-by-layer (LBL) deposition of chitosan (CS) and water-soluble heparin-mimicking polysaccharides (i.e., sulfated Cantharellus cibarius polysaccharides, SCP) onto their surface. The surface chemical compositions, growth manner, surface morphologies, and wetting ability of CS/SCP multilayer-modified CA membranes were characterized, respectively. The systematical evaluation of hemocompatibility revealed that CS/SCP multilayer-modified CA membranes significantly improved blood compatibility including resistance to non-specific protein adsorption, suppression of platelet adhesion and activation, prolongation of coagulation times, inhibition of complement activation, as well as reduction in blood hemolysis. Meanwhile, CS/SCP multilayer-modified CA membranes exhibited strong growth inhibition against Escherichia coli and Staphylococcus aureus, as well as high scavenging abilities against superoxide and hydroxyl radicals. In summary, the CS/SCP multilayers could confer CA membranes with integrated hemocompatibility and antibacterial and antioxidant activities, which might have great potential application in the biomedical field.

  20. Glycoprotein isolated from Styrax japonica Siebold et al. Zuccarini inhibits oxidative and pro-inflammatory responses in HCT116 colonic epithelial cells and dextran sulfate sodium-treated ICR mice.

    PubMed

    Lee, Sei-Jung; Lee, Jin; Song, Sooyeon; Lim, Kye-Taek

    2016-01-01

    This study was carried out to investigate the anti-inflammatory potentials of a 38 kDa glycoprotein isolated from Styrax japonica Siebold et al Zuccarini (SJSZ glycoprotein). We found that SJSZ glycoprotein has concentration-dependent scavenging activity against DPPH and hydroxyl radicals in the cell-free systems. In colonic epithelial cells (HCT116 cells), the results showed that SJSZ glycoprotein inhibits the production of reactive oxygen species (ROS) induced by glucose/glucose oxidase (G/GO) in a concentration-dependent manner. Experimental mouse colitis was induced by adding dextran sulfate sodium (DSS) to the drinking water at a concentration of 4% (w/v) for 7 days. We figured out that administration of SJSZ glycoprotein (10 mg/kg) lowers the levels of disease activity index, myeloperoxidase activity, and histological inflammation in DSS-treated mice. In addition, SJSZ glycoprotein inhibited plasmic thiobarbituric acid reactive substances (TBARS) formation, nitric oxide (NO) production, and lactate dehydrogenase (LDH) release, accompanying the inhibition of colonic inflammatory signal proteins (NF-κB, iNOS, and COX-2) and inflammation-related cytokines (IL-1β, IL-6, and TNF-α). These results indicate that SJSZ glycoprotein inhibits oxidative and pro-inflammatory responses in mouse colitis.

  1. Synthesis of a targeted library of heparan sulfate hexa- to dodecasaccharides as inhibitors of β-secretase: potential therapeutics for Alzheimer's disease.

    PubMed

    Schwörer, Ralf; Zubkova, Olga V; Turnbull, Jeremy E; Tyler, Peter C

    2013-05-17

    Heparan sulfates (HS) are a class of sulfated polysaccharides that function as dynamic biological regulators of the functions of diverse proteins. The structural basis of these interactions, however, remains elusive, and chemical synthesis of defined structures represents a challenging but powerful approach for unravelling the structure-activity relationships of their complex sulfation patterns. HS has been shown to function as an inhibitor of the β-site cleaving enzyme β-secretase (BACE1), a protease responsible for generating the toxic Aβ peptides that accumulate in Alzheimer's disease (AD), with 6-O-sulfation identified as a key requirement. Here, we demonstrate a novel generic synthetic approach to HS oligosaccharides applied to production of a library of 16 hexa- to dodecasaccharides targeted at BACE1 inhibition. Screening of this library provided new insights into structure-activity relationships for optimal BACE1 inhibition, and yielded a number of potent non-anticoagulant BACE1 inhibitors with potential for development as leads for treatment of AD through lowering of Aβ peptide levels.

  2. Sulfate and thiosulfate inhibit oxalate transport via a dPrestin (Slc26a6)-dependent mechanism in an insect model of calcium oxalate nephrolithiasis.

    PubMed

    Landry, Greg M; Hirata, Taku; Anderson, Jacob B; Cabrero, Pablo; Gallo, Christopher J R; Dow, Julian A T; Romero, Michael F

    2016-01-15

    Nephrolithiasis is one of the most common urinary tract disorders, with the majority of kidney stones composed of calcium oxalate (CaOx). Given its prevalence (US occurrence 10%), it is still poorly understood, lacking progress in identifying new therapies because of its complex etiology. Drosophila melanogaster (fruitfly) is a recently developed model of CaOx nephrolithiasis. Effects of sulfate and thiosulfate on crystal formation were investigated using the Drosophila model, as well as electrophysiological effects on both Drosophila (Slc26a5/6; dPrestin) and mouse (mSlc26a6) oxalate transporters utilizing the Xenopus laevis oocyte heterologous expression system. Results indicate that both transport thiosulfate with a much higher affinity than sulfate Additionally, both compounds were effective at decreasing CaOx crystallization when added to the diet. However, these results were not observed when compounds were applied to Malpighian tubules ex vivo. Neither compound affected CaOx crystallization in dPrestin knockdown animals, indicating a role for principal cell-specific dPrestin in luminal oxalate transport. Furthermore, thiosulfate has a higher affinity for dPrestin and mSlc26a6 compared with oxalate These data indicate that thiosulfate's ability to act as a competitive inhibitor of oxalate via dPrestin, can explain the decrease in CaOx crystallization seen in the presence of thiosulfate, but not sulfate. Overall, our findings predict that thiosulfate or oxalate-mimics may be effective as therapeutic competitive inhibitors of CaOx crystallization.

  3. Sulfate and thiosulfate inhibit oxalate transport via a dPrestin (Slc26a6)-dependent mechanism in an insect model of calcium oxalate nephrolithiasis

    PubMed Central

    Landry, Greg M.; Hirata, Taku; Anderson, Jacob B.; Cabrero, Pablo; Gallo, Christopher J. R.; Dow, Julian A. T.

    2015-01-01

    Nephrolithiasis is one of the most common urinary tract disorders, with the majority of kidney stones composed of calcium oxalate (CaOx). Given its prevalence (US occurrence 10%), it is still poorly understood, lacking progress in identifying new therapies because of its complex etiology. Drosophila melanogaster (fruitfly) is a recently developed model of CaOx nephrolithiasis. Effects of sulfate and thiosulfate on crystal formation were investigated using the Drosophila model, as well as electrophysiological effects on both Drosophila (Slc26a5/6; dPrestin) and mouse (mSlc26a6) oxalate transporters utilizing the Xenopus laevis oocyte heterologous expression system. Results indicate that both transport thiosulfate with a much higher affinity than sulfate Additionally, both compounds were effective at decreasing CaOx crystallization when added to the diet. However, these results were not observed when compounds were applied to Malpighian tubules ex vivo. Neither compound affected CaOx crystallization in dPrestin knockdown animals, indicating a role for principal cell-specific dPrestin in luminal oxalate transport. Furthermore, thiosulfate has a higher affinity for dPrestin and mSlc26a6 compared with oxalate These data indicate that thiosulfate's ability to act as a competitive inhibitor of oxalate via dPrestin, can explain the decrease in CaOx crystallization seen in the presence of thiosulfate, but not sulfate. Overall, our findings predict that thiosulfate or oxalate-mimics may be effective as therapeutic competitive inhibitors of CaOx crystallization. PMID:26538444

  4. Separation of lacquer polysaccharides and interaction with poly-L-lysine.

    PubMed

    Bai, Yuting; Yoshida, Takashi

    2013-10-15

    A naturally occurring acidic lacquer polysaccharide with glucuronic acid at the terminals of the complex branches has specific biological activities including promotion of blood coagulation and antitumor activities. The polysaccharide has two molecular weight fractions M¯n=10×10(4) and M¯n=3.0×10(4). In the present work, two pure fractions were isolated for the first time by Sephadex G-100 column chromatography. Then, each fraction was treated with diluted alkaline solution to decrease the molecular weights to M¯n=3.0×10(4) and M¯n=1.4×10(4), respectively. The NMR and IR spectra and specific rotations of the fractionated and original lacquer polysaccharides were almost identical, suggesting that the lacquer polysaccharides are an associated structure with several low molecular weight polysaccharides of M¯n=1.4×10(4). Interactions between each lacquer polysaccharide and poly-L-lysine, a model compound of proteins and peptides with positively-charged amino groups, were investigated by surface plasmon resonance (SPR) to elucidate the biological mechanism. The apparent dissociation-rate (kd), association-rate (ka), and dissociation constant (KD) obtained by SPR indicate that the lacquer polysaccharides had weaker interactions with poly-L-lysine than sulfated polysaccharides and that the interaction depended on the molecular weight. These SPR results suggest that the specific biological activities of lacquer polysaccharides originate from electrostatic interaction.

  5. O-acetylation of low-molecular-weight polysaccharide from Enteromorpha linza with antioxidant activity.

    PubMed

    Zhang, Zhongshan; Wang, Xiaomei; Zhao, Mingxing; Qi, Huimin

    2014-08-01

    Polysaccharide extracted from green algae Enteromorpha linza (EP) is a sulfated polysaccharide, which possesses excellent antioxidant activities. In present study, the acetylated derivatives of low-molecular-weight polysaccharide (LEP) was prepared with the method of response surface quadratic model. And then the antioxidant activities of the derivatives were investigated including scavenging effects of superoxide and hydroxyl radicals. The results of chemical analysis and FT-IR spectrum showed the acetylation was successful. And in addition, certain derivative with different degree of substitution (DS) exhibited different antioxidant activity.

  6. Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the Toll-like receptor 2 pathway

    PubMed Central

    Liu, Yi; Zhang, Lingyun; Zhu, Xiangxiang; Wang, Yuehua; Liu, WenWei; Gong, Wei

    2015-01-01

    Gr-1+ CD11b+ myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing animals and play a critical negative role during tumor immunotherapy. Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy. Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti-cancer activity, but the underlying mechanism of this is poorly understood. Here, pAbM directly activated the purified MDSCs through inducing the expression of interleukin-6 (IL-6), IL-12, tumour necrosis factor and inducible nitric oxide synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer and T cells in the presence of Gr-1+ CD11b+ monocytic MDSCs. On further analysis, we demonstrated that pAbM could selectively block the Toll-like receptor 2 (TLR2) signal of Gr-1+ CD11b+ MDSCs and increased their M1-type macrophage characteristics, such as producing IL-12, lowering expression of Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr-1+ CD11b+ MDSCs by pAbM treatment had less ability to convert the CD4+ CD25− cells into CD4+ CD25+ phenotype. Moreover, result from selective depletion of specific cell populations in xenograft mice model suggested that the anti-tumour effect of pAbM was dependent on Gr-1+ CD11b+ monocytes, nether CD8+ T cells nor CD4+ T cells. In addition to, pAbM did not inhibit tumour growth in TLR2–/– mice. All together, these results suggested that pAbM, a natural product commonly used for cancer treatment, was a specific TLR2 agonist and had potent anti-tumour effects through the opposite of the suppressive function of Gr-1+ CD11b+ MDSCs. PMID:26194418

  7. Structural analysis and anticoagulant activities of the novel sulfated fucan possessing a regular well-defined repeating unit from sea cucumber.

    PubMed

    Wu, Mingyi; Xu, Li; Zhao, Longyan; Xiao, Chuang; Gao, Na; Luo, Lan; Yang, Lian; Li, Zi; Chen, Lingyun; Zhao, Jinhua

    2015-04-13

    Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC-MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2) and (1→3)-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants.

  8. Structural Analysis and Anticoagulant Activities of the Novel Sulfated Fucan Possessing a Regular Well-Defined Repeating Unit from Sea Cucumber

    PubMed Central

    Wu, Mingyi; Xu, Li; Zhao, Longyan; Xiao, Chuang; Gao, Na; Luo, Lan; Yang, Lian; Li, Zi; Chen, Lingyun; Zhao, Jinhua

    2015-01-01

    Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC–MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2) and (1→3)-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants. PMID:25871288

  9. Pleurotus tuber-regium Polysaccharides Attenuate Hyperglycemia and Oxidative Stress in Experimental Diabetic Rats

    PubMed Central

    Huang, Hui-Yu; Korivi, Mallikarjuna; Chaing, Ying-Ying; Chien, Ting-Yi; Tsai, Ying-Chieh

    2012-01-01

    Pleurotus tuber-regium contains polysaccharides that are responsible for pharmacological actions, and medicinal effects of these polysaccharides have not yet been studied in diabetic rats. We examined the antidiabetic, antihyperlipidemic, and antioxidant properties of P. tuber-regium polysaccharides in experimental diabetic rats. Forty rats were equally assigned as diabetic high-fat (DHF) diet and polysaccharides treated DHF groups (DHF+1P, DHF+2P, and DHF+3P, 20 mg/kg bodyweight/8-week). Diabetes was induced by chronic low-dose streptozotocin injections and a high-fat diet to mimic type 2 diabetes. Polysaccharides (1P, 2P, and 3P) were extracted from three different strains of P. tuber-regium. Fasting blood glucose and glycosylated hemoglobin (HbA1c) levels substantially decreased, while serum insulin levels were restored by polysaccharides treatment compared to DHF. Furthermore, plasma total cholesterol, triglycerides, and low-density lipoprotein levels were significantly (P < 0.01) lower in polysaccharide groups. High-density lipoprotein levels were attenuated with polysaccharides against diabetes condition. Polysaccharides inhibited (P < 0.01) the lipid peroxidation index (malondialdehyde), and restored superoxide dismutase and glutathione peroxidase activities in the liver of diabetic rats. The antihyperglycemic property of polysaccharides perhaps boosts the antioxidant system that attenuates oxidative stress. We emphasize that P. tuber-regium polysaccharides can be considered as an alternative medicine to treat hyperglycemia and oxidative stress in diabetic rats. PMID:22973406

  10. Influences of acidic reaction and hydrolytic conditions on monosaccharide composition analysis of acidic, neutral and basic polysaccharides.

    PubMed

    Wang, Qing-Chi; Zhao, Xia; Pu, Jiang-Hua; Luan, Xiao-Hong

    2016-06-05

    Monosaccharide composition analysis is important for structural characterization of polysaccharides. To investigate the influences of acidic reaction and hydrolytic conditions on monosaccharide composition analysis of polysaccharides, we chose alginate, starch, chitosan and chondroitin sulfate as representative of acidic, neutral, basic and complex polysaccharides to compare the release degree of monosaccharides under different hydrolytic conditions. The hydrolysis stability of 10 monosaccharide standards was also explored. Results showed that the basic sugars were hard to release but stable, the acidic sugars (uronic acids) were easy to release but unstable, and the release and stability of neutral sugars were in between acidic and basic sugars. In addition, the hydrolysis process was applied to monosaccharide composition analysis of Hippocampus trimaculatus polysaccharide and the appropriate hydrolytic condition was accorded with that of the above four polysaccharides. Thus, different hydrolytic conditions should be used for the monosaccharide composition analysis of polysaccharides based on their structural characteristics.

  11. Brittlestars contain highly sulfated chondroitin sulfates/dermatan sulfates that promote fibroblast growth factor 2-induced cell signaling

    PubMed Central

    Ramachandra, Rashmi; Namburi, Ramesh B; Ortega-Martinez, Olga; Shi, Xiaofeng; Zaia, Joseph; Dupont, Sam T; Thorndyke, Michael C; Lindahl, Ulf; Spillmann, Dorothe

    2014-01-01

    Glycosaminoglycans (GAGs) isolated from brittlestars, Echinodermata class Ophiuroidea, were characterized, as part of attempts to understand the evolutionary development of these polysaccharides. A population of chondroitin sulfate/dermatan sulfate (CS/DS) chains with a high overall degree of sulfation and hexuronate epimerization was the major GAG found, whereas heparan sulfate (HS) was below detection level. Enzymatic digestion with different chondroitin lyases revealed exceptionally high proportions of di- and trisulfated CS/DS disaccharides. The latter unit appears much more abundant in one of four individual species of brittlestars, Amphiura filiformis, than reported earlier in other marine invertebrates. The brittlestar CS/DS was further shown to bind to growth factors such as fibroblast growth factor 2 and to promote FGF-stimulated cell signaling in GAG-deficient cell lines in a manner similar to that of heparin. These findings point to a potential biological role for the highly sulfated invertebrate GAGs, similar to those ascribed to HS in vertebrates. PMID:24253764

  12. Influenza virus neuraminidase contributes to the dextran sulfate-dependent suppressive replication of some influenza A virus strains.

    PubMed

    Yamada, Hiroshi; Moriishi, Eiko; Haredy, Ahmad M; Takenaka, Nobuyuki; Mori, Yasuko; Yamanishi, Koichi; Okamoto, Shigefumi

    2012-12-01

    Dextran sulfate (DS), a negatively charged, sulfated polysaccharide, suppresses the replication of an influenza A virus strain, and this suppression is associated with inhibition of the hemagglutinin (HA)-dependent fusion activity. However, it remains unknown whether the replication of all or just some influenza A virus strains is suppressed by DS, or whether HA is the only target for the replication suppression. In the present study, we found that DS inhibited the replication of some, but not all influenza A virus strains. The suppression in the DS-sensitive strains was dose-dependent and neutralized by diethylaminoethyl-dextran (DD), which has a positive charge. The suppression by DS was observed not only at the initial stage of viral infection, which includes viral attachment and entry, but also at the late stage, which includes virus assembly and release from infected cells. Electron microscopy revealed that the DS induced viral aggregation at the cell surface. The neuraminidase (NA) activity of the strains whose viral replication was inhibited at the late stage was also more suppressed by DS than that of the strains whose replication was not inhibited, and this inhibition of NA activity was also neutralized by adding positively charged DD. Furthermore, we found that replacing the NA gene of a strain in which viral replication was inhibited by DS at the late stage with the NA gene from a strain in which viral replication was not inhibited, eliminated the DS-dependent suppression. These results suggest that the influenza virus NA contributes to the DS-suppressible virus release from infected cells at the late stage, and the suppression may involve the inhibition of NA activity by DS's negative charge.

  13. Mode of Action of 2-Nitro-1-Butyl Pyridinium Sulfate

    PubMed Central

    Seale, Ron; Weber, Darrell J.

    1970-01-01

    Ten micrograms of 2-nitro-1-butyl pyridinium sulfate (NBPS) per milliliter inhibited the growth of Bacillus subtilis by blocking thymidylate synthetase. The inhibition could be reversed by the addition of thymine or cytosine. PMID:4990766

  14. Fermentation optimization and antioxidant activities of mycelial polysaccharides from Morchella esculenta using soybean residues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mycelial polysaccharides from Morchella esculenta are active ingredients in a number of medicines that play important roles in immunity improvement and tumor growth inhibition. So far, the production of polysaccharides from M. esculenta mycelia has not been commercialized. The aims of this wor...

  15. Sulfated polysaccharide heparin used as carrier to load hydrophobic lappaconitine.

    PubMed

    Sun, Wenxiu; Saldaña, Marleny D A; Fan, Liyan; Zhao, Yujia; Dong, Tungalag; Jin, Ye; Zhang, Ji

    2016-03-01

    One-step self-assembly was used to prepare pH-sensitive lappaconitine-loaded low-molecular-weight heparin (LMWH-LA) and to demonstrate that the sulfur group promotes dissolution and has synergistic effect on the analgesic property of lappaconitine (LA). The LMWH-LA was characterized in terms of releasing behavior, pH-sensitivity, analgesic activity and anticoagulation property. The drug loading level of LA in low-molecular-weight heparin (LMWH) reached 24.3% (w/w). The LA, self-assembled in LMWH, released faster in an acidic environment than that in neutral or alkaline environments. Analgesic experiments showed that the LMWH-LA had earlier onset time and longer duration than the LA. Compared with LMWH, the LMWH-LA can reduce clotting time more effectively. These results suggest that the LMWH is a good template and has great potential to achieve synergistic effect of LA. In addition, similar macromolecular structure can be used as a new natural polymeric carrier for loading hydrophobic alkaloids.

  16. Gucosamine-6-sulfamate Analogs of Heparan Sulfate as Inhibitors of Endosulfatases

    PubMed Central

    Schelwies, Mathias; Brinson, Diana; Otsuki, Shuhei; Hong, Young-Hoon; Lotz, Martin K.; Wong, Chi-Huey; Hanson, Sarah R.

    2011-01-01

    Keeping Sulfate. The extracellular endosulfatases, which modulate signalling pathways by removing sulfate groups from heparan, can be inhibited by replacing the 6-sulfate destined for cleavage with an inhibitory sulfamate motif, as demonstrated by simple glucosamine-6-sulfamate analogs of heparan sulfate. PMID:20973023

  17. Identification of keratan sulfate disaccharide at C-3 position of glucuronate of chondroitin sulfate from Mactra chinensis

    PubMed Central

    Higashi, Kyohei; Takeda, Keita; Mukuno, Ann; Okamoto, Yusuke; Masuko, Sayaka; Linhardt, Robert J.; Toida, Toshihiko

    2016-01-01

    Glycosaminoglycans (GAGs), including chondroitin sulfate (CS), dermatan sulfate, heparin, heparan sulfate and keratan sulfate (KS) are linear sulfated repeating disaccharide sequences containing hexosamine and uronic acid [or galactose (Gal) in the case of KS]. Among the GAGs, CS shows structural variations, such as sulfation patterns and fucosylation, which are responsible for their physiological functions through CS interaction with CS-binding proteins. Here, we solved the structure of KS-branched CS-E derived from a clam, Mactra chinensis. KS disaccharide [d-GlcNAc6S-(1→3)-β-d-Gal-(1→] was attached to the C-3 position of GlcA, and consecutive KS-branched disaccharide sequences were found in a CS chain. KS-branched polysaccharides clearly exhibited resistance to degradation by chondroitinase ABC or ACII (at low concentrations) compared with typical CS structures. Furthermore, KS-branched polysaccharides stimulated neurite outgrowth of hippocampal neurons. These results strongly suggest that M. chinensis is a rich source of KS-branched CS, and it has important biological activities. PMID:27647934

  18. Dead Nano-Sized Lactobacillus plantarum Inhibits Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer in Balb/c Mice.

    PubMed

    Lee, Hyun Ah; Kim, Hyunung; Lee, Kwang-Won; Park, Kun-Young

    2015-12-01

    The chemopreventive effects of dead nano-sized Lactobacillus plantarum (nLp) on colon carcinogenesis, induced by dextran sulfate sodium and azoxymethane, were evaluated using Balb/c mice and compared with the effects of pure live L. plantarum (pLp). nLp is a dead shrunken form of L. plantarum derived from kimchi and has a particle size of 0.5-1.0 μm. Animals fed nLp showed less weight loss, longer colons, lower colon weight/length ratios, and fewer colonic tumors compared with pLp. In addition, the administration of nLp significantly reduced the expression of inflammatory markers, mediated the expression of cell cycle and apoptotic markers in colon tissues, and elevated fecal IgA levels more than pLp. Accordingly, the present study shows that the anticolorectal cancer activities of nLp are greater than those of pLp and suggests this is due to the suppression of inflammation, the induction of cell cycle arrest and apoptosis, and enhanced IgA secretion.

  19. Zinc sulfate inhibited inflammation of Der p2-induced airway smooth muscle cells by suppressing ERK1/2 and NF-κB phosphorylation.

    PubMed

    Shih, Chia-Ju; Chiou, Ya-Ling

    2013-06-01

    Inflammation of airway smooth muscle cells (ASMCs) is believed to be important in causing airway hyperresponsiveness. However, zinc has been reported to be implicated in many kinds of cell inflammation. Little is known about the effect of zinc treatment on Der p2 (group II Dermatophagoides pteronyssinus)-induced inflammation from ASMCs. This study investigated effects and mechanisms of zinc in Der p2-treated ASMCs. Der p2-treated primary ASMCs were cultured with various concentrations of zinc sulfate (ZnSO₄) 6 μM, 12 μM, 24 μM, and 96 μM. The proteins and mRNAs of cytokines in ASMCs were examined by ELISA and real-time PCR. Intracellular zinc was stained with Zinquin fluorescence. The cell signaling protein expression was detected by Western blot. Der p2 was used to induce interleukin (IL)-6, IL-8, IL-1, and monocyte chemotactic protein-1 production of ASMCs. However, we found that 24 μM ZnSO₄ reduced these inflammatory mediators production of Der p2-treated primary ASMCs. Der p2-induced extracellular signal-regulated kinases (ERK) and nuclear factor-kappa B (NF-κB) phosphorylation were suppressed by supplementation of 24 μM ZnSO₄. Zinc is an anti-inflammatory agent that reduces inflammation of Der p2-treated ASMCs through the suppression of the ERK and NF-κB pathway. The results may be helpful for the development of effective treatments.

  20. Microbial extracellular polysaccharides and plagioclase dissolution

    SciTech Connect

    Welch, S.A.; Barker, W.W.; Banfield, J.F.

    1999-05-01

    Bytownite feldspar was dissolved in batch reactors in solutions of starch (glucose polymer), gum xanthan (glucose, mannose, glucuronic acid), pectin (poly-galacturonic acid), and four alginates (mannuronic and guluronic acid) with a range of molecular weights (low, medium, high and uncharacterized) to evaluate the effect of extracellular microbial polymers on mineral dissolution rates. Solutions were analyzed for dissolved Si and Al as an indicator of feldspar dissolution. At neutral pH, feldspar dissolution was inhibited by five of the acid polysaccharides, gum xanthan, pectin, alginate low, alginate medium, alginate high, compared to an organic-free control. An uncharacterized alginate substantially enhanced both Si and Al release from the feldspar. Starch, a neutral polysaccharide, had no apparent effect. Under mildly acidic conditions, initial pH {approx} 4, all of the polymers enhanced feldspar dissolution compared to the inorganic controls. Si release from feldspar in starch solution exceeded the control by a factor of three. Pectin and gum xanthan increased feldspar dissolution by a factor of 10, and the alginates enhanced feldspar dissolution by a factor of 50 to 100. Si and Al concentrations increased with time, even though solutions were supersaturated with respect to several possible secondary phases. Under acidic conditions, initial pH {approx} 3, below the pK{sub a} of the carboxylic acid groups, dissolution rates increased, but the relative increase due to the polysaccharides is lower, approximately a factor of two to ten. Microbial extracellular polymers play a complex role in mineral weathering. Polymers appear to inhibit dissolution under some conditions, possibly by irreversibly binding to the mineral surfaces. The extracellular polysaccharides can also enhance dissolution by providing protons and complexing with ions in solution.

  1. Characterization of polysaccharides extracted from spent coffee grounds by alkali pretreatment.

    PubMed

    Ballesteros, Lina F; Cerqueira, Miguel A; Teixeira, José A; Mussatto, Solange I

    2015-01-01

    Spent coffee grounds (SCG), obtained during the processing of coffee powder with hot water to make soluble coffee, are the main coffee industry residues and retain approximately seventy percent of the polysaccharides present in the roasted coffee beans. The purpose of this study was to extract polysaccharides from SCG by using an alkali pretreatment with sodium hydroxide at 25°C, and determine the chemical composition, as well as the antioxidant and antimicrobial properties of the extracted polysaccharides. Galactose (60.27%mol) was the dominant sugar in the recovered polysaccharides, followed by arabinose (19.93%mol), glucose (15.37%mol) and mannose (4.43%mol). SCG polysaccharides were thermostable, and presented a typical carbohydrate pattern. Additionally, they showed good antioxidant activity through different methods and presented high antimicrobial percent inhibition against Phoma violacea and Cladosporium cladosporioides (41.27% and 54.60%, respectively). These findings allow identifying possible applications for these polysaccharides in the food industry.

  2. Anticancer properties of polysaccharides isolated from fungi of the Basidiomycetes class

    PubMed Central

    Rzeski, Wojciech

    2012-01-01

    Basidiomycete mushrooms represent a valuable source of biologically active compounds with anticancer properties. This feature is primarily attributed to polysaccharides and their derivatives. The anticancer potential of polysaccharides is linked to their origin, composition and chemical structure, solubility and method of isolation. Moreover, their activity can be significantly increased by chemical modifications. Anticancer effects of polysaccharides can be expressed indirectly (immunostimulation) or directly (cell proliferation inhibition and/or apoptosis induction). Among the wide range of polysaccharides with documented anticancer properties, lentinan, polysaccharide-K (PSK) and schizophyllan deserve special attention. These polysaccharides for many years have been successfully applied in cancer treatment and their mechanism of action is the best known. PMID:23788896

  3. mTOR Inhibition Attenuates Dextran Sulfate Sodium-Induced Colitis by Suppressing T Cell Proliferation and Balancing TH1/TH17/Treg Profile

    PubMed Central

    Wang, Yilin; Wang, Zhengting; Pei, Yaofei; Fan, Rong; Liu, Xiqiang; Wang, Lei; Zhou, Jie; Zheng, Sichang; Zhang, Tianyu; Lin, Yun; Zhang, Maochen; Tao, Ran; Zhong, Jie

    2016-01-01

    It has been established that mammalian target of Rapamycin (mTOR) inhibitors have anti-inflammatory effects in models of experimental colitis. However, the underlying mechanism is largely unknown. In this research, we investigate the anti-inflammatory effects of AZD8055, a potent mTOR inhibitor, on T cell response in dextran sulfate sodium (DSS)-induced colitis in mice, a commonly used animal model of inflammatory bowel diseases (IBD). Severity of colitis is evaluated by changing of body weight, bloody stool, fecal consistency, histology evaluation and cytokine expression. We find that AZD8055 treatment attenuates DSS-induced body weight loss, colon length shortening and pathological damage of the colon. And AZD8055 treatment decreases colonic expression of genes encoding the pro-inflammatory cytokines interferon-γ, interleukin (IL)-17A, IL-1β,IL-6 and tumor necrosis factor(TNF)-a and increases colonic expression of anti-inflammatory cytokines IL-10. We show that AZD8055 treatment decreases the percentages of CD4+ T cells and CD8+ T cells in spleen, lymph nodes and peripheral blood of mice. We also find that AZD8055 treatment significantly reduces the number of T helper 1(TH1) cells and TH17 cells and increases regulatory T (Treg) cells in the lamina propria and mesenteric lymph nodes. Furthermore, we demonstrates that AZD8055 suppresses the proliferation of CD4+ and CD8+ T cells and the differentiation of TH1/TH17 cells and expands Treg cells in vitro. The results suggest that, in experimental colitis, AZD8055 exerts anti-inflammatory effect by regulating T helper cell polarization and proliferation. PMID:27128484

  4. Inhibition of hydrogen sulfide, methane, and total gas production and sulfate-reducing bacteria in in vitro swine manure by tannins, with focus on condensed quebracho tannins.

    PubMed

    Whitehead, Terence R; Spence, Cheryl; Cotta, Michael A

    2013-09-01

    Management practices from large-scale swine production facilities have resulted in the increased collection and storage of manure for off-season fertilization use. Odor and emissions produced during storage have increased the tension among rural neighbors and among urban and rural residents. Production of these compounds from stored manure is the result of microbial activity of the anaerobic bacteria populations during storage. In the current study, the inhibitory effects of condensed quebracho tannins on in vitro swine manure for reduction of microbial activity and reduced production of gaseous emissions, including the toxic odorant hydrogen sulfide produced by sulfate-reducing bacteria (SRB), was examined. Swine manure was collected from a local swine facility, diluted in anaerobic buffer, and mixed with 1 % w/v fresh feces. This slurry was combined with quebracho tannins, and total gas and hydrogen sulfide production was monitored over time. Aliquots were removed periodically for isolation of DNA to measure the SRB populations using quantitative PCR. Addition of tannins reduced overall gas, hydrogen sulfide, and methane production by greater than 90 % after 7 days of treatment and continued to at least 28 days. SRB population was also significantly decreased by tannin addition. qRT-PCR of 16S rDNA bacteria genes showed that the total bacterial population was also decreased in these incubations. These results indicate that the tannins elicited a collective effect on the bacterial population and also suggest a reduction in the population of methanogenic microorganisms as demonstrated by reduced methane production in these experiments. Such a generalized effect could be extrapolated to a reduction in other odor-associated emissions during manure storage.

  5. CAPSULAR POLYSACCHARIDE OF AZOTOBACTER AGILIS.

    PubMed

    COHEN, G H; JOHNSTONE, D B

    1964-12-01

    Cohen, Gary H. (University of Vermont, Burlington), and Donald B. Johnstone. Capsular polysaccharide of Azotobacter agilis. J. Bacteriol. 88:1695-1699. 1964.-Capsular polysaccharide from Azotobacter agilis strain 132 was recovered from washed cells by alkaline digestion. The polysaccharide was purified by centrifugation, repeated alcohol precipitation, Sevag deproteinization, and treatment with ribonuclease and charcoal-cellulose. Methods of isolation and purification appeared to provide a polymer showing no evidence of heterogeneity when examined by chemical and physical methods. Colorimetric, paper chromatographic, and enzymatic analyses on both intact and acid-hydrolyzed polysaccharide indicated that the polymer contained galactose and rhamnose at a molar ratio of approximately 1.0:0.7. A sialic acid-like component was also present in the polysaccharide. The study shows significant differences in the chemical composition of the extra-cellular polysaccharide of A. agilis and that of A. vinelandii. This adds further biochemical evidence for the right of these species to independent status.

  6. Chlorate: a reversible inhibitor of proteoglycan sulfation

    SciTech Connect

    Humphries, D.E.; Silbert, J.E.

    1988-07-15

    Bovine aorta endothelial cells were cultured in medium containing (/sup 3/H)glucosamine, (/sup 35/S)sulfate, and various concentrations of chlorate. Cell growth was not affected by 10 mM chlorate, while 30 mM chlorate had a slight inhibitory effect. Chlorate concentrations greater than 10 mM resulted in significant undersulfation of chondroitin. With 30 mM chlorate, sulfation of chondroitin was reduced to 10% and heparan to 35% of controls, but (/sup 3/H)glucosamine incorporation on a per cell basis did not appear to be inhibited. Removal of chlorate from the culture medium of cells resulted in the rapid resumption of sulfation.

  7. Ferrous Sulfate (Iron)

    MedlinePlus

    Ferrous sulfate provides the iron needed by the body to produce red blood cells. It is used to ... Ferrous sulfate comes as regular, coated, and extended-release (long-acting) tablets; regular and extended-release capsules; and ...

  8. Impact of sulfation pattern on the conformation and dynamics of sulfated fucan oligosaccharides as revealed by NMR and MD.

    PubMed

    Queiroz, Ismael N L; Wang, Xiaocong; Glushka, John N; Santos, Gustavo R C; Valente, Ana P; Prestegard, James H; Woods, Robert J; Mourão, Paulo A S; Pomin, Vitor H

    2015-05-01

    Sulfated fucans from sea urchin egg jelly express well-defined chemical structures that vary with species. This species specificity regulates the sperm acrosome reaction, a critical step to assure intra-specific fertilization. In addition, these polysaccharides are involved in other biological activities such as anticoagulation. Although sulfation patterns are relevant to the levels of response in both activities, conformation and dynamics of these glycans are also contributing factors. However, data about these features of sulfated fucans are very rare. To address this, we have employed nuclear magnetic resonance experiments combined with molecular dynamics on structurally defined oligosaccharides derived from two sulfated fucans. The results have indicated that the oligosaccharides are flexible in solution. Ring conformation of their composing units displays just the (1)C4 chair configuration. In a particular octasaccharide, composed of two tetrasaccharide sequences, inter-residual hydrogen bonds play a role to decrease dynamics in these repeating units. Conversely, the linking disaccharide [-3)-α-L-Fucp-2(OSO3(-))-(1-3)-α-L-Fucp-4(OCO3(-))-(1-] located right between the two tetrasaccharide units has amplified motions suggested to be promoted by electrostatic repulsion of sulfates on opposite sides of the central glycosidic bond. This conjunction of information about conformation and dynamics of sulfated fucan oligosaccharides provides new insights to explain how these glycans behave free in solution and influenced by sulfation patterns. It may also serve for future studies concerning structure-function relationship of sulfated fucans, especially those involving sea urchin fertilization and anticoagulation.

  9. Anticoagulant and antithrombotic activities of low-molecular-weight propylene glycol alginate sodium sulfate (PSS).

    PubMed

    Xin, Meng; Ren, Li; Sun, Yang; Li, Hai-hua; Guan, Hua-Shi; He, Xiao-Xi; Li, Chun-Xia

    2016-05-23

    Propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide derivative, has been used as a heparinoid drug to prevent and treat hyperlipidemia and ischemic cardio-cerebrovascular diseases in China for nearly 30 years. To extend the applications of PSS, a series of low-molecular-weight PSSs (named FPs) were prepared by oxidative-reductive depolymerization, and the antithrombotic activities were investigated thoroughly in vitro and in vivo. The bioactivity evaluation demonstrated a positive correlation between the molecular weight and the anticoagulant and antithrombotic activities of FPs. FPs could prolong the APTT and clotting time and reduce platelet aggregation significantly. FPs could also effectively inhibit factor IIa in the presence of AT-III and HC-II. FPs decreased the wet weights and lengths of the thrombus and increased occlusion times in vivo. FP-6k, a PSS fragment with a molecular weight of 6 kDa, is an optimal antithrombotic candidate for further study and showed little chance for hemorrhagic action.

  10. Acetate production from oil under sulfate-reducing conditions in bioreactors injected with sulfate and nitrate.

    PubMed

    Callbeck, Cameron M; Agrawal, Akhil; Voordouw, Gerrit

    2013-08-01

    Oil production by water injection can cause souring in which sulfate in the injection water is reduced to sulfide by resident sulfate-reducing bacteria (SRB). Sulfate (2 mM) in medium injected at a rate of 1 pore volume per day into upflow bioreactors containing residual heavy oil from the Medicine Hat Glauconitic C field was nearly completely reduced to sulfide, and this was associated with the generation of 3 to 4 mM acetate. Inclusion of 4 mM nitrate inhibited souring for 60 days, after which complete sulfate reduction and associated acetate production were once again observed. Sulfate reduction was permanently inhibited when 100 mM nitrate was injected by the nitrite formed under these conditions. Pulsed injection of 4 or 100 mM nitrate inhibited sulfate reduction temporarily. Sulfate reduction resumed once nitrate injection was stopped and was associated with the production of acetate in all cases. The stoichiometry of acetate formation (3 to 4 mM formed per 2 mM sulfate reduced) is consistent with a mechanism in which oil alkanes and water are metabolized to acetate and hydrogen by fermentative and syntrophic bacteria (K. Zengler et al., Nature 401:266-269, 1999), with the hydrogen being used by SRB to reduce sulfate to sulfide. In support of this model, microbial community analyses by pyrosequencing indicated SRB of the genus Desulfovibrio, which use hydrogen but not acetate as an electron donor for sulfate reduction, to be a major community component. The model explains the high concentrations of acetate that are sometimes found in waters produced from water-injected oil fields.

  11. Acetate Production from Oil under Sulfate-Reducing Conditions in Bioreactors Injected with Sulfate and Nitrate

    PubMed Central

    Callbeck, Cameron M.; Agrawal, Akhil

    2013-01-01

    Oil production by water injection can cause souring in which sulfate in the injection water is reduced to sulfide by resident sulfate-reducing bacteria (SRB). Sulfate (2 mM) in medium injected at a rate of 1 pore volume per day into upflow bioreactors containing residual heavy oil from the Medicine Hat Glauconitic C field was nearly completely reduced to sulfide, and this was associated with the generation of 3 to 4 mM acetate. Inclusion of 4 mM nitrate inhibited souring for 60 days, after which complete sulfate reduction and associated acetate production were once again observed. Sulfate reduction was permanently inhibited when 100 mM nitrate was injected by the nitrite formed under these conditions. Pulsed injection of 4 or 100 mM nitrate inhibited sulfate reduction temporarily. Sulfate reduction resumed once nitrate injection was stopped and was associated with the production of acetate in all cases. The stoichiometry of acetate formation (3 to 4 mM formed per 2 mM sulfate reduced) is consistent with a mechanism in which oil alkanes and water are metabolized to acetate and hydrogen by fermentative and syntrophic bacteria (K. Zengler et al., Nature 401:266–269, 1999), with the hydrogen being used by SRB to reduce sulfate to sulfide. In support of this model, microbial community analyses by pyrosequencing indicated SRB of the genus Desulfovibrio, which use hydrogen but not acetate as an electron donor for sulfate reduction, to be a major community component. The model explains the high concentrations of acetate that are sometimes found in waters produced from water-injected oil fields. PMID:23770914

  12. Functional Exploration of the Polysaccharide Lyase Family PL6

    PubMed Central

    Mathieu, Sophie; Henrissat, Bernard; Labre, Flavien; Skjåk-Bræk, Gudmund; Helbert, William

    2016-01-01

    Alginate, the main cell-wall polysaccharide of brown algae, is composed of two residues: mannuronic acid (M-residues) and, its C5-epimer, guluronic acid (G-residues). Alginate lyases define a class of enzymes that cleave the glycosidic bond of alginate by β-elimination. They are classified according to their ability to recognize the distribution of M- and G-residues and are named M-, G- or MG-lyases. In the CAZy database, alginate lyases have been grouped by sequence similarity into seven distinct polysaccharide lyase families. The polysaccharide lyase family PL6 is subdivided into three subfamilies. Subfamily PL6_1 includes three biochemically characterized enzymes (two alginate lyases and one dermatan sulfatase lyase). No characterized enzymes have been described in the two other subfamilies (PL6_2 and PL6_3). To improve the prediction of polysaccharide-lyase activity in the PL6 family, we re-examined the classification of the PL6 family and biochemically characterized a set of enzymes reflecting the diversity of the protein sequences. Our results show that subfamily PL6_1 includes two dermatan sulfates lyases and several alginate lyases that have various substrate specificities and modes of action. In contrast, subfamilies PL6_2 and PL6_3 were found to contain only endo-poly-MG-lyases. PMID:27438604

  13. Heparan sulfate and heparin interactions with proteins

    PubMed Central

    Meneghetti, Maria C. Z.; Hughes, Ashley J.; Rudd, Timothy R.; Nader, Helena B.; Powell, Andrew K.; Yates, Edwin A.; Lima, Marcelo A.

    2015-01-01

    Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell surface and extracellular matrix of all multicellular animals, whereas heparin is present within mast cells and can be viewed as a more sulfated, tissue-specific, HS variant. HS and heparin regulate biological processes through interactions with a large repertoire of proteins. Owing to these interactions and diverse effects observed during in vitro, ex vivo and in vivo experiments, manifold biological/pharmacological activities have been attributed to them. The properties that have been thought to bestow protein binding and biological activity upon HS and heparin vary from high levels of sequence specificity to a dependence on charge. In contrast to these opposing opinions, we will argue that the evidence supports both a level of redundancy and a degree of selectivity in the structure–activity relationship. The relationship between this apparent redundancy, the multi-dentate nature of heparin and HS polysaccharide chains, their involvement in protein networks and the multiple binding sites on proteins, each possessing different properties, will also be considered. Finally, the role of cations in modulating HS/heparin activity will be reviewed and some of the implications for structure–activity relationships and regulation will be discussed. PMID:26289657

  14. Heparan sulfate and heparin interactions with proteins.

    PubMed

    Meneghetti, Maria C Z; Hughes, Ashley J; Rudd, Timothy R; Nader, Helena B; Powell, Andrew K; Yates, Edwin A; Lima, Marcelo A

    2015-09-06

    Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell surface and extracellular matrix of all multicellular animals, whereas heparin is present within mast cells and can be viewed as a more sulfated, tissue-specific, HS variant. HS and heparin regulate biological processes through interactions with a large repertoire of proteins. Owing to these interactions and diverse effects observed during in vitro, ex vivo and in vivo experiments, manifold biological/pharmacological activities have been attributed to them. The properties that have been thought to bestow protein binding and biological activity upon HS and heparin vary from high levels of sequence specificity to a dependence on charge. In contrast to these opposing opinions, we will argue that the evidence supports both a level of redundancy and a degree of selectivity in the structure-activity relationship. The relationship between this apparent redundancy, the multi-dentate nature of heparin and HS polysaccharide chains, their involvement in protein networks and the multiple binding sites on proteins, each possessing different properties, will also be considered. Finally, the role of cations in modulating HS/heparin activity will be reviewed and some of the implications for structure-activity relationships and regulation will be discussed.

  15. A sulfated alpha-L-fucan from sea cucumber.

    PubMed

    Ribeiro, A C; Vieira, R P; Mourão, P A; Mulloy, B

    1994-03-04

    A purified sulfated alpha-L-fucan from the sea cucumber body wall was studied, before and after almost complete desulfation, using methylation analysis and NMR spectroscopy. NMR analysis indicates that 2,4-di-O-sulfo-L-fucopyranose and unsubstituted fucopyranose are present in equal proportions, and that 2-O-sulfo-L-fucopyranose is present in twice that proportion. There is some NMR evidence that a regular repeating sequence of four residues comprises most or all of the polysaccharide chain.

  16. Extraction, Structural Characterization, and Potential Antioxidant Activity of the Polysaccharides from Four Seaweeds.

    PubMed

    He, Jinzhe; Xu, Yaoyang; Chen, Hongbo; Sun, Peilong

    2016-11-28

    Four seaweed polysaccharides were extracted from Sarcodia ceylonensis, Ulva lactuca L., Gracilaria lemaneiformis, and Durvillaea antarctica, respectively, by microwave-assisted extraction. The effect of three significant variables (extraction time, extraction temperature, and the ratio of water to raw material) on the process for extracting polysaccharides was investigated, along with the optimization of the extraction using the response surface method (RSM) with a Box-Behnken design. The polysaccharide structure, monosaccharide composition, degree of sulfation, and molecular weight (MW) distribution were analyzed by infrared (IR) spectrometry, gas chromatography (GC), and high-performance gel permeation chromatography (HPGPC). IR spectrometry showed that Sarcodia ceylonensis polysaccharide (SCP), Ulva lactuca L. polysaccharide (ULLP), and Durvillaea antarctica polysaccharide (DAP) were all sulfated polysaccharides and, except Gracilaria lemaneiformis polysaccharide (GLP), all belong to β-pyranosidic polysaccharides. The average molecular weight (MW) of SCP, ULLP, GLP, and DAP was 466, 404, 591, and 482 kDa, respectively. The quantitative and comparative results with external standards indicated that the main monosaccharide in SCP and ULLP was mannose; and GLP and DAP were mainly composed of galactose and glucose, respectively. Then the in vitro antioxidant activity of all of the polysaccharides was evaluated using different assays-2,2-azino -bis (3-ethylbenzthiazoline-6- sulfonate) (ABTS), hydroxyl radical, nitrite scavenging capacity, and reducing power-and the relationship between their antioxidant activity and chemical characteristics were also examined. ULLP presented the highest ABTS radical scavenging activity; ULLP, SCP and DAP also showed a strong effect on the ABTS radical scavenging activity. SCP and ULLP exhibited excellent hydroxyl radical scavenging activities, about 83.33% ± 2.31% and 80.07% ± 2.17%, respectively, at 4 mg/mL. The reducing power of

  17. Extraction, Structural Characterization, and Potential Antioxidant Activity of the Polysaccharides from Four Seaweeds

    PubMed Central

    He, Jinzhe; Xu, Yaoyang; Chen, Hongbo; Sun, Peilong

    2016-01-01

    Four seaweed polysaccharides were extracted from Sarcodia ceylonensis, Ulva lactuca L., Gracilaria lemaneiformis, and Durvillaea antarctica, respectively, by microwave-assisted extraction. The effect of three significant variables (extraction time, extraction temperature, and the ratio of water to raw material) on the process for extracting polysaccharides was investigated, along with the optimization of the extraction using the response surface method (RSM) with a Box–Behnken design. The polysaccharide structure, monosaccharide composition, degree of sulfation, and molecular weight (MW) distribution were analyzed by infrared (IR) spectrometry, gas chromatography (GC), and high-performance gel permeation chromatography (HPGPC). IR spectrometry showed that Sarcodia ceylonensis polysaccharide (SCP), Ulva lactuca L. polysaccharide (ULLP), and Durvillaea antarctica polysaccharide (DAP) were all sulfated polysaccharides and, except Gracilaria lemaneiformis polysaccharide (GLP), all belong to β-pyranosidic polysaccharides. The average molecular weight (MW) of SCP, ULLP, GLP, and DAP was 466, 404, 591, and 482 kDa, respectively. The quantitative and comparative results with external standards indicated that the main monosaccharide in SCP and ULLP was mannose; and GLP and DAP were mainly composed of galactose and glucose, respectively. Then the in vitro antioxidant activity of all of the polysaccharides was evaluated using different assays—2,2–azino –bis (3-ethylbenzthiazoline-6- sulfonate) (ABTS), hydroxyl radical, nitrite scavenging capacity, and reducing power—and the relationship between their antioxidant activity and chemical characteristics were also examined. ULLP presented the highest ABTS radical scavenging activity; ULLP, SCP and DAP also showed a strong effect on the ABTS radical scavenging activity. SCP and ULLP exhibited excellent hydroxyl radical scavenging activities, about 83.33% ± 2.31% and 80.07% ± 2.17%, respectively, at 4 mg/mL. The

  18. Iodine-Catalyzed Polysaccharide Esterification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A review is provided of the recent reports to use iodine-catalyzed esterification reaction to produce esters from polysaccharides. The process entails reaction of the polysaccharide with an acid anhydride in the presence of a catalytic level of iodine, and in the absence of additional solvents. T...

  19. Comparative evaluation of polysaccharides isolated from Astragalus, oyster mushroom, and yacon as inhibitors of α-glucosidase.

    PubMed

    Zhu, Zhen-Yuan; Zhang, Jing-Yi; Chen, Li-Jing; Liu, Xiao-Cui; Liu, Yang; Wang, Wan-Xiao; Zhang, Yong-Min

    2014-04-01

    The incidence of diabetes has increased considerably, and become the third serious chronic disease following cancer and cardiovascular diseases. Though acarbose, metformin, and 1-deoxynojirimycin have good efficacy for clinical application as hypoglycemic drugs, their expensive costs and some degree of side effects have limited their clinical application. Recently, increasing attention has concentrated on the polysaccharides from natural plant and animal sources for diabetes. In order to illustrate the pharmaceutical activity of polysaccharides as natural hypoglycemic agents, polysaccharides isolated from Astragalus, oyster mushroom, and Yacon were evaluated for their inhibitory effects on α-glucosidase. Polysaccharides were extracted and purified from Astragalus, Oyster mushroom, and Yacon with hot water at 90 °C for 3 h, respectively. The total sugar content of the polysaccharide was determined by the phenol-sulfuric acid method. The α-glucosidase inhibitory activity was measured by the glucose oxidase method. The results exhibited that the inhibitory effects on α-glucosidase were in decreasing order, Astragalus > oyster mushroom > Yacon. The α-glucosidase inhibition percentage of Astragalus polysaccharide and oyster mushroom polysaccharide were over 40% at the polysaccharide concentration of 0.4 mg·mL(-1). The IC50 of Astragalus polysaccharide and oyster mushroom polysaccharide were 0.28 and 0.424 mg·mL(-1), respectively. The information obtained from this work is beneficial for the use polysaccharides as a dietary supplement for health foods and therapeutics for diabetes.

  20. Development of affinity-based delivery of NGF from a chondroitin sulfate biomaterial

    PubMed Central

    Butterfield, Karen Chao; Conovaloff, Aaron W.; Panitch, Alyssa

    2011-01-01

    Chondroitin sulfate is a major component of the extracellular matrix in both the central and peripheral nervous systems. Chondroitin sulfate is upregulated at injury, thus methods to promote neurite extension through chondroitin sulfate-rich matrices and synthetic scaffolds are needed. We describe the use of both chondroitin sulfate and a novel chondroitin sulfate-binding peptide to control the release of nerve growth factor. Interestingly, the novel chondroitin sulfate-binding peptide enhances the controlled release properties of the chondroitin sulfate gels. While introduction of chondroitin sulfate into a scaffold inhibits primary cortical outgrowth, the combination of chondroitin sulfate, chondroitin sulfate-binding peptide and nerve growth factor promotes primary cortical neurite outgrowth in chondroitin sulfate gels. PMID:23507746

  1. Sulfation of fucogalactan from Agaricus bisporus: Different patterns in the chemical structure and their effects on anticoagulant activity.

    PubMed

    Román Ochoa, Yony; Iacomini, Marcello; Sassaki, Guilherme Lanzi; Cipriani, Thales Ricardo

    2017-04-01

    A fucogalactan from Agaricus bisporus was sulfated by two methodologies based on an optimized sulfation method. The direct action of chlorosulfonic acid and SO3-pyridine complex over the sulfation reaction and its effects on anticoagulant activity were evaluated. The products of chemical sulfations were two sulfated fucogalactans named E100 and ESL respectively. Clotting assays (APTT, PT and TT) showed that both sulfated polysaccharides have anticoagulant activity, and that ESL was more potent compared to E100. The FXa, T and FXIIa activities in the presence of the sulfated polysaccharides were determined. The better anticoagulant activity of ESL could be related to anti-FXIIa activity and also probably to its higher bioavailability. The HPSEC analysis showed similar Mw of 1.08×10(4)gmol(-1) and 1.00×10(4)gmol(-1) for E100 and ESL respectively. NMR and methylation analyses indicated a heterogeneous sulfation pattern for E100, whereas ESL showed conserved unsulfated (1→6)-linked α-d-Galp residues in the main-chain and a more homogeneous sulfation pattern. The DS values of ESL and E100 were 1.0 and 2.8 respectively, indicating that the sulfation pattern is more important for the anticoagulant activity than the amount of sulfate.

  2. Why were polysaccharides necessary?

    PubMed

    Tolstoguzov, Vladimir

    2004-12-01

    The main idea of this paper is that the primordial soup may be modelled by food systems whose structure-property relationship is based on non-specific interactions between denatured biopolymers. According to the proposed hypothesis, polysaccharides were the first biopolymers that decreased concentration of salts in the primordial soup, 'compatibilised' and drove the joint evolution of proto-biopolymers. Synthesis of macromolecules within the polysaccharide-rich medium could have resulted in phase separation of the primordial soup and concentration of the polypeptides and nucleic acids in the dispersed phase particles. The concentration of proto-biopolymer mixtures favoured their cross-linking in hybrid supermacromolecules of conjugates. The cross-linking of proto-biopolymers could occur by hydrophobic, electrostatic interactions, H-bonds due to freezing aqueous mixed biopolymer dispersions and/or by covalent bonds due to the Maillard reaction. Cross-linking could have increased the local concentration of chemically different proto-biopolymers, fixed their relative positions and made their interactions reproducible. Attractive-repulsive interactions between cross-linked proto-biopolymer chains could develop pairing of the monomer units, improved chemical stability (against hydrolysis) and led to their mutual catalytic activity and coding. Conjugates could probably evolve to the first self-reproduced entities and then to specialized cellular organelles. Phase separation of the primordial soup with concentration of conjugates in the dispersed particles has probably resulted in proto-cells.

  3. Why Were Polysaccharides Necessary?

    NASA Astrophysics Data System (ADS)

    Tolstoguzov, Vladimir

    2004-12-01

    The main idea of this paper is that the primordial soup may be modelled by food systems whose structure-property relationship is based on non-specific interactions between denatured biopolymers. According to the proposed hypothesis, polysaccharides were the first biopolymers that decreased concentration of salts in the primordial soup, `compatibilised' and drove the joint evolution of proto-biopolymers. Synthesis of macromolecules within the polysaccharide-rich medium could have resulted in phase separation of the primordial soup and concentration of the polypeptides and nucleic acids in the dispersed phase particles. The concentration of proto-biopolymer mixtures favoured their cross-linking in hybrid supermacromolecules of conjugates. The cross-linking of proto-biopolymers could occur by hydrophobic, electrostatic interactions, H-bonds due to freezing aqueous mixed biopolymer dispersions and/or by covalent bonds due to the Maillard reaction. Cross-linking could have increased the local concentration of chemically different proto-biopolymers, fixed their relative positions and made their interactions reproducible. Attractive-repulsive interactions between cross-linked proto-biopolymer chains could develop pairing of the monomer units, improved chemical stability (against hydrolysis) and led to their mutual catalytic activity and coding. Conjugates could probably evolve to the first self-reproduced entities and then to specialized cellular organelles. Phase separation of the primordial soup with concentration of conjugates in the dispersed particles has probably resulted in proto-cells.

  4. Polysaccharides and bacterial plugging

    SciTech Connect

    Fogler, H.S.

    1991-11-01

    Before any successful application of Microbial Enhanced Oil Recovery process can be realized, an understanding of the cells' transport and retentive mechanisms in porous media is needed. Cell transport differs from particle transport in their ability to produce polysaccharides, which are used by cells to adhere to surfaces. Cell injection experiments have been conducted using Leuconostoc cells to illustrate the importance of cellular polysaccharide production as a transport mechanism that hinders cell movement and plugs porous media. Kinetic studies of the Leuconostoc cells, carried out to further understand the plugging rates of porous media, have shown that the cells' growth rates are approximately equal when provided with monosaccharide (glucose and fructose) or sucrose. The only difference in cell metabolism is the production of dextran when sucrose is supplied as a carbon source. Experimentally it has also been shown that the cells' growth rate is weakly dependent upon the sucrose concentration in the media, and strongly dependent upon the concentration of yeast extract. The synthesis of cellular dextran has been found to lag behind cell generation, thus indicating that the cells need to reach maturity before they are capable of expressing the detransucrase enzyme and synthesizing insoluble dextran. Dextran yields were found to be dependent upon the sucrose concentration in the media. 10 refs., 9 figs., 9 tabs.

  5. Polysaccharides from Extremophilic Microorganisms

    NASA Astrophysics Data System (ADS)

    Nicolaus, B.; Moriello, V. Schiano; Lama, L.; Poli, A.; Gambacorta, A.

    2004-02-01

    Several marine thermophilic strains were analyzed for exopolysaccharide production. The screening process revealed that a significant number of thermophilic microorganisms were able to produce biopolymers, and some of them also revealed interesting chemical compositions. We have identified four new polysaccharides from thermophilic marine bacteria, with complex primary structures and with different repetitive units: a galacto-mannane type from strain number 4004 and mannane type for the other strains. The thermophilic Bacillus thermantarcticus produces two exocellular polysaccharides (EPS 1, EPS 2) that give the colonies a typical mucous character. The exopolysaccharide fraction was produced with all substrates assayed, although a higher yield 400 mg liter-1 was obtained with mannose as carbon and energy source. NMR spectra confirmed that EPS 1 was a heteropolysaccharide of which the repeating unit was constituted by four different α-D-mannoses and three different β-D-glucoses. It seems to be close to some xantan polymers. EPS 2 was a mannan. Four different α-D-mannoses were found as the repeating unit. Production and chemical studies of biopolymers produced by halophilic archaea, Haloarcula species were also reported.

  6. Biological functions of iduronic acid in chondroitin/dermatan sulfate.

    PubMed

    Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

    2013-05-01

    The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease.

  7. Benzene oxidation coupled to sulfate reduction

    USGS Publications Warehouse

    Lovley, D.R.; Coates, J.D.; Woodward, J.C.; Phillips, E.J.P.

    1995-01-01

    Highly reduced sediments from San Diego Bay, Calif., that were incubated under strictly anaerobic conditions metabolized benzene within 55 days when they were exposed initially to I ??M benzene. The rate of benzene metabolism increased as benzene was added back to the benzene-adapted sediments. When a [14C]benzene tracer was included with the benzene added to benzene-adapted sediments, 92% of the added radioactivity was recovered as 14CO2. Molybdate, an inhibitor of sulfate reduction, inhibited benzene uptake and production of 14CO2 from [14C]benzene. Benzene metabolism stopped when the sediments became sulfate depleted, and benzene uptake resumed when sulfate was added again. The stoichiometry of benzene uptake and sulfate reduction was consistent with the hypothesis that sulfate was the principal electron acceptor for benzene oxidation. Isotope trapping experiments performed with [14C]benzene revealed that there was no production of such potential extracellular intermediates of benzene oxidation as phenol, benzoate, p-hydroxybenzoate, cyclohexane, catechol, and acetate. The results demonstrate that benzene can be oxidized in the absence of O2, with sulfate serving as the electron acceptor, and suggest that some sulfate reducers are capable of completely oxidizing benzene to carbon dioxide without the production of extracellular intermediates. Although anaerobic benzene oxidation coupled to chelated Fe(III) has been documented previously, the study reported here provides the first example of a natural sediment compound that can serve as an electron acceptor for anaerobic benzene oxidation.

  8. The molecular basis of polysaccharide cleavage by lytic polysaccharide monooxygenases

    PubMed Central

    Frandsen, Kristian E. H.; Simmons, Thomas J.; Dupree, Paul; Poulsen, Jens-Christian N.; Hemsworth, Glyn R.; Ciano, Luisa; Johnston, Esther M.; Tovborg, Morten; Johansen, Katja S.; von Freiesleben, Pernille; Marmuse, Laurence; Fort, Sébastien; Cottaz, Sylvain; Driguez, Hugues; Henrissat, Bernard; Lenfant, Nicolas; Tuna, Floriana; Baldansuren, Amgalanbaatar; Davies, Gideon J.; Leggio, Leila Lo; Walton, Paul H.

    2016-01-01

    Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes which oxidatively break down recalcitrant polysaccharides such as cellulose and chitin. Since their discovery LPMOs have become integral factors in the industrial utilization of biomass, especially in the sustainable generation of cellulosic bioethanol. We report here the first structural determination of an LPMO–oligosaccharide complex, yielding detailed insights into the mechanism of action of these enzymes. Using a combination of structure and electron paramagnetic resonance spectroscopy, we reveal the means by which LPMOs interact with saccharide substrates. We further uncover electronic and structural features of the enzyme active site, showing how LPMOs orchestrate the reaction of oxygen with polysaccharide chains. PMID:26928935

  9. Sulfate in fetal development.

    PubMed

    Dawson, Paul A

    2011-08-01

    Sulfate (SO(4)(2-)) is an important nutrient for human growth and development, and is obtained from the diet and the intra-cellular metabolism of sulfur-containing amino acids, including methionine and cysteine. During pregnancy, fetal tissues have a limited capacity to produce sulfate, and rely on sulfate obtained from the maternal circulation. Sulfate enters and exits placental and fetal cells via transporters on the plasma membrane, which maintain a sufficient intracellular supply of sulfate and its universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) for sulfate conjugation (sulfonation) reactions to function effectively. Sulfotransferases mediate sulfonation of numerous endogenous compounds, including proteins and steroids, which biotransforms their biological activities. In addition, sulfonation of proteoglycans is important for maintaining normal structure and development of tissues, as shown for reduced sulfonation of cartilage proteoglycans that leads to developmental dwarfism disorders and four different osteochondrodysplasias (diastrophic dysplasia, atelosteogenesis type II, achondrogenesis type IB and multiple epiphyseal dysplasia). The removal of sulfate via sulfatases is an important step in proteoglycan degradation, and defects in several sulfatases are linked to perturbed fetal bone development, including mesomelia-synostoses syndrome and chondrodysplasia punctata 1. In recent years, interest in sulfate and its role in developmental biology has expanded following the characterisation of sulfate transporters, sulfotransferases and sulfatases and their involvement in fetal growth. This review will focus on the physiological roles of sulfate in fetal development, with links to human and animal pathophysiologies.

  10. Antiviral Potential of Algae Polysaccharides Isolated from Marine Sources: A Review

    PubMed Central

    Ahmadi, Azin; Zorofchian Moghadamtousi, Soheil; Abubakar, Sazaly; Zandi, Keivan

    2015-01-01

    From food to fertilizer, algal derived products are largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. Among different chemical compositions isolated from algae, polysaccharides are the most well-established compounds, which were subjected to a variety of studies due to extensive bioactivities. Over the past few decades, the promising results for antiviral potential of algae-derived polysaccharides have advocated them as inordinate candidates for pharmaceutical research. Numerous studies have isolated various algal polysaccharides possessing antiviral activities, including carrageenan, alginate, fucan, laminaran, and naviculan. In addition, different mechanisms of action have been reported for these polysaccharides, such as inhibiting the binding or internalization of virus into the host cells or suppressing DNA replication and protein synthesis. This review strives for compiling previous antiviral studies of algae-derived polysaccharides and their mechanism of action towards their development as natural antiviral agents for future investigations. PMID:26484353

  11. Electrospun cellulose acetate membrane for size separating and antibacterial screening of crude polysaccharides.

    PubMed

    Chumpol, Jiraporn; Siri, Sineenat

    2016-12-01

    This study aims to produce electrospun cellulose acetate (CA) membrane as the alternative supporting medium for a separation of crude polysaccharides by electrophoresis and a screening of their antibacterial activity. Among the tested conditions of fabrication, electrospun CA membrane at 57% porosity showed the best separation of each polysaccharide from the standard mixture and the crude extract of Aloe vera via electrophoresis. As compared with the commercial CA membrane, the produced electrospun CA membrane demonstrated more separated spots of polysaccharides. The antibacterial activity of the electrophoretic polysaccharide was also determined against Escherichia coli and Staphylococcus aureus as the inhibition zone after the bacterial culture agar was overlaid on the membrane and incubated for 24 h. The results of this study suggested the potential application of electrospun CA membrane combining with electrophoresis as a simple method for separating crude polysaccharides and screening for their antibacterial activity.

  12. Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with a neurite outgrowth promoting activity.

    PubMed

    Nadanaka, S; Clement, A; Masayama, K; Faissner, A; Sugahara, K

    1998-02-06

    A mouse brain chondroitin sulfate (CS) proteoglycan, DSD-1-PG, bears the DSD-1 epitope and has neurite outgrowth promoting properties. Shark cartilage CS-C inhibits the interactions between the DSD-1-specific monoclonal antibody 473HD and the CS chains of the DSD-1-PG, which is expressed on the mouse glial cells (Faissner, A., Clement, A., Lochter, A., Streit, A., Mandl, C., and Schachner, M. (1994) J. Cell Biol. 126, 783-799). On the other hand, several hexasaccharides isolated from commercial shark cartilage CS-D, which contains a higher proportion of characteristic D units (GlcUA(2-sulfate)beta1-3GalNAc(6-sulfate)) as compared with CS-C, has the A-D tetrasaccharide sequence composed of an A disaccharide unit (GlcUAbeta1-3GalNAc(4-sulfate)) and a D disaccharide unit (Nadanaka, S. and Sugahara, K. (1997) Glycobiology 7, 253-263). In this study, the biological activities and the structure of shark cartilage CS-D were investigated. CS-D inhibited the interactions between monoclonal antibody 473HD and DSD-1-PG and also promoted neurite outgrowth of embryonic day 18 hippocampal neurons. Eight octasaccharide fractions were isolated from CS-D after partial digestion with bacterial chondroitinase ABC by means of gel filtration chromatography and anion-exchange high performance liquid chromotography to investigate the frequency and the arrangement of the A-D tetrasaccharide unit in the polymer sequence. Structural analysis performed by a combination of enzymatic digestions with 500-MHz 1H NMR spectroscopy demonstrated that the isolated octasaccharides shared the common core structure DeltaHexAalpha1-3GalNAcbeta1-4(GlcUAbeta1-3GalNAc)3 with four, five, and six sulfate esters at various hydroxyl groups in different combinations. In the structure, DeltaHexA and GlcUA represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid and glucuronic acid, respectively. No D-D tetrasaccharide sequence was found, and discrete D disaccharide units were demonstrated exclusively as A

  13. Sulfation pathways in plants.

    PubMed

    Koprivova, Anna; Kopriva, Stanislav

    2016-11-25

    Plants take up sulfur in the form of sulfate. Sulfate is activated to adenosine 5'-phosphosulfate (APS) and reduced to sulfite and then to sulfide when it is assimilated into amino acid cysteine. Alternatively, APS is phosphorylated to 3'-phosphoadenosine 5'-phosphosulfate (PAPS), and sulfate from PAPS is transferred onto diverse metabolites in its oxidized form. Traditionally, these pathways are referred to as primary and secondary sulfate metabolism, respectively. However, the synthesis of PAPS is essential for plants and even its reduced provision leads to dwarfism. Here the current knowledge of enzymes involved in sulfation pathways of plants will be summarized, the similarities and differences between different kingdoms will be highlighted, and major open questions in the research of plant sulfation will be formulated.

  14. Heparan sulfate in skeletal muscle development

    SciTech Connect

    Noonan, D.M.

    1985-01-01

    In this study, chick breast skeletal muscle cells developing in vitro from myoblasts to myotubes were found to synthesize heparan sulfate (HS), chrondroitin-6-sulfate, chrondroitin-4-sulfate, dermatan sulfate, unsulfated chrondroitin and hyaluronic acid in both the substratum attached material (SAM) and the cellular fraction. SAM was found to contain predominantly chrondroitin-6-sulfate and relatively little HS whereas the cellular fraction contained relatively higher levels of HS and lower levels of chrondroitin-6-sulfate. Hyaluronic acid was also a major component in both fractions with the other glycosaminoglycan isomers present as minor components. Muscle derived fibroblast cultures had higher levels of dermatan sulfate in the cell layer and higher levels of HS in the SAM fraction than did muscle cultures. The structure of the proteoglycans were partially characterized in /sup 35/SO/sub 4//sup 2 -/ radio-labeled cultures which indicated an apparent increase in the hydrodynamic size of the cell fraction heparan sulfate proteoglycan (HS PG). Myotubes incorporated /sup 35/SO/sub 4//sup 2 -/ into HS PG at a rate 3 times higher than myoblasts. The turnover rate of HS in the cellular fraction was the same for myoblasts and myotubes, with a t/sub 1/2/ of approximately 5 hours. Fibroblasts in culture synthesized the smallest HS PG, and incorporated /sup 35/SO/sub 4//sup 2 -/ into HS PG at a rate lower than that of myotubes. Studies in which fusion was reversibly inhibited with decreased medium (Ca/sup + +/) closely linked the increased synthesis of cell fraction, but not SAM fraction, HS with myotube formation. However, decreasing medium calcium appeared to cause significant alterations in the metabolism of inorganic sulfate.

  15. Heparan Sulfate Proteoglycans

    PubMed Central

    Sarrazin, Stephane; Lamanna, William C.; Esko, Jeffrey D.

    2011-01-01

    Heparan sulfate proteoglycans are found at the cell surface and in the extracellular matrix, where they interact with a plethora of ligands. Over the last decade, new insights have emerged regarding the mechanism and biological significance of these interactions. Here, we discuss changing views on the specificity of protein–heparan sulfate binding and the activity of HSPGs as receptors and coreceptors. Although few in number, heparan sulfate proteoglycans have profound effects at the cellular, tissue, and organismal level. PMID:21690215

  16. Relative toxicity of inhaled metal sulfate salts for pulmonary macrophages

    SciTech Connect

    Skornik, W.A.; Brain, J.D.

    1983-08-01

    The effects of metal sulfate aerosols on respiratory defense mechanisms in hamsters were studied. Pulmonary macrophage phagocytic rates were measured by determining the in vivo uptake of radioactive colloidal gold (/sup 198/Au) 1, 24, or 48 h after a single 4-h exposure. The concentrations of sulfate aerosols causing a 50% inhibition in pulmonary macrophage endocytosis (EC/sub 50/) were determined. When hamsters were exposed for 4 h to cupric sulfate (greater than or equal to 4.8 mg/m/sup 3/), zinc sulfate (greater than or equal to 3.1 mg/m/sup 3/), ferric sulfate (greater than or equal to 7.8 mg/m/sup 3/), or zinc ammonium sulfate (greater than or equal to 10.0 mg/m/sup 3/), macrophage endocytosis was significantly reduced 1 h after exposure compared with that in unexposed control animals. Although the response was variable, 24 h after exposures to the higher sulfate concentrations the percent of gold ingested by pulmonary macrophages remained depressed. By 48 h, the rate of macrophage endocytosis in hamsters had returned to normal control values except in hamsters exposed to 4.8 mg/m/sup 3/ cupric sulfate or 9.8 mg/m/sup 3/ ferric sulfate. These hamsters showed significant increases in phagocytosis. The EC/sub 50/ values in milligrams of sulfate per cubic meter for cupric sulfate, zinc sulfate, ferric sulfate, and zinc ammonium sulfate were 2.7, 4.5, 7.5, and 17.9, respectively. These results are negatively correlated with the ranking of sulfates using the criteria of relative irritant potency, as measured by increases in pulmonary flow resistance. Thus, rankings of related chemical structures are not absolute. Their relative toxicities vary depending on the end point selected.

  17. Relative toxicity of inhaled metal sulfate salts for pulmonary macrophages.

    PubMed

    Skornik, W A; Brain, J D

    1983-08-01

    The effects of metal sulfate aerosols on respiratory defense mechanisms in hamsters were studied. Pulmonary macrophage phagocytic rates were measured by determining the in vivo uptake of radioactive colloidal gold (198Au) 1, 24, or 48 h after a single 4-h exposure. The concentrations of sulfate aerosols causing a 50% inhibition in pulmonary macrophage endocytosis (EC50) were determined. When hamsters were exposed for 4 h to cupric sulfate (greater than or equal to 4.8 mg/m3), zinc sulfate (greater than or equal to 3.1 mg/m3), ferric sulfate (greater than or equal to 7.8 mg/m3), or zinc ammonium sulfate (greater than or equal to 10.0 mg/m3), macrophage endocytosis was significantly reduced 1 h after exposure compared with that in unexposed control animals. Although the response was variable, 24 h after exposures to the higher sulfate concentrations the percent of gold ingested by pulmonary macrophages remained depressed. By 48 h, the rate of macrophage endocytosis in hamsters had returned to normal control values except in hamsters exposed to 4.8 mg/m3 cupric sulfate or 9.8 mg/m3 ferric sulfate. These hamsters showed significant increases in phagocytosis. The EC50 values in milligrams of sulfate per cubic meter for cupric sulfate, zinc sulfate, ferric sulfate, and zinc ammonium sulfate were 2.7, 4.5, 7.5, and 17.9, respectively. These results are negatively correlated with the ranking of sulfates using the criteria of relative irritant potency, as measured by increases in pulmonary flow resistance. Thus, rankings of related chemical structures are not absolute. Their relative toxicities vary depending on the end point selected.

  18. Heparin and related polysaccharides: Synthesis using recombinant enzymes and metabolic engineering

    PubMed Central

    Suflita, Matthew; Fu, Li; He, Wenqin; Koffas, Mattheos; Linhardt, Robert J.

    2015-01-01

    Glycosaminoglycans are linear anionic polysaccharides that exhibit a number of important biological and pharmacological activities. The two most prominent members of this class of polysaccharides are heparin/heparan sulfate and the chondroitin sulfates (including dermatan sulfate). These polysaccharides, having complex structures and polydispersity, are biosynthesized in the Golgi of most animal cells. The chemical synthesis of these glycosaminoglycans is precluded by their structural complexity. Today, we depend on food animal tissues for their isolation and commercial production. Ton quantities of these glycosaminoglycans are used annually as pharmaceuticals and nutraceuticals. The variability of animal-sourced glycosaminoglycans, their inherent impurities, the limited availability of source tissues, the poor control of these source materials, and their manufacturing processes, suggest a need for new approaches for their production. Over the past decade there have been major efforts in the biotechnological production of these glycosaminoglycans. This mini-review focuses on the use of recombinant enzymes and metabolic engineering for the production of heparin and chondroitin sulfates. PMID:26219501

  19. Attenuation of Magnesium Sulfate on CoCl₂-Induced Cell Death by Activating ERK1/2/MAPK and Inhibiting HIF-1α via Mitochondrial Apoptotic Signaling Suppression in a Neuronal Cell Line.

    PubMed

    Huang, Chih-Yang; Hsieh, You-Liang; Ju, Da-Tong; Lin, Chien-Chung; Kuo, Chia-Hua; Liou, Yi-Fan; Ho, Tsung-Jung; Tsai, Chang-Hai; Tsai, Fuu-Jen; Lin, Jing-Ying

    2015-08-31

    Magnesium sulfate (MgSO₄) ameliorates hypoxia/ischemia-induced neuronal apoptosis in a rat model. This study aimed to investigate the mechanisms governing the anti-apoptotic effect of MgSO₄ on cobalt chloride (CoCl₂)-exposed NB41A3 mouse neuroblastoma cells. MgSO₄ increased the viability of NB41A3 cells treated with CoCl₂ in a dose-dependent manner. MgSO₄ treatment was shown to lead to an increase in the anti-apoptotic Bcl-2 family proteins, with a concomitant decrease in the pro-apoptotic proteins. MgSO₄ also attenuated the CoCl₂-induced disruption of mitochondrial membrane potential (ΔΨ(m)) and reduced the release of cytochrome c form the mitochondria to the cytosol. Furthermore, exposure to CoCl₂ caused activation of the hypoxia-inducible factor 1α (HIF-1α). On the other hand, MgSO₄ markedly reduced CoCl₂-induced HIF-1α activation and suppressed HIF-1α downstream protein BNIP3. MgSO₄ treatment induced ERK1/2 activation and attenuated CoCl₂-induced activation of p38 and JNK. Addition of the ERK1/2 inhibitor U0126 significantly reduced the ability of MgSO₄ to protect neurons from CoCl₂-induced mitochondrial apoptotic events. However, incubation of cultures with the p38 and JNK inhibitors did not significantly affect MgSO₄-mediated neuroprotection. MgSO₄ appears to suppress CoCl₂-induced NB41A3 cell death by activating ERK1/2/ MAPK pathways, which further modulates the role of Bcl-2 family proteins and mitochondria in NB41A3 cells. Our data suggest that MgSO₄ may act as a survival factor that preserves mitochondrial integrity and inhibits apoptotic pathways.

  20. A threading receptor for polysaccharides

    NASA Astrophysics Data System (ADS)

    Mooibroek, Tiddo J.; Casas-Solvas, Juan M.; Harniman, Robert L.; Renney, Charles M.; Carter, Tom S.; Crump, Matthew P.; Davis, Anthony P.

    2016-01-01

    Cellulose, chitin and related polysaccharides are key renewable sources of organic molecules and materials. However, poor solubility tends to hamper their exploitation. Synthetic receptors could aid dissolution provided they are capable of cooperative action, for example by multiple threading on a single polysaccharide molecule. Here we report a synthetic receptor designed to form threaded complexes (polypseudorotaxanes) with these natural polymers. The receptor binds fragments of the polysaccharides in aqueous solution with high affinities (Ka up to 19,000 M-1), and is shown—by nuclear Overhauser effect spectroscopy—to adopt the threading geometry. Evidence from induced circular dichroism and atomic force microscopy implies that the receptor also forms polypseudorotaxanes with cellulose and its polycationic analogue chitosan. The results hold promise for polysaccharide solubilization under mild conditions, as well as for new approaches to the design of biologically active molecules.

  1. Structural characterization of a homogalacturonan from Capparis spinosa L. fruits and anti-complement activity of its sulfated derivative.

    PubMed

    Wang, Huijun; Wang, Hongwei; Shi, Songshan; Duan, Jinyou; Wang, Shunchun

    2012-08-01

    A water-soluble polysaccharide CSPS-2B-2 with a molecular mass of 8.8 kDa, was obtained from the fruits of Capparis spinosa L. Chemical and NMR spectral analysis verified CSPS-2B-2 was a linear poly-(1-4)-α-D-galactopyranosyluronic acid in which 12.9±0.4% of carboxyl groups existed as methyl ester and 2.6±0.1% of D-GalpA residues were acetylated. A sulfated derivative Sul-2B-2 with a sulfation degree of 0.88±0.02 was prepared via the substitution of C-2 and/or C-3 of GalpA residues in CSPS-2B-2. Bioassay on the complement and coagulation system demonstrated that Sul-2B-2 (CH(50): 3.5±0.2 μg/mL) had a stronger inhibitory effect on the activation of complement system through the classic pathway than that of heparin (CH(50): 8.9±0.3 μg/mL). Interestingly, Sul-2B-2 at low dose even middle dose (for example 52 μg/mL) had no effect on coagulation system, which was totally different from heparin. Thus, our observation indicated that Sul-2B-2 was more efficient than heparin in inhibiting the activation of the complement system through classical pathway and exhibiting a relatively less anti-coagulant activity. These results suggested that the sulfated derivative Sul-2B-2 prepared from the homogalacturonan in the fruits of Capparis spinosa L, might be a promising drug candidate in case of necessary therapeutic complement inhibition.

  2. Antimicrosporidian activity of sulphated polysaccharides from algae and their potential to control honeybee nosemosis.

    PubMed

    Roussel, M; Villay, A; Delbac, F; Michaud, P; Laroche, C; Roriz, D; El Alaoui, H; Diogon, M

    2015-11-20

    Nosemosis is one of the most common and widespread diseases of adult honeybees. The causative agents, Nosema apis and Nosema ceranae, belong to microsporidia some obligate intracellular eukaryotic parasites. In this study, 10 sulphated polysaccharides from algae were evaluated for their antimicrosporidian activity. They were first shown to inhibit the in vitro growth of the mammal microsporidian model, Encephalitozoon cuniculi. The most efficient polysaccharides were then tested for their ability to inhibit the growth of Nosema ceranae in experimentally-infected adult honeybees. Two polysaccharides extracted from Porphyridium spp. did not show any toxicity in honeybees and one of them allowed a decrease of both parasite load and mortality rate due to N. ceranae infection. A decrease in parasite abundance but not in mortality rate was also observed with an iota carrageenan. Our results are promising and suggest that algal sulphated polysaccharides could be used to prevent and/or control bee nosemosis.

  3. Secondary Storage of Dermatan Sulfate in Sanfilippo Disease*

    PubMed Central

    Lamanna, William C.; Lawrence, Roger; Sarrazin, Stéphane; Esko, Jeffrey D.

    2011-01-01

    Mucopolysaccharidoses are a group of genetically inherited disorders that result from the defective activity of lysosomal enzymes involved in glycosaminoglycan catabolism, causing their intralysosomal accumulation. Sanfilippo disease describes a subset of mucopolysaccharidoses resulting from defects in heparan sulfate catabolism. Sanfilippo disorders cause severe neuropathology in affected children. The reason for such extensive central nervous system dysfunction is unresolved, but it may be associated with the secondary accumulation of metabolites such as gangliosides. In this article, we describe the accumulation of dermatan sulfate as a novel secondary metabolite in Sanfilippo. Based on chondroitinase ABC digestion, chondroitin/dermatan sulfate levels in fibroblasts from Sanfilippo patients were elevated 2–5-fold above wild-type dermal fibroblasts. Lysosomal turnover of chondroitin/dermatan sulfate in these cell lines was significantly impaired but could be normalized by reducing heparan sulfate storage using enzyme replacement therapy. Examination of chondroitin/dermatan sulfate catabolic enzymes showed that heparan sulfate and heparin can inhibit iduronate 2-sulfatase. Analysis of the chondroitin/dermatan sulfate fraction by chondroitinase ACII digestion showed dermatan sulfate storage, consistent with inhibition of iduronate 2-sulfatase. The discovery of a novel storage metabolite in Sanfilippo patients may have important implications for diagnosis and understanding disease pathology. PMID:21193389

  4. Secondary storage of dermatan sulfate in Sanfilippo disease.

    PubMed

    Lamanna, William C; Lawrence, Roger; Sarrazin, Stéphane; Esko, Jeffrey D

    2011-03-04

    Mucopolysaccharidoses are a group of genetically inherited disorders that result from the defective activity of lysosomal enzymes involved in glycosaminoglycan catabolism, causing their intralysosomal accumulation. Sanfilippo disease describes a subset of mucopolysaccharidoses resulting from defects in heparan sulfate catabolism. Sanfilippo disorders cause severe neuropathology in affected children. The reason for such extensive central nervous system dysfunction is unresolved, but it may be associated with the secondary accumulation of metabolites such as gangliosides. In this article, we describe the accumulation of dermatan sulfate as a novel secondary metabolite in Sanfilippo. Based on chondroitinase ABC digestion, chondroitin/dermatan sulfate levels in fibroblasts from Sanfilippo patients were elevated 2-5-fold above wild-type dermal fibroblasts. Lysosomal turnover of chondroitin/dermatan sulfate in these cell lines was significantly impaired but could be normalized by reducing heparan sulfate storage using enzyme replacement therapy. Examination of chondroitin/dermatan sulfate catabolic enzymes showed that heparan sulfate and heparin can inhibit iduronate 2-sulfatase. Analysis of the chondroitin/dermatan sulfate fraction by chondroitinase ACII digestion showed dermatan sulfate storage, consistent with inhibition of iduronate 2-sulfatase. The discovery of a novel storage metabolite in Sanfilippo patients may have important implications for diagnosis and understanding disease pathology.

  5. Chemoenzymatic synthesis and structural characterization of 2-O-sulfated glucuronic acid-containing heparan sulfate hexasaccharides

    PubMed Central

    Hsieh, Po-Hung; Xu, Yongmei; Keire, David A; Liu, Jian

    2014-01-01

    Heparan sulfate and heparin are highly sulfated polysaccharides that consist of a repeating disaccharide unit of glucosamine and glucuronic or iduronic acid. The 2-O-sulfated iduronic acid (IdoA2S) residue is commonly found in heparan sulfate and heparin; however, 2-O-sulfated glucuronic acid (GlcA2S) is a less abundant monosaccharide (∼<5% of total saccharides). Here, we report the synthesis of three GlcA2S-containing hexasaccharides using a chemoenzymatic approach. For comparison purposes, additional IdoA2S-containing hexasaccharides were synthesized. Nuclear magnetic resonance analyses were performed to obtain full chemical shift assignments for the GlcA2S- and IdoA2S-hexasaccharides. These data show that GlcA2S is a more structurally rigid saccharide residue than IdoA2S. The antithrombin (AT) binding affinities of a GlcA2S- and an IdoA2S-hexasaccharide were determined by affinity co-electrophoresis. In contrast to IdoA2S-hexasaccharides, the GlcA2S-hexasaccharide does not bind to AT, confirming that the presence of IdoA2S is critically important for the anticoagulant activity. The availability of pure synthetic GlcA2S-containing oligosaccharides will allow the investigation of the structure and activity relationships of individual sites in heparin or heparan sulfate. PMID:24770491

  6. Adeno-associated virus type 2 binding study on model heparan sulfate surface

    NASA Astrophysics Data System (ADS)

    Negishi, Atsuko; Liu, Jian; McCarty, Douglas; Samulski, Jude; Superfine, Richard

    2003-11-01

    Understanding the mechanisms involved in virus infections is useful in its application in areas such as gene therapy, drug development and delivery, and biosensors. In collaboration with UNC Gene Therapy Center and School of Pharmacy, we are specifically looking at the interaction between human parvovirus adeno-associated virus type 2 (AAV2), a potential viral vector, and heparan sulfate proteoglycan (HSPG), a known cell surface receptor for AAV2. Recent development in glycobiology has shown that some protein-polysaccharide binding is sugar sequence dependent. Heparan sulfate (HS) is a polysaccharide chain of sulfated iduronic/glucuronic and sulfate glucosamine residues and can be differentiated into sequence specific structures by enzymes. These enzymatic modifications, known as heparan sulfate sulfotransferase modified modifications, have been shown to change the biological nature of heparan sulfate such as specific binding to proteins and viruses. For understanding HS-assisted viral infection mechanisms, we are interested in investigating the binding affinity and stability of AAV to different HS structures. We have developed a model heparan sulfate surface in which AAV adsorption studies are done and analyzed using the atomic force microscope (AFM). In addition, a miniArray assay has been created to facilitate to this study. Adsorption studies are done in 4 white LED wells with approximately 3 mm2 reaction areas which minimize sample use and waste.

  7. Preparation of polysaccharides from wax gourd.

    PubMed

    Huang, Gangliang; Tan, Jiantao; Tan, Xianchun; Peng, Daquan

    2011-08-01

    Preparation of polysaccharides from the wax gourd was studied. The crude polysaccharides were extracted by ethanol precipitation, and deproteinized by the hydrochloric acid method. The deproteinized polysaccharides were separated by column chromatography to obtain the pure polysaccharides. The pure polysaccharides have a β-D-pyranosidic bond, and their molecular weight distribution is about 22,500. It was indicated that the final product had much more purity by IR spectrum analysis, UV absorption spectrum analysis, and phenol-sulfuric acid method, respectively. It was proved that wax gourd polysaccharides were composed of rhamnose, xylose, arabinose, mannose, glucose, and galactose by thin layer chromatography.

  8. Biochemical And Genetic Modification Of Polysaccharides

    NASA Technical Reports Server (NTRS)

    Kern, Roger G.; Petersen, Gene R.; Richards, Gil F.

    1993-01-01

    Bacteriophages producing endopolysaccharase-type enzymes used to produce, isolate, and purify high yields of modified polysaccharides from polysaccharides produced by, and incorporated into capsules of, certain bacteria. Bacteriophages used in conversion of native polysaccharide materials into polymers of nearly uniform high molecular weight or, alternatively, into highly pure oligosaccharides. Also used in genetic selection of families of polysaccharides structurally related to native polysaccharide materials, but having altered properties. Resulting new polysaccharides and oligosaccharides prove useful in variety of products, including pharmaceutical chemicals, coating materials, biologically active carbohydrates, and drag-reducing additives for fluids.

  9. A zinc complex of heparan sulfate destabilises lysozyme and alters its conformation

    SciTech Connect

    Hughes, Ashley J.; Hussain, Rohanah; Cosentino, Cesare; Guerrini, Marco; Siligardi, Giuliano; Yates, Edwin A.; Rudd, Timothy R.

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Zinc-heparan sulfate complex destabilises lysozyme, a model amyloid protein. Black-Right-Pointing-Pointer Addition of zinc, without heparan sulfate, stabilises lysozyme. Black-Right-Pointing-Pointer Heparan sulfate cation complexes provide alternative protein folding routes. -- Abstract: The naturally occurring anionic cell surface polysaccharide heparan sulfate is involved in key biological activities and is implicated in amyloid formation. Following addition of Zn-heparan sulfate, hen lysozyme, a model amyloid forming protein, resembled {beta}-rich amyloid by far UV circular dichroism (increased {beta}-sheet: +25%), with a significantly reduced melting temperature (from 68 to 58 Degree-Sign C) by fluorescence shift assay. Secondary structure stability of the Zn-heparan sulfate complex with lysozyme was also distinct from that with heparan sulfate, under stronger denaturation conditions using synchrotron radiation circular dichroism. Changing the cation associated with heparan sulfate is sufficient to alter the conformation and stability of complexes formed between heparan sulfate and lysozyme, substantially reducing the stability of the protein. Complexes of heparan sulfate and cations, such as Zn, which are abundant in the brain, may provide alternative folding routes for proteins.

  10. Isolation and partial characterization of a novel amino sugar-containing fucan sulfate from commercial Fucus vesiculosus fucoidan.

    PubMed

    Nishino, T; Nishioka, C; Ura, H; Nagumo, T

    1994-03-04

    Commercial crude fucoidan (Sigma) from the brown seaweed Fucus vesiculosus was fractionated into its polysaccharide components by gel filtration and anion-exchange chromatography to clarify the structure-anticoagulant activity relationship. The products comprised a wide spectrum of fucans ranging from typical fucoidans (major components) containing mainly fucose, sulfate, and no uronic acid to low sulfate-containing heteropolysaccharide-like fucans (minor components) being composed of neutral sugars other than fucose and a high content of uronic acid(s). The polysaccharide components also had a wide range of molecular weight. The typical fucoidans showed a potent anticoagulant activity, whereas the other fucans had no or only slight activity. One of the fractions found as a minor component, was a novel polysaccharide containing an appreciable amount (11.5%) of glucosamine and a small amount (5.2%) of protein in addition to fucose and sulfate, and having a low apparent molecular weight of 6800. This is the first report that a proteoglycan-like, amino sugar-containing fucan sulfate, composed of fucose, galactose, glucose, mannose, xylose, uronic acid, glucosamine, and sulfate in the molar ratio of 1.00:0.04:0.01:0.48:0.24:0.18:0.56:1.90, could be obtained from brown seaweed. However, this polysaccharide showed no anticoagulant activity.

  11. Salinity-Induced Anti-Angiogenesis Activities and Structural Changes of the Polysaccharides from Cultured Cordyceps Militaris

    PubMed Central

    Zeng, Yangyang; Han, Zhangrun; Qiu, Peiju; Zhou, Zijing; Tang, Yang; Zhao, Yue; Zheng, Sha; Xu, Chenchen; Zhang, Xiuli; Yin, Pinghe; Jiang, Xiaolu; Lu, Hong; Yu, Guangli; Zhang, Lijuan

    2014-01-01

    Cordyceps is a rare and exotic mushroom that grows out of the head of a mummified caterpillar. Many companies are cultivating Cordyceps to meet the increased demand for its medicinal applications. However, the structures and functions of polysaccharides, one of the pharmaceutical active ingredients in Cordyceps, are difficult to reproduce in vitro. We hypothesized that mimicking the salty environment inside caterpillar bodies might make the cultured fungus synthesize polysaccharides with similar structures and functions to that of wild Cordyceps. By adding either sodium sulfate or sodium chloride into growth media, we observed the salinity-induced anti-angiogenesis activities of the polysaccharides purified from the cultured C. Militaris. To correlate the activities with the polysaccharide structures, we performed the 13C-NMR analysis and observed profound structural changes including different proportions of α and β glycosidic bonds and appearances of uronic acid signals in the polysaccharides purified from the culture after the salts were added. By coupling the techniques of stable 34S-sulfate isotope labeling, aniline- and D5-aniline tagging, and stable isotope facilitated uronic acid-reduction with LC-MS analysis, our data revealed for the first time the existence of covalently linked sulfate and the presence of polygalacuronic acids in the polysaccharides purified from the salt added C. Militaris culture. Our data showed that culturing C. Militaris with added salts changed the biosynthetic scheme and resulted in novel polysaccharide structures and functions. These findings might be insightful in terms of how to make C. Militaris cultures to reach or to exceed the potency of wild Cordyceps in future. PMID:25203294

  12. Methanogenesis and sulfate reduction: Competitive and noncompetitive substrates in estuarine sediments

    USGS Publications Warehouse

    Oremland, Ronald S.; Polcin, Sandra

    1982-01-01

    Sulfate ions did not inhibit methanogenesis in estuarine sediments supplemented with methanol, trimethylamine, or methionine. However, sulfate greatly retarded methanogenesis when hydrogen or acetate was the substrate. Sulfate reduction was stimulated by acetate, hydrogen, and acetate plus hydrogen, but not by methanol or trimethylamine. These results indicate that sulfate-reducing bacteria will outcompete methanogens for hydrogen, acetate, or both, but will not compete with methanogens for compounds like methanol, trimethylamine, or methionine, thereby allowing methanogenesis and sulfate reduction to operate simultaneously within anoxic, sulfate-containing sediments.

  13. Purification, chemical modification and immunostimulating activity of polysaccharides from Tremella aurantialba fruit bodies*

    PubMed Central

    Du, Xiu-ju; Zhang, Jing-song; Yang, Yan; Tang, Qing-jiu; Jia, Wei; Pan, Ying-jie

    2010-01-01

    Ultrafiltration and a series of chromatographic steps were used to isolate and purify polysaccharides from Tremella aurantialba fruit bodies. Three crude fractions (TAP50w, TAP10–50w, and TAP1–10w), five semi-purified fractions (TAPA–TAPE), and one purified fraction (TAPA1) were obtained. A sulfated derivative of TAPA1 (TAPA1-s) was prepared by chemical modification. The immunostimulating activity of the polysaccharide fractions in vitro was determined using the mouse spleen lymphocyte proliferation assay. Of the three crude fractions tested, cell proliferation rates were increased most by TAP50w. Furthermore, TAPA1-s was markedly more stimulatory than TAPA1, indicating that sulfonation was an effective way to enhance the immunostimulating activity of polysaccharide. PMID:20506575

  14. The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity

    PubMed Central

    Jin, Weihua; Zhang, Wenjing; Liang, Hongze; Zhang, Quanbin

    2015-01-01

    In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic acid (UA) content, linkage, branching, and the type of monosaccharide. It was shown that the larger the molecular weights, the better the activities. The molar ratio of galactose (Gal) to fucose (Fuc) was a positive factor at a concentration lower than 10 µg/mL, while it had no effect at a concentration more than 10 µg/mL. In addition, sulfate was necessary; however, the sulfate content, the sulfate pattern, linkage and branching had no effect at a concentration of more than 10 µg/mL. Moreover, the type of monosaccharide had no effect. Laminaran and UA fractions had no activity; however, they could reduce the activity by decreasing the effective concentration of the active composition when they were mixed with the active compositions. The effect of the extraction methods could not be determined. Finally, it was observed that sulfated galactofucan showed good anti-complement activity after separation. PMID:26712768

  15. The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity.

    PubMed

    Jin, Weihua; Zhang, Wenjing; Liang, Hongze; Zhang, Quanbin

    2015-12-25

    In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic acid (UA) content, linkage, branching, and the type of monosaccharide. It was shown that the larger the molecular weights, the better the activities. The molar ratio of galactose (Gal) to fucose (Fuc) was a positive factor at a concentration lower than 10 µg/mL, while it had no effect at a concentration more than 10 µg/mL. In addition, sulfate was necessary; however, the sulfate content, the sulfate pattern, linkage and branching had no effect at a concentration of more than 10 µg/mL. Moreover, the type of monosaccharide had no effect. Laminaran and UA fractions had no activity; however, they could reduce the activity by decreasing the effective concentration of the active composition when they were mixed with the active compositions. The effect of the extraction methods could not be determined. Finally, it was observed that sulfated galactofucan showed good anti-complement activity after separation.

  16. Rheologically interesting polysaccharides from yeasts

    NASA Technical Reports Server (NTRS)

    Petersen, G. R.; Nelson, G. A.; Cathey, C. A.; Fuller, G. G.

    1989-01-01

    We have examined the relationships between primary, secondary, and tertiary structures of polysaccharides exhibiting the rheological property of friction (drag) reduction in turbulent flows. We found an example of an exopolysaccharide from the yeast Cryptococcus laurentii that possessed high molecular weight but exhibited lower than expected drag reducing activity. Earlier correlations by Hoyt showing that beta 1 --> 3, beta 2 --> 4, and alpha 1 --> 3 linkages in polysaccharides favored drag reduction were expanded to include correlations to secondary structure. The effect of sidechains in a series of gellan gums was shown to be related to sidechain length and position. Disruption of secondary structure in drag reducing polysaccharides reduced drag reducing activity for some but not all exopolysaccharides. The polymer from C. laurentii was shown to be more stable than xanthan gum and other exopolysaccharides under the most vigorous of denaturing conditions. We also showed a direct relationship between extensional viscosity measurements and the drag reducing coefficient for four exopolysaccharides.

  17. Mitochondrial protection and anti-aging activity of Astragalus polysaccharides and their potential mechanism.

    PubMed

    Li, Xing-Tai; Zhang, Ya-Kui; Kuang, Hai-Xue; Jin, Feng-Xin; Liu, De-Wen; Gao, Ming-Bo; Liu, Ze; Xin, Xiao-Juan

    2012-01-01

    The current study was performed to investigate mitochondrial protection and anti-aging activity of Astragalus polysaccharides (APS) and the potential underlying mechanism. Lipid peroxidation of liver and brain mitochondria was induced by Fe(2+)-Vit C in vitro. Thiobarbituric acid (TBA) colorimetry was used to measure the content of thiobarbituric acid reactive substances (TBARS). Mouse liver mitochondrial permeability transition (PT) was induced by calcium overload in vitro and spectrophotometry was used to measure it. The scavenging activities of APS on superoxide anion (O(2) (•-)) and hydroxyl radical (•OH), which were produced by reduced nicotinamide adenine dinucleotide (NADH)-N-Methylphenazonium methyl sulfate (PMS) and hydrogen peroxide (H(2)O(2))-Fe(2+) system respectively, were measured by 4-nitrobluetetrazolium chloride (NBT) reduction and Fenton reaction colorimetry respectively. The Na(2)S(2)O(3) titration method was used to measure the scavenging activities of APS on H(2)O(2). APS could inhibit TBARS production, protect mitochondria from PT, and scavenge O(2) (•-), •OH and H(2)O(2) significantly in a concentration-dependent manner respectively. The back of the neck of mice was injected subcutaneously with D-galactose to induce aging at a dose of 100 mg/kg/d for seven weeks. Moreover, the activities of catalase (CAT), surperoxide dismutase (SOD) and glutathione peroxidase (GPx) and anti-hydroxyl radical which were assayed by using commercial monitoring kits were increased significantly in vivo by APS. According to this research, APS protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial PT and increasing the activities of antioxidases. Therefore, APS has the effect of promoting health.

  18. Structural characterization of polysaccharide obtained from red seaweed Gracilaria caudata (J Agardh).

    PubMed

    Barros, Francisco C N; da Silva, Draulio C; Sombra, Venicios G; Maciel, Jeanny S; Feitosa, Judith P A; Freitas, Ana L P; de Paula, Regina C M

    2013-01-30

    Seaweeds are considered an important source of bioactive molecules. In this work the marine red alga Gracilaria caudata was submitted to aqueous extraction of their polysaccharides for 2 h at 100 °C. The polysaccharide fraction (PGC) presented a recovery of 32.8%. The sulfate content of PGC, calculated by S%, is 1 ± 0.2% and the degree of sulfation accounts for 0.13 ± 0.2. High-Performance Size-Exclusion Chromatography demonstrated that PGC consists of a high molecular weight polysaccharide (2.5 × 10(5)gmol(-1)). Chemical analysis of PGC was performed by microanalysis, infrared (FT-IR) and nuclear magnetic resonance (NMR, 1 and 2D) spectroscopy. The structure of PGC is mainly constituted by the alternating residues 3-linked-β-D-galactopyranose and 4-linked-3,6-α-L-anhydrogalactose; however some hydroxyl groups were substituted by methyl groups and pyruvic acid acetal. The biological precursor of 3,6-α-L-anhydrogalactose (6-sulfate-α-l-galactose) was also detected.

  19. Microwave-assisted extraction of polysaccharides from Cyphomandra betacea and its biological activities.

    PubMed

    C, Senthil Kumar; M, Sivakumar; K, Ruckmani

    2016-11-01

    Response Surface Methodology (RSM) was used to optimize the parameters for microwave-assisted extraction of polysaccharides from Cyphomandra betacea. The results showed a good fit with a second-order polynomial equation that was statistically acceptable at P<0.05. Optimal conditions for the extraction of polysaccharides were: extraction time, 2h; microwave power, 400W; extraction temperature, 60°C; and ratio of raw material to water 1:40 (g/mL). Under the optimized conditions, the yield of polysaccharides was found to be relatively high (about 36.52%). The in vitro biological activities of antioxidant and antitumor were evaluated. The IC50 value of polysaccharides was found to be 3mg/mL. The percentage of Cell viability was determined by MTT assay. Our results showed that polysaccharides inhibited proliferation of MCF-7 (Breast carcinoma), A549 (Human lung carcinoma) and HepG2 (Liver carcinoma) with an IC50 of 0.23mg/mL, 0.17mg/mL and 0.62mg/mL respectively after 48h incubation. Polysaccharides were shown to promote apoptosis as seen in the nuclear morphological examination study using acridine orange (AO) and ethidium bromide (EB) staining. This is the first report on the effects of polysaccharides extracted from Cyphomandra betacea which exhibited stronger antioxidant and antitumor activities.

  20. In Vitro Antioxidant and Anti-Proliferation Activities of Polysaccharides from Various Extracts of Different Mushrooms

    PubMed Central

    Li, Xiaoyu; Wang, Zhenyu; Wang, Lu; Walid, Elfalleh; Zhang, Hua

    2012-01-01

    Polysaccharides were extracted from eight kinds of Chinese mushrooms using three solvents and were evaluated for their total carbohydrate, polyphenolic and protein contents, and antioxidant and anti-proliferation activities. The results suggested that all the polysaccharides had significant antioxidant capacities (EC50 ranged from 1.70 ± 0.42 to 65.98 ± 1.74 μM TE/g crude polysaccharide inhibition of ABTS+, EC50 ranged from 5.06 ± 0.12 to 127.38 ± 1.58 mg VCE/g CP scavenging of OH· and EC50 ranged from 0.70 ± 0.04 to 33.54 ± 0.49 mg VCE/g CP inhibition of lipid peroxidation) (TE: trolox equivalent; VCE: VC equivalent; CP: crude polysaccharide). The acid extracts of Russula vinosa Lindblad had the highest ABTS+ scavenging activity. Aqueous extracts of Dictyophora indusiata and Hohenbuehelia serotina possessed, respectively, the highest OH· scavenging capacity and ability to inhibit lipid peroxidation. Mushroom extracts also inhibited proliferation of HeLa and HepG2 cells in a dose-dependent manner. These results indicate that the mushroom polysaccharides might be potential antioxidant resources. PMID:22754332

  1. Boreal pollen contain ice-nucleating as well as ice-binding ‘antifreeze’ polysaccharides

    NASA Astrophysics Data System (ADS)

    Dreischmeier, Katharina; Budke, Carsten; Wiehemeier, Lars; Kottke, Tilman; Koop, Thomas

    2017-02-01

    Ice nucleation and growth is an important and widespread environmental process. Accordingly, nature has developed means to either promote or inhibit ice crystal formation, for example ice-nucleating proteins in bacteria or ice-binding antifreeze proteins in polar fish. Recently, it was found that birch pollen release ice-nucleating macromolecules when suspended in water. Here we show that birch pollen washing water exhibits also ice-binding properties such as ice shaping and ice recrystallization inhibition, similar to antifreeze proteins. We present spectroscopic evidence that both the ice-nucleating as well as the ice-binding molecules are polysaccharides bearing carboxylate groups. The spectra suggest that both polysaccharides consist of very similar chemical moieties, but centrifugal filtration indicates differences in molecular size: ice nucleation occurs only in the supernatant of a 100 kDa filter, while ice shaping is strongly enhanced in the filtrate. This finding may suggest that the larger ice-nucleating polysaccharides consist of clusters of the smaller ice-binding polysaccharides, or that the latter are fragments of the ice-nucleating polysaccharides. Finally, similar polysaccharides released from pine and alder pollen also display both ice-nucleating as well as ice-binding ability, suggesting a common mechanism of interaction with ice among several boreal pollen with implications for atmospheric processes and antifreeze protection.

  2. Boreal pollen contain ice-nucleating as well as ice-binding ‘antifreeze’ polysaccharides

    PubMed Central

    Dreischmeier, Katharina; Budke, Carsten; Wiehemeier, Lars; Kottke, Tilman; Koop, Thomas

    2017-01-01

    Ice nucleation and growth is an important and widespread environmental process. Accordingly, nature has developed means to either promote or inhibit ice crystal formation, for example ice-nucleating proteins in bacteria or ice-binding antifreeze proteins in polar fish. Recently, it was found that birch pollen release ice-nucleating macromolecules when suspended in water. Here we show that birch pollen washing water exhibits also ice-binding properties such as ice shaping and ice recrystallization inhibition, similar to antifreeze proteins. We present spectroscopic evidence that both the ice-nucleating as well as the ice-binding molecules are polysaccharides bearing carboxylate groups. The spectra suggest that both polysaccharides consist of very similar chemical moieties, but centrifugal filtration indicates differences in molecular size: ice nucleation occurs only in the supernatant of a 100 kDa filter, while ice shaping is strongly enhanced in the filtrate. This finding may suggest that the larger ice-nucleating polysaccharides consist of clusters of the smaller ice-binding polysaccharides, or that the latter are fragments of the ice-nucleating polysaccharides. Finally, similar polysaccharides released from pine and alder pollen also display both ice-nucleating as well as ice-binding ability, suggesting a common mechanism of interaction with ice among several boreal pollen with implications for atmospheric processes and antifreeze protection. PMID:28157236

  3. The beneficial properties of marine polysaccharides in alleviation of allergic responses.

    PubMed

    Vo, Thanh-Sang; Ngo, Dai-Hung; Kang, Kyong-Hwa; Jung, Won-Kyo; Kim, Se-Kwon

    2015-01-01

    Marine polysaccharides have been found as the principle component in cell wall structures of seaweeds or exoskeletons of crustaceans. Due to numerous pharmaceutical properties of marine polysaccharides such as antioxidant, anti-inflammatory, antiallergic, antitumor, antiobesity, antidiabetes, anticoagulant, antiviral, immunomodulatory, cardioprotective, and antihepatopathy activities, they have been applied in many fields of biomaterials, food, cosmetic, and pharmacology. Recently, several marine polysaccharides such alginate, porphyran, fucoidan, and chitin and its derivatives have been evidenced as downregulators of allergic responses due to enhancement of innate immune system, alteration of Th1/Th2 balance forward to Th1 cells, inhibition of IgE production, and suppression of mast cell degranulation. This contribution, therefore, focuses on antiallergic properties of marine polysaccharides and emphasizes their potential application as bioactive food ingredients as well as nutraceuticals for prevention of allergic disorders.

  4. [The role of cellular mediators in the development of the phenomenon of inhibition induced by barium sulfate luminol-dependent chemiluminescence of blood under the influence of non-steroidal anti-inflammatory drugs in patients with intolerance to these drugs].

    PubMed

    Chausova, S V; Gurevich, K G; Bondareva, G P; Filatov, O Ju; Malyshev, I Y

    2015-01-01

    We investigated contribution mediator mechanism in the development of the phenomenon of inhibition induced by barium sulfate luminol-dependent chemiluminescence (SLCHL) of blood under the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with intolerance to these drugs. It was found that the phenomenon of suppression SLCHL blood under the influence of NSAIDs in patients with intolerance is mediated by the participation of mediators, and the contribution of H1--and H2--histamine receptors, 5-HT2 serotonin receptors and Cys-leukotriene receptors in the development of that phenomenon depends on the chemical nature of NSAIDs and the clinical manifestations of intolerance.

  5. Isolation and chemical characterization of dissolved and particulate polysaccharides in Mikawa Bay

    NASA Astrophysics Data System (ADS)

    Sakugawa, Hiroshi; Handa, Nobuhiko

    1985-05-01

    Isolation and chemical elucidation of dissolved and particulate polysaccharides in seawater were conducted. The water samples were collected in Mikawa Bay, Japan during a red tide bloom of the dinoflagellate, Prorocentrum minimum. Dissolved polysaccharides were concentrated from 5-101 of seawater with dialysis followed by separation by gel flitration, and isolation by ethanol precipitation. A heteropolysaccharide consisting of glucose, galactose, mannose, xylose, arabinose, fucose and rhamnose and a glucan were isolated from the polysaccharide component having a molecular weight more than 4,000 Dalton and were characterized by several chemical analyses. The heteropolysaccharide is a mucilaginous polysaccharide having a highly branched structure and a molecular weight of 10 4-5 × 10 6 Daltons and probably contains a sulfate half ester: the glucan is a polysaccharide with β-1,3- and 1,6-linkages (chrysolaminaran type). Concentrations of these were respectively ca. 20 and 67 μg l -1 at 1 m, and 2 and 26 μg l -1 at 6 m. A similar heteropolysaccharide was found in the boiling water extract of the particulate matter, while β-glucan was isolated in a much less purified form than the seawater β-glucan. In addition, a large amount of β-1,4 glucan was found in the strong alkali extract of the particulate matter, indicating that this glucan must be a cell wall polysaccharide derived from phytoplankton. These results strongly suggest that the heteropolysaccharide and chrysolaminaran type polysaccharide dissolved in seawater were derived from water soluble carbohydrates of phytoplankton through extracellular release or cell lysis.

  6. Formation of 3-(glutathion-S-YL)-N-methyl-4-aminoazobenzene and inhibition of aminoazo dye-nucleic acid binding in vitro by reaction of glutathione with metabolically-generated N-methyl-4-aminoazobenzene-N-sulfate.

    PubMed

    Kadlubar, F F; Ketterer, B; Flammang, T J; Christodoulides, L

    1980-09-01

    The reaction of glutathione (GSH) with metabolically-formed N-methyl-4-aminoazobenzene-N-sulfate (MAB-N-sulfate), a presumed ultimate carcinogenic metabolite of N,N-dimethyl-4-aminoazobenzene (DAB), was investigated using a hepatic sulfotransferase incubation mixture containing GSH and the proximate carcinogen, N-hydroxy-N-methyl-4-aminoazobenzene (N-HO-MAB). Under these conditions, 6--16% of the MAB-N-sulfate formed could be trapped as an aminoazo dye-GSH adduct. Upon subsequent purification, the adduct was shown to be chromatographically and spectrally identical to 3-(glutathion-S-yl)-N-methyl-4-aminoazobenzene (3-GS-MAB), a known biliary metabolite of DAB and a product of the reaction of the synthetic ultimate carcinogen, N-benzoyloxy-N-methyl-4-aminoazobenzene(N-BzO-MAB), with GSH. Neither 2'- nor 4'-GS-MAB, both products of the latter reaction, were detected in the sulfotransferase incubation mixture. GSH-S-transferases did not appear to be involved in the reaction of MAB-N-sulfate of N-BzO-MAB with GSH. The addition of triethyltin, a potent GSH-S-transferase inhibitor, had no effect on the yield of 3-GS-MAB in (N-HO-MAB sulfotransferase)-GSH incubations; and the addition of cytosol or purified GSH transferases A and B to a (N-BzO-MAB)-GSH reaction mixture did not increase the amount of 3-GS-MAB formed.

  7. Preparation and antifouling property of polyurethane film modified by chondroitin sulfate

    NASA Astrophysics Data System (ADS)

    Yuan, Huihui; Xue, Jing; Qian, Bin; Chen, Huaying; Zhu, Yonggang; Lan, Minbo

    2017-02-01

    An antifouling polyurethane film modified by chondroitin sulfate (PU-CS) was prepared by chemical grafting with N-Boc-1,3-propanediamine as a spacer. The different mass fraction of N-Boc-1,3-propanediamine was investigated to obtain PU-CS films with different CS grafting density. The surface properties of PU-CS films were comprehensively characterized. Proteins adsorption and glycosaminoglycans adhesion on films were evaluated. Moreover, inorganic salt deposition on film with highest CS grafting density (3.70 μg/cm2) was briefly investigated. The results showed that the increase of CS grafting density improved not only the hydrophilicity but the antifouling performance of films. The best antifouling film reduced the adsorption of fibrinogen (BFG), human serum albumin (HSA) and lysozyme (LYS) by 81.4%, 95.0% and 76.5%, respectively, and the adhesion of chondroitin (CS), heparin (HP) and hyaluronic acid (HA) by 70.6%, 87.4% and 81.3%, respectively. In addition, the co-adsorption of proteins and glycosaminoglycans reduced up to 86.9% and 75.5%, respectively. Changes in inorganic salt deposition after co-adsorption of proteins and glycosaminoglycans on PU-CS(3) suggested that the proteins promoted the inorganic salt deposition, while glycosaminoglycans inhibited the crystal growth. The negatively charged polysaccharides might promote the generation of smaller crystals which could be conducive to provide theoretical and practical guide to develop novel urinary stents with significant anti-encrustation properties.

  8. Manipulation of cellulose nanocrystal surface sulfate groups toward biomimetic nanostructures in aqueous media.

    PubMed

    Zoppe, Justin O; Johansson, Leena-Sisko; Seppälä, Jukka

    2015-08-01

    We report a facile aqueous procedure to create multivalent displays of sulfonated ligands on CNCs for future applications as viral inhibitors. CNCs were decorated with model compounds containing sulfonate groups via reactions of epoxides and isothiocyanates with amines under alkaline conditions. At first, surface sulfate groups of CNCs were hydrolytically cleaved by alkaline hydrolysis to increase the number of available surface hydroxyls. Success of desulfation was confirmed via dynamic light scattering (DLS), zeta potential measurements and thermogravimetric analysis (TGA). CNC surface hydroxyl groups were then activated with epichlorohydrin before subsequent reactions. As proof of concept toward aqueous pathways for functionalizing nanoparticles with sulfonated ligands, 3-chloro-2-hydroxy-1-propanesulfonic acid sodium salt hydrate (CPSA) and 4-sulfophenyl isothiocyanate sodium salt monohydrate (4-SPITC) were chosen as model compounds to react with homobifunctional 2,2'-(ethylenedioxy)bis(ethylamine) (EBEA) molecular spacer. The approaches presented are not only applicable to polysaccharide nanocrystals, but also other classes of polymeric and inorganic substrates presenting surface hydroxyl groups, as in the case of poly(2-hydroxyethyl methacrylate) (PHEMA), silica or glass. CNCs carrying sulfonated ligands were characterized by ATR-FTIR and UV-vis spectroscopy. Surface chemical compositions of desired elements were determined via X-ray photoelectron spectroscopy (XPS). We anticipate that with these facile aqueous procedures as the proof of concept, a diverse library of target-specific functionalities can be conjugated to CNCs for applications in nanomedicine, especially related to viral inhibition.

  9. Polysaccharides templates for assembly of nanosilver.

    PubMed

    Emam, Hossam E; Ahmed, Hanan B

    2016-01-01

    Polysaccharides are particularly attractive in biomedical applications due to its biodegradability and biocompatibility. In addition to its ecofriendly effects and easy processing into different hydrogel shapes, made polysaccharides used on a large scale as suitable media for preparation of silver nanoparticles (AgNPs). In spite of, most of polysaccharides are water insoluble, but it has shown to be quite efficient capping agents and/or nanoreactor matrices for production of AgNPs. Several methods have been developed to get the benefit of multi-functionality for polysaccharides' macromolecules in preparation of AgNPs. Therefore, recently, preparation of nanosilver using different polysaccharides have been the focus of an exponentially increasing number of works devoted to develop nanocomposites by blending AgNPs with different polysaccharides matrices. The current review represents a wide survey for the published studies which interested in using of polysaccharides in nanosilver preparations.

  10. Review: prospects for the use of extracts and polysaccharides from marine algae to prevent and treat the diseases caused by Helicobacter pylori.

    PubMed

    Besednova, Natalya N; Zaporozhets, Tatyana S; Somova, Larisa M; Kuznetsova, Tatyana A

    2015-04-01

    Helicobacter pylori possesses a broad spectrum of pathogenic factors that allow it to survive and colonize the gastric mucosa, and thus, the pathogenetic targets, which have the same diversity, require search for and the development of alternative, effective, and innocuous means for the eradication of H. pylori. In recent years, fucoidans have been extensively studied due to the numerous interesting biological activities, including the anti-adhesive, anti-oxidative, antitoxic, immunomodulatory, anticoagulant, and anti-infection effects. This review summarizes the data on the effects of extracts and sulfated polysaccharides of marine algae, mainly fucoidans, on pathogenic targets in Helicobacter infection. The pathogenetic targets for therapeutic agents after H. pylori infection, such as flagellas, urease, and other enzymes, including adhesins, cytotoxin A (VacA), phospholipase, and L-8, are characterized here. The main target for the sulfated polysaccharides of seaweed is cell receptors of the gastric mucosa. This review presents the published data about the pleiotropic anti-inflammatory effects of polysaccharides on the gastric mucosa. It is known that fucoidan and other sulfated polysaccharides from algae have anti-ulcer effects, prevent the adhesion of H. pylori to, and reduce the formation of biofilm. The authors speculate that the effect of sulfated polysaccharides on the infectious process caused by H. pylori is related to their action on innate and adaptive immunity cells, and also anti-oxidant and antitoxic potential. Presented in the review are materials indicated for the study of extracts and sulfated polysaccharides from seaweed during H. pylori infection, as these compounds are characterized by multimodality actions. Based on the analysis of literary materials in recent years, the authors concluded that fucoidan can be attributed to the generation of new candidates to create drugs intended for the inclusion in the scheme of eradication therapy of

  11. Tandem Mass Spectrometry of Heparan Sulfate Negative Ions: Sulfate Loss Patterns and Chemical Modification Methods for Improvement of Product Ion Profiles

    NASA Astrophysics Data System (ADS)

    Shi, Xiaofeng; Huang, Yu; Mao, Yang; Naimy, Hicham; Zaia, Joseph

    2012-09-01

    Heparan sulfate (HS) is a polysaccharide modified with sulfation, acetylation, and epimerization that enable its binding with protein ligands and regulation of important biological processes. Tandem mass spectrometry has been employed to sequence linear biomolecules e.g., proteins and peptides. However, its application in structural characterization of HS is limited due to the neutral loss of sulfate (SO3) during collisional induced dissociation (CID). In this report, we studied the dissociation patterns of HS disaccharides and demonstrate that the N-sulfate (N-S) bond is especially facile during CID. We identified factors that influence the propensities of such losses from precursor ions and proposed a Free Proton Index (FPI) to help select ions that are able to produce meaningful backbone dissociations. We then investigated the thermodynamics and kinetics of SO3 loss from sulfates that are protonated, deprotonated, and metal-adducted using density functional theory computations. The calculations showed that sulfate loss from a protonated site was much more facile than that from a deprotonated or metal-adducted site. Further, the loss of SO3 from N-sulfate was energetically favored by 3-8 kcal/mol in transition states relative to O-sulfates, making it more prone to this process by a substantial factor. In order to reduce the FPI, representing the number of labile sulfates in HS native chains and oligosaccharides, we developed a series of chemical modifications to selectively replace the N-sulfates of the glucosamine with deuterated acetyl group. These modifications effectively reduced the sulfate density on the HS oligosaccharides and generated considerably more backbone dissociation using on-line LC/tandem MS.

  12. Effects of sulfate on microcystin production, photosynthesis, and oxidative stress in Microcystis aeruginosa.

    PubMed

    Chen, Lei; Gin, Karina Y H; He, Yiliang

    2016-02-01

    Increasing sulfate in freshwater systems, caused by human activities and climate change, may have negative effects on aquatic organisms. Microcystis aeruginosa (M. aeruginosa) is both a major primary producer and a common toxic cyanobacterium, playing an important role in the aquatic environment. This study first investigated the effects of sulfate on M. aeruginosa. The experiment presented here aims at analyzing the effects of sulfate on physiological indices, molecular levels, and its influencing mechanism. The results of our experiment showed that sulfate (at 40, 80, and 300 mg L(-1)) inhibited M. aeruginosa growth, increased both intracellular and extracellular toxin contents, and enhanced the mcyD transcript level. Sulfate inhibited the photosynthesis of M. aeruginosa, based on the decrease in pigment content and the down-regulation of photosynthesis-related genes after sulfate exposure. Furthermore, sulfate decreased the maximum electron transport rate, causing the cell to accumulate surplus electrons and form reactive oxygen species (ROS). Sulfate also i