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Sample records for sulfated polysaccharide inhibits

  1. In vivo molybdate inhibition of sulfate transfer to porphyridium capsular polysaccharide.

    PubMed

    Ramus, J

    1974-12-01

    Active transport of exogenous sulfate into log phase cells of Porphyridium aerueineum followed Michaelis-Menten kinetics, and the apparent Km for sulfate transport is approximately 2.5 x 10(-6)m. Molybdate, also a group VI anion, is a competitive inhibitor of sulfate transport, and the inhibition is freely reversible. Once in the cell, molybdate depresses the rate of sulfate pool utilization by blocking sulfate transfer to polysaccharides destined for secretion to the cell surface. Specifically, molybdate inhibits the formation of adenosine 5'-phosphosulfate and in turn the formation of adenosine 3'-phosphate 5'-phosphosulfate, the activated donor for sulfate transfer reactions. Combined with the previous identification of adenosine 3'-phosphate 5'-phosphosulfate, this is taken as evidence that the adenosine 5'-phosphosulfate/adenosine 3'-phosphate 5'-phosphosulfate enzymatic sequence for sulfate activation and sulfate donor reactions is operating in Porphyridium. Thiosulfate is utilized as effectively as sulfate as both a sulfur source for growth and polysaccharide synthesis.

  2. Fucoidan, a Sulfated Polysaccharide, Inhibits Osteoclast Differentiation and Function by Modulating RANKL Signaling

    PubMed Central

    Kim, Young Woo; Baek, Seung-Hoon; Lee, Sang-Han; Kim, Tae-Ho; Kim, Shin-Yoon

    2014-01-01

    Multinucleated osteoclasts differentiate from hematopoietic progenitors of the monocyte/macrophage lineage. Because of its pivotal role in bone resorption, regulation of osteoclast differentiation is a potential therapeutic approach to the treatment of erosive bone disease. In this study, we have found that fucoidan, a sulfated polysaccharide extracted from brown seaweed, inhibited osteoclast differentiation. In particular, addition of fucoidan into the early stage osteoclast cultures significantly inhibited receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast formation, thus suggesting that fucoidan affects osteoclast progenitors. Furthermore, fucoidan significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases (MAPKs) such as JNK, ERK, and p38, and also c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. In addition, the activation of NF-κB, which is an upstream transcription factor modulating NFATc1 expression, was alleviated in the fucoidan-treated cells. These results collectively suggest that fucoidan inhibits osteoclastogenesis from bone marrow macrophages by inhibiting RANKL-induced p38, JNK, ERK and NF-κB activation, and by downregulating the expression of genes that partake in both osteoclast differentiation and resorption. PMID:25334060

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

    PubMed

    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

  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 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. PMID:27474644

  7. 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.

  8. 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

    2016-06-01

    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.

  9. In vitro anti-influenza virus activities of sulfated polysaccharide fractions from Gracilaria lemaneiformis.

    PubMed

    Chen, Mei-Zhen; Xie, Hao-Gui; Yang, La-Wei; Liao, Zao-Hui; Yu, Jie

    2010-10-01

    In this paper, in vitro anti-influenza virus activities of sulfated polysaccharide fractions from Gracilaria lemaneiformis were investigated. Cytotoxicities and antiviral activities of Gracilaria lemaneiformis polysaccharides (PGL), Gracilaria lemaneiformis polysaccharide fraction-1 (GL-1), Gracilaria lemaneiformis polysaccharide fraction-2 (GL-2) and Gracilaria lemaneiformis polysaccharide fraction-3 (GL-3) were studied by the Methyl thiazolyl tetrazolium (MTT) method, and the inhibitory effect against Human influenza virus H1-364 induced cytopathic effect (CPE) on MDCK cells were observed by the CPE method. In addition, the antiviral mechanism of PGL was explored by Plaque forming unit (PFU), MTT and CPE methods. The results showed: i) Cytotoxicities were not significantly revealed, and H1-364 induced CPE was also reduced treated with sulfated polysaccharide fractions from Gracilaria lemaneiformis; ii) Antiviral activities were associated with the mass percentage content of sulfate groups in polysaccharide fractions, which was about 13%, in polysaccharides (PGL and GL-2) both of which exhibited higher antiviral activity; iii) A potential antiviral mechanism to explain these observations is that viral adsorption and replication on host cells were inhibited by sulfated polysaccharides from Gracilaria lemaneiformis. In conclusion, Anti-influenza virus activities of sulfated polysaccharide fractions from Gracilaria lemaneiformis were revealed, and the antiviral activities were associated with content of sulfate groups in polysaccharide fractions.

  10. Rising from the Sea: Correlations between Sulfated Polysaccharides and Salinity in Plants

    PubMed Central

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

    2011-01-01

    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. PMID:21552557

  11. Sulfated Polysaccharide Isolated from the Sea Cucumber Stichopus japonicus Against PC12 Hypoxia/Reoxygenation Injury by Inhibition of the MAPK Signaling Pathway.

    PubMed

    Cui, Chao; Cui, Ningshan; Wang, Peng; Song, Shuliang; Liang, Hao; Ji, Aiguo

    2015-11-01

    In this report, the sulfated polysaccharide (SJP) isolated from the sea cucumber Stichopus japonicus can protect PC12 from Na2S2O4-induced hypoxia/reoxygenation (H/R) injury. SJP effectively improves cell viability and reduces extracellular LDH release in PC12 cells after H/R. Moreover, SJP significantly increases SOD activity but decreases MDA levels. Our experiments showed that SJP could significantly reduce cell apoptosis caused by H/R. Our current results demonstrate that SJP suppressed the activation of MAPKs, resulting in a significant decrease in Bax/Bcl-2 ratio, cleaved caspase-3/caspase-3, p53 phosphorylation, and cytochrome c release in a concentration-dependent manner. MAPK is closely related to H/R injury. SJP inhibited JNK1/2 and p38 MAPK activation but did not affect the increased ERK1/2 expression. These results suggested that JNK1/2 and p38 MAPK pathways could be involved in SJP-mediated attenuation of PC12 H/R injury. SJP prevented PC12 H/R injury in a dose-dependent manner, indicating that SJP may be developed as a candidate drug to prevent or treat cerebral ischemia-reperfusion injury.

  12. 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.

  13. 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

  14. 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.

  15. Sulfated polysaccharides and cell differentiation in the sea urchin embryo.

    PubMed

    Løvtrup-Rein, H; Løvtrup, S

    1984-01-01

    The synthesis of sulfated polysaccharides during the embryonic development of Paracentrotus lividus has been investigated by incorporation of radioactive sulfate, glucose, glucosamine and fucose. The following substances become labelled: fucan sulfate (approximately 60%), heparan sulfate (approximately 20%) and dermatan sulfate (approximately 20%), and possibly a very slight amount of chondroitin sulfate. In animalized and vegetalized embryos, the rate of incorporation is significantly reduced, and furthermore dermatan sulfate is almost absent in animalized embryos. It is concluded that this substance is associated with the differentiation of vegetative cells, possibly the mesenchyme cells.

  16. 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.

  17. Evaluation of Macroalgae Sulfated Polysaccharides on the Leishmania (L.) amazonensis Promastigote

    PubMed Central

    Pires, Camila Lehnhardt; Rodrigues, Selma Dzimidas; Bristot, Daniel; Gaeta, Henrique Hessel; de Oliveira Toyama, Daniela; Farias, Wladimir Ronald Lobo; Toyama, Marcos Hikari

    2013-01-01

    The sulfated polysaccharides from Solieria filiformis (Sf), Botryocladia occidentalis (Bo), Caulerpa racemosa (Cr) and Gracilaria caudata (Gc) were extracted and extensively purified. These compounds were then subjected to in vitro assays to evaluate the inhibition of these polysaccharides on the growth of Leishmania (L.) amazonensis promastigotes. Under the same assay conditions, only three of the four sulfated polysaccharides were active against L. amazonensis, and the polysaccharide purified from Cr was the most potent (EC50 value: 34.5 μg/mL). The polysaccharides derived from Bo and Sf demonstrated moderate anti-leishmanial activity (EC50 values of 63.7 μg/mL and 137.4 μg/mL). In addition, we also performed in vitro cytotoxic assays toward peritoneal macrophages and J774 macrophages. For the in vitro cytotoxicity assay employing J774 cells, all of the sulfated polysaccharides decreased cell survival, with CC50 values of 27.3 μg/mL, 49.3 μg/mL, 73.2 μg/mL, and 99.8 μg/mL for Bo, Cr, Gc, and Sf, respectively. However, none of the sulfated polysaccharides reduced the cell growth rate of the peritoneal macrophages. These results suggest that macroalgae contain compounds with various chemical properties that can control specific pathogens. According to our results, the assayed sulfated polysaccharides were able to modulate the growth rate and cell survival of Leishmania (L.) amazonensis promastigotes in in vitro assays, and these effects involved the interaction of the sulfated polysaccharides on the cell membrane of the parasites. PMID:23519148

  18. 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. PMID:25499892

  19. 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.

  20. 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.

  1. Sulfated Polysaccharides in Marine Sponges: Extraction Methods and Anti-HIV Activity

    PubMed Central

    Esteves, Ana I. S.; Nicolai, Marisa; Humanes, Madalena; Goncalves, Joao

    2011-01-01

    The extraction, fractionation and HIV-1 inhibition potential of polysaccharides extracted from three species of marine sponges, Erylus discophorus, Cliona celata and Stelletta sp., collected in the Northeastern Atlantic, is presented in this work. The anti-HIV activity of 23 polysaccharide pellets and three crude extracts was tested. Crude extracts prepared from Erylus discophorus specimens were all highly active against HIV-1 (90 to 95% inhibition). Cliona celata pellets showed low polysaccharide content (bellow 38.5%) and almost no anti-HIV activity (<10% inhibition). Stelletta sp. pellets, although quite rich in polysaccharide (up to 97.3%), showed only modest bioactivity (<36% HIV-1 inhibition). Erylus discophorus pellets were among the richest in terms of polysaccharide content (up to 98%) and the most active against HIV-1 (up to 95% inhibition). Chromatographic fractionation of the polysaccharide pellet obtained from a specimen of Erylus discophorus (B161) yielded only modestly active fractions. However, we could infer that the active molecule is most probably a high molecular weight sulfated polysaccharide (>2000 kDa), whose mechanism is possibly preventing viral attachment and entry (fusion inhibitor). PMID:21339952

  2. Antioxidant activities of sulfated polysaccharides from brown and red seaweeds

    PubMed Central

    Rocha de Souza, Micheline Cristiane; Marques, Cybelle Teixeira; Guerra Dore, Celina Maria; Ferreira da Silva, Fernando Roberto; Oliveira Rocha, Hugo Alexandre

    2006-01-01

    The in vitro antioxidant activities of the following six sulfated polysaccharides were investigated: iota, kappa and lambda carrageenans, which are widely used in the food industry, fucoidan (homofucan) from the edible seaweed Fucus vesiculosus and fucans (heterofucans) F0.5 and F1.1 from the seaweed Padina gymnospora. With respect to the inhibition of superoxide radical formation, fucoidan had an IC50 (the half maximal inhibitory concentration) of 0.058 mg·mL−1, while the IC50 for the kappa, iota and lambda carrageenans were 0.112, 0.332 and 0.046 mg·mL−1, respectively. All of the samples had an inhibitory effect on the formation of hydroxyl radicals. The results of peroxidation tests showed that fucoidan had an IC50 of 1.250 mg·mL−1 and that the kappa, iota and lambda carrageenans had an IC50 of 2.753 and 2.338 and 0.323 mg·mL−1, respectively. Fucan fractions showed low antioxidant activity relative to fucoidan. These results clearly indicate the beneficial effect of algal polysaccharides as antioxidants. PMID:19396353

  3. 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

  4. 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.

  5. The specificity of interactions between proteins and sulfated polysaccharides.

    PubMed

    Mulloy, Barbara

    2005-12-01

    Sulfated polysaccharides are capable of binding with proteins at several levels of specificity. As highly acidic macromolecules, they can bind non-specifically to any basic patch on a protein surface at low ionic strength, and such interactions are not likely to be physiologically significant. On the other hand, several systems have been identified in which very specific substructures of sulfated polysaccharides confer high affinity for particular proteins; the best-known example of this is the pentasaccharide in heparin with high affinity for antithrombin, but other examples may be taken from the study of marine invertebrates: the importance of the fine structure of dermatan sulfate (DS) to its interaction with heparin cofactor II (HCII), and the involvement of sea urchin egg-jelly fucans in species specific fertilization. A third, intermediate, kind of specific interaction is described for the cell-surface glycosaminoglycan heparan sulfate (HS), in which patterns of sulfate substitution can show differential affinities for cytokines, growth factors, and morphogens at cell surfaces and in the intracellular matrix. This complex interplay of proteins and glycans is capable of influencing the diffusion of such proteins through tissue, as well as modulating cellular responses to them. PMID:16341442

  6. The specificity of interactions between proteins and sulfated polysaccharides.

    PubMed

    Mulloy, Barbara

    2005-12-01

    Sulfated polysaccharides are capable of binding with proteins at several levels of specificity. As highly acidic macromolecules, they can bind non-specifically to any basic patch on a protein surface at low ionic strength, and such interactions are not likely to be physiologically significant. On the other hand, several systems have been identified in which very specific substructures of sulfated polysaccharides confer high affinity for particular proteins; the best-known example of this is the pentasaccharide in heparin with high affinity for antithrombin, but other examples may be taken from the study of marine invertebrates: the importance of the fine structure of dermatan sulfate (DS) to its interaction with heparin cofactor II (HCII), and the involvement of sea urchin egg-jelly fucans in species specific fertilization. A third, intermediate, kind of specific interaction is described for the cell-surface glycosaminoglycan heparan sulfate (HS), in which patterns of sulfate substitution can show differential affinities for cytokines, growth factors, and morphogens at cell surfaces and in the intracellular matrix. This complex interplay of proteins and glycans is capable of influencing the diffusion of such proteins through tissue, as well as modulating cellular responses to them.

  7. 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

  8. 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

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

    PubMed Central

    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.

    2011-01-01

    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

  10. Structure and anticoagulant activity of a fucosylated chondroitin sulfate from echinoderm. Sulfated fucose branches on the polysaccharide account for its high anticoagulant action.

    PubMed

    Mourão, P A; Pereira, M S; Pavão, M S; Mulloy, B; Tollefsen, D M; Mowinckel, M C; Abildgaard, U

    1996-09-27

    A polysaccharide isolated from the body wall of the sea cucumber Ludwigothurea grisea has a backbone like that of mammalian chondroitin sulfate: [4-beta-D-GlcA-1-->3-beta-D-GalNAc-1]n but substituted at the 3-position of the beta--glucuronic acid residues with sulfated alpha--fucopyranosyl branches (Vieira, R. P., Mulloy, B., and Mourão, P. A. S. (1991) J. Biol. Chem. 266, 13530-13536). Mild acid hydrolysis removes the sulfated alpha--fucose branches, and cleaved residues have been characterized by 1H NMR spectroscopy; the most abundant species is fucose 4-O-monosulfate, but 2,4- and 3, 4-di-O-sulfated residues are also present. Degradation of the remaining polysaccharide with chondroitin ABC lyase shows that the sulfated alpha-L-fucose residues released by mild acid hydrolysis are concentrated toward the non-reducing end of the polysaccharide chains; enzyme-resistant polysaccharide material includes the reducing terminal and carries acid-resistant -fucose substitution. The sulfated alpha-L-fucose branches confer anticoagulant activity on the polysaccharide. The specific activity of fucosylated chondroitin sulfate in the activated partial thromboplastin time assay is greater than that of a linear homopolymeric alpha-L-fucan with about the same level of sulfation; this activity is lost on defucosylation or desulfation but not on carboxyl-reduction of the polymer. Assays with purified reagents show that the fucosylated chondroitin sulfate can potentiate the thrombin inhibition activity of both antithrombin and heparin cofactor II.

  11. Structure and anticancer activity of sulfated O-polysaccharide from marine bacterium Cobetia litoralis KMM 3880(T).

    PubMed

    Kokoulin, Maxim S; Kuzmich, Alexandra S; Kalinovsky, Anatoly I; Tomshich, Svetlana V; Romanenko, Lyudmila A; Mikhailov, Valery V; Komandrova, Nadezhda A

    2016-12-10

    We presented the structure of the polysaccharide moiety and anticancer activity in vitro of the sulfated lipopolysaccharide isolated from the marine bacterium Cobetia litoralis KMM 3880(T). The structure of O-polysaccharide was investigated by chemical methods along with (1)H and (13)C NMR spectroscopy. The O-polysaccharide was built up of branched trisaccharide repeating units consist of D-glucose (D-Glcр), D-mannose (D-Manр) and sulfated 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo5S): →7-β-Kdoр4Ac5S-(2→4)-[β-d-Glcp-(1→2)-]-β-d-Manр6Ac-1→. We demonstrated that the lipopolysaccharide and О-deacetylated O-polysaccharide from Cobetia litoralis KMM 3880(T) inhibited a colony formation of human melanoma SK-MEL-28 and colorectal carcinoma HTC-116 cells. PMID:27577896

  12. 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. PMID:26724686

  13. 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.

  14. 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.

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

    PubMed

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

    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

  16. 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

  17. Antiangiogenic activity and direct antitumor effect from a sulfated polysaccharide isolated from seaweed.

    PubMed

    Guerra Dore, Celina Maria P; Faustino Alves, Monique Gabriela C; Santos, Nednaldo D; Cruz, Ana Katarina M; Câmara, Rafael Barros G; Castro, Allisson Jonathan G; Guimarães Alves, Luciana; Nader, Helena B; Leite, Edda Lisboa

    2013-07-01

    Angiogenesis is a dynamic proliferation and differentiation process. It requires endothelial proliferation, migration and tube formation. In this context, endothelial cells are a preferred target for several studies and therapies. Anionic polysaccharides (SV1 and PSV1) from brown seaweed Sargassum vulgare were fractionated (SV1), purified (PSV1) and displayed with high total sugars, sulfate content and very low level of protein. The antiangiogenic efficacy of polysaccharides was examined in vivo in the chick chorioallantoic membrane (CAM) model by using fertilized eggs. Decreases in the density of the capillaries were assessed and scored. The results showed that SV1 and PSV1 have an inhibitory effect on angiogenesis. These results were also confirmed by the inhibition of tubulogenesis in rabbit aorta endothelial cell (RAEC) in matrigel. These compounds were assessed in an apoptosis assay (Annexin V-FITC/PI) and cell viability by MTT assay of RAEC. These polysaccharides did not affect the viability and did not have apoptotic or necrotic action. RAEC cell when incubated with SV1and PSV1 showed inhibition of VEGF secretion, observed when compounds were incubated at 25, 50 and 100 μg/μL. The VEGF secretion with the RAEC cell line for 24 h was more effective for PSV1 at 50 μg/μL (71.4%) than for SV1 at 100 μg/μL (75.9%). SV1 and PSV1 had an antiproliferative action (47%) against tumor cell line HeLa. Our results indicate that these sulfated polysaccharides have antiangiogenic and antitumor actions. PMID:23507505

  18. 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.

  19. The ammonium sulfate inhibition of human angiogenin.

    PubMed

    Chatzileontiadou, Demetra S M; Tsirkone, Vicky G; Dossi, Kyriaki; Kassouni, Aikaterini G; Liggri, Panagiota G V; Kantsadi, Anastassia L; Stravodimos, George A; Balatsos, Nikolaos A A; Skamnaki, Vassiliki T; Leonidas, Demetres D

    2016-09-01

    In this study, we investigate the inhibition of human angiogenin by ammonium sulfate. The inhibitory potency of ammonium sulfate for human angiogenin (IC50 = 123.5 ± 14.9 mm) is comparable to that previously reported for RNase A (119.0 ± 6.5 mm) and RNase 2 (95.7 ± 9.3 mm). However, analysis of two X-ray crystal structures of human angiogenin in complex with sulfate anions (in acidic and basic pH environments, respectively) indicates an entirely distinct mechanism of inhibition. While ammonium sulfate inhibits the ribonucleolytic activity of RNase A and RNase 2 by binding to the active site of these enzymes, sulfate anions bind only to peripheral substrate anion-binding subsites of human angiogenin, and not to the active site. PMID:27483019

  20. Gellan sulfate inhibits Plasmodium falciparum growth and invasion of red blood cells in vitro

    PubMed Central

    Recuenco, Frances Cagayat; Kobayashi, Kyousuke; Ishiwa, Akiko; Enomoto-Rogers, Yukiko; Fundador, Noreen Grace V.; Sugi, Tatsuki; Takemae, Hitoshi; Iwanaga, Tatsuya; Murakoshi, Fumi; Gong, Haiyan; Inomata, Atsuko; Horimoto, Taisuke; Iwata, Tadahisa; Kato, Kentaro

    2014-01-01

    Here, we assessed the sulfated derivative of the microbial polysaccharide gellan gum and derivatives of λ and κ-carrageenans for their ability to inhibit Plasmodium falciparum 3D7 and Dd2 growth and invasion of red blood cells in vitro. Growth inhibition was assessed by means of flow cytometry after a 96-h exposure to the inhibitors and invasion inhibition was assessed by counting ring parasites after a 20-h exposure to them. Gellan sulfate strongly inhibited invasion and modestly inhibited growth for both P. falciparum 3D7 and Dd2; both inhibitory effects exceeded those achieved with native gellan gum. The hydrolyzed λ-carrageenan and oversulfated κ-carrageenan were less inhibitory than their native forms. In vitro cytotoxicity and anticoagulation assays performed to determine the suitability of the modified polysaccharides for in vivo studies showed that our synthesized gellan sulfate had low cytotoxicity and anticoagulant activity. PMID:24740150

  1. 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).

  2. Adjuvanticity of compound astragalus polysaccharide and sulfated epimedium polysaccharide per os.

    PubMed

    Chen, Xingying; Chen, Xiaolan; Qiu, Shulei; Hu, Yuanliang; Wang, Deyun; Liu, Xu; Zhao, Xiaojuan; Liu, Cui; Chen, Xinghui

    2013-11-01

    On the basis of previous researches, compound astragalus polysaccharide (APS) and sulfated epimedium polysaccharide (sEPS) oral liquid (AEO) was prepared. Three hundred and twenty 14-day-old chickens were randomly assigned into eight groups and vaccinated with ND vaccine except for blank control (BC) group, repeated vaccination at 28 days old. At the same time of each vaccination, the chickens in three experimental groups were taken orally with AEO, respectively, at three doses, in two component control groups with APS and sEPS, once a day for three successive days; in injection control group were injected with AEI once, and in vaccination control (VC) and BC groups were not administrated. On days 7, 14, 21, 28 and 35 after the first vaccination, peripheral lymphocyte proliferation, the serum antibody titer, IFN-γ and IL-2 concentrations and on day 35 immune organ index were measured. The results showed that AEO at high and medium doses could significantly promote lymphocyte proliferation and development of immune organ, enhance antibody titer and IFN-γ and IL-2 concentration, which was stronger than actions of AEI and two components. The results confirmed that AEO possessed reliable immunoenhancement and could be exploited into an oral immunopotentiator.

  3. 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.

  4. A sulfated polysaccharide from the sarcoplasmic reticulum of sea cucumber smooth muscle is an endogenous inhibitor of the Ca(2+)-ATPase.

    PubMed

    Landeira-Fernandez, A M; Aiello, K R; Aquino, R S; Silva, L C; Meis, L d; Mourão, P A

    2000-08-01

    Vesicles derived from the endoplasmic reticulum of sea cucumber smooth muscle retain a membrane bound Ca(2+)-ATPase that is able to transport Ca(2+) into the vesicles at the expense of ATP hydrolysis. In contrast with vesicles obtained from rabbit muscles, the activity of the Ca(2+)-dependent ATPase from sea cucumber is dependent on monovalent cations (K(+)>Na(+)>Li(+)). With the addition of highly sulfated polysaccharide to vesicle preparations from rabbit muscle, Ca(2+) uptake decreases sharply and becomes highly sensitive to monovalent cations, as observed with vesicles from sea cucumber muscle. These results led us to investigate the possible occurrence of a highly sulfated polysaccharide on vesicles from the endoplasmic reticulum of sea cucumber smooth muscle, acting as an "endogenous" Ca(2+)-ATPase inhibitor. In fact, vesicles derived from the invertebrate, but not from rabbit muscle, contain a highly sulfated polysaccharide. This compound inhibits Ca(2+) uptake in vesicles obtained from rabbit muscle and the inhibition is antagonized by monovalent cation. In addition, sea cucumber muscles contain high concentrations of another polysaccharide, which surrounds the muscle fibers, and was characterized as a fucosylated chondroitin sulfate. Possibly the occurrence of sulfated polysaccharides in the sea cucumber muscles is related with unique properties of the invertebrate body wall, which can rapidly and reversibly alter its mechanical properties, with change in length by more than 200%.

  5. 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.

  6. Seminal fluid from sea urchin (Lytechinus variegatus) contains complex sulfated polysaccharides linked to protein.

    PubMed

    Cinelli, Leonardo P; Vilela-Silva, Ana-Cristina E S; Mourão, Paulo A S

    2009-09-01

    The eggs of sea urchins are covered by a jelly coat, which contains high concentrations of sulfated polysaccharides. These carbohydrates show species-specificity in inducing the sperm acrosome reaction. Several studies about the egg jelly of sea urchins have been published, but there is no information about the composition of the seminal fluid of these echinoderms. Here we report for the first time the occurrence of complex sulfated polysaccharides in the seminal fluid of the sea urchin Lytechinus variegatus. These polysaccharides occur as three fractions that differ mostly in their carbohydrate/protein ratios. The native molecular masses of the polymers are very high (> or = 200 kDa) but, after digestion with papain the size decreases to approximately 8 kDa. All fractions have a similar carbohydrate composition, containing mostly galactose, glucosamine and mannose. The heterogeneous sulfated polysaccharides differ from vertebrate glycosaminoglycans and also from all previously described polysaccharides from invertebrates. The physiological role of the sulfated carbohydrates from seminal fluid is not yet determined. However, by analogy with the effects proposed for some glycoproteins found in vertebrate seminal fluid, it may be possible that the sulfated polysaccharides from invertebrate are also involved in fertilization process.

  7. 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

    2016-01-01

    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

  8. 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

  9. 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.

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

    PubMed

    Burg, Ariela; Oshrat, Levy-Ontman

    2015-10-01

    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, 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. PMID:26492255

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

    PubMed

    Burg, Ariela; Oshrat, Levy-Ontman

    2015-10-01

    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, 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.

  12. 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. PMID:26050894

  13. 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.

  14. Precursor-Product Relationships during Sulfate Incorporation into Porphyridium Capsular Polysaccharide.

    PubMed

    Ramus, J; Groves, S T

    1974-03-01

    This study describes the kinetics of (35)S-incorporation during in vivo sulfate esterification of Porphyridium aerugineum capsular polysaccharide. Techniques were developed to isolate the precursor pool (free sulfate), cell-associated product, and extracellular product. Specific radioactivities of these three fractions were monitored during pulse-chase sequences. Label rapidly appeared in the pool during the pulse, then declined asymptotically during the chase as equilibrium was approached. Efflux of small quantities of isotope from the cell during chase periods was not the result of backleakage, but the result of washing untransported isotope from the free-space. During the pulse, intracellular product was labeled at 25% of the rate at which the pool was labeled. Fully 50% of the label which left the pool was incorporated into the polysaccharide as ester sulfate, indicating that polysaccharide esterification is a major metabolic pathway for sulfate. The specific radioactivity of the extracellular product increased slowly throughout pulse and chase periods.Porphyridium was shown to be highly dependent on exogenous supplies of sulfate, the cells lysing when denied adequate quantities of this nutrient. The free sulfate pool size was measured as 33 x 10(6) sulfate ions per cell in log phase. 3'-Phosphoadenosine-5'-phosphosulfate was tentatively identified in the water-soluble cell extract and is thought to be the "activitated" donor for sulfate transfer reactions.

  15. 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

  16. Chemical Fucosylation of a Polysaccharide: A Semisynthetic Access to Fucosylated Chondroitin Sulfate.

    PubMed

    Laezza, Antonio; Iadonisi, Alfonso; Castro, Cristina De; De Rosa, Mario; Schiraldi, Chiara; Parrilli, Michelangelo; Bedini, Emiliano

    2015-07-13

    Chemical O-glycosylation of polysaccharides is an almost unexplored reaction. This is mainly due to the difficulties in derivatizing such complex biomacromolecules in a quantitative manner and with a fine control of the obtained structural parameters. In this work, chondroitin raw material from a microbial source was chemo- and regioselectively protected to give two polysaccharide intermediates, that acted in turn as glycosyl acceptors in fucosylation reactions. Further manipulations on the fucosylated polysaccharides, including multiple de-O-benzylation and sulfation, furnished for the first time nonanimal sourced fucosylated chondroitin sulfates (fCSs)-polysaccharides obtained so far exclusively from sea cucumbers (Echinoidea, Holothuroidea) and showing several very interesting biological activities. A semisynthetic fCS was characterized from a structural point of view by means of 2D-NMR techniques, and preliminarily assayed in an anticoagulant test.

  17. 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. PMID:27316763

  18. Evaluation of sulfated polysaccharides from the brown seaweed Dictyopteris justii as antioxidant agents and as inhibitors of the formation of calcium oxalate crystals.

    PubMed

    Melo, Karoline Rachel Teodosio; Camara, Rafael Barros Gomes; Queiroz, Moacir Fernandes; Vidal, Arthur Anthunes Jacome; Lima, Camila Renata Machado; Melo-Silveira, Raniere Fagundes; Almeida-Lima, Jailma; Rocha, Hugo Alexandre Oliveira

    2013-01-01

    Oxalate crystals and other types of crystals are the cause of urolithiasis, and these are related to oxidative stress. The search for new compounds with antioxidant qualities and inhibitors of these crystal formations is therefore necessary. In this study, we extracted four sulfated polysaccharides, a fucoglucoxyloglucuronan (DJ-0.3v), a heterofucan (DJ-0.4v), and two glucans (DJ-0.5v and DJ-1.2v), from the marine alga Dictyopteris justii. The presence of sulfated polysaccharides was confirmed by chemical analysis and FT-IR. All the sulfated polysaccharides presented antioxidant activity under different conditions in some of the in vitro tests and inhibited the formation of calcium oxalate crystals. Fucan DJ-0.4v was the polysaccharide that showed the best antioxidant activity and was one of the best inhibitors of the crystallization of calcium oxalate. Glucan DJ-0.5v was the second most potent inhibitor of the formation of oxalate crystals, as it stabilized dehydrated oxalate crystals (less aggressive form), preventing them from transforming into monohydrate crystals (more aggressive form). The obtained data lead us to propose that these sulfated polysaccharides are promising agents for use in the treatment of urolithiasis. PMID:24287990

  19. [Antiviral action and pathogenetic targets for seaweed sulfated polysaccharides in herpesvirus infections].

    PubMed

    Besednova, N N; Makarenkova, I D; Zvyagintseva, T N; Imbs, T I; Somova, L M; Zaporozhets, T S

    2016-03-01

    The review summarizes results of studies of effects of sulfated polysaccharides from seaweed on herpesviruses and the course of herpesvirus infections. Importance of this problem is determined by the prevalence of herpesviruses that can persist in the human body and demonstrate a high degree of immune mimicry and resistance to antiviral agents. A wide range of physiological action of sulfated polysaccharides, receptor agonists of innate and adaptive immune cells, which possess potent antiviral, antioxidant and anti-inflammatory activities, open the possibility of their use for creation of new generation pharmacological substances and agents with associated activity for the treatment of herpesvirus infections. PMID:27420612

  20. 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

  1. Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiella maindroni ink.

    PubMed

    Zong, Aizhen; Zhao, Ting; Zhang, Yan; Song, Xinlei; Shi, Yikang; Cao, Hongzhi; Liu, Chunhui; Cheng, Yanna; Qu, Xianjun; Cao, Jichao; Wang, Fengshan

    2013-01-01

    A previous study demonstrated that SIP-SII, a sulfated Sepiella maindroni ink polysaccharide, suppressed the invasion and migration of cancer cells via the inhibition of the proteolytic activity of matrix metalloproteinase-2 (MMP-2). Therefore, this study investigated the anti-metastatic effect of SIP-SII in vivo. SIP-SII (15 and 30 mg/kg d) markedly decreased B16F10 pulmonary metastasis in mice models by 85.9% and 88.0%, respectively. Immunohistochemistry showed that SIP-SII decreased the expression of the intercellular adhesion molecule 1 (ICAM-1) and basic fibroblast growth factor (bFGF) in lung metastasis nodules. In addition, SIP-SII inhibited neovascularization in chick chorioallantoic membrane assay at 0.08-2 mg/mL. In the in vitro experiments, SIP-SII (0.8-500 μg/mL) significantly decreased the protein and mRNA expression of ICAM-1 and bFGF in SKOV3 and EA.hy926 cells, respectively. These results suggested that SIP-SII might suppress melanoma metastasis via the inhibition of the tumor adhesion mediated by ICAM-1 and the angiogenesis mediated by bFGF, as well as resulting in depression of the invasion and migration of carcinoma cells.

  2. 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.

  3. 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.

  4. Sulfated modification and immunomodulatory activity of water-soluble polysaccharides derived from fresh Chinese persimmon fruit.

    PubMed

    Zhang, Yali; Lu, Xiaoyun; Zhang, Yuning; Qin, Liguo; Zhang, Jianbao

    2010-01-01

    In this study, three kinds of chemically sulfated polysaccharides (PFP-S) were derived from a water-soluble polysaccharide of persimmon fruit with chlorosulfonic acid-pyridine method. Relationship between the degree of substitution and immunomodulatory activity of PFP-S was examined with the splenocytes experiment. The results showed that the splenocytes-activating activity was significantly enhanced by PFP-S in all the groups compared with control group (P<0.01). PFP-SII exhibited the most potent splenocytes-activating activity by increased cytokine production and NO release. It also suggested that the sulfate groups and molecular weight of polysaccharides are key factors to regulate the immunomodulatory activities.

  5. Antiviral activity of sulfated Chuanmingshen violaceum polysaccharide against Newcastle disease virus.

    PubMed

    Song, Xu; Yin, Zhongqiong; Zhao, Xinghong; Cheng, Anchun; Jia, Renyong; Yuan, Guiping; Xu, Jiao; Fan, Qiaojia; Dai, Shujun; Lu, Hongke; Lv, Cheng; Liang, Xiaoxia; He, Changliang; Su, Gang; Zhao, Ling; Ye, Gang; Shi, Fei

    2013-10-01

    Newcastle disease virus (NDV) is a member of Paramyxovirinae subfamily and can infect most species of birds causing severe economic losses. The current control measure is vaccination, but infections cannot be completely prevented. It remains a constant threat to the poultry industry and new control measures are urgently needed. This study demonstrates that sulfated Chuanmingshen violaceum polysaccharides (sCVPSs) were potent inhibitors of NDV, with 50 % inhibitory concentrations (IC50) ranging from 62.55 to 76.31 µg ml(-1) in Baby hamster kidney fibroblasts clone 21 (BHK-21) and from 101.57 to 125.90 µg ml(-1) in chicken embryo fibroblasts (CEF). sCVPS is more effective than heparan sulfate (HS; as a positive control) with IC50 values of 99.28 µg ml(-1) in BHK-21 and 118.79 µg ml(-1) in CEF. sCVPSs and HS exhibit anti-NDV activity by prevention of the early stages of viral life. The mechanism of action study indicated that virus adsorption in BHK-21, and both virus adsorption and penetration in CEF were inhibited by sCVPSs. When the number of viruses was increased to an m.o.i. of 0.1 in the immunofluorescence study and to an m.o.i. of 1 in the fluorescent quantitative PCR study, viral infection was also significantly suppressed; the antiviral activity of sCVPSs was independent of the m.o.i. sCVPSs also prevented the cell-to-cell spread of NDV. In vivo tests carried out on specific pathogen-free (SPF) chickens showed that sCVPSs also inhibited virus multiplication in heart, liver, spleen, lung and kidney. These results indicated that sCVPSs perform more effectively than HS as antiviral agents against NDV, and can be further examined for their potential as an alternative control measure for NDV infection.

  6. 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.

  7. Sulfated polysaccharides from common smooth hound: Extraction and assessment of anti-ACE, antioxidant and antibacterial activities.

    PubMed

    Abdelhedi, Ola; Nasri, Rim; Souissi, Nabil; Nasri, Moncef; Jridi, Mourad

    2016-11-01

    The present study investigates biological activities of sulfated polysaccharides (SPs) isolated from smooth hound by precipitation with cetylpyridinium chloride (SP1) or ethanol (SP2). SP1 showed the highest amounts of sulfated groups (10.2%) and proteins (7.84%) and high molecular weight sugars. Infrared spectroscopic analysis showed typical peaks of sulfated polysaccharides, particularly for the SP1 that was characterized by the presence of O=S=O groups and acetyl groups. Interestingly, SPs displayed important angiotensin I converting enzyme (ACE) inhibitory (IC50=1.04 and 0.75mg/ml for SP1 and SP2, respectively), antibacterial (Gram+ and Gram-) and antioxidant activities (reducing power, metal chelating activity, β-carotene bleaching inhibition and DNA nicking assay). Moreover, SPs fractionation by DEAE-cellulose column chromatography showed one peak during the buffer elution phase and three major fractions during the linear gradient of NaCl. The overall data suggested that SPs could be used as natural antioxidant, antimicrobial and anti-ACE ingredient to formulate functional foods. PMID:27516310

  8. Sulfated modification, characterization and property of a water-insoluble polysaccharide from Ganoderma atrum.

    PubMed

    Zhang, Hui; Wang, Jun-Qiao; Nie, Shao-Ping; Wang, Yuan-Xing; Cui, Steve W; Xie, Ming-Yong

    2015-08-01

    Sulfated modification was carried out to modify a water-insoluble polysaccharide from Ganoderma atrum (AGAP). The effects of sulfation on structure, physicochemical and functional properties of AGAP were investigated. Three sulfated derivatives were prepared, designated as S-1, S-2 and S-3 with degree of substitution (DS) of 0.35, 0.74 and 1.14, respectively. AGAP was elucidated as an α-(1→3)-glucan with few branches terminated by single mannose or xylose residues. The molecular weight (Mw) and radius of gyration (Rg) were estimated to be 1665 kDa and 65.49 nm, respectively. After sulfated modification, non-selective sulfation occurred preferably at O-6, partially at O-2 and O-4 positions of the glucosyl residues. The water-solubility of the derivatives was significantly improved in a DS-dependent manner. Mw of the derivatives showed a sharp decrease, and the chain conformation was estimated to be expanded stiff in phosphate buffer. In vitro tests showed that sulfated modification improved its antioxidant activities and anti-proliferative ability against S-180 tumor cells. This study suggested that sulfated modification was an effective approach to improve the water-solubility and functional properties of insoluble polysaccharides.

  9. Neuroprotective effect of sulfated polysaccharide isolated from sea cucumber Stichopus japonicus on 6-OHDA-induced death in SH-SY5Y through inhibition of MAPK and NF-κB and activation of PI3K/Akt signaling pathways.

    PubMed

    Cui, Chao; Cui, Ningshan; Wang, Peng; Song, Shuliang; Liang, Hao; Ji, Aiguo

    2016-02-01

    The purpose of this study is to investigate the protective effect and molecular mechanism of the sulfated polysaccharide (SJP) isolated from the sea cucumber Stichopus japonicus against 6-OHDA-induced toxicity in SH-SY5Y cells. The results showed that SJP could protect SH-SY5Y cells against 6-OHDA-induced cell injury. We found that SJP effectively improves cell viability, decreases LDH leakage, and reverses morphological damage. Moreover, SJP significantly increases SOD activity but decreases MDA levels and ROS generation. Effect of SJP on 6-OHDA-induced cell death in SH-SY5Y cells is associated with an arrest in the G1/S phase of the cell cycle and inhibits the expression of Cyclin D3. 6-OHDA-induced intracellular generation of ROS and mitochondrial dysfunctions, release of cytochrome c, imbalance of Bax/Bcl-2, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 ratio, and p-p53 activation were strikingly attenuated by SJP pretreatment. Meanwhile, SJP counteracted NF-κB activation, thereby preventing up-regulation of iNOS and intracellular NO release. The data provide the first evidence that SJP protects SH-SY5Y cells against 6-OHDA toxicity possibly by inhibiting MAPK and NF-κB and activating PI3K/Akt signaling pathways. Thus, SJP is a candidate for further evaluation of its protective effects against neurodegeneration in PD.

  10. Neuroprotective effect of sulfated polysaccharide isolated from sea cucumber Stichopus japonicus on 6-OHDA-induced death in SH-SY5Y through inhibition of MAPK and NF-κB and activation of PI3K/Akt signaling pathways.

    PubMed

    Cui, Chao; Cui, Ningshan; Wang, Peng; Song, Shuliang; Liang, Hao; Ji, Aiguo

    2016-02-01

    The purpose of this study is to investigate the protective effect and molecular mechanism of the sulfated polysaccharide (SJP) isolated from the sea cucumber Stichopus japonicus against 6-OHDA-induced toxicity in SH-SY5Y cells. The results showed that SJP could protect SH-SY5Y cells against 6-OHDA-induced cell injury. We found that SJP effectively improves cell viability, decreases LDH leakage, and reverses morphological damage. Moreover, SJP significantly increases SOD activity but decreases MDA levels and ROS generation. Effect of SJP on 6-OHDA-induced cell death in SH-SY5Y cells is associated with an arrest in the G1/S phase of the cell cycle and inhibits the expression of Cyclin D3. 6-OHDA-induced intracellular generation of ROS and mitochondrial dysfunctions, release of cytochrome c, imbalance of Bax/Bcl-2, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 ratio, and p-p53 activation were strikingly attenuated by SJP pretreatment. Meanwhile, SJP counteracted NF-κB activation, thereby preventing up-regulation of iNOS and intracellular NO release. The data provide the first evidence that SJP protects SH-SY5Y cells against 6-OHDA toxicity possibly by inhibiting MAPK and NF-κB and activating PI3K/Akt signaling pathways. Thus, SJP is a candidate for further evaluation of its protective effects against neurodegeneration in PD. PMID:26773499

  11. 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. PMID:26572384

  12. 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.

  13. Mobilization of stem/progenitor cells by sulfated polysaccharides does not require selectin presence

    PubMed Central

    Sweeney, Elizabeth A.; Priestley, Gregory V.; Nakamoto, Betty; Collins, Robert G.; Beaudet, Arthur L.; Papayannopoulou, Thalia

    2000-01-01

    Employing carbohydrate ligands, which have been extensively used to block selectin function in vitro and in vivo, we have examined the involvement of such ligands in stem/progenitor cell mobilization in mice and monkeys. We found that sulfated fucans, branched and linear, are capable of increasing mature white cells in the periphery and mobilizing stem/progenitor cells of all classes (up to 32-fold) within a few hours posttreatment in a dose-dependent manner. To elicit the effect, the presence of sulfate groups was necessary, yet not sufficient, as certain sulfated hexosamines tested (chondroitin sulfates A or B) were ineffective. Significant mobilization of stem/progenitor cells and leukocytosis was elicited in selectin-deficient mice (L−/−, PE−/−, or LPE−/−) similar to that of wild-type controls, suggesting that the mode of action of sulfated fucans is not through blockade of known selectins. Other mechanisms have been entertained, in particular, the release of chemokines/cytokines, including some previously implicated in mobilization. Significant increases were documented in the levels of seven circulating chemokines/cytokines within a few hours after fucan sulfate treatment and support such a proposition. Additionally, an increase was noted in plasma metalloproteinase (MMP) 9, which might independently contribute to the mobilization process by enzymatically facilitating chemokine/cytokine release. Mobilization by sulfated polysaccharides provides a distinct paradigm in the mobilization process and uncovers an additional novel in vivo biological role for sulfated glycans. As similarly sulfated compounds were ineffective in vivo, the data also underscore the fact that polysaccharides with similar structures may elicit diverse in vivo effects. PMID:10841555

  14. 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.

  15. 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.

  16. On the dielectric behaviour of collagen-algal sulfated polysaccharide blends: effect of glutaraldehyde crosslinking.

    PubMed

    Figueiró, S D; Macêdo, A A M; Melo, M R S; Freitas, A L P; Moreira, R A; de Oliveira, R S; Góes, J C; Sombra, A S B

    2006-03-20

    In this paper, impedance measurements in the frequency range from 10(-2) to 10(6) Hz are presented for collagen and algal sulfated polysaccharide crosslinked films. We are considering the development of new biomaterials which have potential applications in coating of cardiovascular prostheses, support for cellular growth and in systems for controlled drug delivery. The effect of crosslink sulfated polysaccharide on the physical chemical properties of collagen was studied using FT-infrared spectroscopy, differential scanning calorimetry (DSC), dielectric spectroscopy. The resulting films crosslinked with glutaraldehyde (GA) in concentrations of 0.001% and 0.05% when analysed by DSC, showed that the GA treatment not only left the thermal stability of the collagen unaffected, but it also decreased the thermal transition energy. Dielectric spectroscopy shows that the effect of the crosslink on the blend film was associated to the decrease and stabilization of the dielectric permittivity at low frequencies and decreased its conductivity.

  17. 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

  18. 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

  19. 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

  20. Degradation of sulfated polysaccharides from Enteromorpha prolifera and their antioxidant activities.

    PubMed

    Li, Bing; Liu, Song; Xing, Ronge; Li, Kecheng; Li, Rongfeng; Qin, Yukun; Wang, Xueqin; Wei, Zhenhua; Li, Pengcheng

    2013-02-15

    The effects of degradation on molecular weights (Mws) of polysaccharides from Enteromorpha prolifera were investigated. Microwave-assistance could highly accelerate reaction rate. Six representative sulfated polysaccharides (Mw 446.5, 247.0, 76.1, 19.0, 5.0 and 3.1 KDa) were prepared by a microwave-assistance acid hydrolysis method. Chemical analysis and FT-IR spectrum showed only glycosidic linkages were cleft without breaking significant structural units. Antioxidant activities of representative polysaccharides revealed that all samples showed great inhibitory effects on superoxide radical at a low concentration compared to Vitamin C and samples with high Mws exhibited higher inhibitory effects. On the contrary, samples with low Mws possessed stronger inhibitory effects on hydroxyl radical, IC(50) of Mw 3.1 KDa was 0.39 mg/mL. The chelating effect of Mw 3.1 KDa was 77.3% at 5mg/mL, which was twice more than initial polysaccharide. The study indicated Mw was the most significant factor to influence antioxidant activities of polysaccharides from E. prolifera.

  1. 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

  2. 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

  3. 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.

  4. Polysaccharides sulfated at the time of gastrulation in embryos of the sea urchin Clypeaster japonicus.

    PubMed

    Yamaguchi, M; Kinoshita, S

    1985-08-01

    Based on the fact that the development of sea urchin embryos is arrested at the blastula stage in sulfate-free sea water (SFSW), we attempted in the present study to elucidate the nature of sulfated polysaccharides (PSs) which appear at the time of gastrulation in embryos of the sea urchin Clypeaster japonicus. Electrophoretic analysis of PSs prepared from embryos at different developmental stages revealed that three kinds of PSs (3A, 3B, 3C) appear de novo at the gastrula stage, and that these PSs are not found in embryos at the hatching blastula stage, nor are they found in permanent blastula reared in SFSW. These, three PSs were mostly of extracellular matrix origin. Among them, 3C was identified as dermatan sulfate on the basis of its electrophoretic mobility and sensitivity to enzymatic digestion. 3A and 3B remained to be identified. Further, a plausible precursor of 3C, which was sulfated under normal conditions, was detected as 6D in the embryos reared in SFSW. Autoradiographic analysis using [35S]sulfate revealed that these three PSs, accounted for more than 90% of [35S]sulfate incorporated into the acid PS fraction during gastrulation.

  5. 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. PMID:27474578

  6. 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.

  7. Polysaccharide structural features that are critical for the binding of sulfated fucans to bindin, the adhesive protein from sea urchin sperm.

    PubMed

    DeAngelis, P L; Glabe, C G

    1987-10-15

    We have investigated the structural features of sulfated fucose-containing polysaccharides which are responsible for their selective binding to Strongylocentrotus purpuratus bindin. The data presented demonstrate that the sulfate esters and a molecular weight in excess of approximately 15,000 are required for high affinity binding of the fucans to bindin. Desulfation destroys the binding activity of the fucans, which can be fully restored by chemical resulfation. Fucan fragments of an average molecular weight of 15,000 were nearly as active as the starting material (Mr 10(6)). The observed IC50 value for fragments of Mr congruent to 10,000 and Mr congruent to 5,000 were 1 and 2 orders of magnitude higher, respectively. The binding of fucoidan to bindin is stable in high salt (50% at 1.2 M NaCl) whereas the binding of fucoidan to DEAE-cellulose or polylysine is inhibited by the concentrations of salt normally found in sea water (50% at 0.2 and 0.5 M NaCl, respectively). This result suggests that the binding mechanism is not a simple ionic interaction and that hydrogen bonding and cooperativity may also be important determinants of the binding mechanism. We also found that polyvinyl sulfate binds to bindin with high affinity and inhibits the bindin-mediated agglutination of sea urchin eggs. The results of these investigations suggest that the spatial orientation of the sulfate esters plays a critical role in determining the selectivity of sulfated polysaccharide binding and that the polysaccharide backbone does not play a direct role in the binding mechanism.

  8. 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.

  9. 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. PMID:27474595

  10. Perspective on the Use of Sulfated Polysaccharides from Marine Organisms as a Source of New Antithrombotic Drugs

    PubMed Central

    Mourão, Paulo A. S.

    2015-01-01

    Thromboembolic diseases are increasing worldwide and always require anticoagulant therapy. We still need safer and more secure antithrombotic drugs than those presently available. Sulfated polysaccharides from marine organisms may constitute a new source for the development of such drugs. Investigation of these compounds usually attempts to reproduce the therapeutic effects of heparin. However, we may need to follow different routes, focusing particularly in the following aspects: (1) defining precisely the specific structures required for interaction of these sulfated polysaccharides with proteins of the coagulation system; (2) looking for alternative mechanisms of action, distinct from those of heparin; (3) identifying side effects (mostly pro-coagulant action and hypotension rather than bleeding) and preparing derivatives that retain the desired antithrombotic action but are devoid of side effects; (4) considering that sulfated polysaccharides with low anticoagulant action on in vitro assays may display potent effects on animal models of experimental thrombosis; and finally (5) investigating the antithrombotic effect of these sulfated polysaccharides after oral administration or preparing derivatives that may achieve this effect. If these aspects are successfully addressed, sulfated polysaccharides from marine organisms may conquer the frontier of antithrombotic therapy and open new avenues for treatment or prevention of thromboembolic diseases. PMID:25955754

  11. 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.

  12. In vitro antioxidant activities of sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum.

    PubMed

    Abu, Ryogo; Jiang, Zedong; Ueno, Mikinori; Okimura, Takasi; Yamaguchi, Kenichi; Oda, Tatsuya

    2013-08-01

    Antioxidant activities of sulfated polysaccharide ascophyllan from Ascophyllum nodosum was investigated in vitro by various assays, and compared with those of fucoidan. A chemiluminescence (CL) analysis using a luminol analog, L-012, showed that ascophyllan scavenges superoxide, and the activity is greater than fucoidan. However, in the presence of 10μg/ml of ascophyllan or 10μg/ml and 100μg/ml of fucoidan, slightly enhanced CL-responses were observed. Since EDTA-treatment resulted in disappearance of the enhancement effects, it was suggested that metal ions especially iron ions in the polysaccharides might be involved in this phenomenon. In fact, metal element analysis revealed that ascophyllan and fucoidan inherently contain iron and other metal elements. EDTA-treatment resulted in significant increase in Fe(2+)-chelating activities of these polysaccharides. In an electron spin resonance (ESR)-spin trapping analysis in which direct UV-radiation to hydrogen peroxide was used as a source of hydroxyl radical, ascophyllan and fucoidan showed potent hydroxyl radical scavenging activity with similar extent. Reducing power of ascophyllan was stronger than that of fucoidan. Our results indicate that ascophyllan can exhibit direct and potent antioxidant activity. PMID:23643974

  13. 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. PMID:26616455

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Oral zinc sulfate solutions inhibit sweet taste perception.

    PubMed

    Keast, Russell S J; Canty, Thomas M; Breslin, Paul A S

    2004-07-01

    We investigated the ability of zinc sulfate (5, 25, 50 mM) to inhibit the sweetness of 12 chemically diverse sweeteners, which were all intensity matched to 300 mM sucrose [800 mM glucose, 475 mM fructose, 3.25 mM aspartame, 3.5 mM saccharin, 12 mM sodium cyclamate, 14 mM acesulfame-K, 1.04 M sorbitol, 0.629 mM sucralose, 0.375 mM neohesperidin dihydrochalcone (NHDC), 1.5 mM stevioside and 0.0163 mM thaumatin]. Zinc sulfate inhibited the sweetness of most compounds in a concentration dependent manner, peaking with 80% inhibition by 50 mM. Curiously, zinc sulfate never inhibited the sweetness of Na-cyclamate. This suggests that Na-cyclamate may access a sweet taste mechanism that is different from the other sweeteners, which were inhibited uniformly (except thaumatin) at every concentration of zinc sulfate. We hypothesize that this set of compounds either accesses a single receptor or multiple receptors that are inhibited equally by zinc sulfate at each concentration.

  20. 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

  1. Polysaccharides from Polygonatum Inhibit the Proliferation of Prostate Cancer-Associated Fibroblasts.

    PubMed

    Han, Shu-Yu; Hu, Ming-Hua; Qi, Guan-Yun; Ma, Chao-Xiong; Wang, Yuan-Yuan; Ma, Fang-Li; Tao, Ning; Qin, Zhi-Hai

    2016-01-01

    Inhibition of cancer-associated broblasts (CAFs) may improve the efficacy of cancer therapy. Polysaccharide extracted from polygonatum can selectively inhibit the growth of prostate-CAFs (<.001) without inhibiting the growth of normal broblasts (NAFs). Polysaccharides from polygonatum stimulate autophagy of prostate-CAFs. 3-methyl-adenine(3-MA) is an autophagy inhibitor. 3-MA was added to prostate-CAFs with polysaccharide from polygonatum to determine whether autophagy plays an important role in the restrained effect. Finally, polysaccharide from polygonatum treatment significantly increased the activation of Beclin-1 and LC3, key autophagy proteins. Polysaccharides from polygonatum stimulate autophagy of prostate-CAFs and inhibits prostate-CAF growth, indicating that a novel anti-cancer strategy involves inhibiting the growth of prostate- CAFs. PMID:27644624

  2. 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.

  3. Anti-metastatic effects of the sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on B16 melanoma.

    PubMed

    Abu, Ryogo; Jiang, Zedong; Ueno, Mikinori; Isaka, Shogo; Nakazono, Satoru; Okimura, Takasi; Cho, Kichul; Yamaguchi, Kenichi; Kim, Daekyung; Oda, Tatsuya

    2015-03-20

    We previously found that ascophyllan, a sulfated polysaccharide isolated from brown seaweed Ascophyllum nodosum, exhibited antitumor activity in sarcoma-180 tumor-bearing mice. In this study, we found that ascophyllan inhibited the migration and adhesion of B16 melanoma cells by reducing the expression of N-cadherin and enhancing the expression of E-cadherin in a concentration-dependent manner. Transwell invasion assay revealed that ascophyllan suppressed the invasion ability of B16 cells. It also inhibited the expression of matrix metalloprotease-9 (MMP-9) mRNA and the secretion of MMP-9 protein in B16 cells, a process that may involve the extracellular signal-regulated kinase (ERK) signaling pathway. Furthermore, ascophyllan administered intraperitoneally at 25 mg/kg showed anti-metastatic activity in a mouse model of metastasis induced by intravenous injection of B16 cells, and the number of lung surface metastatic nodules in ascophyllan-treated mice was significantly reduced compared to that in the untreated control mice. Since splenic natural killer cell activity enhanced in the mice injected with ascophyllan intraperitoneally, we suggest that ascophyllan may exhibit in vivo anti-metastatic activity on B16 melanoma cells through activation of the host immune system in addition to a direct action on cancer cells.

  4. Anti-metastatic effects of the sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on B16 melanoma.

    PubMed

    Abu, Ryogo; Jiang, Zedong; Ueno, Mikinori; Isaka, Shogo; Nakazono, Satoru; Okimura, Takasi; Cho, Kichul; Yamaguchi, Kenichi; Kim, Daekyung; Oda, Tatsuya

    2015-03-20

    We previously found that ascophyllan, a sulfated polysaccharide isolated from brown seaweed Ascophyllum nodosum, exhibited antitumor activity in sarcoma-180 tumor-bearing mice. In this study, we found that ascophyllan inhibited the migration and adhesion of B16 melanoma cells by reducing the expression of N-cadherin and enhancing the expression of E-cadherin in a concentration-dependent manner. Transwell invasion assay revealed that ascophyllan suppressed the invasion ability of B16 cells. It also inhibited the expression of matrix metalloprotease-9 (MMP-9) mRNA and the secretion of MMP-9 protein in B16 cells, a process that may involve the extracellular signal-regulated kinase (ERK) signaling pathway. Furthermore, ascophyllan administered intraperitoneally at 25 mg/kg showed anti-metastatic activity in a mouse model of metastasis induced by intravenous injection of B16 cells, and the number of lung surface metastatic nodules in ascophyllan-treated mice was significantly reduced compared to that in the untreated control mice. Since splenic natural killer cell activity enhanced in the mice injected with ascophyllan intraperitoneally, we suggest that ascophyllan may exhibit in vivo anti-metastatic activity on B16 melanoma cells through activation of the host immune system in addition to a direct action on cancer cells. PMID:25623538

  5. A sulfated polysaccharide, fucans, isolated from brown algae Sargassum vulgare with anticoagulant, antithrombotic, antioxidant and anti-inflammatory effects.

    PubMed

    Dore, Celina Maria P Guerra; das C Faustino Alves, Monique Gabriela; Will, Luiza Sheyla E Pofírio; Costa, Thiago G; Sabry, Diego A; de Souza Rêgo, Leonardo Augusto R; Accardo, Camila M; Rocha, Hugo Alexandre O; Filgueira, Luciana Guimarães A; Leite, Edda Lisboa

    2013-01-01

    Fucan (SV1) sulfated polysaccharides from the brown algae Sargassum vulgare were extracted, fractionated in acetone and examined with respect to chemical composition, anticoagulant, anti-inflammatory, antithrombotic effects and cellular proliferation. These polysaccharides contain low levels of protein, high level of carbohydrate and sulfate. Monosaccharides analysis revealed that SV1 was composed of fucose, galactose, xylose, glucuronic acid and mannose. SV1 polysaccharide prolonged activated partial thromboplastin time (aPTT) and exhibited high antithrombotic action in vivo, with a concentration ten times higher than heparin activity. PSV1, a purified form in gel filtration showed very low biological activities. SV1 stimulated the enzymatic activity of FXa. Its action on DPPH radical scavenging activity was 22%. This polymer has no cytotoxic action (hemolytic) on ABO and Rh blood types in different erythrocyte groups. It displays strong anti-inflammatory action at all concentrations tested in the carrageenan-induced paw edema model, demonstrated by reduced edema and cellular infiltration. PMID:23044157

  6. Ulvan, a Sulfated Polysaccharide from Green Algae, Activates Plant Immunity through the Jasmonic Acid Signaling Pathway

    PubMed Central

    Jaulneau, Valérie; Lafitte, Claude; Jacquet, Christophe; Fournier, Sylvie; Salamagne, Sylvie; Briand, Xavier; Esquerré-Tugayé, Marie-Thérèse; Dumas, Bernard

    2010-01-01

    The industrial use of elicitors as alternative tools for disease control needs the identification of abundant sources of them. We report on an elicitor obtained from the green algae Ulva spp. A fraction containing most exclusively the sulfated polysaccharide known as ulvan-induced expression of a GUS gene placed under the control of a lipoxygenase gene promoter. Gene expression profiling was performed upon ulvan treatments on Medicago truncatula and compared to phytohormone effects. Ulvan induced a gene expression signature similar to that observed upon methyl jasmonate treatment (MeJA). Involvement of jasmonic acid (JA) in ulvan response was confirmed by detecting induction of protease inhibitory activity and by hormonal profiling of JA, salicylic acid (SA) and abscisic acid (ABA). Ulvan activity on the hormonal pathway was further consolidated by using Arabidopsis hormonal mutants. Altogether, our results demonstrate that green algae are a potential reservoir of ulvan elicitor which acts through the JA pathway. PMID:20445752

  7. Sulfated Astragalus polysaccharide can regulate the inflammatory reaction induced by LPS in Caco2 cells.

    PubMed

    Wang, Xiaofei; Wang, Siyu; Li, Yulong; Wang, Fei; Yang, Xiaojun; Yao, Junhu

    2013-09-01

    This study evaluates the effect of sulfated Astragalus polysaccharide (SAPS) on inflammatory reaction induced by LPS in Caco2 cells. Sulfated modification was conducted using the chlorosulfonic acid-pyridine method. Caco2 cells were cultured with 25, 50 and 100 μg/mL SAPS or 100 μg/mL Astragalus polysaccharide (APS) for 24 h. Then, 1 μg/mL LPS was added for the next 24 h to trigger an inflammatory response. DMEM culture medium was used as a blank control. In present study, LPS stimulation significantly increased the mRNA expression of TNF-α, IL-1β, IL-8 and TLR4, and reduced the expression of ZO-1 and occludin. Compared with the LPS control group, APS (100 μg/mL) or SAPS (100 μg/mL) administration decreased the expression of TNF-α, IL-1β and IL-8. Moreover, 25 μg/mL and 50 μg/mL SAPS down-regulated TNF-α and IL-1β expression. APS administration (100 μg/mL) up-regulated occludin expression, but did not affect ZO-1 expression. However, the expression of ZO-1 and occludin was up-regulated by lower dose SAPS administration (25 μg/mL and 50 μg/mL). Compared with the other groups, the expression of TLR4 was lower in the SAPS group at all concentrations of SAPS. These results suggest that SAPS was to be a more effective anti-inflammatory agent than APS in vitro.

  8. 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.

  9. Amorphous nanodrugs prepared by complexation with polysaccharides: carrageenan versus dextran sulfate.

    PubMed

    Cheow, Wean Sin; Kiew, Tie Yi; Hadinoto, Kunn

    2015-03-01

    Amorphous nanodrugs prepared by electrostatic complexation of drug molecules with oppositely charged polysaccharides represent a promising bioavailability enhancement strategy for poorly-soluble drugs owed to their high supersaturation generation capability and simple preparation. Using ciprofloxacin (CIP) as the model drug, we investigated the effects of using dextran sulfate (DXT) or carrageenan (CGN) on the (1) preparation efficiency, (2) physical characteristics, (3) supersaturation generation, (4) antimicrobial activity, and (5) cytotoxicity of the amorphous drug-polysaccharide nanoparticle complex (nanoplex) produced. Owing to the higher charge density and chain flexibility of DXT, coupled with the greater hydrophobicity of CGN, the CIP-DXT nanoplex exhibited superior preparation efficiency and larger size than the CIP-CGN nanoplex. Whereas the low solubility and high gelation tendency of CGN resulted in superior supersaturation generation capability for the CIP-DXT nanoplex. The non-cytotoxicity, antimicrobial activity, colloidal, and amorphous state stability were established for both nanoplexes, making them an ideal supersaturated drug delivery system. PMID:25498670

  10. Isolation, characterization and bioactivities of a new polysaccharide from Annona squamosa and its sulfated derivative.

    PubMed

    Tu, Wensong; Zhu, Jianhua; Bi, Sixue; Chen, Dehong; Song, Liyan; Wang, Lishan; Zi, Jiachen; Yu, Rongmin

    2016-11-01

    A new water-soluble polysaccharide, designated as ASPW80-1, was first isolated from the fruit pulp of Annona squamosa. The structure of ASPW80-1 was elucidated based on the physicochemical and instrumental analyses. The results indicated that ASPW80-1 was a homogeneous heteropolysaccharide with an average molecular weight of 2.29×10(5)Da. Another novel modified polysaccharide, the sulfated derivative of ASPW80-1 namely as ASPW80-M1, was also synthesized. The ultra-structures of both ASPW80-1 and ASPW80-M1 were further characterized by scanning electron microscopy and atomic force microscopy. The antioxidant assays showed that ASPW80-1 and ASPW80-M1 exhibited DPPH and hydroxyl radicals scavenging activities. The results of immunomodulatory assays in vitro showed that ASPW80-1 and ASPW80-M1 could markedly promote the proliferation of mouse splenocytes. These results proposed that ASPW80-M1 might be proposed to be developed as a potential value-added product with the activities of immunomodulator and free-radical inhibitors. PMID:27516275

  11. Isolation, characterization and bioactivities of a new polysaccharide from Annona squamosa and its sulfated derivative.

    PubMed

    Tu, Wensong; Zhu, Jianhua; Bi, Sixue; Chen, Dehong; Song, Liyan; Wang, Lishan; Zi, Jiachen; Yu, Rongmin

    2016-11-01

    A new water-soluble polysaccharide, designated as ASPW80-1, was first isolated from the fruit pulp of Annona squamosa. The structure of ASPW80-1 was elucidated based on the physicochemical and instrumental analyses. The results indicated that ASPW80-1 was a homogeneous heteropolysaccharide with an average molecular weight of 2.29×10(5)Da. Another novel modified polysaccharide, the sulfated derivative of ASPW80-1 namely as ASPW80-M1, was also synthesized. The ultra-structures of both ASPW80-1 and ASPW80-M1 were further characterized by scanning electron microscopy and atomic force microscopy. The antioxidant assays showed that ASPW80-1 and ASPW80-M1 exhibited DPPH and hydroxyl radicals scavenging activities. The results of immunomodulatory assays in vitro showed that ASPW80-1 and ASPW80-M1 could markedly promote the proliferation of mouse splenocytes. These results proposed that ASPW80-M1 might be proposed to be developed as a potential value-added product with the activities of immunomodulator and free-radical inhibitors.

  12. Mechanism of sulfate transport inhibition by cycloheximide in plant tissues.

    PubMed

    Renosto, F; Ferrari, G

    1975-10-01

    Inhibition by cycloheximide of sulfate transport in both barley roots (Hordeum vulgare L.) and potato tuber (Solanum tuberosum L.) increases with increasing inhibitor concentration only to a limited extent, depending on the length of the tissue incubation with the inhibitor. In contrast to this, increasing concentrations of dinitrophenol have a rapid and total inhibitory effect on the active transport. Leucine transport in the same tissues is strongly inhibited by dinitrophenol but is not affected by cycloheximide, whereas incorporation into protein is mainly inhibited by cycloheximide. It appears that the mechanism of transport inhibition by cycloheximide in plant tissues consists in stopping new carrier synthesis and not in the disruption of energy flow. Sulfate carriers show comparable decay rates in barley roots and potato tuber, the mean life being shorter than that of the leucine carriers. These appear more stable in roots than in storage tissues.

  13. Sulfated polysaccharide fraction from marine algae Solieria filiformis: Structural characterization, gastroprotective and antioxidant effects.

    PubMed

    Sousa, Willer M; Silva, Renan O; Bezerra, Francisco F; Bingana, Rudy D; Barros, Francisco Clark N; Costa, Luís E C; Sombra, Venicios G; Soares, Pedro M G; Feitosa, Judith P A; de Paula, Regina C M; Souza, Marcellus H L P; Barbosa, André Luiz R; Freitas, Ana Lúcia P

    2016-11-01

    A sulfated polysaccharide (SFP) fraction from the marine alga Solieria filiformis was extracted and submitted to microanalysis, molar mass estimation and spectroscopic analysis. We evaluated its gastroprotective potential in vivo in an ethanol-induced gastric damage model and its in vitro antioxidant properties (DPPH, chelating ferrous ability and total antioxidant capacity). Its chemical composition revealed to be essentially an iota-carrageenan with a molar mass of 210.9kDa and high degree of substitution for sulfate groups (1.08). In vivo, SFP significantly (P<0.05) reduced, in a dose dependent manner, the ethanol-induced gastric damage. SFP prevents glutathione consume and increase of malondialdehyde and hemoglobin levels. SFP presented an IC50 of 1.77mg/mL in scavenging DPPH. The chelating ferrous ability was 38.98%, and the total antioxidant capacity was 2.01mg/mL. Thus, SFP prevents the development of ethanol-induced gastric damage by reducing oxidative stress in vivo and possesses relevant antioxidant activity in vitro.

  14. Sulfated polysaccharide fraction from marine algae Solieria filiformis: Structural characterization, gastroprotective and antioxidant effects.

    PubMed

    Sousa, Willer M; Silva, Renan O; Bezerra, Francisco F; Bingana, Rudy D; Barros, Francisco Clark N; Costa, Luís E C; Sombra, Venicios G; Soares, Pedro M G; Feitosa, Judith P A; de Paula, Regina C M; Souza, Marcellus H L P; Barbosa, André Luiz R; Freitas, Ana Lúcia P

    2016-11-01

    A sulfated polysaccharide (SFP) fraction from the marine alga Solieria filiformis was extracted and submitted to microanalysis, molar mass estimation and spectroscopic analysis. We evaluated its gastroprotective potential in vivo in an ethanol-induced gastric damage model and its in vitro antioxidant properties (DPPH, chelating ferrous ability and total antioxidant capacity). Its chemical composition revealed to be essentially an iota-carrageenan with a molar mass of 210.9kDa and high degree of substitution for sulfate groups (1.08). In vivo, SFP significantly (P<0.05) reduced, in a dose dependent manner, the ethanol-induced gastric damage. SFP prevents glutathione consume and increase of malondialdehyde and hemoglobin levels. SFP presented an IC50 of 1.77mg/mL in scavenging DPPH. The chelating ferrous ability was 38.98%, and the total antioxidant capacity was 2.01mg/mL. Thus, SFP prevents the development of ethanol-induced gastric damage by reducing oxidative stress in vivo and possesses relevant antioxidant activity in vitro. PMID:27516258

  15. 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

    2016-11-01

    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. PMID:27516316

  16. Differential effects of polysulfated polysaccharide on experimental encephalomyelitis, proliferation of autoimmune T cells, and inhibition of heparanase activity.

    PubMed

    Hershkoviz, R; Mor, F; Miao, H Q; Vlodavsky, I; Lider, O

    1995-10-01

    The extravasation of activated T lymphocytes through blood vessel walls and their migration to inflammatory loci are associated with secretion of extracellular matrix (ECM)-degrading enzymes, such as heparanase, which degrades heparan sulfate (HS) moieties of the ECM. The HS-degrading activity of heparanase was found to be inhibited by HS and heparin. Since induction of experimental autoimmune encephalomyelitis (EAE) requires extravasation and migration of autoimmune T cells, degradation of ECM by heparanase is expected to be involved in induction of the disease. Herein, we examined whether laminarin sulfate, a polysulfated polysaccharide (PSS) isolated from the cell walls of seaweeds and subjected to chemical sulfation, could inhibit ECM degradation by mammalian heparanase, and could prevent EAE. PSS was a more potent inhibitor of heparanase-mediated degradation of ECM than heparin. In-vivo, PSS, injected once a week, inhibited the severity of actively-induced EAE in rats. However, inhibition of EAE was not due to an overall suppression of autoimmune T cells, since PSS enhanced the proliferation of myelin basic protein (MBP)-specific, encephalitogenic T cells. PSS-activated autoimmune T cells, but not MBP-activated cells, failed to induce EAE in recipient rats. Moreover, rats injected with PSS-activated T cells were resistant to induction of EAE by anti-MBP CD4+ T cells. Thus, PSS may have potential clinical applications in the treatment of autoimmune diseases. PMID:8579728

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

    PubMed

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

    2015-12-29

    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.

  18. Sulfated polysaccharide isolated from the sea cucumber Stichopus japonicus promotes neurosphere migration and differentiation via up-regulation of N-cadherin.

    PubMed

    Sheng, Xiehuang; Li, Min; Song, Shuliang; Zhang, Nannan; Wang, Yunshan; Liang, Hao; Wang, Weili; Ji, Aiguo

    2012-04-01

    In this report, the sulfated polysaccharide (SJP) from the body wall of the sea cucumber Stichopus japonicas was extracted and tested for its capacity to affect migration and differentiation of neural stem/progenitor cells. SJP is an intensely sulfated polysaccharide with a molecular weight of 1.79 × 10(5) Da that is capable of promoting neurosphere attachment and migration in a dose-dependent manner. Moreover, SJP effectively maintains cell viability even after being deprived of mitogens. Our current results demonstrate that neurosphere are differentiated into neuronal and glial cells when exposed to SJP. These effects were accompanied by an up-regulation of the adhesion molecule, N-cadherin. In addition, we observed that blocking of PI3K activity inhibited N-cadherin-mediated activity. This SJP-induced up-regulation of N-cadherin mediates neurosphere adhesion migration and differentiation via the PI3K/Akt signaling pathway. These results suggest that SJP could be used as a therapeutic agent to mobilize neuroblast migration under conditions of brain injury and disease.

  19. 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

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

    PubMed

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

    2016-01-01

    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

  1. Effects of partial desulfation on antioxidant and inhibition of DLD cancer cell of Ulva fasciata polysaccharide.

    PubMed

    Shao, Ping; Pei, Yaping; Fang, Zhongxian; Sun, Peilong

    2014-04-01

    Ulva fasciata belonging to the family Ulvaceae, commonly known as 'sea lettuce', is an abundantly growing green seaweed in coastal seashore of South China. Three different molecular weight sulfated polysaccharides (UFP1, UFP2 and UFP3) were extracted and separated from U. fasciata by hot water extraction and ultrafiltration. The three native UFP fractions had partial desulfurization by solvolytic desulfation respectively and the effect of sulfate content on the exhibition of the antioxidant and anti-tumor capacities had been evaluated and compared. The results showed that each native polysaccharide (UFP1, UFP2, UFP3) with high sulfate content exhibited better antioxidant activities compared with the partial desulfated polysaccharides (DS-UFP1, DS-UFP2, DS-UFP3). Specifically, UFP2 with relatively high sulfate content, molecular weight and uronic acid content had consistently excellent antioxidant performances. However, UFP2 demonstrated the minimal inhibitory effects on growth of DLD intestinal cancer cells. Instead, DS-UFP3 with the lowest sulfate content but highest uronic acid content and molecular weight exhibited the best antitumor activity.

  2. Molecular Basis of the Receptor Interactions of Polysialic Acid (polySia), polySia Mimetics, and Sulfated Polysaccharides.

    PubMed

    Zhang, Ruiyan; Loers, Gabriele; Schachner, Melitta; Boelens, Rolf; Wienk, Hans; Siebert, Simone; Eckert, Thomas; Kraan, Stefan; Rojas-Macias, Miguel A; Lütteke, Thomas; Galuska, Sebastian P; Scheidig, Axel; Petridis, Athanasios K; Liang, Songping; Billeter, Martin; Schauer, Roland; Steinmeyer, Jürgen; Schröder, Jens-Michael; Siebert, Hans-Christian

    2016-05-01

    Polysialic acid (polySia) and polySia glycomimetic molecules support nerve cell regeneration, differentiation, and neuronal plasticity. With a combination of biophysical and biochemical methods, as well as data mining and molecular modeling techniques, it is possible to correlate specific ligand-receptor interactions with biochemical processes and in vivo studies that focus on the potential therapeutic impact of polySia, polySia glycomimetics, and sulfated polysaccharides in neuronal diseases. With this strategy, the receptor interactions of polySia and polySia mimetics can be understood on a submolecular level. As the HNK-1 glycan also enhances neuronal functions, we tested whether similar sulfated oligo- and polysaccharides from seaweed could be suitable, in addition to polySia, for finding potential new routes into patient care focusing on an improved cure for various neuronal diseases. The knowledge obtained here on the structural interplay between polySia or sulfated polysaccharides and their receptors can be exploited to develop new drugs and application routes for the treatment of neurological diseases and dysfunctions. PMID:27136597

  3. 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. PMID:25577148

  4. 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.

  5. Enhancing effect of a sea cucumber Stichopus japonicus sulfated polysaccharide on neurosphere formation in vitro.

    PubMed

    Zhang, Yuejie; Song, Shuliang; Liang, Hao; Wang, Yunshan; Wang, Weili; Ji, Aiguo

    2010-10-01

    Neural stem/progenitor cells (NSPCs) exhibit therapeutic potential in neuronal diseases. Previously, we reported that a sulfated polysaccharide (HS) from the sea cucumber Stichopus japonicus increased the proliferation of NSPCs. Since the formation of neurospheres is related with NSPCs proliferation, we investigated the mechanism leading to neurosphere formation with and without HS. The results showed that HS significantly promoted neurosphere formation in a dose-dependent manner at concentrations between 2 and 8 μg/ml. Cell cycle analysis showed that HS increased the percentage of cells in S phase by 2.8-fold, as compared with the control. On the other hand, we observed a significantly rapid aggregation of NSPCs, resulting in formation of neurospheres as early as 2 h after HS treatment. However, the aggregation was not caused by chemotactic migration of NSPCs, as evidenced by the transwell chamber assay. Furthermore, the effect of HS on NSPCs was similar to the tumor necrosis factor-α (TNF-α) that activated nuclear factor NF-κB. Thus, we demonstrated that HS was able to promote cell proliferation and aggregation of NSPCs which could lead to the formation of neurospheres, and suggested that HS can serve as an adjuvant for promoting proliferation of NSPCs and formation of neurospheres.

  6. 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

  7. Mass preparation of oligosaccharides by the hydrolysis of chondroitin sulfate polysaccharides with a subcritical water microreaction system.

    PubMed

    Yamada, Shuhei; Matsushima, Keiichiro; Ura, Haruo; Miyamoto, Nobuyuki; Sugahara, Kazuyuki

    2013-04-19

    The biological functions of chondroitin sulfate (CS) are executed by the interaction of specific oligosaccharide sequences in the polysaccharide chain with effective proteins. Thus, CS oligosaccharides are expected to have pharmacological applications. Furthermore, the demand for CS in health food supplements and medication is growing. However, the absorbency of CS polysaccharides in the digestive system is very low. Since the activity of orally administered CS is expected to increase by depolymerization, industrial production of CS oligosaccharides is required. In this study, hydrolysis with subcritical and super-critical water was applied to the depolymerization of CS for the first time, and hydrolytic conditions for oligosaccharide production were examined. CS oligosaccharides principally containing an N-acetyl-D-galactosamine residue at their reducing ends were successfully obtained. No significant desulfation was found in CS oligosaccharides prepared under optimized conditions. The production of CS oligosaccharides by this method will have a strong influence on the CS-related materials market.

  8. Mass preparation of oligosaccharides by the hydrolysis of chondroitin sulfate polysaccharides with a subcritical water microreaction system.

    PubMed

    Yamada, Shuhei; Matsushima, Keiichiro; Ura, Haruo; Miyamoto, Nobuyuki; Sugahara, Kazuyuki

    2013-04-19

    The biological functions of chondroitin sulfate (CS) are executed by the interaction of specific oligosaccharide sequences in the polysaccharide chain with effective proteins. Thus, CS oligosaccharides are expected to have pharmacological applications. Furthermore, the demand for CS in health food supplements and medication is growing. However, the absorbency of CS polysaccharides in the digestive system is very low. Since the activity of orally administered CS is expected to increase by depolymerization, industrial production of CS oligosaccharides is required. In this study, hydrolysis with subcritical and super-critical water was applied to the depolymerization of CS for the first time, and hydrolytic conditions for oligosaccharide production were examined. CS oligosaccharides principally containing an N-acetyl-D-galactosamine residue at their reducing ends were successfully obtained. No significant desulfation was found in CS oligosaccharides prepared under optimized conditions. The production of CS oligosaccharides by this method will have a strong influence on the CS-related materials market. PMID:23454651

  9. 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

  10. 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.

  11. Fucosylated chondroitin sulfate inhibits Plasmodium falciparum cytoadhesion and merozoite invasion.

    PubMed

    Bastos, Marcele F; Albrecht, Letusa; Kozlowski, Eliene O; Lopes, Stefanie C P; Blanco, Yara C; Carlos, Bianca C; Castiñeiras, Catarina; Vicente, Cristina P; Werneck, Claudio C; Wunderlich, Gerhard; Ferreira, Marcelo U; Marinho, Claudio R F; Mourão, Paulo A S; Pavão, Mauro S G; Costa, Fabio T M

    2014-01-01

    Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect to P. falciparum cytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.

  12. Fucosylated Chondroitin Sulfate Inhibits Plasmodium falciparum Cytoadhesion and Merozoite Invasion

    PubMed Central

    Bastos, Marcele F.; Albrecht, Letusa; Kozlowski, Eliene O.; Lopes, Stefanie C. P.; Blanco, Yara C.; Carlos, Bianca C.; Castiñeiras, Catarina; Vicente, Cristina P.; Werneck, Claudio C.; Wunderlich, Gerhard; Ferreira, Marcelo U.; Marinho, Claudio R. F.; Mourão, Paulo A. S.; Pavão, Mauro S. G.

    2014-01-01

    Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect to P. falciparum cytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria. PMID:24395239

  13. Proliferative effects on neural stem/progenitor cells of a sulfated polysaccharide purified from the sea cucumber Stichopus japonicus.

    PubMed

    Zhang, Yuejie; Song, Shuliang; Song, Di; Liang, Hao; Wang, Weili; Ji, Aiguo

    2010-01-01

    To test the effects of a sulfated polysaccharide, Haishen (HS) on the viability and proliferation of neural stem/progenitor cells (NSPCs), we isolated the polysaccharide from the body wall of the sea cucumber Stichopus japonicus by enzymolysis extraction, anion-exchange and gel-permeation chromatography. HS is a highly sulfated fucoidan with a molecular weight of 4.23x10(5) Da. Due to its safety being of invertebrate origin they are less likely to contain infectious agents, the effects of HS on the viability and proliferation of NSPCs in vitro were examined by MTT assay, BrdU labeling and neurosphere formation assay, respectively. Our results showed that HS alone increased NSPC viability in a dose-dependent manner. Moreover, HS acted synergistically with fibroblast growth factor-2 (FGF-2) but not epidermal growth factor (EGF) to enhance the proliferation of NSPCs. Finally, HS did not induce apoptosis of NSPCs. Our findings suggest that HS can serve as an adjuvant for promoting the proliferation of NSPCs.

  14. 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. PMID:26778161

  15. Simple and Rapid Quality Control of Sulfated Glycans by a Fluorescence Sensor Assay—Exemplarily Developed for the Sulfated Polysaccharides from Red Algae Delesseria sanguinea

    PubMed Central

    Lühn, Susanne; Grimm, Juliane C.; Alban, Susanne

    2014-01-01

    Sulfated polysaccharides (SP) from algae are of great interest due to their manifold biological activities. Obstacles to commercial (especially medical) application include considerable variability and complex chemical composition making the analysis and the quality control challenging. The aim of this study was to evaluate a simple microplate assay for screening the quality of SP. It is based on the fluorescence intensity (FI) increase of the sensor molecule Polymer-H by SP and was originally developed for direct quantification of SP. Exemplarily, 65 SP batches isolated from the red alga Delesseria sanguinea (D.s.-SP) and several other algae polysaccharides were investigated. Their FI increase in the Polymer-H assay was compared with other analytical parameters. By testing just one concentration of a D.s.-SP sample, quality deviations from the reference D.s.-SP and thus both batch-to-batch variability and stability can be detected. Further, structurally distinct SP showed to differ in their concentration-dependent FI profiles. By using corresponding reference compounds, the Polymer-H assay is therefore applicable as identification assay with high negative predictability. In conclusion, the Polymer-H assay showed to represent not only a simple method for quantification, but also for characterization identification and differentiation of SP of marine origin. PMID:24727392

  16. 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.

  17. Highly acidic glycans from sea cucumbers. Isolation and fractionation of fucose-rich sulfated polysaccharides from the body wall of Ludwigothurea grisea.

    PubMed

    Mourão, P A; Bastos, I G

    1987-08-01

    The body wall of the sea cucumber contains high amounts of sulfated glycans, which differ in structure from glycosaminoglycans of animal tissues and also from the fucose-rich sulfated polysaccharides isolated from marine algae and from the jelly coat of sea urchin eggs. In Ludwigothurea grisea, glycans can be separated into three fractions which differ in molecular mass and chemical composition. The fraction containing a high-molecular-mass component has a high proportion of fucose and small amounts of amino sugars, whereas another fraction contains primarily a sulfated fucan. The third fraction, which represents the major portion of the sea cucumber polysaccharides, contains besides fucose, approximately equimolar proportions of glucuronic acid and amino sugars, and has a sulfate content higher than that in the other two fractions. Both D and L-isomers of fucose are found in these polysaccharides, and the sulfate is linked to the O-3 position of the fucose residues. The attachment position of the sulfate groups to the glucuronic acid units and amino sugars is still undetermined. It is possible that these compounds are involved in maintaining the integrity of the sea cucumber's body wall, in analogy with the role of other macromolecules in the vertebrate connective tissue.

  18. 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.

  19. 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.

  20. Inactivation of thrombin by a fucosylated chondroitin sulfate from echinoderm.

    PubMed

    Mourão, P A; Boisson-Vidal, C; Tapon-Bretaudière, J; Drouet, B; Bros, A; Fischer, A

    2001-04-15

    A polysaccharide extracted from the sea cucumber body wall has the same backbone structure as the mammalian chondroitin sulfate, but some of the glucuronic acid residues display sulfated fucose branches. These branches confer high anticoagulant activity to the polysaccharide. Since the sea cucumber chondroitin sulfate has analogy in structure with mammalian glycosaminoglycans and sulfated fucans from brown algae, we compared its anticoagulant action with that of heparin and of a homopolymeric sulfated fucan with approximately the same level of sulfation as the sulfated fucose branches found in the sea cucumber polysaccharide. These various compounds differ not only in their anticoagulant potencies but also in the mechanisms of thrombin inhibition. Fucosylated chondroitin sulfate, like heparin, requires antithrombin or heparin cofactor II for thrombin inhibition. Sulfated fucans from brown algae have an antithrombin effect mediated by antithrombin and heparin cofactor II, plus a direct antithrombin effect more pronounced for some fractions. But even in the case of these two polysaccharides, we observed some differences. In contrast with heparin, total inhibition of thrombin in the presence of antithrombin is not achieved with fucosylated chondroitin sulfate, possibly reflecting a less specific interaction. Fucosylated chondroitin sulfate is able to inhibit thrombin generation after stimulation by both contact-activated and thromboplastin-activated systems. It delayed only the contact-induced thrombin generation, as expected for an anticoagulant without direct thrombin inhibition. Overall, the specific spatial array of the sulfated fucose branches in the fucosylated chondroitin sulfate not only confer high anticoagulant activity to the polysaccharide but also determine differences in the way it inhibits thrombin.

  1. 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.

  2. 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

  3. 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.

  4. 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

    2015-01-01

    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.

  5. 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. PMID:25605207

  6. 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

    2015-03-01

    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.

  7. 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.

  8. 2-O-Sulfated Domains in Syndecan-1 Heparan Sulfate Inhibit Neutrophil Cathelicidin and Promote Staphylococcus aureus Corneal Infection*

    PubMed Central

    Hayashida, Atsuko; Amano, Shiro; Gallo, Richard L.; Linhardt, Robert J.; Liu, Jian; Park, Pyong Woo

    2015-01-01

    Ablation of syndecan-1 in mice is a gain of function mutation that enables mice to significantly resist infection by several bacterial pathogens. Syndecan-1 shedding is induced by bacterial virulence factors, and inhibition of shedding attenuates bacterial virulence, whereas administration of purified syndecan-1 ectodomain enhances virulence, suggesting that bacteria subvert syndecan-1 ectodomains released by shedding for their pathogenesis. However, the pro-pathogenic functions of syndecan-1 ectodomain have yet to be clearly defined. Here, we examined how syndecan-1 ectodomain enhances Staphylococcus aureus virulence in injured mouse corneas. We found that syndecan-1 ectodomain promotes S. aureus corneal infection in an HS-dependent manner. Surprisingly, we found that this pro-pathogenic activity is dependent on 2-O-sulfated domains in HS, indicating that the effects of syndecan-1 ectodomain are structure-based. Our results also showed that purified syndecan-1 ectodomain and heparan compounds containing 2-O-sulfate motifs inhibit S. aureus killing by antimicrobial factors secreted by degranulated neutrophils, but does not affect intracellular phagocytic killing by neutrophils. Immunodepletion of antimicrobial factors with staphylocidal activities demonstrated that CRAMP, a cationic antimicrobial peptide, is primarily responsible for S. aureus killing among other factors secreted by degranulated neutrophils. Furthermore, we found that purified syndecan-1 ectodomain and heparan compounds containing 2-O-sulfate units potently and specifically inhibit S. aureus killing by synthetic CRAMP. These results provide compelling evidence that a specific subclass of sulfate groups, and not the overall charge of HS, permits syndecan-1 ectodomains to promote S. aureus corneal infection by inhibiting a key arm of neutrophil host defense. PMID:25931123

  9. 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.

  10. Morphological transformation and proliferation of rat astrocytes as induced by sulfated polysaccharides from the sea cucumber Stichopus japonicus.

    PubMed

    Sheng, Xiehuang; Zhang, Nannan; Song, Shuliang; Li, Min; Liang, Hao; Zhang, Yuejie; Wang, Yunshan; Ji, Aiguo

    2011-09-26

    In this report, we demonstrate that the sulfated polysaccharide, Haishen (HS), which was isolated from the body wall of the sea cucumber Stichopus japonicus can induce morphological transformation and proliferation of astrocytes in vitro when combined with basic fibroblast growth factor 2 (FGF-2). Cell morphology showed no change when induced by HS or FGF-2 alone. However, combinational treatment of HS and FGF-2 promoted transformation of normal astrocyte into a stella morphology (stellation), along with an increase in the expression and rearrangement of glial fibrillary acidic protein (GFAP). Further analysis of HS- and FGF-2-treated cells indicated a reduced percentage of cells in the G0/G1 phase, whereas the cell proliferation index (S phase) was increased. The proportion of 5-bromo-2-deoxyuridine (BrdU)-positive cells increased in response to the combination of HS and FGF-2. With respect to cell cycle signaling, immunoblotting assay demonstrated an accumulation of Cyclin D1. These observations suggest that HS may play a role in astrocyte morphological transformation and proliferation, and this activation requires a synergism with FGF-2.

  11. 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.

  12. 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

  13. 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...

  14. Pharmacologic approaches to butterfly wing patterning: sulfated polysaccharides mimic or antagonize cold shock and alter the interpretation of gradients of positional information.

    PubMed

    Serfas, Michael S; Carroll, Sean B

    2005-11-15

    Butterflies produce complex and diverse wing patterns by mechanisms that are generally unknown. We have employed a pharmacological approach to explore the molecular mechanisms of pattern formation. In a screen of over 200 compounds injected into developing Junonia coenia pupae, we identified several specific sulfated polysaccharides that caused widespread, dose-dependent effects on adult wing patterns. These compounds were well tolerated and permitted butterflies to eclose normally and take flight at moderate levels of effect. Heparin and closely related chondroitin sulfates caused stage-specific expansion of distal and proximal band systems and reduction and repatterning of eyespots. Dextran sulfate and fucoidan, whose structures are widely divergent from heparin and one another, caused contraction of distal and proximal systems, but had no effect on eyespots. Nonsulfated or nonpolymeric saccharides were without effect. Pattern alterations were indistinguishable from those reported for extreme cold shock and exposure to sodium tungstate and "molsin". When administered after cold shock or coinjected with heparin, dextran sulfate reversed all patterning effects. We suggest that the primary effect of polysaccharide treatments is to alter the interpretation of gradients of positional information along the proximodistal axis of the pupal wing. PMID:16216238

  15. Pharmacologic approaches to butterfly wing patterning: sulfated polysaccharides mimic or antagonize cold shock and alter the interpretation of gradients of positional information.

    PubMed

    Serfas, Michael S; Carroll, Sean B

    2005-11-15

    Butterflies produce complex and diverse wing patterns by mechanisms that are generally unknown. We have employed a pharmacological approach to explore the molecular mechanisms of pattern formation. In a screen of over 200 compounds injected into developing Junonia coenia pupae, we identified several specific sulfated polysaccharides that caused widespread, dose-dependent effects on adult wing patterns. These compounds were well tolerated and permitted butterflies to eclose normally and take flight at moderate levels of effect. Heparin and closely related chondroitin sulfates caused stage-specific expansion of distal and proximal band systems and reduction and repatterning of eyespots. Dextran sulfate and fucoidan, whose structures are widely divergent from heparin and one another, caused contraction of distal and proximal systems, but had no effect on eyespots. Nonsulfated or nonpolymeric saccharides were without effect. Pattern alterations were indistinguishable from those reported for extreme cold shock and exposure to sodium tungstate and "molsin". When administered after cold shock or coinjected with heparin, dextran sulfate reversed all patterning effects. We suggest that the primary effect of polysaccharide treatments is to alter the interpretation of gradients of positional information along the proximodistal axis of the pupal wing.

  16. Drug delivery and cell interaction of adhesive poly(ethyleneimine)/sulfated polysaccharide complex particle films.

    PubMed

    Müller, Martin; Torger, Bernhard; Wehrum, Diana; Vehlow, David; Urban, Birgit; Woltmann, Beatrice; Hempel, Ute

    2015-01-01

    Herein, the authors report and review polyelectrolyte complex (PEC) nanoparticles (NPs) loaded with zoledronate (ZOL) and simvastatin and their effects on bone cells. PEC NPs are intended for modification of bone substitute materials. For characterization, they can be solution casted on germanium (Ge) substrates serving as analytically accessible model substrate. PEC NPs were generated by mixing poly(ethyleneimine) (PEI) either with linear cellulose sulfate (CS) or with branched dextransulfate (DS). Four important requirements for drug loaded PEC NPs and their films are addressed herein, which are the colloidal stability of PEC dispersions (1), interfacial stability (2), cytocompatibility (3), and retarded drug release (4). Dynamic light scattering measurements (DLS) showed that both PEI/CS and PEI/DS PEC NP were obtained with hydrodynamic radii in the range of 35-170 nm and were colloidally stable up to several months. Transmission FTIR spectroscopy evidenced that films of both systems were stable in contact to the release medium up to several days. ZOL-loaded PEI/CS nanoparticles, which were immobilized on an osteoblast-derived extracellular matrix, reduced significantly the resorption and the metabolic activity of human monocyte-derived osteoclasts. FTIR spectroscopy at cast PEC/drug films at Ge substrates revealed retarded drug releases in comparison to the pure drug films.

  17. 2-Bromoethanesulfonate, sulfate, molybdate, and ethanesulfonate inhibit anaerobic dechlorination of polychlorobiphenyls by pasteurized microorganisms

    SciTech Connect

    Ye, D. |; Quensen, J.F. III; Boyd, S.A.; Tiedje, J.M.

    1999-01-01

    Dechlorination of (PCB Aroclor 1242) by pasteurized microorganisms was inhibited by 2-bromoethanesulfonate (BES), sulfate, molybdate, and ethanesulfonate. Consumption of these anions and production of sulfide from BES were detected. The inhibition could not be relieved by hydrogen. Taken together these results suggest that pattern M dechlorination is mediated by spore-forming sulfidogenic bacteria. These results also suggest that BES may inhibit anaerobic dechlorination by nonmethanogens by more than one mechanism.

  18. Effect of Astragalus polysaccharide and its sulfated derivative on growth performance and immune condition of lipopolysaccharide-treated broilers.

    PubMed

    Wang, Xiaofei; Li, Yulong; Shen, Jing; Wang, Siyu; Yao, Junhu; Yang, Xiaojun

    2015-05-01

    This study evaluates the immunomodulating activities of Astragalus polysaccharide (APS) and sulfated APS (SAPS) in LPS-infected broiler chicks. SAPS was derived using the classic chlorosulfonic acid-pyridine method. On day 16, the birds were injected intramuscularly with 0.5 mL of either saline, APS (4 or 8 mg/kg of body weight (BW), shorten as APS-4 or APS-8) or SAPS (4 or 8 mg/kg of BW, shorten as SAPS-4 or SAPS-8) once a day for three successive days. On days 19 and 20, the birds were intraperitoneally injected with 0.5 mL of LPS (1mg/kg of BW). Saline was used as blank control. Compared with the blank control, LPS-treated birds showed lower daily body weight gain (BWG), average daily feed intake (ADFI), villus height and intraepithelial lymphocytes (IEL) number in jejunum, and higher feed conversion ratio (FCR, feed:gain), spleen index, plasma NO concentration, blood heterophil:lymphocyte (H:L) ratio, and the production of NO in the blood T lymphocytes. Compared with the LPS group, birds in APS-4, SAPS-4 and SAPS-8 groups showed decreased FCR (P<0.05). Moreover, SAPS increased BWG and jejunal villus height (P<0.05) at 8 mg/kg BW. Plasma NO concentration was lower in APS-8 group than that in LPS group (P<0.05). Both APS-8 and SAPS-8 treatments elevated the number of jejunal IEL (P<0.05), and decreased blood H:L ratio (P<0.05), respectively. Administration of APS or SAPS did not affect the ADFI, immune organ index, crypt depth and mucosal thickness of the jejunum, and the number of goblet cell. Our findings suggested that APS and SAPS possessed dose-dependent growth-promoting and immunomodulating effect, and was a potential development direction for immunomodulator under early LPS stimulation condition.

  19. Astragalus polysaccharides inhibits PCV2 replication by inhibiting oxidative stress and blocking NF-κB pathway.

    PubMed

    Xue, Hongxia; Gan, Fang; Zhang, Zheqian; Hu, Junfa; Chen, Xingxiang; Huang, Kehe

    2015-11-01

    Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated disease (PCVAD). Astragalus polysaccharide (APS), as one kind of biological macromolecule extracted from Astragalus, has antiviral activities. This study was undertaken to explore the effect of APS on PCV2 replication in vitro and the underlying mechanisms. Our results showed that adding APS before PCV2 infection decreased significantly PCV2 DNA copies, the number of infected cells, MDA level, ROS level and NF-κB activation in PK15 cells and increased significantly GSH contents and SOD activity compared to control without APS. Oxidative stress induced by BSO could eliminate the effect of PCV2 replication inhibition by APS. LPS, as a NF-κB activator, could attenuate the effect of PCV2 replication inhibition by APS. BAY 11-7082, as a NF-κB inhibitor, could increase the effect of PCV2 replication inhibition by APS. In conclusion, APS inhibits PCV2 replication by decreasing oxidative stress and the activation of NF-κB signaling pathway, which suggests that APS might be employed for the prevention of PCV2 infection. PMID:26226456

  20. Astragalus polysaccharides inhibits PCV2 replication by inhibiting oxidative stress and blocking NF-κB pathway.

    PubMed

    Xue, Hongxia; Gan, Fang; Zhang, Zheqian; Hu, Junfa; Chen, Xingxiang; Huang, Kehe

    2015-11-01

    Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated disease (PCVAD). Astragalus polysaccharide (APS), as one kind of biological macromolecule extracted from Astragalus, has antiviral activities. This study was undertaken to explore the effect of APS on PCV2 replication in vitro and the underlying mechanisms. Our results showed that adding APS before PCV2 infection decreased significantly PCV2 DNA copies, the number of infected cells, MDA level, ROS level and NF-κB activation in PK15 cells and increased significantly GSH contents and SOD activity compared to control without APS. Oxidative stress induced by BSO could eliminate the effect of PCV2 replication inhibition by APS. LPS, as a NF-κB activator, could attenuate the effect of PCV2 replication inhibition by APS. BAY 11-7082, as a NF-κB inhibitor, could increase the effect of PCV2 replication inhibition by APS. In conclusion, APS inhibits PCV2 replication by decreasing oxidative stress and the activation of NF-κB signaling pathway, which suggests that APS might be employed for the prevention of PCV2 infection.

  1. 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

  2. Tyrosine-sulfated V2 peptides inhibit HIV-1 infection via coreceptor mimicry.

    PubMed

    Cimbro, Raffaello; Peterson, Francis C; Liu, Qingbo; Guzzo, Christina; Zhang, Peng; Miao, Huiyi; Van Ryk, Donald; Ambroggio, Xavier; Hurt, Darrell E; De Gioia, Luca; Volkman, Brian F; Dolan, Michael A; Lusso, Paolo

    2016-08-01

    Tyrosine sulfation is a post-translational modification that facilitates protein-protein interaction. Two sulfated tyrosines (Tys173 and Tys177) were recently identified within the second variable (V2) loop of the major HIV-1 envelope glycoprotein, gp120, and shown to contribute to stabilizing the intramolecular interaction between V2 and the third variable (V3) loop. Here, we report that tyrosine-sulfated peptides derived from V2 act as structural and functional mimics of the CCR5 N-terminus and potently block HIV-1 infection. Nuclear magnetic and surface plasmon resonance analyses indicate that a tyrosine-sulfated V2 peptide (pV2α-Tys) adopts a CCR5-like helical conformation and directly interacts with gp120 in a CD4-dependent fashion, competing with a CCR5 N-terminal peptide. Sulfated V2 mimics, but not their non-sulfated counterparts, inhibit HIV-1 entry and fusion by preventing coreceptor utilization, with the highly conserved C-terminal sulfotyrosine, Tys177, playing a dominant role. Unlike CCR5 N-terminal peptides, V2 mimics inhibit a broad range of HIV-1 strains irrespective of their coreceptor tropism, highlighting the overall structural conservation of the coreceptor-binding site in gp120. These results document the use of receptor mimicry by a retrovirus to occlude a key neutralization target site and provide leads for the design of therapeutic strategies against HIV-1. PMID:27389109

  3. Inhibition of inflammatory injure by polysaccharides from Bupleurum chinense through antagonizing P-selectin.

    PubMed

    Tong, Haibin; Tian, Dan; Li, Tianbao; Wang, Bo; Jiang, Guiquan; Sun, Xin

    2014-05-25

    P-selectin-mediated adhesion between endothelium and neutrophils is a crucial process leading to acute inflammatory injure. Thus, P-selectin has been considered as promising target for therapeutics of acute inflammatory-related diseases. In the present study, the water-soluble polysaccharides (BCPs) were isolated from Bupleurum chinense, and we evaluated their therapeutical effects on acute inflammatory injure and antagonistic function against P-selectin-mediated neutrophil adhesion. Our results showed that BCPs significantly impaired the leukocyte infiltration and relieve lung injury in LPS-induced acute pneumonia model. BCPs significantly blocked the binding of P-selectin to neutrophils and inhibited P-selectin-mediated neutrophils rolling along CHO-P cell monolayer. The result from in vitro protein binding assay showed a direct evidence indicating that BCPs-treatment significantly eliminated the interaction between rhP-Fc and its physiological ligand PSGL-1 at protein level. Together, these results provide a novel therapeutical strategy for amelioration of inflammation-related disease processes by polysaccharides from B. chinense.

  4. Polysaccharide isolated from Angelica sinensis inhibits hepcidin expression in rats with iron deficiency anemia.

    PubMed

    Liu, Jin-Yu; Zhang, Yu; You, Ru-Xu; Zeng, Fang; Guo, Dan; Wang, Kai-Ping

    2012-10-01

    A novel polysaccharide named Angelica sinensis polysaccharide (ASP) was obtained from the powdered and defatted roots of A. sinensis (Oliv.) Diels. The molecular weight of ASP was determined to be 78 kDa and was 95.0% sugars consisting of mostly arabinose, glucose, and galactose with a molar ratio of 1:5.68:3.91. A previous study indicated that ASP may increase plasma iron levels by suppressing the expression of hepcidin, a negative regulator of body iron metabolism, in the liver. The present study aims to clarify the inhibitory effect of ASP on hepcidin expression in rat models of iron deficiency anemia (IDA), and clarify the mechanisms involved. It was demonstrated that ASP significantly reduced hepcidin expression by inhibiting the expression of mothers against decapentaplegic protein 4 (SMAD4) in liver and stimulating the secretion of erythropoietin, which further downregulated hepcidin by repressing CCAAT/enhancer-binding protein α (C/EBPα) and the phosphorylation of signal transducer and activator of transcription 3/5. The results indicate that ASP can suppress the expression of hepcidin in rats with IDA, and may be useful for the treatment of IDA.

  5. Heparin cofactor II is degraded by heparan sulfate and dextran sulfate.

    PubMed

    Saito, Akio

    2015-02-20

    Heparan sulfate normally binds to heparin cofactor II and modulates the coagulation pathway by inhibiting thrombin. However, when human heparin cofactor II was incubated with heparan sulfate, heparin cofactor II became degraded. Other glycosaminoglycans were tested, including hyaluronic acid, chondroitin sulfates, dermatan sulfate, and heparin, but only dextran sulfate also degraded heparin cofactor II. Pretreatment of heparan sulfate with heparinase reduced its heparin cofactor II-degrading activity. Heparan sulfate and dextran sulfate diminished the thrombin inhibitory activity of heparin cofactor II. Other serpins, including antithrombin III and pigment epithelium-derived factor, were also degraded by heparan sulfate. This is the first evidence of acidic polysaccharides exhibiting protein-degrading activity without the aid of other proteins.

  6. Specific inhibition of in vitro Candida-induced lymphocyte proliferation by polysaccharidic antigens present in the serum of patients with chronic mucocutaneous candidiasis.

    PubMed Central

    Fischer, A; Ballet, J J; Griscelli, C

    1978-01-01

    A specific inhibitory activity of in vitro proliferative responses of normal human lymphocytes to Candida metabolic antigen was found in the serum of 6 out of 23 children with chronic mucocutaneous candidiasis. In each of the six patients, the presence of an inhibitory activity was associated with Candida-specific cellular defects, characterized by a negative-skin test and a lack of in vitro lymphocyte proliferation. The presence of a circulating inhibitor was detected during relapses of the disease and disappeared under antifungal therapy. This inhibitory effect was not associated with any toxicity on tested lymphocytes. The factor was shown to be nondialysable, thermostable, nonprecipitable with ammonium sulfate and absorbable on anti-Candida antibodies or concanavalin A-coupled agarose columns. Altogether, these results suggest that the inhibitory factor is not an immunoglobulin, but rather a polysaccharidic antigen of Candida albicans. An inhibition of Candida-induced proliferative response of normal human lymphocytes was also obtained by addition of polysacharide antigens or purified mannans from C. albicans to cultures. Candida polysaccharidic antigens appeared, therefore, to be involved in specific depression of cellular functions observed in chronic candidiasis. PMID:361754

  7. 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. PMID:26901075

  8. Safflower polysaccharide inhibits the proliferation and metastasis of MCF-7 breast cancer cell.

    PubMed

    Luo, Zhongbing; Zeng, Hongxie; Ye, Yongqiang; Liu, Lianbin; Li, Shaojin; Zhang, Junyi; Luo, Rongcheng

    2015-06-01

    Breast cancer accounts for 22.9% of all types of cancer in females worldwide. Safflower polysaccharide (SPS) is an active fraction purified from safflower petals (Carthamus tinctorius L). The present study investigated the effects of safflower polysaccharide on the proliferation and metastasis of breast cancer cells. Cell viability was analyzed using an MTT assay following treatment of the MCF‑7 cells with increasing concentrations of SPS. The results demonstrated that the SPS compound significantly inhibited the proliferation of the MCF‑7 human breast cancer cell line and these inhibitory effects increased in a dose‑ and time‑dependent manner. The half maximal inhibitory concentration (IC50) value of SPS on breast cancer cells, following treatment for 72 h, was detected using an MTT assay and was calculated as 0.12 mg/ml. The apoptotic rate was detected using flow cytometry in the MCF‑7 human breast cancer cell line and the results revealed that SPS induced cell apoptosis. The apoptotic rate of the MCF‑7 cells treated with SPS was significantly higher compared with that of the untreated cells and increased in a dose‑dependent manner. The expression of B‑cell lymphoma 2 (Bcl‑2) was downregulated and the expression of Bcl‑2‑associated X protein was upregulated in the MCF‑7 cells treated with SPS in a time‑dependent manner. Additionally, the expression of matrix metalloproteinase‑9 was significantly reduced and the expression of tissue inhibitor of metalloproteinase‑1 was increased in the MCF‑7 human breast cancer cell treated with SPS. These results demonstrated that SPS inhibited the metastasis of MCF‑7 breast cancer cells and understanding the underlying mechanisms may provide novel strategies in breast cancer therapy.

  9. 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...

  10. 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...

  11. Magnesium sulfate inhibits sufentanil-induced cough during anesthetic induction.

    PubMed

    An, Li-Jun; Gui, Bo; Su, Zhen; Zhang, Yang; Liu, Hai-Lin

    2015-01-01

    Sufentanil-induced cough is a common phenomenon during the induction of anesthesia. This double-blind, randomized, and placebo-controlled study was designed to investigate the effects of prophylactic magnesium sulfate (MgSO4) on the incidence and severity of sufentanil-induced cough. A total of 165 patients who were scheduled for elective surgery under general anesthesia were allocated into three groups (I, II, and III; n = 55 each) that were injected with either 50 ml of normal saline, 30 or 50 mg/kg of MgSO4 (diluted with normal saline into 50 ml). One minute following the injection, all patients were injected with 1.0 μg/kg of sufentanil within 5 s. The incidence and severity of cough were recorded 30 s after the sufentanil injection. The hemodynamic parameters and plasma magnesium concentration of the patients were also noted. Three patients dropped out the study due to an obvious burning sensation during the injection of 50 mg/kg of MgSO4. Although the injection of 50 mg/kg of MgSO4 increased the plasma magnesium level, the increase remained within the therapeutic range (2-4 mmol/L). The incidence of cough was much higher in group I than in groups II and III (47.1% vs. 16.4% and 7.6%, respectively, P < 0.05). Compared with group I, group III had the lowest incidence of mild cough and both groups II and III had lower incidence of moderate and severe cough (P < 0.05). There were no differences in the hemodynamic data at three timepoints among the three groups. In conclusion, sufentanil-induced cough may be suppressed effectively and safely by prophylactic use of 30 mg/kg of MgSO4 during anesthetic induction.

  12. Magnesium sulfate inhibits sufentanil-induced cough during anesthetic induction

    PubMed Central

    An, Li-Jun; Gui, Bo; Su, Zhen; Zhang, Yang; Liu, Hai-Lin

    2015-01-01

    Sufentanil-induced cough is a common phenomenon during the induction of anesthesia. This double-blind, randomized, and placebo-controlled study was designed to investigate the effects of prophylactic magnesium sulfate (MgSO4) on the incidence and severity of sufentanil-induced cough. A total of 165 patients who were scheduled for elective surgery under general anesthesia were allocated into three groups (I, II, and III; n = 55 each) that were injected with either 50 ml of normal saline, 30 or 50 mg/kg of MgSO4 (diluted with normal saline into 50 ml). One minute following the injection, all patients were injected with 1.0 μg/kg of sufentanil within 5 s. The incidence and severity of cough were recorded 30 s after the sufentanil injection. The hemodynamic parameters and plasma magnesium concentration of the patients were also noted. Three patients dropped out the study due to an obvious burning sensation during the injection of 50 mg/kg of MgSO4. Although the injection of 50 mg/kg of MgSO4 increased the plasma magnesium level, the increase remained within the therapeutic range (2-4 mmol/L). The incidence of cough was much higher in group I than in groups II and III (47.1% vs. 16.4% and 7.6%, respectively, P < 0.05). Compared with group I, group III had the lowest incidence of mild cough and both groups II and III had lower incidence of moderate and severe cough (P < 0.05). There were no differences in the hemodynamic data at three timepoints among the three groups. In conclusion, sufentanil-induced cough may be suppressed effectively and safely by prophylactic use of 30 mg/kg of MgSO4 during anesthetic induction. PMID:26550339

  13. Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen

    PubMed Central

    Zhao, Yanli; Harmatz, Jerold S; Epstein, Carol R; Nakagawa, Yukako; Kurosaki, Chie; Nakamura, Tetsuro; Kadota, Takumi; Giesing, Dennis; Court, Michael H; Greenblatt, David J

    2015-01-01

    Aims The antiviral agent favipiravir is likely to be co-prescribed with acetaminophen (paracetamol). The present study evaluated the possiblility of a pharmacokinetic interaction between favipiravir and acetaminophen, in vitro and in vivo. Methods The effect of favipivir on the transformation of acetaminophen to its glucuronide and sulfate metabolites was studied using a pooled human hepatic S9 fraction in vitro. The effect of acute and extended adminstration of favipiravir on the pharmacokinetics of acetaminophen and metabolites was evaluated in human volunteers. Results Favipiravir inhibited the in vitro formation of acetaminophen sulfate, but not acetaminophen glucuronide. In human volunteers, both acute (1 day) and extended (6 days) administration of favipiravir slightly but significantly increased (by about 20 %) systemic exposure to acetaminophen (total AUC), whereas Cmax was not significantly changed. AUC for acetaminophen glucuronide was increased by 23 to 35 % above control by favipiravir, while AUC for acetaminophen sulfate was reduced by about 20 % compared to control. Urinary excretion of acetaminophen sulfate was likewise reduced to 44 to 65 % of control values during favipiravir co-administration, while excretion of acetaminophen glucuronide increased to 17 to 32 % above control. Conclusion Favipiravir inhibits acetaminophen sulfate formation in vitro and in vivo. However the increase in systemic exposure to acetaminophen due to favipiravir co-administration, though statistically significant, is small in magnitude and unlikely to be of clinical importance. PMID:25808818

  14. 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.

  15. 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.

  16. Important Determinants for Fucoidan Bioactivity: A Critical Review of Structure-Function Relations and Extraction Methods for Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds

    PubMed Central

    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. PMID:22073012

  17. Presence of sulfate does not inhibit low-temperature dolomite precipitation

    NASA Astrophysics Data System (ADS)

    Sánchez-Román, Mónica; McKenzie, Judith A.; de Luca Rebello Wagener, Angela; Rivadeneyra, Maria A.; Vasconcelos, Crisógono

    2009-07-01

    The hypothesis that sulfate inhibits dolomite formation evolved from geochemical studies of porewaters from deep-sea sedimentary sequences and has been tested with hydrothermal experiments. We examined the sulfate inhibition factor using aerobic culture experiments with Virgibacillus marismortui and Halomonas meridiana, two moderately halophilic aerobic bacteria, which metabolize independent of sulfate concentration. The culture experiments were conducted at 25 and 35 °C using variable SO 42- concentrations (0, 14, 28 and 56 mM) and demonstrate that halophilic aerobic bacteria mediate direct precipitation of dolomite with or without SO 42- in the culture media which simulate dolomite occurrences commonly found under the Earth's surface conditions. Hence, we report that the presence of sulfate does not inhibit dolomite precipitation. Further, we hypothesize that, if sedimentary dolomite is a direct precipitate, as in our low-temperature culture experiments, the kinetic factors involved are likely to be quite different from those governing a dolomite replacement reaction, such as in hydrothermal experiments. Consequently, the occurrence and, presumably, growth of dolomite in SO 42--rich aerobic cultures may shed new light on the long-standing Dolomite Problem.

  18. Astragalus mongholicus polysaccharide inhibits lipopolysaccharide-induced production of TNF-α and interleukin-8

    PubMed Central

    Yuan, Yuan; Sun, Mei; Li, Ke-Shen

    2009-01-01

    AIM: To explore the effect of Astragalus mongholicus polysaccharide (APS) on gene expression and mitogen-activated protein kinase (MAPK) transcriptional activity in intestinal epithelial cells (IEC). METHODS: IEC were divided into control group, lipopolysaccharide (LPS) group, LPS+ 50 μg/mL APS group, LPS+ 100 μg/mL APS group, LPS+ 200 μg/mL APS group, and LPS+ 500 μg/mL APS group. Levels of mRNAs in LPS-induced inflammatory factors, tumor necrosis factor (TNF)-α and interleukin (IL)-8, were measured by reverse transcription-polymerase chain reaction. MAPK protein level was measured by Western blotting. RESULTS: The levels of TNF-α and IL-8 mRNAs were significantly higher in IEC with LPS-induced damage than in control cells. APS significantly abrogated the LPS-induced expression of the TNF-α and IL-8 genes. APS did not block the activation of extracellular signal-regulated kinase or c Jun amino-terminal kinase, but inhibited the activation of p38, suggesting that APS inhibits LPS-induced production of TNF-α and IL-8 mRNAs, possibly by suppressing the p38 signaling pathway. CONCLUSION: APS-modulated bacterial product-mediated p38 signaling represents an attractive strategy for prevention and treatment of intestinal inflammation. PMID:19653348

  19. Inhibition of sulfate reducing bacteria in aquifer sediment by iron nanoparticles.

    PubMed

    Kumar, Naresh; Omoregie, Enoma O; Rose, Jerome; Masion, Armand; Lloyd, Jonathan R; Diels, Ludo; Bastiaens, Leen

    2014-03-15

    Batch microcosms were setup to determine the impact of different sized zero valent iron (Fe(0)) particles on microbial sulfate reduction during the in situ bio-precipitation of metals. The microcosms were constructed with aquifer sediment and groundwater from a low pH (3.1), heavy-metal contaminated aquifer. Nano (nFe(0)), micro (mFe(0)) and granular (gFe(0)) sized Fe(0) particles were added to separate microcosms. Additionally, selected microcosms were also amended with glycerol as a C-source for sulfate-reducing bacteria. In addition to metal removal, Fe(0) in microcosms also raised the pH from 3.1 to 6.5, and decreased the oxidation redox potential from initial values of 249 to -226 mV, providing more favorable conditions for microbial sulfate reduction. mFe(0) and gFe(0) in combination with glycerol were found to enhance microbial sulfate reduction. However, no sulfate reduction occurred in the controls without Fe(0) or in the microcosm amended with nFe(0). A separate dose test confirmed the inhibition for sulfate reduction in presence of nFe(0). Hydrogen produced by Fe(0) was not capable of supporting microbial sulfate reduction as a lone electron donor in this study. Microbial analysis revealed that the addition of Fe(0) and glycerol shifted the microbial community towards Desulfosporosinus sp. from a population initially dominated by low pH and metal-resisting Acidithiobacillus ferrooxidans.

  20. Monitoring and Modeling Microbial Sulfate Reduction and Inhibition in a Mesoscale Tank Experiment

    NASA Astrophysics Data System (ADS)

    Hubbard, C. G.; Wu, Y.; Li, L.; Piceno, Y. M.; Cheng, Y.; Bill, M.; Coates, J. D.; Andersen, G. L.; Conrad, M. E.; Ajo Franklin, J. B.

    2014-12-01

    Subsurface biogeochemical cycling at the field-scale is controlled by a complex interplay between hydrological, geochemical and biological parameters. Mesoscale tank experiments can help to bridge the gap in complexity and understanding between well constrained batch and column experiments, and the interpretation of field data. In this contribution we present the results of a tank experiment investigating microbial sulfate reduction and inhibition in a porous media (20-30 mesh Ottawa sand). Microbial sulfate reduction is a process of wide biogeochemical significance, including in the context of oil reservoirs where the generation of sulfide can result in corrosion of steel infrastructure and additional downstream processing. Inhibition of sulfate reduction is therefore a high priority for this industry. Tracer experiments were conducted at the start and end of the experiment to constrain flow pathways and heterogeneities. The tank was inoculated with a San Francisco Bay mud/water enrichment utilizing acetate as the electron donor and continuous flow was initiated using bay-water with 10 mM acetate. Samples were taken from an array of 12 steel boreholes and showed spatiotemporal heterogeneities in the development of sulfidogenesis, reaching a peak of ~5 mM dissolved sulfide 71 days after inoculation. 10 mM perchlorate was then added to the influent to inhibit sulfidogenesis and dissolved sulfide decreased to ~0.03 mM by day 95. Stable isotope analysis of dissolved sulfate showed an increase in δ34S by ~10‰ compared with influent values but δ34S did not return to influent values by day 95, which may be indicative of the mixing between new and residual sulfate in the tank. Ongoing microbial community analyses are being used to help constrain microbial metabolisms. Finally, all the data is being integrated into a reactive transport model to better constrain the observed interplay between hydrology, geochemistry and biology.

  1. 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.

  2. Biphasic role of chondroitin sulfate in cardiac differentiation of embryonic stem cells through inhibition of Wnt/β-catenin signaling.

    PubMed

    Prinz, Robert D; Willis, Catherine M; van Kuppevelt, Toin H; Klüppel, Michael

    2014-01-01

    The glycosaminoglycan chondroitin sulfate is a critical component of proteoglycans on the cell surface and in the extracellular matrix. As such, chondroitin sulfate side chains and the sulfation balance of chondroitin play important roles in the control of signaling pathways, and have a functional importance in human disease. In contrast, very little is known about the roles of chondroitin sulfate molecules and sulfation patterns during mammalian development and cell lineage specification. Here, we report a novel biphasic role of chondroitin sulfate in the specification of the cardiac cell lineage during embryonic stem cell differentiation through modulation of Wnt/beta-catenin signaling. Lineage marker analysis demonstrates that enzymatic elimination of endogenous chondroitin sulfates leads to defects specifically in cardiac differentiation. This is accompanied by a reduction in the number of beating cardiac foci. Mechanistically, we show that endogenous chondroitin sulfate controls cardiac differentiation in a temporal biphasic manner through inhibition of the Wnt/beta-catenin pathway, a known regulatory pathway for the cardiac lineage. Treatment with a specific exogenous chondroitin sulfate, CS-E, could mimic these biphasic effects on cardiac differentiation and Wnt/beta-catenin signaling. These results establish chondroitin sulfate and its sulfation balance as important regulators of cardiac cell lineage decisions through control of the Wnt/beta-catenin pathway. Our work suggests that targeting the chondroitin biosynthesis and sulfation machinery is a novel promising avenue in regenerative strategies after heart injury.

  3. A Small Molecule Inhibits Virion Attachment to Heparan Sulfate- or Sialic Acid-Containing Glycans

    PubMed Central

    Colpitts, Che C.

    2014-01-01

    ABSTRACT Primary attachment to cellular glycans is a critical entry step for most human viruses. Some viruses, such as herpes simplex virus type 1 (HSV-1) and hepatitis C virus (HCV), bind to heparan sulfate, whereas others, such as influenza A virus (IAV), bind to sialic acid. Receptor mimetics that interfere with these interactions are active against viruses that bind to either heparan sulfate or to sialic acid. However, no molecule that inhibits the attachment of viruses in both groups has yet been identified. Epigallocatechin gallate (EGCG), a green tea catechin, is active against many unrelated viruses, including several that bind to heparan sulfate or to sialic acid. We sought to identify the basis for the broad-spectrum activity of EGCG. Here, we show that EGCG inhibits the infectivity of a diverse group of enveloped and nonenveloped human viruses. EGCG acts directly on the virions, without affecting the fluidity or integrity of the virion envelopes. Instead, EGCG interacts with virion surface proteins to inhibit the attachment of HSV-1, HCV, IAV, vaccinia virus, adenovirus, reovirus, and vesicular stomatitis virus (VSV) virions. We further show that EGCG competes with heparan sulfate for binding of HSV-1 and HCV virions and with sialic acid for binding of IAV virions. Therefore, EGCG inhibits unrelated viruses by a common mechanism. Most importantly, we have identified EGCG as the first broad-spectrum attachment inhibitor. Our results open the possibility for the development of small molecule broad-spectrum antivirals targeting virion attachment. IMPORTANCE This study shows that it is possible to develop a small molecule antiviral or microbicide active against the two largest groups of human viruses: those that bind to glycosaminoglycans and those that bind to sialoglycans. This group includes the vast majority of human viruses, including herpes simplex viruses, cytomegalovirus, influenza virus, poxvirus, hepatitis C virus, HIV, and many others. PMID

  4. 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

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

    PubMed

    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

  6. Safflower polysaccharide induces NSCLC cell apoptosis by inhibition of the Akt pathway.

    PubMed

    Li, Jian-Ying; Yu, Jun; Du, Xu-Sheng; Zhang, Hui-Min; Wang, Bo; Guo, Hua; Bai, Jie; Wang, Juan-Hong; Liu, An; Wang, Yi-Li

    2016-07-01

    Lung cancer is the leading cause of cancer death in the world. Safflower polysaccharide (SPS) has been used for the improvement of immunomodulatory activities and treatment of cancers. However, studies on the effect of SPS on the progression of lung cancer have rarely been reported. To study the antitumor effect of SPS on human lung cancer and its potential mechanism, non-small cell lung cancer cell lines (NSCLC), A549 and YTMLC-90 were treated with SPS at various concentrations ranging from 0.04 to 2.56 mg/ml and BALB/c nude tumor-bearing mice were injected intraperitoneally with SPS at concentrations ranging from 15 to 135 mg/kg. Results showed that SPS suppressed the proliferation of A549 and YTMLC-90 cells and induced apoptosis by increasing mRNA levels of bax and caspase-3, and inhibited tumor growth in vivo. SPS induced cell cycle arrest in the G2/M phase by decreasing the expression of cdc25B and cyclin B1. Moreover, SPS decreased the expression of Akt, p-Akt and PI3K. In mice, SPS injection enhanced immunomodulatory activities by increasing levels of TNF-α and IL-6 in tumor-bearing mice. Our findings suggest that SPS suppresses tumor growth by enhancing immunomodulatory activities and blocking the PI3K/Akt pathway. This study provides new insight into the anticancer mechanism of SPS. PMID:27177149

  7. EGFR Activation Mediates Inhibition of Axon Regeneration by Myelin and Chondroitin Sulfate Proteoglycans

    NASA Astrophysics Data System (ADS)

    Koprivica, Vuk; Cho, Kin-Sang; Park, Jong Bae; Yiu, Glenn; Atwal, Jasvinder; Gore, Bryan; Kim, Jieun A.; Lin, Estelle; Tessier-Lavigne, Marc; Chen, Dong Feng; He, Zhigang

    2005-10-01

    Inhibitory molecules associated with myelin and the glial scar limit axon regeneration in the adult central nervous system (CNS), but the underlying signaling mechanisms of regeneration inhibition are not fully understood. Here, we show that suppressing the kinase function of the epidermal growth factor receptor (EGFR) blocks the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth. In addition, regeneration inhibitors trigger the phosphorylation of EGFR in a calcium-dependent manner. Local administration of EGFR inhibitors promotes significant regeneration of injured optic nerve fibers, pointing to a promising therapeutic avenue for enhancing axon regeneration after CNS injury.

  8. 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.

  9. 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.

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

    PubMed

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

    2015-09-24

    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.

  11. [Inhibition of chlorobenzene formation via various routes during waste incineration by ammonium sulfate and urea].

    PubMed

    Yan, Mi; Qi, Zhi-Fu; Li, Xiao-Dong; Hu, Yan-Jun; Chen, Tong

    2014-01-01

    Chlorobenzene (CBz) is the precursor of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) generated in the processes of waste incineration, and it is regarded as a good indicator of PCDD/Fs for realizing PCDD/Fs online monitoring, moreover, pentachlorobenzene (PeCBz) and Hexachlorobenzene (HxCBz) belong to Persistent Organic Pollutants (POPs). However, the emission control of CBz in waste incineration does not attract enough attention, so this study focused on the inhibition of the 3 CBz formation routes in waste combustion by ammonium sulfate and urea, including CB formation from fly ash, CB formation from 1,2-dichlorobenzene (1,2-DiCBz) and the combustion of model medical waste. The results showed that both ammonium sulfate and urea reduced CBz yield during these three thermal processes. For instance, the inhibition rates of tetrachlorobenzene (TeCBz), PeCBz and HxCBz were 66.8%, 57.4% and 50.4%, respectively, when 1% urea was co-combusted with medical waste. By comparing the effect of ammonium sulfate and urea on CBz formation by three routes, urea was considered as a comparatively stable inhibitor for CBz.

  12. 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. PMID:18712535

  13. 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.

  14. Inhibition of cytochrome P450 isozymes and ornithine decarboxylase activities by polysaccharides from soybeans fermented with Phellinus igniarius or Agrocybe cylindracea.

    PubMed

    Shon, Yun-Hee; Nam, Kyung-Soo

    2004-01-01

    Polysaccharides (5, 10, 25, 50 and 100 microg ml(-1)) from soybeans and soybeans fermented with Phellinus igniarius or Agrocybe cylindracea inhibited cytochrome P450 1A1, cytochrome P450 1A2 and cytochrome P450 2B1 activities in rat liver microsomes. The polysaccharides (5, 10 and 25 microg ml(-1)) also suppressed 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity. The most potent inhibitors of cytochrome P450 isozymes and ornithine decarboxylase activities were the polysaccharides from soybeans fermented with Agrocybe cylindracea. PMID:15000485

  15. Structural characterization and inhibition on α-d-glucosidase activity of non-starch polysaccharides from Fagopyrum tartaricum.

    PubMed

    Wang, Xiao-Ting; Zhu, Zhen-Yuan; Zhao, Liang; Sun, Hui-Qing; Meng, Meng; Zhang, Jin-Yu; Zhang, Yong-Min

    2016-11-20

    In the present study, the crude polysaccharide was extracted from Fagopyrum tartaricum and purified by Sephadex G-25 and G-75 column to produce a polysaccharide fraction termed TBP-II. Its average molecular weight was 26kDa. The structural characterization of TBP-II was investigated by gas chromatography, periodate oxidation-Smith degradation, Methylation and NMR. Congo red was applied to explore its advanced structures. The results revealed that chemical composition and structural characteristic of TBP-II was mainly consisted of galactose, arabinose, xylose and glucose with a molar ratio of 0.7:1:6.3:74.2. The backbone of TBP-II was composed of (1→4)-linked α-d-glucopyranosyl (Glcp), while the branches comprised of (1→3)-linked α-d-glucopyranosyl (Glcp), (1→6)-linked α-d-galactopyranosyl (Galp) and (1→2,4)-linked α-d-rhamnopyranosyl (Rhap). The structure of TBP-II was 1,3 and 1,6-branched-galactorhamnoglucan that had a linear backbone of (1→4)-linked α-d-glucopyranose (Glcp). Using Congo red assay showed that it was absent of triple helix structure. The α-d-glucosidase inhibitory activity of TBP-II was determined using acarbose as positive control. The result showed that the inhibition rate depended on the concentration of polysaccharides. PMID:27561539

  16. The Antitumor Effect of Gekko Sulfated Glycopeptide by Inhibiting bFGF-Induced Lymphangiogenesis

    PubMed Central

    Ding, Xiu-Li; Man, Ya-Nan; Hao, Jian; Zhu, Cui-Hong; Liu, Chang; Yang, Xue

    2016-01-01

    Objective. To study the antilymphangiogenesis effect of Gekko Sulfated Glycopeptide (GSPP) on human lymphatic endothelial cells (hLECs). Methods. MTS was conducted to confirm the antiproliferation effect of GSPP on hLECs; flow cytometry was employed to detect hLECs cycle distribution; the antimigration effect of GSPP on hLECs was investigated by wound healing experiment and transwell experiment; tube formation assay was used to examine its inhibitory effect on the lymphangiogenesis; western blotting was conducted to detect the expression of extracellular signal-regulated kinase1/2 (Erk1/2) and p-Erk1/2 after GSPP and basic fibroblast growth factor (bFGF) treatment. Nude mice models were established to investigate the antitumor effect of GSPP in vivo. Decreased lymphangiogenesis caused by GSPP in vivo was verified by immunohistochemical staining. Results. In vitro, GSPP (10 μg/mL, 100 μg/mL) significantly inhibited bFGF-induced hLECs proliferation, migration, and tube-like structure formation (P < 0.05) and antagonized the phosphorylation activation of Erk1/2 induced by bFGF. In vivo, GSPP treatment (200 mg/kg/d) not only inhibited the growth of colon carcinoma, but also inhibited the tumor lymphangiogenesis. Conclusion. GSPP possesses the antitumor ability by inhibiting bFGF-inducing lymphangiogenesis in vitro and in vivo, which may further inhibit tumor lymphatic metastasis. PMID:27190997

  17. The Antitumor Effect of Gekko Sulfated Glycopeptide by Inhibiting bFGF-Induced Lymphangiogenesis.

    PubMed

    Ding, Xiu-Li; Man, Ya-Nan; Hao, Jian; Zhu, Cui-Hong; Liu, Chang; Yang, Xue; Wu, Xiong-Zhi

    2016-01-01

    Objective. To study the antilymphangiogenesis effect of Gekko Sulfated Glycopeptide (GSPP) on human lymphatic endothelial cells (hLECs). Methods. MTS was conducted to confirm the antiproliferation effect of GSPP on hLECs; flow cytometry was employed to detect hLECs cycle distribution; the antimigration effect of GSPP on hLECs was investigated by wound healing experiment and transwell experiment; tube formation assay was used to examine its inhibitory effect on the lymphangiogenesis; western blotting was conducted to detect the expression of extracellular signal-regulated kinase1/2 (Erk1/2) and p-Erk1/2 after GSPP and basic fibroblast growth factor (bFGF) treatment. Nude mice models were established to investigate the antitumor effect of GSPP in vivo. Decreased lymphangiogenesis caused by GSPP in vivo was verified by immunohistochemical staining. Results. In vitro, GSPP (10 μg/mL, 100 μg/mL) significantly inhibited bFGF-induced hLECs proliferation, migration, and tube-like structure formation (P < 0.05) and antagonized the phosphorylation activation of Erk1/2 induced by bFGF. In vivo, GSPP treatment (200 mg/kg/d) not only inhibited the growth of colon carcinoma, but also inhibited the tumor lymphangiogenesis. Conclusion. GSPP possesses the antitumor ability by inhibiting bFGF-inducing lymphangiogenesis in vitro and in vivo, which may further inhibit tumor lymphatic metastasis. PMID:27190997

  18. A polysaccharide from Streptococcus sanguis 34 that inhibits coaggregation of S. sanguis 34 with Actinomyces viscosus T14V.

    PubMed Central

    McIntire, F C; Crosby, L K; Vatter, A E; Cisar, J O; McNeil, M R; Bush, C A; Tjoa, S S; Fennessey, P V

    1988-01-01

    Coaggregation between Actinomyces viscosus T14V and Streptococcus sanguis 34 depends on interaction of a lectin on A. viscosus T14V with a cell surface carbohydrate on S. sanguis 34. This carbohydrate was isolated, and its chemical makeup was established. The carbohydrate remained attached to S. sanguis 34 cells through extraction with Triton X-100 and treatment with pronase. It was cleaved from the cell residue by autoclaving and purified by differential centrifugation and column chromatography on DEAE-Sephacel and Sephadex G-75. The polysaccharide contained phosphate which was neither inorganic nor monoester. Treatment with NaOH-NaBH4, followed by Escherichia coli alkaline phosphatase, or with 48% HF at 4 degrees C, followed by NaBH4, yielded inorganic phosphate and oligosaccharide alditols. Therefore, the polysaccharide is composed of oligosaccharide units joined together by phosphodiester bridges. The structure and stereochemistry of the main oligosaccharide alditol was established previously (F. C. McIntire, C. A. Bush, S.-S. Wu, S.-C. Li, Y.-T. Li, M. McNeil, S. Tjoa, and P. V. Fennessey, Carbohydr. Res. 166:133-143). Permethylation analysis, 1H and 31P nuclear magnetic resonance studies on the whole polysaccharide revealed the position of the phosphodiester linkages. The polysaccharide is mainly a polymer of (6) GalNAc(alpha 1-3)Rha(beta 1-4)Glc(beta 1-6)Galf(beta 1-6)GalNAc(beta 1- 3)Gal(alpha 1)-OPO3. It reacted as a single antigen with antiserum to S. sanguis 34 cells and was a potent inhibitor of coaggregation between A. viscosus T14V and S. sanguis 34. Quantitative inhibition of precipitation assays with oligosaccharides, O-allyl N-acetylgalactosaminides, and simple sugars indicated that specific antibodies were directed to the GalNAc end of the hexasaccharide unit. In contrast, coaggregation was inhibited much more effectively by saccharides containing betaGalNAc. Thus, the specificity of the A. viscosus T14V lectin is strikingly different from that of

  19. 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.

  20. A novel sulfate-reducing bacteria detection method based on inhibition of cysteine protease activity.

    PubMed

    Qi, Peng; Zhang, Dun; Wan, Yi

    2014-11-01

    Sulfate-reducing bacteria (SRB) have been extensively studied in corrosion and environmental science. However, fast enumeration of SRB population is still a difficult task. This work presents a novel specific SRB detection method based on inhibition of cysteine protease activity. The hydrolytic activity of cysteine protease was inhibited by taking advantage of sulfide, the characteristic metabolic product of SRB, to attack active cysteine thiol group in cysteine protease catalytic sites. The active thiol S-sulfhydration process could be used for SRB detection, since the amount of sulfide accumulated in culture medium was highly related with initial bacterial concentration. The working conditions of cysteine protease have been optimized to obtain better detection capability, and the SRB detection performances have been evaluated in this work. The proposed SRB detection method based on inhibition of cysteine protease activity avoided the use of biological recognition elements. In addition, compared with the widely used most probable number (MPN) method which would take up to at least 15days to accomplish whole detection process, the method based on inhibition of papain activity could detect SRB in 2 days, with a detection limit of 5.21×10(2) cfu mL(-1). The detection time for SRB population quantitative analysis was greatly shortened.

  1. 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

  2. Effects of the ultra-high pressure on structure and α-glucosidase inhibition of polysaccharide from Astragalus.

    PubMed

    Zhu, Zhen-Yuan; Luo, You; Dong, Guo-Ling; Ren, Yuan-Yuan; Chen, Li-Jing; Guo, Ming-Zhu; Wang, Xiao-Ting; Yang, Xue-Ying; Zhang, Yongmin

    2016-06-01

    A novel homogeneous polysaccharide fraction (APS) was extracted from Astragalus by hot water and purified by Sephadex G-100 and G-75 column. Its molecular weight was 693kDa. APS and APS with ultra-high pressure treatment exhibited significant inhibitory abilities on a-glucosidase, inhibition rate from high to low in order was 400MPa-APS, 300MPa-APS, 500MPa-APS and APS. The inhibition ​percentage of 400MPa-APS (1.5mg/mL) was 49% (max.). This suggested that the inhibitory activity of APS on a-glucosidase was improved by ultra-high pressure treatment. FT-IR, SEM, CD spectra, atomic force microscope and Congo red test analysis of APS and 400MPa-APS showed ultra-high pressure treatment didn't change the preliminary structure but had an effect on its advanced structure. PMID:26993530

  3. Effects of the ultra-high pressure on structure and α-glucosidase inhibition of polysaccharide from Astragalus.

    PubMed

    Zhu, Zhen-Yuan; Luo, You; Dong, Guo-Ling; Ren, Yuan-Yuan; Chen, Li-Jing; Guo, Ming-Zhu; Wang, Xiao-Ting; Yang, Xue-Ying; Zhang, Yongmin

    2016-06-01

    A novel homogeneous polysaccharide fraction (APS) was extracted from Astragalus by hot water and purified by Sephadex G-100 and G-75 column. Its molecular weight was 693kDa. APS and APS with ultra-high pressure treatment exhibited significant inhibitory abilities on a-glucosidase, inhibition rate from high to low in order was 400MPa-APS, 300MPa-APS, 500MPa-APS and APS. The inhibition ​percentage of 400MPa-APS (1.5mg/mL) was 49% (max.). This suggested that the inhibitory activity of APS on a-glucosidase was improved by ultra-high pressure treatment. FT-IR, SEM, CD spectra, atomic force microscope and Congo red test analysis of APS and 400MPa-APS showed ultra-high pressure treatment didn't change the preliminary structure but had an effect on its advanced structure.

  4. 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.

  5. 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

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

    PubMed

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

    2015-06-11

    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.

  7. 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

  8. Chondroitin Sulfate-E Binds to Both Osteoactivin and Integrin αVβ3 and Inhibits Osteoclast Differentiation.

    PubMed

    Miyazaki, Tatsuya; Miyauchi, Satoshi; Anada, Takahisa; Tawada, Akira; Suzuki, Osamu

    2015-10-01

    Integrins and their ligands have been suggested to be associated with osteoclast-mediated bone resorption. The present study was designed to investigate whether chondroitin sulfate E (CS-E), which is one of the sulfated glycosaminoglycans (GAGs), is involved in osteoactivin (OA) activity, and osteoclast differentiation. The binding affinity of sulfated GAGs to integrin and its ligand was measured using biotin-labeled CS-E, and the osteoclast differentiation was evaluated by tartrate-resistant acid phosphatase staining and a pit formation assay. CS-E as well as CS-B, synthetic chondroitin polysulfate, and heparin inhibited osteoclast differentiation of bone marrow-derived macrophages. Pre-coating of OA to synthetic calcium phosphate-coated plates enhanced the osteoclastic differentiation of RAW264 cells, and addition of a neutralizing antibody to OA inhibited its differentiation. CS-E bound not only to OA, fibronectin, and vitronectin, but also to its receptor integrin αVβ3, and inhibited the direct binding of OA to integrin αVβ3. Furthermore, CS-E blocked the binding of OA to cells and inhibited OA-induced osteoclastic differentiation. On the other hand, heparinase treatment of RAW264 cells inhibited osteoclastic differentiation. Since binding of OA to the cells was inhibited by the presence of heparan sulfate or heparinase treatment of cells, heparan sulfate proteoglycan (HSPG) was also considered to be an OA receptor. Taken together, the present results suggest that CS-E is capable of inhibiting OA-induced osteoclast differentiation by blocking the interaction of OA to integrin αVβ3 and HSPG.

  9. Chondroitin Sulfate-E Binds to Both Osteoactivin and Integrin αVβ3 and Inhibits Osteoclast Differentiation.

    PubMed

    Miyazaki, Tatsuya; Miyauchi, Satoshi; Anada, Takahisa; Tawada, Akira; Suzuki, Osamu

    2015-10-01

    Integrins and their ligands have been suggested to be associated with osteoclast-mediated bone resorption. The present study was designed to investigate whether chondroitin sulfate E (CS-E), which is one of the sulfated glycosaminoglycans (GAGs), is involved in osteoactivin (OA) activity, and osteoclast differentiation. The binding affinity of sulfated GAGs to integrin and its ligand was measured using biotin-labeled CS-E, and the osteoclast differentiation was evaluated by tartrate-resistant acid phosphatase staining and a pit formation assay. CS-E as well as CS-B, synthetic chondroitin polysulfate, and heparin inhibited osteoclast differentiation of bone marrow-derived macrophages. Pre-coating of OA to synthetic calcium phosphate-coated plates enhanced the osteoclastic differentiation of RAW264 cells, and addition of a neutralizing antibody to OA inhibited its differentiation. CS-E bound not only to OA, fibronectin, and vitronectin, but also to its receptor integrin αVβ3, and inhibited the direct binding of OA to integrin αVβ3. Furthermore, CS-E blocked the binding of OA to cells and inhibited OA-induced osteoclastic differentiation. On the other hand, heparinase treatment of RAW264 cells inhibited osteoclastic differentiation. Since binding of OA to the cells was inhibited by the presence of heparan sulfate or heparinase treatment of cells, heparan sulfate proteoglycan (HSPG) was also considered to be an OA receptor. Taken together, the present results suggest that CS-E is capable of inhibiting OA-induced osteoclast differentiation by blocking the interaction of OA to integrin αVβ3 and HSPG. PMID:25820496

  10. 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.

  11. 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. PMID:25935648

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Kinetics and mechanism of permanganate oxidation of iota- and lambda-carrageenan polysaccharides as sulfated carbohydrates in acid perchlorate solutions.

    PubMed

    Hassan, Refat M; Fawzy, Ahmed; Ahmed, Gamal A; Zaafarany, Ishaq A; Asghar, Basim H; Takagi, Hideo D; Ikeda, Yasuhisa

    2011-10-18

    The kinetics of oxidation of iota- and lambda-carrageenan as sulfated carbohydrates by permanganate ion in aqueous perchlorate solutions at a constant ionic strength of 2.0 mol dm(-3) have been investigated spectrophotometrically. The pseudo-first-order plots were found to be of inverted S-shape throughout the entire courses of reactions. The initial rates were found to be relatively slow in the early stages, followed by an increase in the oxidation rates over longer time periods. The experimental observations showed first-order dependences in permanganate and fractional first-order kinetics with respect to both carrageenans concentration for both the induction and autoacceleration periods. The results obtained at various hydrogen ion concentrations showed that the oxidation processes in these redox systems are acid-catalyzed throughout the two stages of oxidation reactions. The added salts lead to the prediction that Mn(III) is the reactive species throughout the autoacceleration periods. Kinetic evidence for the formation of 1:1 intermediate complexes was revealed. The kinetic parameters have been evaluated and tentative reaction mechanisms in good agreement with the kinetic results are discussed.

  17. Fumigaclavine C ameliorates dextran sulfate sodium-induced murine experimental colitis via NLRP3 inflammasome inhibition.

    PubMed

    Guo, Wenjie; Hu, Shasha; Elgehama, Ahmed; Shao, Fenli; Ren, Ren; Liu, Wen; Zhang, Wenjing; Wang, Xinlei; Tan, Renxiang; Xu, Qiang; Sun, Yang; Jiao, Ruihua

    2015-10-01

    In the present study, the effect of Fumigaclavine C, a fungal metabolite, on murine experimental colitis induced by dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro. Oral administration of Fumigaclavine C dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco was also significantly reduced by Fumigaclavine C treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1β and IL-17A, were markedly suppressed by Fumigaclavine C. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in Fumigaclavine C -treated mice which suggested that the NLRP3 inflammasome activation was suppressed. Furthermore, in the LPS plus ATP cell model, we found that Fumigaclavine C dose-dependent inhibited IL-1β release and caspase-1 activation. Taken together, our results demonstrate the ability of Fumigaclavine C to inhibit NLRP3 inflammasome activation and give some evidence for its potential use in the treatment of inflammatory bowel diseases. PMID:26320672

  18. Efficacy of Zhuling polyporus polysaccharide with BCG to inhibit bladder carcinoma.

    PubMed

    Zhang, Guo-Wei; Qin, Gui-Fang; Han, Bo; Li, Cai-Xia; Yang, Hong-Gai; Nie, Pi-Hu; Zeng, Xing

    2015-03-15

    There is growing interest in reducing Bacille Calmette-Guerin (BCG) side effects while keeping intact its therapeutic efficacy. In the present study, we evaluated the efficacy of Sclerotia of Polyporus umbellatus FRIES (Zhuling) and its main ingredient Polyporus Polysaccharide (PPS) to attenuate side effects of BCG therapy in vivo. The results show that bladder cancer development in model rats exhibited significantly reduced cancer invasiveness with Zhuling PPS combined with BCG. Flow cytometric (FCM) analysis showed expression of costimulatory molecules CD86, CD40, and TLR4/CD14 significantly increased with Zhuling PPS in combination with BCG. Similarly, immunohistochemical analysis revealed stronger CD86 and CD40 staining. Our findings show Zhuling PPS strongly reduced side effects and displayed synergistic effects during BCG instillation in rat bladder cancer models. The findings also suggest that the attenuation effect may result from direct activation of dendritic cell (DC) TLR4.

  19. 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

  20. 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

  1. 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

  2. Protein translation inhibition by Stachybotrys chartarum conidia with and without the mycotoxin containing polysaccharide matrix.

    PubMed

    Karunasena, Enusha; Cooley, J Danny; Straus, Douglas; Straus, David C

    2004-07-01

    Recent studies have correlated the presence of Stachybotrys chartarum in structures with SBS. S. chartarum produces mycotoxins that are thought to produce some of the symptoms reported in sick-building syndrome (SBS). The conidia (spores) produced by Stachybotrys species are not commonly found in the air of buildings that have been found to contain significant interior growth of this organism. This could be due in part to the large size of the Stachybotrys spores, or the organism growing in hidden areas such as wall cavities. However, individuals in buildings with significant Stachybotrys growth frequently display symptoms that may be attributed to exposure to the organism's mycotoxins. In addition, Stachybotrys colonies produce a "slime" or polysaccharide (carbohydrate) matrix that coats the hyphae and the spores. The intent of this project was to determine whether the carbohydrate matrix and the mycotoxins embedded in it could be removed from the spores by repeated washings with either aqueous or organic solvents. The results demonstrated that the process of spore washing removed compounds that were toxic in a protein translation assay as compared to spores that were washed with an organic solution, however a correlation between carbohydrate removal during the washing process and the removal of mycotoxins from the spore surface was not observed. These data demonstrated that mycotoxins are not likely to be found exclusively in the carbohydrate matrix of the spores. Therefore, mycotoxin removal from the spore surface can occur without significant loss of polysaccharide. We also showed that toxic substances may be removed from the spore surface with an aqueous solution. These results suggest that satratoxins are soluble in aqueous solutions without being bound to water-soluble moieties, such as the carbohydrate slime matrix. PMID:15487326

  3. 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.

  4. Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits.

    PubMed

    Maysinger, Dusica; Gröger, Dominic; Lake, Andrew; Licha, Kai; Weinhart, Marie; Chang, Philip K-Y; Mulvey, Rose; Haag, Rainer; McKinney, R Anne

    2015-09-14

    Hyperactivity of microglia and loss of functional circuitry is a common feature of many neurological disorders including those induced or exacerbated by inflammation. Herein, we investigate the response of microglia and changes in hippocampal dendritic postsynaptic spines by dendritic polyglycerol sulfate (dPGS) treatment. Mouse microglia and organotypic hippocampal slices were exposed to dPGS and an inflammogen (lipopolysaccharides). Measurements of intracellular fluorescence and confocal microscopic analyses revealed that dPGS is avidly internalized by microglia but not CA1 pyramidal neurons. Concentration and time-dependent response studies consistently showed no obvious toxicity of dPGS. The adverse effects induced by proinflammogen LPS exposure were reduced and dendritic spine morphology was normalized with the addition of dPGS. This was accompanied by a significant reduction in nitrite and proinflammatory cytokines (TNF-α and IL-6) from hyperactive microglia suggesting normalized circuitry function with dPGS treatment. Collectively, these results suggest that dPGS acts anti-inflammatory, inhibits inflammation-induced degenerative changes in microglia phenotype and rescues dendritic spine morphology. PMID:26218295

  5. Specific recognition of sulfate esters by bindin, a sperm adhesion protein from sea urchins.

    PubMed

    DeAngelis, P L; Glabe, C G

    1990-01-19

    Bindin specifically binds to egg surface sulfated fucan polysaccharides and mediates the attachment of sperm to the egg during fertilization. Sulfate esters are critical for this interaction. We have examined the effect of different anionic groups on the relative binding affinities of a series of homologous anionic polymers for bindin to determine the extent to which other charged moieties can substitute for sulfate. We found that bindin displays a remarkable specificity for sulfate- or sulfonic acid-containing polymers. The relative affinities of poly(vinyl sulfate) and poly(styrenesulfonic acid) are four orders of magnitude higher than polymers containing phosphate esters or carboxyl groups. The bindin-mediated aggregation of sea urchin eggs was inhibited by the sulfated polymers but not the other anionic polymers. This high degree of selectivity for sulfated polymers is not observed for the binding of the polyanions to most other proteins and basic polypeptides. These results suggest that the binding is not due to the formation of simple salt bridges, and that all three non-ester oxygen atoms of the sulfate groups are involved in multiple bonding interactions with a complementary 'docking site' on the bindin polypeptide. The orientation of the polysaccharide sulfate oxygen atoms relative to the protein binding site may be an important determinant of the specificity of polysaccharide binding.

  6. Regulation of Pathologic Retinal Angiogenesis in Mice and Inhibition of VEGF-VEGFR2 Binding by Soluble Heparan Sulfate

    PubMed Central

    Nishiguchi, Koji M.; Kataoka, Keiko; Kachi, Shu; Komeima, Keiichi; Terasaki, Hiroko

    2010-01-01

    Development of the retinal vascular network is strictly confined within the neuronal retina, allowing the intraocular media to be optically transparent. However, in retinal ischemia, pro-angiogenic factors (including vascular endothelial growth factor-A, VEGF-A) induce aberrant guidance of retinal vessels into the vitreous. Here, we show that the soluble heparan sulfate level in murine intraocular fluid is high particularly during ocular development. When the eyes of young mice with retinal ischemia were treated with heparan sulfate-degrading enzyme, the subsequent aberrant angiogenesis was greatly enhanced compared to PBS-injected contralateral eyes; however, increased angiogenesis was completely antagonized by simultaneous injection of heparin. Intraocular injection of heparan sulfate or heparin alone in these eyes resulted in reduced neovascularization. In cell cultures, the porcine ocular fluid suppressed the dose-dependent proliferation of human umbilical vein endothelial cells (HUVECs) mediated by VEGF-A. Ocular fluid and heparin also inhibited the migration and tube formation by these cells. The binding of VEGF-A and HUVECs was reduced under a high concentration of heparin or ocular fluid compared to lower concentrations of heparin. In vitro assays demonstrated that the ocular fluid or soluble heparan sulfate or heparin inhibited the binding of VEGF-A and immobilized heparin or VEGF receptor 2 but not VEGF receptor 1. The recognition that the high concentration of soluble heparan sulfate in the ocular fluid allows it to serve as an endogenous inhibitor of aberrant retinal vascular growth provides a platform for modulating heparan sulfate/heparin levels to regulate angiogenesis. PMID:20975989

  7. Inhibition of migration and induction of apoptosis in LoVo human colon cancer cells by polysaccharides from Ganoderma lucidum.

    PubMed

    Liang, Zeng-Enni; Yi, You-Jin; Guo, Yu-Tong; Wang, Ren-Cai; Hu, Qiu-Long; Xiong, Xing-Yao

    2015-11-01

    Ganoderma lucidum polysaccharides (GLPs), which were purified from the medicinal herb G. lucidum followed by ethanol precipitation, protein depletion using the Sevage assay, purification using DEAE‑cellulose (DE-52), dialysis and the use of ultrafiltration membranes, are used as an ingredient in traditional anticancer treatments in China. The aim of the current study was to evaluate the anticancer effects and investigate the underlying molecular mechanisms of GLPs on LoVo human colon cancer cells. The results demonstrated that the GLP‑mediated anticancer effect in LoVo cells was characterized by cytotoxicity, migration inhibition, enhanced DNA fragmentation, morphological alterations and increased lactate dehydrogenase release. Furthermore, the activation of caspases‑3, ‑8 and ‑9 was involved in GLP‑stimulated apoptosis. Additionally, treatment with GLPs promoted the expression of Fas and caspase‑3 proteins, whilst reducing the expression of cleaved poly(ADP‑ribose) polymerase. These data indicate that GLPs demonstrate potential antitumor activity in human colon cancer cells, predominantly through the inhibition of migration and induction of apoptosis. Furthermore, activation of the Fas/caspase-dependent apoptosis pathway is involved in the cytotoxicity of GLPs. PMID:26397202

  8. Protein-bound polysaccharide-K (PSK) induces apoptosis and inhibits proliferation of promyelomonocytic leukemia HL-60 cells.

    PubMed

    Hirahara, Noriyuki; Fujioka, Masaki; Edamatsu, Takeo; Fujieda, Ayako; Sekine, Fujio; Wada, Tsutomu; Tanaka, Tsuneo

    2011-09-01

    Protein-bound polysaccharide-K (PSK) is extracted from Coriolus versicolor (CM101), and is clinically used in combination therapy for gastrointestinal cancer and small cell lung carcinoma. PSK is a biological response modifier (BRM), and its mechanism of action is partly mediated, by modulating host immune systems, such as the activation of immune effector cells and the neutralization of transforming growth factor-beta (TGFβ) activity. Direct inhibition of tumor cell proliferation has been reported as another mechanism, but how PSK induces such an effect remains to be elucidated. Here, the anti-proliferative activity of PSK was examined using seven different human malignant cell lines (WiDr, HT29, SW480, KATOIII, AGS, HL60 and U937), and PSK was found to inhibit the proliferation of HL-60 cells most profoundly. Therefore, HL-60 cells were used to clarify the mechanism of anti-proliferative activity. Caspase-3 activation followed by apoptosis are involved at least in part in the PSK-induced anti-proliferative activity against HL-60 cells. PMID:21868514

  9. Inhibition of migration and induction of apoptosis in LoVo human colon cancer cells by polysaccharides from Ganoderma lucidum.

    PubMed

    Liang, Zeng-Enni; Yi, You-Jin; Guo, Yu-Tong; Wang, Ren-Cai; Hu, Qiu-Long; Xiong, Xing-Yao

    2015-11-01

    Ganoderma lucidum polysaccharides (GLPs), which were purified from the medicinal herb G. lucidum followed by ethanol precipitation, protein depletion using the Sevage assay, purification using DEAE‑cellulose (DE-52), dialysis and the use of ultrafiltration membranes, are used as an ingredient in traditional anticancer treatments in China. The aim of the current study was to evaluate the anticancer effects and investigate the underlying molecular mechanisms of GLPs on LoVo human colon cancer cells. The results demonstrated that the GLP‑mediated anticancer effect in LoVo cells was characterized by cytotoxicity, migration inhibition, enhanced DNA fragmentation, morphological alterations and increased lactate dehydrogenase release. Furthermore, the activation of caspases‑3, ‑8 and ‑9 was involved in GLP‑stimulated apoptosis. Additionally, treatment with GLPs promoted the expression of Fas and caspase‑3 proteins, whilst reducing the expression of cleaved poly(ADP‑ribose) polymerase. These data indicate that GLPs demonstrate potential antitumor activity in human colon cancer cells, predominantly through the inhibition of migration and induction of apoptosis. Furthermore, activation of the Fas/caspase-dependent apoptosis pathway is involved in the cytotoxicity of GLPs.

  10. Inhibition of Na+-Taurocholate Co-transporting Polypeptide-mediated Bile Acid Transport by Cholestatic Sulfated Progesterone Metabolites*

    PubMed Central

    Abu-Hayyeh, Shadi; Martinez-Becerra, Pablo; Sheikh Abdul Kadir, Siti H.; Selden, Clare; Romero, Marta R.; Rees, Myrddin; Marschall, Hanns-Ulrich; Marin, Jose J. G.; Williamson, Catherine

    2010-01-01

    Sulfated progesterone metabolite (P4-S) levels are raised in normal pregnancy and elevated further in intrahepatic cholestasis of pregnancy (ICP), a bile acid-liver disorder of pregnancy. ICP can be complicated by preterm labor and intrauterine death. The impact of P4-S on bile acid uptake was studied using two experimental models of hepatic uptake of bile acids, namely cultured primary human hepatocytes (PHH) and Na+-taurocholate co-transporting polypeptide (NTCP)-expressing Xenopus laevis oocytes. Two P4-S compounds, allopregnanolone-sulfate (PM4-S) and epiallopregnanolone-sulfate (PM5-S), reduced [3H]taurocholate (TC) uptake in a dose-dependent manner in PHH, with both Na+-dependent and -independent bile acid uptake systems significantly inhibited. PM5-S-mediated inhibition of TC uptake could be reversed by increasing the TC concentration against a fixed PM5-S dose indicating competitive inhibition. Experiments using NTCP-expressing Xenopus oocytes confirmed that PM4-S/PM5-S are capable of competitively inhibiting NTCP-mediated uptake of [3H]TC. Total serum PM4-S + PM5-S levels were measured in non-pregnant and third trimester pregnant women using liquid chromatography-electrospray tandem mass spectrometry and were increased in pregnant women, at levels capable of inhibiting TC uptake. In conclusion, pregnancy levels of P4-S can inhibit Na+-dependent and -independent influx of taurocholate in PHH and cause competitive inhibition of NTCP-mediated uptake of taurocholate in Xenopus oocytes. PMID:20177056

  11. 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.

  12. 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.

  13. Raspberry pulp polysaccharides inhibit tumor growth via immunopotentiation and enhance docetaxel chemotherapy against malignant melanoma in vivo.

    PubMed

    Yang, Yong-Jing; Xu, Han-Mei; Suo, You-Rui

    2015-09-01

    It has been reported previously that the systemic efficacy of chemotherapeutic agents is substantially restricted for some cancer types, including malignant melanoma. Therefore, the development of more effective treatment modalities remains a critical, albeit elusive, goal in anticancer therapy. The study presented here evaluates the antitumor activity of raspberry pulp polysaccharides (RPPs) against malignant melanoma using a murine tumor-bearing model. Furthermore, the underlying mechanism of this antitumor activity has also been investigated. The results show that while RPP exhibits no direct cytotoxic effect on HT-29, MGC-803, HeLa, Bel-7402, L02 and B16F10 cells in vitro, it does demonstrate a dose-dependent growth inhibition of melanoma in vivo with an inhibition ratio of 59.95% at a dose of 400 mg kg(-1). Besides this, the body weight and spleen index in tumor-bearing mice have also been improved in RPP-treated groups. RPP is also found to induce splenocyte proliferation and is able to upregulate the activity of immune-related enzymes, including acid phosphatase (ACP), alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in the spleen of tumor-bearing mice. The levels of tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) and interleukin 2 (IL-2) in the serum of tumor-bearing mice show to be effectively increased upon RPP treatment. Histopathological analyses show that RPP induces tumor tissue necrosis by increasing inflammatory cell infiltration and causes no lesions to liver and kidney tissues. Remarkably, RPP further enhances the antitumor effect of the chemotherapeutic drug docetaxel and alleviates docetaxel-induced liver and kidney lesions in tumor-bearing mice. These findings indicate that RPP exhibits antitumor activity in vivo against malignant melanoma, partly by enhancing the cellular immune response of the host organism. In summary, RPP features critical properties to potentially find use as an

  14. A new sulfated beta-galactan from clams with anti-HIV activity.

    PubMed

    Amornrut, C; Toida, T; Imanari, T; Woo, E R; Park, H; Linhardt, R; Wu, S J; Kim, Y S

    1999-09-15

    A new polysaccharide composed of galactan sulfate with a beta-(1-->3)-glycosidic linkage has been isolated from the marine clam species Meretrix petechialis. The polysaccharide was homogeneous in its composition containing D-galactose. The glycosidic linkage was examined by 2D DQF-COSY and 2D NOESY spectroscopy. The coupling constant of anomeric proton was 7.8 Hz, suggesting a beta-galacto configuration. The downfield shift of H-2 of galactose residue demonstrated the presence of 2-O-sulfonate group. TQF-COSY confirmed that the C-6 position was substituted with a sulfonate group. The anti-HIV activity of the polysaccharides has been evaluated by the inhibition of syncytia formation. The fusion index and percentage fusion inhibition of sulfated galactan were 0.34 and 56% at 200 micrograms/mL.

  15. Fucosylated chondroitin sulfate inhibits plasma thrombin generation via targeting of the factor IXa heparin-binding exosite.

    PubMed

    Buyue, Yang; Sheehan, John P

    2009-10-01

    Depolymerized holothurian glycosaminoglycan (DHG) is a fucosylated chondroitin sulfate with antithrombin-independent antithrombotic properties. Heparin cofactor II (HCII)-dependent and -independent mechanisms for DHG inhibition of plasma thrombin generation were evaluated. When thrombin generation was initiated with 0.2 pM tissue factor (TF), the half maximal effective concentration (EC(50)) for DHG inhibition was identical in mock- or HCII-depleted plasma, suggesting a serpin-independent mechanism. In the presence of excess TF, the EC(50) for DHG was increased 13- to 27-fold, suggesting inhibition was dependent on intrinsic tenase (factor IXa-factor VIIIa) components. In factor VIII-deficient plasma supplemented with 700 pM factor VIII or VIIIa, and factor IX-deficient plasma supplemented with plasma-derived factor IX or 100 pM factor IXa, the EC(50) for DHG was similar. Thus, cofactor and zymogen activation did not contribute to DHG inhibition of thrombin generation. Factor IX-deficient plasma supplemented with mutant factor IX(a) proteins demonstrated resistance to DHG inhibition of thrombin generation [factor IX(a) R233A > R170A > WT] that inversely correlated with protease-heparin affinity. These results replicate the effect of these mutations with purified intrinsic tenase components, and establish the factor IXa heparin-binding exosite as the relevant molecular target for inhibition by DHG. Glycosaminoglycan-mediated intrinsic tenase inhibition is a novel antithrombotic mechanism with physiologic and therapeutic applications.

  16. 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

  17. Recognition of bacterial capsular polysaccharides and lipopolysaccharides by the macrophage mannose receptor.

    PubMed

    Zamze, Susanne; Martinez-Pomares, Luisa; Jones, Hannah; Taylor, Philip R; Stillion, Richard J; Gordon, Siamon; Wong, Simon Y C

    2002-11-01

    The in vitro binding of the macrophage mannose receptor to a range of different bacterial polysaccharides was investigated. The receptor was shown to bind to purified capsular polysaccharides from Streptococcus pneumoniae and to the lipopolysaccharides, but not capsular polysaccharides, from Klebsiella pneumoniae. Binding was Ca(2+)-dependent and inhibitable with d-mannose. A fusion protein of the mannose receptor containing carbohydrate recognition domains 4-7 and a full-length soluble form of the mannose receptor containing all domains external to the transmembrane region both displayed very similar binding specificities toward bacterial polysaccharides, suggesting that domains 4-7 are sufficient for recognition of these structures. Surprisingly, no direct correlation could be made between polysaccharide structure and binding to the mannose receptor, suggesting that polysaccharide conformation may play an important role in recognition. The full-length soluble form of the mannose receptor was able to bind simultaneously both polysaccharide via the carbohydrate recognition domains and sulfated oligosaccharide via the cysteine-rich domain. The possible involvement of the mannose receptor, either cell surface or soluble, in the innate and adaptive immune responses to bacterial polysaccharides is discussed.

  18. Recognition of bacterial capsular polysaccharides and lipopolysaccharides by the macrophage mannose receptor.

    PubMed

    Zamze, Susanne; Martinez-Pomares, Luisa; Jones, Hannah; Taylor, Philip R; Stillion, Richard J; Gordon, Siamon; Wong, Simon Y C

    2002-11-01

    The in vitro binding of the macrophage mannose receptor to a range of different bacterial polysaccharides was investigated. The receptor was shown to bind to purified capsular polysaccharides from Streptococcus pneumoniae and to the lipopolysaccharides, but not capsular polysaccharides, from Klebsiella pneumoniae. Binding was Ca(2+)-dependent and inhibitable with d-mannose. A fusion protein of the mannose receptor containing carbohydrate recognition domains 4-7 and a full-length soluble form of the mannose receptor containing all domains external to the transmembrane region both displayed very similar binding specificities toward bacterial polysaccharides, suggesting that domains 4-7 are sufficient for recognition of these structures. Surprisingly, no direct correlation could be made between polysaccharide structure and binding to the mannose receptor, suggesting that polysaccharide conformation may play an important role in recognition. The full-length soluble form of the mannose receptor was able to bind simultaneously both polysaccharide via the carbohydrate recognition domains and sulfated oligosaccharide via the cysteine-rich domain. The possible involvement of the mannose receptor, either cell surface or soluble, in the innate and adaptive immune responses to bacterial polysaccharides is discussed. PMID:12196537

  19. 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

  20. Inhibition of barium sulfate deposition by polycarboxylates of various molecular structures

    SciTech Connect

    van der Leeden, M.C.; van Rosmalen, G.M. )

    1990-02-01

    To establish a relationship between the molecular structure of polycarboxylates and their growth-retarding influence on barium sulfate, seeded-suspension-growth experiments were performed at various inhibitor concentrations and pH values. Two types of polycarboxylates with a molecular structure based on their polyacrylic or maleic acid were studied. The molecular structure of these compounds were varied by particle substitution with monomers containing hydroxyl, amide, and sulfonic acid, as well as hydrophobic groups. Hydrophobic groups are detrimental to good inhibitor performance, whereas the introduction of OH, NH {sub 2}, or SO {sub 3} H groups presents opportunities to enhance the inhibitor effectiveness. The sequence in performance of the compounds on barium sulfate was compared with the sequence formerly obtained for calcium sulfate dihydrate.

  1. [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.

  2. 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. PMID:21744069

  3. Serpin-independent anticoagulant activity of a fucosylated chondroitin sulfate.

    PubMed

    Glauser, Bianca F; Pereira, Mariana S; Monteiro, Robson Q; Mourão, Paulo A S

    2008-09-01

    Fucosylated chondroitin sulfate is a glycosaminoglycan from sea cucumber composed of a chondroitin sulfate-like core with branches of sulfated fucose. This glycosaminoglycan has high anticoagulant and antithrombotic activities. Its serpin-dependent anticoagulant activity is mostly due to activating thrombin inhibition by heparin cofactor II. Here, we evaluated the anticoagulant activity of fucosylated chondroitin sulfate using antithrombin- and heparin cofactor II-free plasmas. In contrast to mammalian heparin, the invertebrate glycosaminoglycan is still able to prolong coagulation time and delay thrombin and factor Xa generation in serpin-free plasmas. These observations suggest that fucosylated chondroitin sulfate has a serpin-independent anticoagulant effect. We further investigated this effect using purified blood coagulation proteins. Clearly, fucosylated chondroitin sulfate inhibits the intrinsic tenase and prothrombinase complexes, which are critical for thrombin generation. It is possible that the invertebrate chondroitin sulfate inhibits interactions between cofactor Va and factor Xa. We also employed chemically modified polysaccharides in order to trace a structure versus activity relationship. Removal of the sulfated fucose branches, but not reduction of the glucuronic acid residues to glucose, abolished its activity. In conclusion, fucosylated chondroitin sulfate has broader effects on the coagulation system than mammalian glycosaminoglycans. In addition to its serpin-dependent inhibition of coagulation protease, it also inhibits the generation of factor Xa and thrombin by the tenase and prothrombinase complexes, respectively. In plasma systems, the serpin-independent anticoagulant effect of fucosylated chondroitin sulfate predominates over its serpin-dependent action. This glycosaminoglycan opens new avenues for the development of antithrombotic agents.

  4. 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...

  5. 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. PMID:27126499

  6. 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. PMID:15278311

  7. 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.

  8. 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

  9. Polysaccharide-modified synthetic polymeric biomaterials.

    PubMed

    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

  10. Isolation and partial characterization of fucan sulfates from the body wall of sea cucumber Stichopus japonicus and their ability to inhibit osteoclastogenesis.

    PubMed

    Kariya, Yutaka; Mulloy, Barbara; Imai, Kyoko; Tominaga, Akihiro; Kaneko, Takuji; Asari, Akira; Suzuki, Kiyoshi; Masuda, Hiroyuki; Kyogashima, Mamoru; Ishii, Tadashi

    2004-05-17

    Two types of fucan sulfate were isolated from chloroform/methanol extract of the body wall of the sea cucumber Stichopus japonicus. One type (type A) contained 3.41 mmol fucose/g and 2.35 mmol sulfate/g, and the molecular mass was determined to be 9 kDa by gel permeation chromatography (GPC). Structural analysis suggested that type A consists of a backbone of (1-->3)-linked fucosyl residues that are substituted at C-4 with fucosyl residues, and that fucosyl residues are sulfated at C-2 and/or C-4. Another type (type B) contained 3.90 mmol fucose/g and 3.07 mmol sulfate/g, and the molecular mass was determined to be 32kDa by GPC. Structural analysis showed that type B is largely composed of unbranched (1-->3)-linked fucosyl residues, and that sulfate substitution(s) occur at C-2 and/or C-4. The potential of both types to inhibit osteoclastogenesis was examined by an in vitro assay system, showing that both types of fucan sulfate inhibit osteoclastogenesis more than 95% at 50 microg/mL concentration. These results suggest that types A and B fucan sulfate from sea cucumber are potent inhibitors of osteoclastogenesis.

  11. 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.

  12. 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.

  13. 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

  14. Sustained inhibition of intimal thickening. In vitro and in vivo effects of polymeric beta-cyclodextrin sulfate.

    PubMed Central

    Bachinsky, W B; Barnathan, E S; Liu, H; Okada, S S; Kuo, A; Raghunath, P N; Muttreja, M; Caron, R J; Tomaszewski, J E; Golden, M A

    1995-01-01

    Intimal thickening after vascular injury may be modulated in part by heparin binding growth factors. We hypothesized that placement of a therapeutic polymer in the periadventitial space capable of tightly binding growth factors might alter the vascular response to injury. We first demonstrated that incubation of rat aortic smooth muscle cells with an insoluble, sulfated polymer of beta-cyclodextrin (P-CDS) was associated with a dose-dependent inhibition of proliferation induced by fetal calf serum, fibroblast growth factor-2 (FGF-2), platelet-derived growth factor BB, or epidermal growth factor. Preincubation studies of P-CDS with FGF-2 revealed a very rapid removal of mitogenic activity. Using radiolabeled FGF-2 (0.25 microg/ml), we observed a very rapid association rate (0.34 +/- 0.07 min-1, n=4) and a very slow dissociation rate (3.3 +/- 0.2 X 10(-7) min-1) at 37 degrees C, suggesting a high affinity interaction. Using both Transwell and linear under-agarose assays, we demonstrated a significant inhibition of random migration (chemokinesis) by P-CDS. Unsulfated polymeric beta-cyclodextrin (P-CD) had little if any of these effects, suggesting that the high negative charge density of P-CDS was important for the effects. Finally, rats undergoing carotid artery balloon injury were randomized to treatment with periadventitial P-CDS or no treatment, and were killed at 4 (n=20), 14 (n=59), and 88 d (n=14). Morphometric analysis demonstrated significant and sustained inhibition of intimal thickening in P-CDS-treated rats at 14 (P < 0.01) and 88 d (P < 0.05) using absolute intimal area or intima/media area ratios. No inhibition was seen in a group of rats treated with P-CD. In P-CDS-treated rats, bromodeoxyuridine labeling studies revealed fewer labeled smooth muscle cells in the intima at 14 d (P=0.01), while staining with Evans blue revealed enhanced late endothelial cell regrowth. Thus, periadventitially applied sulfated beta-cyclodextrin polymer, which can tightly

  15. Immunomodulatory effects of a polysaccharide from Tamarindus indica.

    PubMed

    Sreelekha, T T; Vijayakumar, T; Ankanthil, R; Vijayan, K K; Nair, M K

    1993-04-01

    A polysaccharide isolated and purified from Tamarindus indica shows immunomodulatory activities such as phagocytic enhancement, leukocyte migration inhibition and inhibition of cell proliferation. These properties suggest that this polysaccharide from T. indica may have some biological applications.

  16. The in ovo conversion of oestrone to oestrone sulfate is rapid and subject to inhibition by Bisphenol A.

    PubMed

    Paitz, Ryan T; Bowden, Rachel M

    2015-04-01

    Vertebrate embryos develop in the presence of maternally derived steroids. While these steroids can influence development, embryonic enzymes are thought to buffer some steroid sensitive processes, such as gonadal differentiation, from the effects of maternal steroids. Many of these same enzymes may also buffer the embryo from chemicals present in the environment, but this may alter their capacity to metabolize maternal steroids. Here, we characterized the ability of red-eared slider (Trachemys scripta) embryos to metabolize oestrone immediately following oviposition and tested whether a prevalent environmental chemical, Bisphenol A (BPA), would affect the in ovo conversion of oestrone to oestrone sulfate. We found that tritiated oestrone applied at the time of oviposition is mostly converted to oestrone sulfate within 6 h. However, when BPA is present, that conversion is inhibited, resulting in elevated oestrone levels. Our finding of rapid in ovo metabolism of steroids suggests that maternally derived enzymes are present in the egg and can alter embryonic exposure to exogenous chemicals. The disruption of this metabolism by BPA demonstrates how environmental chemicals might change embryonic exposure to endogenous substances within the egg. Taken together, these findings highlight the dynamic nature of the early endocrine environment in developing vertebrates. PMID:25904318

  17. Dextran Sulfate Suppression of Viruses in the HIV Family: Inhibition of Virion Binding to CD4+ Cells

    NASA Astrophysics Data System (ADS)

    Mitsuya, Hiroaki; Looney, David J.; Kuno, Sachiko; Ueno, Ryuji; Wong-Staal, Flossie; Broder, Samuel

    1988-04-01

    The first step in the infection of human T lymphocytes by human immunodeficiency virus type 1 (HIV-1) is attachment to the target cell receptor, the CD4 antigen. This step may be vulnerable to attack by antibodies, chemicals, or small peptides. Dextran sulfate (molecular weight approximately 8000), which has been given to patients as an anticoagulant or antilipemic agent for more than two decades, was found to block the binding of virions to various target T lymphocytes, inhibit syncytia formation, and exert a potent inhibitory effect against HIV-1 in vitro at concentrations that may be clinically attainable in human beings. This drug also suppressed the replication of HIV-2 in vitro. These observations could have theoretical and clinical implications in the strategy to develop drugs against HIV types 1 and 2.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Inhibition of cell proliferation and migration by chondroitin sulfate-g-polyethylenimine-mediated miR-34a delivery.

    PubMed

    Liang, Shaojun; Duan, Yan; Xing, Zhen; Han, Haobo; Zhang, Aijun; Li, Li; Yang, Yan; Li, Quanshun

    2015-12-01

    Chondroitin sulfate was chemically conjugated to PEI25K through Michael addition to construct a non-viral gene carrier CS-PEI, and then the carrier was employed in miR-34a delivery to achieve the inhibition of cell proliferation and migration, using prostate tumor cell PC-3 as a model. The nanoparticle from CS-PEI and miR-34a at a mass ratio of 10 was prepared with particle size and zeta potential of 170.7 nm and +42.2 mV, respectively. Flow cytometry and fluorescence microscopy revealed that CS-PEI could efficiently induce the cellular uptake of miR-34a in a CD44-mediated endocytosis manner. Through CS-PEI-mediated miR-34a transfection, obvious cell apoptosis was observed with early apoptotic cells of 47.49%, and meanwhile the activation of caspase-3, -8 and -9, and decreased expression level of Bcl-2 were detected. Moreover, wound healing assay showed that CS-PEI/miR-34a transfection could inhibit the cell migration. Overall, CS-PEI is potentially employed as a promising tumor-targeting system for miR-34a delivery in tumor gene therapy.

  3. An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

    PubMed Central

    Marano, Grazia; Gronewold, Claas; Frank, Martin; Merling, Anette; Kliem, Christian; Sauer, Sandra; Wiessler, Manfred; Frei, Eva

    2012-01-01

    Summary Oligosaccharides aberrantly expressed on tumor cells influence processes such as cell adhesion and modulation of the cell’s microenvironment resulting in an increased malignancy. Schmidt’s imidate strategy offers an effective method to synthesize libraries of various oligosaccharide mimetics. With the aim to perturb interactions of tumor cells with extracellular matrix proteins and host cells, molecules with 3,4-bis(hydroxymethyl)furan as core structure were synthesized and screened in biological assays for their abilities to interfere in cell adhesion and other steps of the metastatic cascade, such as tumor-induced angiogenesis. The most active compound, (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF), inhibited the activation of matrix-metalloproteinase-2 (MMP-2) as well as migration of the human melanoma cells of the lines WM-115 and WM-266-4 in a two-dimensional migration assay. GSF inhibited completely the adhesion of WM-115 cells to the extracellular matrix (ECM) proteins, fibrinogen and fibronectin. In an in vitro angiogenesis assay with human endothelial cells, GSF very effectively inhibited endothelial tubule formation and sprouting of blood vessels, as well as the adhesion of endothelial cells to ECM proteins. GSF was not cytotoxic at biologically active concentrations; neither were 3,4-bis{[(β-D-galactopyranosyl)oxy]methyl}furan (BGF) nor methyl β-D-galactopyranoside nor 3,4-bis(hydroxymethyl)furan, which were used as controls, eliciting comparable biological activity. In silico modeling experiments, in which binding of GSF to the extracellular domain of the integrin αvβ3 was determined, revealed specific docking of GSF to the same binding site as the natural peptidic ligands of this integrin. The sulfate in the molecule coordinated with one manganese ion in the binding site. These studies show that this chemically easily accessible molecule GSF, synthesized in three steps from 3,4-bis

  4. 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.

  5. Zinc-Stabilized Chitosan-Chondroitin Sulfate Nanocomplexes for HIV-1 Infection Inhibition Application.

    PubMed

    Wu, Danjun; Ensinas, Agathe; Verrier, Bernard; Primard, Charlotte; Cuvillier, Armelle; Champier, Gaël; Paul, Stephane; Delair, Thierry

    2016-09-01

    Polyelectrolyte complexes (PECs) constituted of chitosan and chondroitin sulfate (ChonS) were formed by the one-shot addition of default amounts of polyanion to an excess of polycation. Key variables of the formulation process (e.g., degree of depolymerization, charge mixing ratio, the concentration, and pH of polyelectrolyte solutions) were optimized based on the PECs sizes and polydispersities. The PECs maintained their colloidal stability at physiological salt concentration and pH thanks to the complexation of polyelectrolytes with zinc(II) ion during the nanoPECs formation process. The PECs were capable of encapsulating an antiretroviral drug tenofovir (TF) with a minimal alteration on the colloidal stability of the dispersion. Moreover, the particle interfaces could efficiently be functionalized with anti-OVA or anti-α4β7 antibodies with conservation of the antibody biorecognition properties over 1 week of storage in PBS at 4 °C. In vitro cytotoxicity studies showed that zinc(II) stabilized chitosan-ChonS nanoPECs were noncytotoxic to human peripheral blood mononuclear cells (PBMCs), and in vitro antiviral activity test demonstrated that nanoparticles formulations led to a dose-dependent reduction of HIV-1 infection. Using nanoparticles as a drug carrier system decreases the IC50 (50% inhibitory concentration) from an aqueous TF of 4.35 μmol·L(-1) to 1.95 μmol·L(-1). Significantly, zinc ions in this system also exhibited a synergistic effect in the antiviral potency. These data suggest that chitosan-ChonS nanoPECs can be promising drug delivery system to improve the antiviral potency of drugs to the viral reservoirs for the treatment of HIV infection. PMID:27454202

  6. 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

  7. 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

  8. 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

  9. 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.

  10. Inonotus obliquus-derived polysaccharide inhibits the migration and invasion of human non-small cell lung carcinoma cells via suppression of MMP-2 and MMP-9.

    PubMed

    Lee, Ki Rim; Lee, Jong Seok; Song, Jeong Eun; Ha, Suk Jin; Hong, Eock Kee

    2014-12-01

    Polysaccharides isolated from the fruiting body of Inonotus obliquus (PFIO) are known to possess various pharmacological properties including antitumor activity. However, the anti-metastatic effect and its underlying mechanistic signaling pathway involved these polysaccharides in human non-small cell lung carcinoma remain unknown. The present study therefore aimed to determine the anti-metastatic potential and signaling pathways of PFIO in the highly metastatic A549 cells. We found that PFIO suppressed the migration and invasive ability of A549 cells while decreasing the expression levels and activity of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, PFIO decreased the phosphorylation levels of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) as well as the expression level of COX-2, and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in A549 cells. These results suggested that PFIO could suppress the invasion and migration of human lung carcinoma by reducing the expression levels and activity of MMP-2 and MMP-9 via suppression of MAPKs, PI3K/AKT, and NF-κB signaling pathways.

  11. Fucosylated chondroitin sulfate as a new oral antithrombotic agent.

    PubMed

    Fonseca, Roberto J C; Mourão, Paulo A S

    2006-12-01

    Fucosylated chondroitin sulfate is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of sulfated fucose branches. We have shown that intravascular injection of fucosylated chondroitin sulfate inhibits thrombus formation in a venous and an arterial shunt model in rats. Since this compound resists digestion by enzymes that cleave mammalian glycosaminoglycans, we investigated the possibility that fucosylated chondroitin sulfate might be absorbed after oral administration. In fact, after oral administration of fucosylated chondroitin sulfate to rats, we observed a dose-dependent increase in the plasma anticoagulant activity, as assessed by assays for activated partial thromboplastin time (aPTT) and thrombin time (TT) (about 3- and 5-fold, respectively) and by anti-IIa activity. Furthermore, animals receiving daily oral doses of this glycosaminoglycan showed a decrease in thrombus weight on experimental models of venous and arterial shunt thrombosis. This antithrombotic action clearly has a strong relationship with anticoagulant activity. Similar doses of heparin administered orally had no effect on the plasma anticoagulant activity or on the thrombus weight. Finally, we observed that fucosylated chondroitin sulfate given orally to rats did not modify the bleeding time. Overall, our results indicate that fucosylated chondroitin sulfate is absorbed after oral administration and could become a promising oral anticoagulant.

  12. 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. PMID:27466498

  13. Vitamin A Inhibits Development of Dextran Sulfate Sodium-Induced Colitis and Colon Cancer in a Mouse Model

    PubMed Central

    Okayasu, Isao; Hana, Kiyomi; Nemoto, Noriko; Yoshida, Tsutomu; Saegusa, Makoto; Yokota-Nakatsuma, Aya; Song, Si-Young; Iwata, Makoto

    2016-01-01

    Vitamin A is essential to mucosal immunity and cell differentiation. The fact that lack of it might involve chronic inflammation and increased risk of cancer has been reported. Little is known about the mechanism of vitamin A deficiency in the development of colitis and its influence on development of colorectal cancer. To determine the influence of vitamin A deficiency on colitis and colorectal cancer development, an experimental study using a colitis mouse model was performed. Dextran sulfate sodium (DSS) colitis was induced in vitamin A-deficient and vitamin A-supplemented mice. Further, colorectal carcinoma was induced by a combination of azoxymethane preinjection and DSS colitis. Results were compared between the two groups mainly by immunohistochemical analysis. Colitis was more severe and recovery from colitis was slower in vitamin A-deficient mice than in vitamin A-supplemented mice. Compared with vitamin A-supplemented mice, vitamin A-deficient mice had decreases in colonic subepithelial myofibroblasts and the ratio of mucosal IgA+/IgG+ cells, increases in CD11c+ dendritic cells, and a higher rate of development of colorectal carcinoma with colitis following azoxymethane. Vitamin A lipid droplets in subepithelial myofibroblasts were decreased in vitamin A-deficient mice, suggesting alterations in colonic crypt niche function. Thus, vitamin A inhibited colitis and the development of colorectal cancer. PMID:27298823

  14. Inhibition of vasoactive intestinal polypeptide (VIP) induces resistance to dextran sodium sulfate (DSS)-induced colitis in mice.

    PubMed

    Vu, John P; Million, Mulugeta; Larauche, Muriel; Luong, Leon; Norris, Joshua; Waschek, James A; Pothoulakis, Charalabos; Pisegna, Joseph R; Germano, Patrizia M

    2014-01-01

    VIP is highly expressed in the colon and regulates motility, vasodilatation, and sphincter relaxation. However, its role in the development and progress of colitis is still controversial. Our aim was to determine the participation of VIP on dextran sodium sulfate (DSS)-induced colonic mucosal inflammation using VIP(-/-) and WT mice treated with VIP antagonists. Colitis was induced in 32 adult VIP(-/-) and 14 age-matched WT litter-mates by giving 2.5 % DSS in the drinking water. DSS-treated WT mice were injected daily with VIP antagonists, VIPHyb (n = 22), PG 97-269 (n = 9), or vehicle (n = 31). After euthanasia, colons were examined; colonic cytokines mRNA were quantified. VIP(-/-) mice were remarkably resistant to DSS-induced colitis compared to WT. Similarly, DSS-treated WT mice injected with VIPHyb (1 μM) or PG 97-269 (1 nM) had significantly reduced clinical signs of colitis. Furthermore, colonic expression of IL-1ϐ, TNF-α, and IL-6 was significantly lower in VIP(-/-) and VIPHyb or PG 97-269 compared to vehicle-treated WT. Genetic deletion of VIP or pharmacological inhibition of VIP receptors resulted in resistance to colitis. These data demonstrate a pro-inflammatory role for VIP in murine colitis and suggest that VIP antagonists may be an effective clinical treatment for human inflammatory bowel diseases.

  15. Chondroitin Sulfate Proteoglycans Potently Inhibit Invasion and Serve as a Central Organizer of the Brain Tumor Microenvironment

    PubMed Central

    Siebzehnrubl, Florian A.; Schildts, Michela J.; Yachnis, Anthony T.; Smith, George M.; Smith, Amy A.; Scheffler, Bjorn; Reynolds, Brent A.; Silver, Jerry; Steindler, Dennis A.

    2013-01-01

    Glioblastoma (GBM) remains the most pervasive and lethal of all brain malignancies. One factor that contributes to this poor prognosis is the highly invasive character of the tumor. GBM is characterized by microscopic infiltration of tumor cells throughout the brain, whereas non-neural metastases, as well as select lower grade gliomas, develop as self-contained and clearly delineated lesions. Illustrated by rodent xenograft tumor models as well as pathological human patient specimens, we present evidence that one fundamental switch between these two distinct pathologies–invasion and noninvasion–is mediated through the tumor extracellular matrix. Specifically, noninvasive lesions are associated with a rich matrix containing substantial amounts of glycosylated chondroitin sulfate proteoglycans (CSPGs), whereas glycosylated CSPGs are essentially absent from diffusely infiltrating tumors. CSPGs, acting as central organizers of the tumor microenvironment, dramatically influence resident reactive astrocytes, inducing their exodus from the tumor mass and the resultant encapsulation of noninvasive lesions. Additionally, CSPGs induce activation of tumor-associated microglia. We demonstrate that the astrogliotic capsule can directly inhibit tumor invasion, and its absence from GBM presents an environment favorable to diffuse infiltration. We also identify the leukocyte common antigen-related phosphatase receptor (PTPRF) as a putative intermediary between extracellular glycosylated CSPGs and noninvasive tumor cells. In all, we present CSPGs as critical regulators of brain tumor histopathology and help to clarify the role of the tumor microenvironment in brain tumor invasion. PMID:24068827

  16. 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

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

    PubMed

    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

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

    PubMed

    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.

  19. 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.

  20. Inhibition of in vitro adhesion and virulence of Porphyromonas gingivalis by aqueous extract and polysaccharides from Rhododendron ferrugineum L. A new way for prophylaxis of periodontitis?

    PubMed

    Löhr, G; Beikler, T; Hensel, A

    2015-12-01

    The effect of an aqueous extract from the leaves of Rhododendron ferrugineum (RF) was investigated for its capacity of inhibiting the adhesion of Porphyromonas gingivalis cells to epithelial buccal KB cells. RF was characterized by HPLC (12.1% taxifolin-3-O-β-l-arabinopyranoside, 1.6% hyperoside, 0.9% isoquercitrin, 1.6% chlorogenic acid and a tannin content of 8.7%). Additionally raw polysaccharides (RPS) were obtained from the leaves of R. ferrugineum by aqueous extraction. RF and RPS interacted in a dose-dependent manner (max. 25% reduction at 1mg/ml each) with the adhesion of P. gingivalis by influencing bacterial outer membrane proteins. On protein level a time- and concentration-dependent inhibition of Arg-gingipain activity by RF was observed, while the Lys-gingipain activity remained unaltered. In addition, RF and RPS inhibited the bacterial hemagglutinin. RF affected the P. gingivalis adhesion also by interacting with KB cells in pre-incubation assays of the eukaryotic host cells, leading to reduced bacterial adhesion of about 75%. Gene expression analysis by RT-PCR indicated significant downregulation for arginine-specific gingipain rgpA by RF, while lysin-specific gingipain kgp and fimbrillinA fimA were strongly upregulated. Moreover, pre-incubation with RF abolished the P. gingivalis induced expression of IL-1β, IL-6, IL-8 and TNFα in KB cells. Results of this study indicate that an aqueous extract from R. ferrugineum combines cytoprotective and antimicrobial effects by both downregulating the expression of pro-inflammatory genes and inhibiting the adhesion of P. gingivalis. Thus RF may be potential candidate for the development of an adjunctive antimicrobial approach in the prevention of periodontal diseases.

  1. The marked inhibition of the bitter taste of Polymyxin B sulfate and trimethoprim x sulfamethoxazole by flavored BMI-60 in pediatric patients.

    PubMed

    Saito, M; Hoshi, M; Igarashi, A; Ogata, H; Edo, K

    1999-09-01

    Taste acceptability of ground Polymyxin B sulfate and Bactramin C tablets was examined when flavored BMI-60, a food additive, was added. Both adult and child volunteers found the bitter taste of the two drugs markedly inhibited, making it clinically useful. Noncompliance, due to this bitterness, was improved using flavored BMI-60. The most striking characteristic of flavored BMI-60 is the ease of preparation compared with the manufacture of other hospital pharmaceuticals such as jelly, gummi and candy done to mask bitterness.

  2. SCP, a polysaccharide from Schisandra chinensis, induces apoptosis in human renal cell carcinoma Caki-1 cells through mitochondrial-dependent pathway via inhibition of ERK activation.

    PubMed

    Liu, Shi-Jian; Qu, Hai-Ming; Ren, Ye-Ping

    2014-06-01

    This study is the first to investigate the anticancer effect of Schisandra chinensis polysaccharide (SCP) in renal cell carcinoma (RCC) cells. The results revealed that SCP treatment showed high cytotoxic potency in Caki-1 cells by inducing apoptosis, which is associated with the disruption of mitochondrial membrane potential (MMP), release of cytochrome c into the cytosol, increase of Bax/Bcl-2 ratio, activation of caspase-3/9, and cleavage of poly(ADP-ribose) polymerase (PARP). Furthermore, pan-caspase inhibitor (z-VAD-fmk) significantly blocked SCP-induced apoptosis and PARP cleavage in Caki-1 cells. As well, we also observed that SCP inhibited the phosphorylation of ERK1/2, whereas it had no significant inhibition effect on the phospho-p38 and phospho-JNK activity. All the above parameters provided scientific evidence that SCP induced mitochondrial-mediated apoptosis in Caki-1 cells through the inactivation of ERK pathways, which may shed further light on its potential application as a cancer chemopreventive agent against RCC.

  3. Composition and anti-inflammatory effect of polysaccharides from Sargassum horneri in RAW264.7 macrophages.

    PubMed

    Wen, Zheng-Shun; Xiang, Xing-Wei; Jin, Huo-Xi; Guo, Xiang-Yang; Liu, Li-Jia; Huang, Yan-Na; OuYang, Xiao-Kun; Qu, You-Le

    2016-07-01

    Sulfated polysaccharides extracted from brown marine algae have been shown to possess a variety of biological activities. We assessed the potential activity of the sulfated polysaccharide from Sargassum horneri (SP) and its isolated two major components (fraction-1 (F1) and fraction-2 (F2)), on anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In the present study, analysis of polysaccharide chemical composition found that the constituent ratios of sulfate ester and fucose in SP and F1 were 4.95% vs 7.6%, and 4.48% vs 55.9%, respectively, suggesting that F1 may be a major sulfated polysaccharide containing fucose. Meanwhile, our findings demonstrated that TNF-α secretion levels were significantly (P<0.05) decreased by SP and F1 treatments in LPS-stimulated RAW264.7 cells in a dose-dependent manner under the preventive and repair experimental models. Pro-/anti-inflammatory (TNF-α/IL-10) cytokines secretion ratios by LPS-stimulated RAW264.7 macrophages were significantly (P<0.05) inhibited by SP and F1 treatments, particularly by F1 (at high dose, 200μg/ml). Moreover, NO release and iNOS activity were significantly (P<0.05) inhibited by F1. Collectively, the present study suggested that purified component, F1 from SP, had strong anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages in the preventive and repair manner through inhibiting TNF-α secretion levels and NO release. PMID:26879911

  4. 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.

  5. 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. PMID:25663459

  6. Chondroitin sulfate and hyaluronic acid (500-730 kda) inhibit stromelysin-1 synthesis in human osteoarthritic chondrocytes.

    PubMed

    Monfort, J; Nacher, M; Montell, E; Vila, J; Verges, J; Benito, P

    2005-01-01

    Chondroitin sulfate (CS) and 500-730 kDa hyaluronic acid (HA) are symptomatic slow-acting drugs for the treatment of osteoarthritis (OA). In addition, a growing body of evidence suggests a role for CS and this specific HA as modifiers of the course of OA. The therapeutic efficacy of CS and HA lies in their different mechanisms of action. Stromelysin-1 (metalloprotease-3 [MMP-3]) is a cartilage proteolytic enzyme, which induces cartilage destruction and acts as a mediator of the inflammatory response. However, there are few studies evaluating the in vitro effect of CS and HA on MMP-3 synthesis in human chondrocyte cultures from OA patients. Thus, the aim of the present study was to analyze the effect of CS and HA (500-730 kDa) on MMP-3 synthesis induced by interleukin-1beta (IL-1beta) in chondrocytes from patients with hip OA. Chondrocyte cultures were incubated for 48 h with IL-1beta (2.5 ng/ml) in the absence or presence of different HA 500-730 kDa (Hyalgan, Bioibérica Farma, Barcelona, Spain) concentrations, or alternatively, CS (Condro.san, Bioibérica Farma) at concentrations of 10, 50, 100, 150, 200 and 1,000 microg/ml. The results revealed that both CS and HA (500-730 kDa) inhibited MMP-3 synthesis induced by IL-1beta in human OA chondrocytes. Specifically, CS and HA (500-730 kDa) reduced MMP-3 expression levels at all tested concentrations. Therefore, our study provides new data on the mechanism of action of these drugs, which could help to explain their clinical efficacy in OA patients.

  7. 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. PMID:25767120

  8. 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 Central

    Kuusk, Silja; Sørlie, Morten; Väljamäe, Priit

    2015-01-01

    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 14C-labeled crystalline polymeric substrates 14C chitin nanowhiskers and 14C-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. PMID:25767120

  9. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Activity of Porphyridium sp. polysaccharide against herpes simplex viruses in vitro and in vivo.

    PubMed

    Huheihel, Mahmoud; Ishanu, Vladimir; Tal, Jacov; Arad, Shoshana Malis

    2002-01-01

    The cell wall sulfated polysaccharide of the red microalga Porphyridium sp. exhibited impressive antiviral activity against herpes simplex virus types 1 and 2 (HSV-1 and -2) both in vitro (cell culture) and in vivo (rats and rabbits). Depending on the concentration, this polysaccharide completely inhibited or slowed down the development of the cytopathic effect in HSV-infected cells, but did not show any cytotoxic effects on vero cells even when a concentration as high as 250 microg/ml was used. There was indirect evidence for a strong interaction between the polysaccharide and HSV and a weak interaction with the cell surface. When tested in vivo, Porphyridium sp. polysaccharide conferred significant and efficient protection against HSV-1 infection: at a concentration as low as 100 microg/ml, it prevented the appearance and development of symptoms of HSV-1 infection in rats and rabbits. The polysaccharide did not exhibit any cytotoxic effects at a concentration of 2 mg/ml in vivo.

  12. Heparan sulfate modification of the transmembrane receptor CD47 is necessary for inhibition of T cell receptor signaling by thrombospondin-1.

    PubMed

    Kaur, Sukhbir; Kuznetsova, Svetlana A; Pendrak, Michael L; Sipes, John M; Romeo, Martin J; Li, Zhuqing; Zhang, Lijuan; Roberts, David D

    2011-04-29

    Cell surface proteoglycans on T cells contribute to retroviral infection, binding of chemokines and other proteins, and are necessary for some T cell responses to the matricellular glycoprotein thrombospondin-1. The major cell surface proteoglycans expressed by primary T cells and Jurkat T cells have an apparent M(r) > 200,000 and are modified with chondroitin sulfate and heparan sulfate chains. Thrombospondin-1 bound in a heparin-inhibitable manner to this proteoglycan and to a soluble form released into the medium. Based on mass spectrometry, knockdown, and immunochemical analyses, the proteoglycan contains two major core proteins as follows: amyloid precursor-like protein-2 (APLP2, apparent M(r) 230,000) and CD47 (apparent M(r) > 250,000). CD47 is a known thrombospondin-1 receptor but was not previously reported to be a proteoglycan. This proteoglycan isoform of CD47 is widely expressed on vascular cells. Mutagenesis identified glycosaminoglycan modification of CD47 at Ser(64) and Ser(79). Inhibition of T cell receptor signaling by thrombospondin-1 was lost in CD47-deficient T cells that express the proteoglycan isoform of APLP2, indicating that binding to APLP2 is not sufficient. Inhibition of CD69 induction was restored in CD47-deficient cells by re-expressing CD47 or an S79A mutant but not by the S64A mutant. Therefore, inhibition of T cell receptor signaling by thrombospondin-1 is mediated by CD47 and requires its modification at Ser(64).

  13. 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.

  14. A polysaccharide from Ganoderma atrum inhibits tumor growth by induction of apoptosis and activation of immune response in CT26-bearing mice.

    PubMed

    Zhang, Shenshen; Nie, Shaoping; Huang, Danfei; Huang, Jianqin; Feng, Yanling; Xie, Mingyong

    2014-09-24

    Ganoderma atrum is one species of edible and pharmaceutical mushroom with various biological activities. Recently, a novel polysaccharide, PSG-1, was purified from G. atrum. The antitumor activity and its mechanism of action were studied. In vitro, PSG-1 has little effect on inhibiting proliferation of CT26 tumor cells. However, the tumor size was significantly decreased in PSG-1-treated mice. The results showed that PSG-1 induced apoptosis in CT26 cells. Moreover, the intracellular cyclic AMP (cAMP) level and protein kinase A (PKA) activity were markedly increased in PSG-1-treated mice. In contrast, the contents of cyclic GMP and DAG and the PKC activity were decreased. Similarly, the expression of PKA protein was upregulated, while PKC protein expression in PSG-1-treated group was lowered. Additionally, PSG-1 increased the immune organ index and serum biochemistry parameter. In general, PSG-1 enhances the antitumor immune response, induces apoptosis in CT26-bearing mice, and could be a safe and effective adjuvant for tumor therapy or functional food.

  15. 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

  16. Sulfated glycosaminoglycan deposition and processing at the basal epithelial surface in branching and beta-D-xyloside-inhibited embryonic salivary glands

    SciTech Connect

    Spooner, B.S.; Bassett, K.; Stokes, B.

    1985-05-01

    The authors investigated whether the inhibition of proteoglycan synthesis and salivary branching morphogenesis by beta-D-xyloside was related to the deposition and processing of newly synthesized glycosaminoglycans at the basal epithelial surface that correlates with normal branching activity. Forty eight-hour cultures of control and 0.5 mM beta-xyloside-treated submandibular rudiments were labeled for 2 hr with (/sup 35/S)sulfate and fixed and processed for autoradiography, immediately or after 2, 4, 6, or 8 hr of postlabeling chase in nonradioactive medium. The data demonstrated that deposition of chondroitin sulfate-rich material at the basal epithelial surface was strikingly reduced in beta-xyloside-treated rudiments, while patterns of label loss during postlabeling chase were not altered.

  17. Astragalus polysaccharide inhibits isoprenaline-induced cardiac hypertrophy via suppressing Ca²⁺-mediated calcineurin/NFATc3 and CaMKII signaling cascades.

    PubMed

    Dai, Hongliang; Jia, Guizhi; Liu, Xin; Liu, Zhining; Wang, Hongxin

    2014-07-01

    Pathological cardiac hypertrophy induced by increased sympathetic drive can subsequently lead to congestive heart failure, which represents the major cause of morbidity and mortality worldwide. Astragalus polysaccharide (APS) is an active compound extracted from Chinese herb Astragalus membranaceus (AM), a frequently used "Qi-invigorating" herbal medicine in traditional medicine broadly used for the treatment of cardiovascular and other diseases. Currently, little is known about the effect of APS on cardiac hypertrophy. In the present study, we aimed to investigate its effect on cardiac hypertrophy and to clarify its possible mechanisms. In vitro cardiac hypertrophic model induced by isoprenaline (ISO) was employed to explore the anti-hypertrophic action of APS. We found that 10 μM ISO treatment for 48 h caused cultured cardiomyocytes to undergo significant increases in cell surface area, total protein content, protein synthesis as well as the expression of hypertrophic markers, including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which were effectively inhibited by APS in a dose dependent manner. Moreover, we found that APS pretreatment alleviated the augment of intracellular free calcium during cardiac hypertrophy induced by ISO. Our further study revealed that the upregulated expression of calcineurin, translocation of nuclear factor of activated T cells, cytoplasmic 3 (NFATc3) into nucleus and activation of calmodulin kinase II (reflected by p-CaMKII) were dose dependently suppressed by the application of APS. According to this research, APS exerted its anti-hypertrophic action via inhibiting Ca(2+)-mediated calcineurin/NFATc3 and CaMKII signaling cascades, which provided new insights into the application of APS to the therapy of heart diseases.

  18. 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. PMID:26681734

  19. 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.

  20. The potent activity of sulfated polysaccharide, ascophyllan, isolated from Ascophyllum nodosum to induce nitric oxide and cytokine production from mouse macrophage RAW264.7 cells: Comparison between ascophyllan and fucoidan.

    PubMed

    Jiang, Zedong; Okimura, Takasi; Yamaguchi, Kenichi; Oda, Tatsuya

    2011-11-30

    Ascophyllan isolated from the brown alga Ascophyllum nodosum is a fucose-containing sulfated polysaccharide, which has similar but distinct characteristic monosaccharide composition and entire chemical structure to fucoidan. In this study, we examined the effects of ascophyllan, fucoidan isolated from A. nodosum (A-fucoidan), and fucoidan from Sigma (S-fucoidan) as a representative fucoidan derived from other source (Fucus vesiculosus) on mouse macrophage cell line RAW264.7 cells. No significant cytotoxic effects of ascophyllan and A-fucoidan on RAW264.7 cells were observed up to 1000μg/ml, while S-fucoidan showed cytotoxic effect in a concentration-dependent manner. Ascophyllan induced extremely higher level of nitric oxide (NO) production from RAW264.7 cells than those induced by fucoidans over the concentration range tested (0-200μg/ml). Reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis revealed that expression level of inducible NO synthase (iNOS) in ascophyllan-treated RAW264.7 cells was much higher than the levels detected in the cells treated with fucoidans. Furthermore, the activities of ascophyllan to induce the secretion of tumor necrosis factor-α (TNF-α) and granulocyte colony-stimulating factor (G-CSF) from RAW264.7 cells were also greater than those induced by fucoidans especially at lower concentration range (3.1-50μg/ml). The activities of ascophyllan to induce NO and cytokine production in mouse peritoneal macrophages were also stronger than those of fucoidans. Electrophoretic mobility shift assay (EMSA) using infrared dye labeled nuclear factor-kappa B (NF-κB) and AP-1 consensus sequences suggested that ascophyllan can strongly activate these transcription factors. Marked increase in the nuclear translocation of p65, and the phosphorylation and degradation of IκB-α were also observed in ascophyllan-treated RAW264.7 cells. Analysis using mitogen-activated protein (MAP) kinase inhibitors and western blot

  1. Anticoagulant Heparan Sulfate: Structural Specificity and Biosynthesis

    PubMed Central

    Liu, Jian; Pedersen, Lars C.

    2007-01-01

    Summary Heparan sulfate (HS) is present on the surface of endothelial and surrounding tissues in large quantities. It plays important roles in regulating numerous functions of the blood vessel wall, including blood coagulation, inflammation response and cell differentiation. HS is a highly sulfated polysaccharide containing glucosamine and glucuronic/iduronic acid repeating disaccharide units. The unique sulfated saccharide sequences of HS determine its specific functions. Heparin, an analogue of heparan sulfate, is the most commonly used anticoagulant drug. Because of its wide range of biological functions, HS has become an interesting molecule to biochemists, medicinal chemists and developmental biologists. Here, we summarize recent progress towards understanding the interaction between heparan sulfate and blood coagulating factors, the biosynthesis of anticoagulant heparan sulfate and the mechanism of action of heparan sulfate biosynthetic enzymes. Further, knowledge of the biosynthesis of HS facilitates the development of novel enzymatic approaches to synthesize HS from bacterial capsular polysaccharides and to produce polysaccharide end products with high specificity for the biological target. These advancements provide the foundation for the development of polysaccharide-based therapeutic agents. PMID:17131147

  2. Chondroitin sulfate

    MedlinePlus

    ... is usually manufactured from animal sources, such as shark and cow cartilage. Chondroitin sulfate is used for ... contain chondroitin sulfate, in combination with glucosamine sulfate, shark cartilage, and camphor. Some people also inject chondroitin ...

  3. A procoagulant chemically sulfated mannan.

    PubMed

    Gracher, Ana Helena P; Santana, Aline G; Cipriani, Thales R; Iacomini, Marcello

    2016-01-20

    Disorders of hemostasis can produce innumerous problems. Polysaccharides have been studied both as anticoagulant and as procoagulant agents. A mannan with a main chain of α-(1 → 6)-linked-Manp units, branched at O-2 mainly by side-chains of 2-O-linked-α-Manp units was chemically sulfated, structurally characterized by NMR and GC-MS (methylation, desulfation and methylation with trideuterated iodomethane), and tested in vitro and in vivo on blood coagulation models. Chemical analyses indicate a high degree of substitution on the sulfated polysaccharide. This polymer acted as a procoagulant agent, increasing blood coagulation in normal and hemophilic plasma, activated platelet aggregation and also decreased ex vivo aPTT. Polymers such as the sulfated mannan could be a helpful source of hemostatic agents to prevent hemorrhagic states. PMID:26572344

  4. 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

  5. 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.

  6. 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.

  7. Heparan Sulfate Proteoglycans May Promote or Inhibit Cancer Progression by Interacting with Integrins and Affecting Cell Migration

    PubMed Central

    Soares, Mariana A.; Teixeira, Felipe C. O. B.; Fontes, Miguel; Arêas, Ana Lúcia; Leal, Marcelo G.; Pavão, Mauro S. G.; Stelling, Mariana P.

    2015-01-01

    The metastatic disease is one of the main consequences of tumor progression, being responsible for most cancer-related deaths worldwide. This review intends to present and discuss data on the relationship between integrins and heparan sulfate proteoglycans in health and cancer progression. Integrins are a family of cell surface transmembrane receptors, responsible for cell-matrix and cell-cell adhesion. Integrins' main functions include cell adhesion, migration, and survival. Heparan sulfate proteoglycans (HSPGs) are cell surface molecules that play important roles as cell receptors, cofactors, and overall direct or indirect contributors to cell organization. Both molecules can act in conjunction to modulate cell behavior and affect malignancy. In this review, we will discuss the different contexts in which various integrins, such as α5, αV, β1, and β3, interact with HSPGs species, such as syndecans and perlecans, affecting tissue homeostasis. PMID:26558271

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

    PubMed Central

    Luo, Lan; Wu, Mingyi; Xu, Li; Lian, Wu; Xiang, Jingying; Lu, Feng; Gao, Na; Xiao, Chuang; Wang, Shengmin; Zhao, Jinhua

    2013-01-01

    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. PMID:23385300

  9. 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

    2013-02-01

    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.

  10. Bovine milk-derived α-lactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfate-treated mice.

    PubMed

    Yamaguchi, Makoto; Takai, Shoko; Hosono, Akira; Seki, Taiichiro

    2014-01-01

    Cyclooxygenase-2 is expressed early in colon carcinogenesis and plays crucial role in the progress of the disease. Recently, we found that α-lactalbumin had anti-inflammatory activity by inhibiting cyclooxygenase-2. In experiment 1, we investigated the effects of α-lactalbumin on the colon carcinogenesis initiated with azoxymethane (AOM) followed by promotion with dextran sodium sulfate (DSS) in mice. Dietary treatment with α-lactalbumin decreased fecal occult blood score at 3 days after DSS intake. α-Lactalbumin also decreased the colon tumor at week 9. In experiment 2, AOM-treated mice were sacrificed at 7 days after DSS intake. The plasma and colon prostaglandin E2 (PGE2) levels in AOM/DSS-treated mice were higher than those in the DSS-treated mice without initiation by AOM. α-Lactalbumin decreased PGE2 in both plasma and colon. These results suggest that α-lactalbumin effectively inhibited colon carcinogenesis, and the inhibition may be due to the decreased PGE2 by inhibiting cyclooxygenase-2 at cancer promotion stages. PMID:25036966

  11. Production of immunoregulatory polysaccharides from Crassostrea hongkongensis and their positive effects as a nutrition factor in modulating the effectiveness and toxicity of 5-FU chemotherapy in mice.

    PubMed

    Cai, Bingna; Chen, Hua; Sun, Han; Wan, Peng; Sun, Huili; Pan, Jianyu

    2016-01-01

    Chemotherapy is generally accompanied by undesirable side effects, such as immunosuppression and malnutrition, which reduce tolerance to cancer therapies. Prior studies have shown that immunonutrition improves the clinical outcomes of cancer patients. In this study, immunoregulatory polysaccharides from Crassostrea hongkongensis were included in a nutrition formula that was administered to S180 tumor-bearing mice in combination with 5-fluorouracil (5-FU) treatment. The C30-60% fraction of the polysaccharides was characterized as a branched polysaccharide, with a high amount of d-glucose (96.76% of the total) and the highest uronic acid and sulfate groups' content among all of the polysaccharide fractions. The C30-60% polysaccharide fraction showed a maximal proliferative effect on RAW264.7 cells and T lymphocytes at a concentration of 0.0391 mg mL(-1) and 0.0781 mg mL(-1), respectively. Moreover, the combination treatment of the C30-60% polysaccharide-based nutrition formula (OPNF) with the administration of 5-FU effectively inhibited the growth of tumors and notably increased the leucocyte and lymphocyte counts in S180 tumor-bearing mice. In addition, a slight increase in the erythrocyte and hemoglobin values was observed in the mice treated with the combination of OPNF and 5-FU. These results suggest that supplementation with a C30-60%-based enteral formula would be beneficial for patients undergoing chemotherapy with 5-FU.

  12. Modulation of vascular human endothelial and rat smooth muscle cell growth by a fucosylated chondroitin sulfate from echinoderm.

    PubMed

    Tapon-Bretaudière, J; Drouet, B; Matou, S; Mourão, P A; Bros, A; Letourneur, D; Fischer, A M

    2000-08-01

    Fucosylated chondroitin sulfate is a glycosaminoglycan extracted from the sea cucumber Ludwigothurea grisea. This polysaccharide has the same structure as a mammalian chondroitin sulfate but some of the glucuronic acid residues display sulfated fucose branches. Anticoagulant and antithrombotic properties of fucosylated chondroitin sulfate have already been described. In order to further investigate its potential therapeutic use as an antithrombotic agent, we studied its effect on vascular smooth muscle cell (SMC) proliferation and endothelial cell proliferation, migration and Tissue Factor Pathway Inhibitor (TFPI) release. The experiments were performed on SMC from rat thoracic aorta and on human umbilical vein endothelial cell (HUVEC) in culture with or without added fibroblast growth factors (FGF-1 and FGF-2). Our results showed that: (i) fucosylated chondroitin sulfate had a strong inhibitory effect on SMC proliferation (IC50 =10 +/- 5 microg/ml) and (ii) no effect on HUVEC proliferation and migration assays, in the absence of exogenous FGF, while heparin had inhibitory effects; (iii) fucosylated chondroitin sulfate (10 microg/ml) enhanced FGF-1 and FGF-2 induced HUVEC proliferation by 45% (145.4 +/- 7.2%) and 27% (126.9 +/- 4.2%), respectively; (iv) on FGF-induced HUVEC migration, fucosylated chondroitin sulfate (10 microg/ml) had a strong enhancing effect with FGF-1, +122% (222.2 +/- 15.8%), three times higher than that of heparin, and a lower enhancing effect with FGF-2, +43% (142.7 +/- 4.6%), whereas heparin had no effect; (v) fucosylated chondroitin sulfate stimulated TFPI release, mainly on the free form. +98% (198.2 +/- 25%). In addition, the structural features of the polysaccharide associated with its biological activity were resolved using chemically modified fucosylated chondroitin sulfates. Sulfated fucose branches groups are essential to the potentiating effect of the polysaccharide on HUVEC proliferation and migration. Surprisingly, removal of

  13. Sulfated glycans in network rewiring and plasticity after neuronal injuries.

    PubMed

    Kadomatsu, Kenji; Sakamoto, Kazuma

    2014-01-01

    Biopolymers in the human body belong to three major classes: polynucleotides (DNA, RNA), polypeptides (proteins) and polysaccharides (glycans). Although striking progress in our understanding of neurobiology has been achieved through a focus on polypeptides as the main players, important biological functions are also expected to be attributable to glycans. Nonetheless, the significance of glycans remains largely unexplored. In this review, we focus on the roles of sulfated glycans. Axonal regeneration/sprouting after injuries does not easily occur in the adult mammalian central nervous system. This is due to the low intrinsic potential of regeneration and the emerging inhibitory molecules. The latter include the sulfated long glycans chondroitin sulfate (CS) and keratan sulfate (KS). Enzymatic ablation of CS or KS, and genetic ablation of KS promote functional recovery after spinal cord injury. Interestingly, the combination of CS and KS ablations exhibits neither additive nor synergistic effects. Thus, KS and CS work in the same pathway in inhibition of axonal regeneration/sprouting. Furthermore, CS has been implicated in neural plasticity as a functional component of the perineuronal nets surrounding inhibitory interneurons. Elucidation of the mechanisms of action for KS and CS will pave the way to treatments to promote network rewiring and plasticity after neuronal injuries.

  14. Sulfated alpha-L-galactans from the sea urchin ovary: selective 6-desulfation as eggs are spawned.

    PubMed

    Cinelli, Leonardo P; Andrade, Leonardo; Valente, Ana Paula; Mourão, Paulo A S

    2010-06-01

    The sea urchin eggs are surrounded by a jelly coat, which contains sulfated polysaccharides with unique structures. These molecules are responsible for inducing the species-specific acrosome reaction, an obligatory event for the binding of sperm and fusion with the egg. The mechanism of biosynthesis of these sulfated polysaccharides is virtually unknown. The egg jelly of the sea urchin Echinometra lucunter contains a simple 2-sulfated, 3-linked alpha-L-galactan. Here, we pulse labeled the sea urchin ovary in vitro with (35)S-sulfate to follow the biosynthesis of the sulfated alpha-L-galactan. We found that the ovary contains a 2,6-disulfated, 3-linked alpha-L-galactan, which incorporates (35)S-sulfate more avidly than the 2-sulfated isoform. The 2,6-disulfated alpha-L-galactan was purified by anion exchange chromatography, analyzed by electrophoresis and characterized by 1D and 2D nuclear magnetic resonance spectra. We also investigated the location of the sulfated polysaccharides on the oocytes using histochemical procedures. The stain revealed high amounts of sulfated polysaccharide in mature oocytes and accessory cells. The amount of intracellular sulfated polysaccharides decreased as oocytes are spawned. We speculate that 2,6-disulfated galactan is initially synthesized in the ovary and that 6-sulfate ester is removed when the polysaccharide is secreted into the egg jelly. Similar events related to remodeling of sulfated polysaccharides have been reported in other biological systems.

  15. Arvelexin inhibits colonic inflammation by suppression of NF-κB activation in dextran sulfate sodium-induced mice and TNF-α-induced colonic epithelial cells.

    PubMed

    Cho, Eu-Jin; Shin, Ji-Sun; Chung, Kyung-Sook; Lee, Yong Sup; Cho, Young-Wuk; Baek, Nam-In; Chung, Hae-Gon; Lee, Kyung-Tae

    2012-08-01

    Recently, we reported the anti-inflammatory effects of arvelexin isolated from Brassica rapa in macrophages. In the present study, the effects of arvelexin were investigated in a dextran sulfate sodium (DSS)-induced colitis mouse model and in a cellular model. In the DSS-induced colitis model, arvelexin significantly reduced the severity of colitis, as assessed by disease activity, colonic damage, neutrophil infiltration, and levels of colonic iNOS. Moreover, arvelexin inhibited the expressions of IL-8, IP-10, ICAM-1, and VCAM-1 in HT-29 colonic epithelial cells. Arvelexin also inhibited the TNF-α-induced adhesion of U937 monocytic cells to HT-29 cells. Furthermore, arvelexin reduced p65 NF-κB subunit translocation to the nucleus and IκBα degradation in the colonic tissues and in TNF-α-induced HT-29 cells. These results demonstrate that the ameliorative effects of arvelexin on colonic injury are mainly related to its ability to inhibit the inflammatory responses via NF-κB inactivation, and support its possible therapeutic role in colitis.

  16. Inhibiting mild steel corrosion from sulfate-reducing bacteria using antimicrobial-producing biofilms in Three-Mile-Island process water.

    PubMed

    Zuo, R; Ornek, D; Syrett, B C; Green, R M; Hsu, C-H; Mansfeld, F B; Wood, T K

    2004-04-01

    Biofilms were used to produce gramicidin S (a cyclic decapeptide) to inhibit corrosion-causing, sulfate-reducing bacteria (SRB). In laboratory studies these biofilms protected mild steel 1010 continuously from corrosion in the aggressive, cooling service water of the AmerGen Three-Mile-Island (TMI) nuclear plant, which was augmented with reference SRB. The growth of both reference SRB (Gram-positive Desulfosporosinus orientis and Gram-negative Desulfovibrio vulgaris) was shown to be inhibited by supernatants of the gramicidin-S-producing bacteria as well as by purified gramicidin S. Electrochemical impedance spectroscopy and mass loss measurements showed that the protective biofilms decreased the corrosion rate of mild steel by 2- to 10-fold when challenged with the natural SRB of the TMI process water supplemented with D. orientis or D. vulgaris. The relative corrosion inhibition efficiency was 50-90% in continuous reactors, compared to a biofilm control which did not produce the antimicrobial gramicidin S. Scanning electron microscope and reactor images also revealed that SRB attack was thwarted by protective biofilms that secrete gramicidin S. A consortium of beneficial bacteria (GGPST consortium, producing gramicidin S and other antimicrobials) also protected the mild steel. PMID:12898064

  17. 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

  18. Sulfate reducers can outcompete methanogens at freshwater sulfate concentrations

    SciTech Connect

    Lovley, D.R.; Klug, M.J.

    1983-01-01

    Acetate and hydrogen metabolism by sulfate reducers and methanogens in the profundal sediments of an oligotrophic lake were examined. Inhibition of sulfate reduction with molybdate stimulated methane production from both hydrogen and acetate. Molybdate did not stimulate methane production in sediments that were preincubated to deplete the sulfate pool. Sulfate reduction accounted for 30 to 81% of the total of terminal metabolism proceeding through sulfate reduction and methane production in Eckman grab samples of surface sediments. The ability of sulfate reducers to effectively compete with methanogens for acetate was related to the sulfate reducers lower half-saturation constant for acetate metabolism at in situ sulfate concentrations. Processes other than sulfate reduction and methanogenesis consumed hydrogen at elevated hydrogen partial pressures and prevented a kinetic analysis of hydrogen uptake by sulfate reducers and methanogens. The demonstration that sulfate reducers can successfully compete with methanogens for hydrogen and acetate in sediments at in situ sulfate concentrations of 60 to 105 mM extends the known range of sediment habitats in which sulfate reduction can be a dominant terminal process.

  19. Cloning and characterization of a novel chondroitin sulfate/dermatan sulfate 4-O-endosulfatase from a marine bacterium.

    PubMed

    Wang, Wenshuang; Han, Wenjun; Cai, Xingya; Zheng, Xiaoyu; Sugahara, Kazuyuki; Li, Fuchuan

    2015-03-20

    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.

  20. 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).

  1. 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). PMID:26947454

  2. 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.

  3. 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.

  4. Zinc specifically stimulates the selective binding of a peptide analog of bindin to sulfated fucans.

    PubMed

    DeAngelis, P L; Glabe, C G

    1990-01-01

    A synthetic nonapeptide (Leu-Arg-His-Leu-Arg-His-His-Ser-Asn) derived from the sequence of the sea urchin sperm adhesive protein, bindin, has been shown to bind sulfated fucans in high ionic strength (seawater) conditions. The binding is enhanced by approximately 100-fold in the presence of zinc ions, and no other transition metal tested demonstrates any enhancement. Bindin isolated from sperm contains zinc ion at roughly equimolar concentrations. In the presence of Zn++, the synthetic nonapeptide binds to eggs and inhibits fertilization with a half-maximal effective concentration of 300 microM. The polysaccharide binding selectivity of the peptide/Zn++ complex is similar to bindin but less stringent. Although the order of effectiveness of the inhibitory polysaccharides is the same for bindin and the synthetic peptide, polysaccharides that are only weak inhibitors of fucan binding to bindin show greater effectiveness against the peptide. The effect of chemical modification, pH, and amino acid substitution on the binding properties of the peptide suggest that arginine guanido moieties interact with the sulfated fucans, while histidine groups chelate zinc ions. Although the mechanism of zinc-specific stimulation of fucan binding is not yet clear, one potential explanation is that zinc may stabilize a peptide secondary structure that has a high affinity for fucans.

  5. The Sasa quelpaertensis Leaf Extract Inhibits the Dextran Sulfate Sodium-induced Mouse Colitis Through Modulation of Antioxidant Enzyme Expression

    PubMed Central

    Yeom, Yiseul; Kim, Yuri

    2015-01-01

    Background: Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease. The objective of this study is to investigate the protective effect of Sasa quelpaertensis leaf extract (SQE) against oxidative stress in mice with dextran sulfate sodium (DSS)-induced colitis. Methods: Mice were treated with SQE (100 mg/kg or 300 mg/kg body weight) by gavage in advance two weeks before inflammation was induced. Then, the mice were administered with 2.5% DSS in drinking water for 7 days and normal drinking water for 7 days between two DSS treatment. Disease activity index values, gut motility, and severity of the resulting oxidative DNA damage were analyzed. The antioxidant effect of SQE was evaluated by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) activity in plasma samples. Catalase activity and expressions levels of glutathione peroxidase 1 (Gpx1), SOD1, and SOD2 were also detected in colon tissues. Results: Administration of SQE significantly reduced the severity of DSS-induced colitis compared to the control (Ctrl) group. Levels of 8-oxo-dG, an oxidative DNA damage marker, were significantly lower in the SQE group compared to the untreated DSS Ctrl group. In the SQE (300 mg/kg) group, MDA levels were significantly lower, while SOD and catalase activity levels in the plasma samples were significantly higher compared with the DSS Ctrl group. The expression levels of the antioxidant enzymes, SOD2 and Gpx1, were significantly higher, while the levels of SOD 1 expression were lower, in the colon tissues of the DSS Ctrl group compared with those of the Ctrl group. In contrast, administration of SQE significantly down-regulated SOD2 and Gpx1 expressions and up-regulated SOD1 expression. Conclusions: These results indicate that SQE efficiently suppresses oxidative stress in DSS-induced colitis in mice, and its action is associated with the regulation of antioxidant enzymes. PMID:26151047

  6. 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

  7. The Antiviral Activities and Mechanisms of Marine Polysaccharides: An Overview

    PubMed Central

    Wang, Wei; Wang, Shi-Xin; Guan, Hua-Shi

    2012-01-01

    Recently, the studies on the antiviral activities of marine natural products, especially marine polysaccharides, are attracting more and more attention all over the world. Marine-derived polysaccharides and their lower molecular weight oligosaccharide derivatives have been shown to possess a variety of antiviral activities. This paper will review the recent progress in research on the antiviral activities and the mechanisms of these polysaccharides obtained from marine organisms. In particular, it will provide an update on the antiviral actions of the sulfated polysaccharides derived from marine algae including carrageenans, alginates, and fucans, relating to their structure features and the structure–activity relationships. In addition, the recent findings on the different mechanisms of antiviral actions of marine polysaccharides and their potential for therapeutic application will also be summarized in detail. PMID:23235364

  8. Review on biomedical and bioengineering applications of cellulose sulfate.

    PubMed

    Zhang, Qilei; Lin, Dongqiang; Yao, Shanjing

    2015-11-01

    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.

  9. Review on biomedical and bioengineering applications of cellulose sulfate.

    PubMed

    Zhang, Qilei; Lin, Dongqiang; Yao, Shanjing

    2015-11-01

    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. PMID:26256354

  10. 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. PMID:27223481

  11. Extracellular matrix of smooth muscle cells: interaction of collagen type V with heparan sulfate proteoglycan

    SciTech Connect

    Gay, S.; Hoeoek, M.; Gay, R.E.; Magargal, W.W.; Reynertson, R.H.

    1986-03-05

    Alteration in the extracellular matrix produced by smooth muscle cells may play a role in the development of atherosclerotic lesions. Consequently the authors have initiated studies on the structural organization of the extracellular matrix produced by cultured smooth muscle cells. Immunohisotological examination of this matrix using well-characterized mono- and polyclonal antibodies showed a partial codistribution of heparan sulfate (HS) proteoglycans with a number of different matrix components including collagen types I, III, IV, V and VI, laminin and fibronectin. Subsequent binding studies between isolated matrix proteins and HS showed that the polysaccharide interacts strongly with type V collagen and to a lesser extent with fibronectin as well as collagen types III and VI. The interaction between type V and HS was readily inhibited by heparin and highly sulfated HS but not be dermatan sulfate, chondroitin sulfate or HS with a low sulfate content. Furthermore, (/sup 35/S)-HS proteoglycans isolated from cultured smooth muscle cells could be adsorbed on a column of sepharose conjugated with native type V collagen and eluted in a salt gradient. Hence, the interaction between type V and HS may play a major part in stabilizing the extracellular matrix of the vessel wall.

  12. 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

    2003-02-01

    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

  13. Structure, biology, evolution, and medical importance of sulfated fucans and galactans.

    PubMed

    Pomin, Vitor H; Mourão, Paulo A S

    2008-12-01

    Sulfated fucans and galactans are strongly anionic polysaccharides found in marine organisms. Their structures vary among species, but their major features are conserved among phyla. Sulfated fucans are found in marine brown algae and echinoderms, whereas sulfated galactans occur in red and green algae, marine angiosperms, tunicates (ascidians), and sea urchins. Polysaccharides with 3-linked, beta-galactose units are highly conserved in some taxonomic groups of marine organisms and show a strong tendency toward 4-sulfation in algae and marine angiosperms, and 2-sulfation in invertebrates. Marine algae mainly express sulfated polysaccharides with complex, heterogeneous structures, whereas marine invertebrates synthesize sulfated fucans and sulfated galactans with regular repetitive structures. These polysaccharides are structural components of the extracellular matrix. Sulfated fucans and galactans are involved in sea urchin fertilization acting as species-specific inducers of the sperm acrosome reaction. Because of this function the structural evolution of sulfated fucans could be a component in the speciation process. The algal and invertebrate polysaccharides are also potent anticoagulant agents of mammalian blood and represent a potential source of compounds for antithrombotic therapies. PMID:18796647

  14. Structure, biology, evolution, and medical importance of sulfated fucans and galactans.

    PubMed

    Pomin, Vitor H; Mourão, Paulo A S

    2008-12-01

    Sulfated fucans and galactans are strongly anionic polysaccharides found in marine organisms. Their structures vary among species, but their major features are conserved among phyla. Sulfated fucans are found in marine brown algae and echinoderms, whereas sulfated galactans occur in red and green algae, marine angiosperms, tunicates (ascidians), and sea urchins. Polysaccharides with 3-linked, beta-galactose units are highly conserved in some taxonomic groups of marine organisms and show a strong tendency toward 4-sulfation in algae and marine angiosperms, and 2-sulfation in invertebrates. Marine algae mainly express sulfated polysaccharides with complex, heterogeneous structures, whereas marine invertebrates synthesize sulfated fucans and sulfated galactans with regular repetitive structures. These polysaccharides are structural components of the extracellular matrix. Sulfated fucans and galactans are involved in sea urchin fertilization acting as species-specific inducers of the sperm acrosome reaction. Because of this function the structural evolution of sulfated fucans could be a component in the speciation process. The algal and invertebrate polysaccharides are also potent anticoagulant agents of mammalian blood and represent a potential source of compounds for antithrombotic therapies.

  15. Sulfation of chondroitin. Specificity, degree of sulfation, and detergent effects with 4-sulfating and 6-sulfating microsomal systems

    SciTech Connect

    Sugumaran, G.; Silbert, J.E.

    1988-04-05

    Microsomal preparations from chondroitin 6-sulfate-producing chick embryo epiphyseal cartilage, and from chondroitin 4-sulfate-producing mouse mastocytoma cells, were incubated with UDP-(14C)glucuronic acid and UDP-N-acetylgalactosamine to form non-sulfated proteo(14C)chondroitin. Aliquots of the incubations were then incubated with 3'-phosphoadenylylphosphosulfate (PAPS) in the presence or absence of various detergents. In the absence of detergents, there was good sulfation of this endogenous proteo(14C)chondroitin by the original microsomes from both sources. Detergents, with the exception of Triton X-100, markedly inhibited sulfation in the mast cell system but not in the chick cartilage system. These results indicate that sulfation and polymerization are closely linked on cell membranes and that in some cases this organization can be disrupted by detergents. When aliquots of the original incubation were heat inactivated, and then reincubated with new microsomes from chick cartilage and/or mouse mastocytoma cells plus PAPS, there was no significant sulfation of this exogenous proteo(14C) chondroitin with either system unless Triton X-100 was added. Sulfation of exogenous chondroitin and chondroitin hexasaccharide was compared with sulfation of endogenous and exogenous proteo(14C)chondroitin. Sulfate incorporation into hexasaccharide and chondroitin decreased as their concentrations (based on uronic acid) approached that of the proteo(14C)chondroitin. At the same time, the degree of sulfation in percent of substituted hexosamine increased. However, the degree of sulfation did not reach that of the endogenous proteo(14C)chondroitin. Hexasaccharide and chondroitin sulfation were stimulated by the presence of Triton X-100. However, in contrast to the exogenous proteo(14C)chondroitin, there was some sulfation of hexasaccharide and chondroitin in the absence of this detergent.

  16. 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

  17. Brittlestars contain highly sulfated chondroitin sulfates/dermatan sulfates that promote fibroblast growth factor 2-induced cell signaling.

    PubMed

    Ramachandra, Rashmi; Namburi, Ramesh B; Ortega-Martinez, Olga; Shi, Xiaofeng; Zaia, Joseph; Dupont, Sam T; Thorndyke, Michael C; Lindahl, Ulf; Spillmann, Dorothe

    2014-02-01

    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.

  18. 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.

  19. Role of basic amino acids in the interaction of bindin with sulfated fucans.

    PubMed

    DeAngelis, P L; Glabe, C G

    1988-10-18

    Bindin, the acrosomal sperm adhesion protein of the sea urchin Strongylocentrotus purpuratus, binds specifically and with high affinity (Kd = 10(-8) M) to egg sulfated fucans in the high ionic strength milieu of seawater (0.55 M salt). Previous studies indicated that the negatively charged sulfate groups of the polysaccharide are critical for binding which suggested a binding mechanism involving basic residues of bindin. We found that the binding of fucan to bindin or polyarginine is stable at the ionic strength of seawater, whereas the binding of fucan to polylysine or polyhistidine is inhibited by 50% or more at this ionic strength. Group-specific modification of either arginine, lysine, or histidine residues of bindin results in a substantial inactivation of fucan binding activity. Preincubation of bindin with fucan can almost completely protect bindin from inactivation by arginine-specific reagents, butanedione and phenylglyoxal, but only moderately slowed the inactivation by the histidine reagent diethyl pyrocarbonate. In contrast, prior fucan binding could not prevent loss of activity by the reaction of citraconic anhydride with lysine residues. Other sulfated polysaccharides which do not interact strongly with bindin did not protect binding from phenylglyoxal-mediated inactivation when 800-3000-fold more polysaccharide than fucan was used during the preincubation before modification. We found that the larger and more hydrophobic arginine-modifying reagents, camphorquinone-10-sulfonic acid and cyclohexanedione, fail to inactivate fucan binding, suggesting that essential arginine residues may reside in an environment with restricted accessibility to these reagents. Parallel kinetic studies monitoring [14C]phenylglyoxal incorporation and fucan binding inactivation indicate that several of the four total arginine residues may be critical for fucan binding.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Sulfate retention and release in soils at Panola Mountain, Georgia

    USGS Publications Warehouse

    Shanley, J.B.

    1992-01-01

    Inorganic sulfate pools, sulfate sorption characteristics, and Fe and Al fractions were determined on soils at Panola Mountain, a 41-ha forested watershed in the Georgia Piedmont. Sulfate sorption properties of these soils fall along a continuum between two end members. The "low-adsorbing' end member comprises shallow soils (0-10 cm), with high water-soluble sulfate (Sw), low phosphate-extractable sulfate (Sp-w), high organic matter, low sulfate retention ability, and high sulfate adsorption reversibility. The "high-adsorbing' end member comprises deeper soils (>10 cm), with higher total native sulfate (mostly as Sp-w), low organic matter, high sulfate retention ability, and low sulfate adsorption reversibility. Sulfate retention was only weakly related to Fe and Al fractions, possibly because of inhibition of adsorption by organic matter. Sulfate concentrations in surface waters reflect the spatial distribution of soil sulfate retention properties. -from Author

  1. Effect of Porphyridium sp. polysaccharide on malignant cell transformation by Moloney murine sarcoma virus.

    PubMed

    Huleihel, M; Arad, S

    2001-01-01

    The polysaccharide produced by the red microalga Porphyridium sp. was highly inhibitory for cell transformation of mouse fibroblast cells by an MSV-124 virus stock. This inhibition was most effective if the polysaccharide was added 2 h before or at the time of infection. The finding that the inhibition of cell transformation by MuSV-124 was reversible after removal of the polysaccharide suggested that Porphyridium sp. polysaccharide inhibited a late step after provirus integration into the host genome. Addition of the polysaccharide post-infection significantly reduced the number of transformed cells, but its effect was less marked than that obtained when the polysaccharide was added before or at the time of infection. These findings support the possibility that the polysaccharide may affect early steps in virus replication cycle, such as virus absorption into the host cells, in addition to its effect on a late step after provirus integration.

  2. 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

  3. The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer.

    PubMed

    Tamae, Daniel; Mostaghel, Elahe; Montgomery, Bruce; Nelson, Peter S; Balk, Steven P; Kantoff, Philip W; Taplin, Mary-Ellen; Penning, Trevor M

    2015-06-01

    Prostate cancer is the second leading cause of cancer death in the United States. Treatment of localized high-risk disease and de novo metastatic disease frequently leads to relapse. These metastatic castration resistant prostate cancers (mCRPC) claim a high mortality rate, despite the extended survival afforded by the growing armamentarium of androgen deprivation, radiation and immunotherapies. Here, we review two studies of neoadjuvant treatment of high-risk localized prostate cancer prior to prostatectomy, the total androgen pathway suppression (TAPS) trial and the neoadjuvant abiraterone acetate (AA) trial. These two trials assessed the efficacy of the non-specific P450c17 inhibitor, ketoconazole and the specific P450c17 inhibitor, AA, to inhibit tissue and serum androgen levels. Furthermore, a novel and validated stable isotope dilution liquid chromatography electrospray ionization selected reaction monitoring mass spectrometry assay was used to accurately quantify adrenal and gonadal androgens in circulation during the course of these trials. The adrenal androgens, Δ(4)-androstene-3,17-dione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly reduced in the patients receiving ketoconazole or AA compared to those who did not. However, in both trials, a significant amount of DHEA-S (∼20 μg/dL) persists and thus may serve as a depot for intratumoral conversion to the potent androgen receptor ligands, testosterone (T) and 5α-dihydrotestosterone (DHT). The final step in conversion of Δ(4)-androstene-3,17-dione and 5α-androstanedione to T and DHT, respectively, is catalyzed by AKR1C3. We therefore present the case that in the context of the DHEA-S depot, P450c17 and AKR1C3 inhibition may be an effective combinatorial treatment strategy.

  4. 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.

  5. Sodium Dodecyl Sulfate-Modified Doxorubicin-Loaded Chitosan-Lipid Nanocarrier with Multi Polysaccharide-Lecithin Nanoarchitecture for Augmented Bioavailability and Stability of Oral Administration In Vitro and In Vivo.

    PubMed

    Su, Chia-Wei; Chiang, Min-Yu; Lin, Yu-Ling; Tsai, Nu-Man; Chen, Yen-Po; Li, Wei-Ming; Hsu, Chin-Hao; Chen, San-Yuan

    2016-05-01

    For oral anti-cancer drug delivery, a new chitosan-lipid nanoparticle with sodium dodecyl sulfate modification was designed and synthesized using a double emulsification. TEM examination showed that the DOX-loaded nanoparticles, termed D-PL/TG NPs, exhibited a unique core-shell configuration composed of multiple amphiphilic chitosan-lecithin reverse micelles as the core and a triglyceride shell as a physical barrier to improve the encapsulation efficiency and reduce the drug leakage. In addition, the D-PL/TG NPs with sodium dodecyl sulfate modification on the surface have enhanced stability in the GI tract and increased oral bioavailability of doxorubicin. In vitro transport studies performed on Caco-2 monolayers indicated that the D-PL/TG NPs enhanced the permeability of DOX in the Caco-2 monolayers by altering the transport pathway from passive diffusion to transcytosis. The in vivo intestinal absorption assay suggested that the D-PL/TG NPs were preferentially absorbed through the specialized membranous epithelial cells (M cells) of the Peyer's patches, resulting in a significant improvement (8-fold) in oral bioavailability compared to that of free DOX. The experimental outcomes in this work demonstrate that the D-PL/TG NPs provide an exciting opportunity for advances in the oral administration of drugs with poor bioavailability that are usually used in treating tough and chronic diseases. PMID:27305818

  6. 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

  7. 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.

  8. Structural Analysis and Anti-Complement Activity of Polysaccharides from Kjellmaniella crsaaifolia

    PubMed Central

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

    2015-01-01

    Two polysaccharides, named KCA and KCW, were extracted from Kjellmaniella crassifolia using dilute hydrochloric acid and water, respectively. Composition analysis showed that these polysaccharides predominantly consisted of fucose, with galactose, mannose and glucuronic acid as minor components. After degradation and partial desulfation, electrospray ionization mass spectrometry (ESI-MS) was performed, which showed that the polysaccharides consisted of sulfated fucooligosaccharides, sulfated galactofucooligosaccharides and methyl glycosides of mono-sulfated/multi-sulfated fucooligosaccharides. The structures of the oligomeric fragments were further characterized by electrospray ionization collision-induced dissociation tandem mass spectrometry (ESI-CID-MS2 and ESI-CID-MS3). Moreover, the activity of KCA and KCW against the hemolytic activity of both the classical and alternative complement pathways was determined. The activity of KCA was found to be similar to KCW, suggesting that the method of extraction did not influence the activity. In addition, the degraded polysaccharides (DKCA and DKCW) displayed lower activity levels than the crude polysaccharides (KCA and KCW), indicating that molecular weight had an effect on activity. Moreover, the desulfated fractions (ds-DKCA and ds-DKCW) showed less or no activity, which confirmed that sulfate was important for activity. In conclusion, polysaccharides from K. crassifolia may be good candidates for the treatment of diseases involving the complement pathway. PMID:25786064

  9. Antibiofilm activity of Actinobacillus pleuropneumoniae serotype 5 capsular polysaccharide.

    PubMed

    Karwacki, Michael T; Kadouri, Daniel E; Bendaoud, Meriem; Izano, Era A; Sampathkumar, Vandana; Inzana, Thomas J; Kaplan, Jeffrey B

    2013-01-01

    Cell-free extracts isolated from colony biofilms of Actinobacillus pleuropneumoniae serotype 5 were found to inhibit biofilm formation by Staphylococcus aureus, S. epidermidis and Aggregatibacter actinomycetemcomitans, but not by A. pleuropneumoniae serotype 5 itself, in a 96-well microtiter plate assay. Physical and chemical analyses indicated that the antibiofilm activity in the extract was due to high-molecular-weight polysaccharide. Extracts isolated from a mutant strain deficient in the production of serotype 5 capsular polysaccharide did not exhibit antibiofilm activity. A plasmid harboring the serotype 5 capsule genes restored the antibiofilm activity in the mutant extract. Purified serotype 5 capsular polysaccharide also exhibited antibiofilm activity against S. aureus. A. pleuropneumoniae wild-type extracts did not inhibit S. aureus growth, but did inhibit S. aureus intercellular adhesion and binding of S. aureus cells to stainless steel surfaces. Furthermore, polystyrene surfaces coated with A. pleuropneumoniae wild-type extracts, but not with capsule-mutant extracts, resisted S. aureus biofilm formation. Our findings suggest that the A. pleuropneumoniae serotype 5 capsule inhibits cell-to-cell and cell-to-surface interactions of other bacteria. A. pleuropneumoniae serotype 5 capsular polysaccharide is one of a growing number of bacterial polysaccharides that exhibit broad-spectrum, nonbiocidal antibiofilm activity. Future studies on these antibiofilm polysaccharides may uncover novel functions for bacterial polysaccharides in nature, and may lead to the development of new classes of antibiofilm agents for industrial and clinical applications. PMID:23691104

  10. Antibiofilm Activity of Actinobacillus pleuropneumoniae Serotype 5 Capsular Polysaccharide

    PubMed Central

    Karwacki, Michael T.; Kadouri, Daniel E.; Bendaoud, Meriem; Izano, Era A.; Sampathkumar, Vandana; Inzana, Thomas J.; Kaplan, Jeffrey B.

    2013-01-01

    Cell-free extracts isolated from colony biofilms of Actinobacillus pleuropneumoniae serotype 5 were found to inhibit biofilm formation by Staphylococcus aureus, S. epidermidis and Aggregatibacter actinomycetemcomitans, but not by A. pleuropneumoniae serotype 5 itself, in a 96-well microtiter plate assay. Physical and chemical analyses indicated that the antibiofilm activity in the extract was due to high-molecular-weight polysaccharide. Extracts isolated from a mutant strain deficient in the production of serotype 5 capsular polysaccharide did not exhibit antibiofilm activity. A plasmid harboring the serotype 5 capsule genes restored the antibiofilm activity in the mutant extract. Purified serotype 5 capsular polysaccharide also exhibited antibiofilm activity against S. aureus. A. pleuropneumoniae wild-type extracts did not inhibit S. aureus growth, but did inhibit S. aureus intercellular adhesion and binding of S. aureus cells to stainless steel surfaces. Furthermore, polystyrene surfaces coated with A. pleuropneumoniae wild-type extracts, but not with capsule-mutant extracts, resisted S. aureus biofilm formation. Our findings suggest that the A. pleuropneumoniae serotype 5 capsule inhibits cell-to-cell and cell-to-surface interactions of other bacteria. A. pleuropneumoniae serotype 5 capsular polysaccharide is one of a growing number of bacterial polysaccharides that exhibit broad-spectrum, nonbiocidal antibiofilm activity. Future studies on these antibiofilm polysaccharides may uncover novel functions for bacterial polysaccharides in nature, and may lead to the development of new classes of antibiofilm agents for industrial and clinical applications. PMID:23691104

  11. 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.

  12. 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

  13. G1-4A, a Polysaccharide from Tinospora cordifolia Inhibits the Survival of Mycobacterium tuberculosis by Modulating Host Immune Responses in TLR4 Dependent Manner.

    PubMed

    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

  14. G1-4A, a Polysaccharide from Tinospora cordifolia Inhibits the Survival of Mycobacterium tuberculosis by Modulating Host Immune Responses in TLR4 Dependent Manner.

    PubMed

    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.

  15. Polysaccharides from the green seaweed Codium decorticatum. Structure and cell wall distribution.

    PubMed

    Fernández, Paula Virginia; Raffo, María Paula; Alberghina, Josefina; Ciancia, Marina

    2015-03-01

    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.

  16. [Regulation of sulfates, hydrogen sulfide and heavy metals in technogenic reservoirs by sulfate-reducing bacteria].

    PubMed

    Hudz', S P; Peretiatko, T B; Moroz, O M; Hnatush, S O; Klym, I R

    2011-01-01

    Sulfate-reducing bacteria Desulfovibrio desulfuricans Ya-11 in the presence of sulfates and organic compounds in the medium reduce sulfates to hydrogen sulfide (dissimilatory sulfate reduction). Heavy metals in concentration over 2 mM inhibit this process. Pb2+, Zn2+, Ni2+, Co2+, Fe2+ and Cd2+ ions in concentration 1-1.5 mM display insignificant inhibiting effect on sulfate reduction process, and metals precipitate in the form of sulfides. At concentrations of heavy metals 2-3 mM one can observe a decrease of sulfates reduction intensity, and a percent of metals binding does not exceed 72%. Obtained results give reason to confirm, that sulfate-reducing bacteria play an important role in regulation of the level of sulfates, hydrogen sulfide and heavy metals in reservoirs and they may be used for purification of water environment from these compounds.

  17. 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.

  18. 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. PMID:25954912

  19. Fucosylated chondroitin sulfates from the body wall of the sea cucumber Holothuria forskali: conformation, selectin binding, and biological activity.

    PubMed

    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

    2014-10-10

    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 Le(x) 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 Cu(2+)-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.

  20. 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

  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. 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

  3. 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.

  4. Inter vs. intraglycosidic acetal linkages control sulfation pattern in semi-synthetic chondroitin sulfate.

    PubMed

    Laezza, Antonio; De Castro, Cristina; Parrilli, Michelangelo; Bedini, Emiliano

    2014-11-01

    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.

  5. Effect of Nitrogen on Polysaccharide Production in a Porphyridium sp.

    PubMed

    Arad, S M; Friedman, O D; Rotem, A

    1988-10-01

    Porphyridium cultures grown on either nitrate or ammonium as the nitrogen source showed similar patterns of growth and cell wall polysaccharide production. The effect of nitrogen on growth and cell wall polysaccharide production was studied by applying three regimens of supply: batch mode, in which nitrate was supplied at the beginning of the experiment and became depleted at day 6; continual mode, in which nitrate was added daily; and deficient mode, in which the cells were cultured in a nitrate-free medium. Growth was similar in the batch- and continual-mode cultures, whereas it was totally inhibited in the deficient-mode culture. Polysaccharide content (per volume) was highest in the batch-mode culture and lowest in the deficient-mode culture. However, polysaccharide production per cell was similar in the continual- and deficient-mode cultures, the highest value being found in the batch-mode culture. In addition to its effect on polysaccharide content, nitrogen affected the polysaccharide distribution between soluble and bound polysaccharides. In the deficientmode culture, most of the cell wall polysaccharide was dissolved in the medium.

  6. POLYSACCHARIDE OF COCCIDIOIDES IMMITIS

    PubMed Central

    Pappagianis, D.; Putman, E. W.; Kobayashi, G. S.

    1961-01-01

    Pappagianis, D. (University of California, Berkeley), E. W. Putman, and G. S. Kobayashi. Polysaccharide of Coccidioides immitis. J. Bacteriol. 82:714–723. 1961.—Soluble polysaccharide from mycelia or culture filtrates of Coccidioides immitis was found to consist mainly of mannose, but also included small quantities of galactose and another reducing sugar. Isolation of the polysaccharide by ethanol precipitation provided accompanying nitrogenous material. There was 3 to 4% nitrogen, present in amino acids, but in a nondialyzable (possibly protein or peptide) form. The average molecular weight of the complex was 31,700. Attempts to separate the nitrogenous and polysaccharide materials by chemical methods or by moving boundary electrophoresis were unsuccessful; ultracentrifugation showed a single peak. Despite these findings, there appeared to be several antigenic species present, as indicated by multiple lines of precipitation in double diffusion and quantitative precipitin tests. In the latter, polysaccharide-containing fractions gave precipitates without measurable carbohydrate, suggesting separability of nitrogenous and polysaccharide components. Images PMID:14483753

  7. Effect of sulfide inhibition and organic shock loading on anaerobic biofilm reactors treating a low-temperature, high-sulfate wastewater.

    PubMed

    McDonald, Heather B; Parkin, Gene F

    2009-03-01

    To assess the long-term treatment of sulfate- and carbon-rich wastewater at low temperatures, anaerobic biofilm reactors were operated for over 900 days at 20 degrees C and fed wastewater containing lactate and sulfate. Results showed the reactors could be operated at 20 degrees C with a load rate of 1.3 g-chemical oxygen demand (COD)/L x d or less and a sulfur loading rate (SLR) of 0.2 g-S/L x d, with no significant deterioration in performance. With acclimation periods, load rates of 3.4 g-COD/L x d and SLR of 0.3 g/L x d could be tolerated. Effluent dissolved sulfide and hydrogen sulfide levels were approximately 600 and 150 mg-S/L, respectively, during this period. The effect of organic shock loading was also assessed. Reactors appeared to recover from one, but not two, lactate spikes of approximately 5000 mg-COD/L. Long-term stability was achieved in reactors containing large, stable populations of lactate- and propionate-degrading sulfate-reducing bacteria and aceticlastic methanogens.

  8. 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. PMID:26631293

  9. 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.

  10. 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. PMID:26838028

  11. Chemically sulfated galactomannan from Dimorphandra gardneriana seed: characterization and toxicity evaluation.

    PubMed

    Moura Neto, E; Sombra, V G; Richter, A R; Abreu, C M W S; Maciel, J S; Cunha, P L R; Ono, L; Sierakowski, M R; Feitosa, J P A; de Paula, R C M

    2014-01-30

    Dimorphandra gardneriana galactomannan (DG) was sulfated in pyridine:formamide using chlorosulfonic acid as the sulfation agent. The degree of substitution was 0.32, determined from the sulfur percentage. Confirmation of sulfation was obtained by FTIR spectroscopy through the presence of an asymmetrical SO stretching vibration at 1,259 cm(-1). NMR data showed that the sulfation occurred on primary hydroxyl groups. NMR and GPC data indicate degradation during reaction with elimination of galactose. At the maximum tested concentration of 1,000 μg/mL, unmodified DG polysaccharide did not show a statistically significant cytotoxicity in Vero cells by the MTT method. Therefore, the CC50>1,000 μg/mL obtained for the sulfated polysaccharides from D. gardneriana in Vero cells point to its lower cytotoxicity than the sulfated galactomannan from Mimosa scabrella.

  12. Fractionation and Biological Activities of Water-Soluble Polysaccharides from Sclerotium of Tiger Milk Medicinal Mushroom, Lignosus rhinocerotis (Agaricomycetes).

    PubMed

    Keong, Choong Yew; B, Vimala; Daker, Maelinda; Hamzah, Mohd Yusof; Mohamad, Shaiful Azuar; Lan, Jin; Chen, Xiangdong; Yang, Yu-Ping

    2016-01-01

    This study investigated antioxidant and anti-inflammatory properties, and the direct cytotoxic effect of Lignosus rhinocerotis fractions, especially the polysaccharide fraction, on nasopharyngeal carcinoma cells. L. rhinocerotis crude extract was obtained through hot water extraction. The precipitate saturated with 30% ammonium sulfate was purified with ion-exchanged chromatography. Gel permeation chromatography multiangle laser light scattering analysis equipped with light scattering and UV signals revealed two district groups of polymers. A total of four peaks were observed in the total carbohydrate test. Fraction C, which was the second region of the second peak eluted with 0.3 M NaOH, showed the highest integrated molecular weight, whereas fraction E had the lowest integrated molecular weight of 19,790 Da. Fraction A contained the highest β-D-glucan content. Enzymatic analysis showed that most of the polysaccharide fractions contained β-1-3 and β-1-6 skeletal backbones. The peak eluted with 0.6 M NaOH was separated in fraction D (flask 89-92) and fraction E (93-96). The results showed that fraction E expressed higher antioxidant activities than fraction D whereas fraction D expressed higher chelating activity than fraction E. The extract saturated with 30% ammonium sulfate exhibited higher reducing power than the extract saturated with 100% ammonium sulfate. Fractions D and E significantly inhibited the secretion of tumor necrosis factor-α in lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. There was no apparent difference in the viability of cells exposed or unexposed to L. rhinocerotis fractions. PMID:27279536

  13. Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels.

    PubMed

    Giménez-Bastida, Juan Antonio; González-Sarrías, Antonio; Vallejo, Fernando; Espín, Juan Carlos; Tomás-Barberán, Francisco A

    2016-01-01

    Epidemiological, clinical and preclinical studies have reported the protection offered by citrus consumption, mainly orange, against cardiovascular diseases, which is primarily mediated by the antiatherogenic and vasculoprotective effects of the flavanone hesperetin-7-O-rutinoside (hesperidin). However, flavanone aglycones or glycosides are not present in the bloodstream but their derived phase-II metabolites could be the actual bioactive molecules. To date, only a few studies have explored the effects of circulating hesperetin-derived metabolites (glucuronides and sulfates) on endothelial cells. Herein, we describe for the first time the effects of hesperetin 3'-O-glucuronide, hesperetin 7-O-glucuronide, hesperetin 3'-O-sulfate, hesperetin 7-O-sulfate and hesperetin on human aortic endothelial cell (HAEC) migration upon pro-inflammatory stimuli as an essential step to angiogenesis. Hesperetin and its derived metabolites, at physiologically relevant concentrations (1-10 μM), significantly attenuated cell migration in the presence of the pro-inflammatory cytokine TNF-α (50 ng mL(-1)), which was accompanied and perhaps mediated by a significant decrease in the levels of the thrombogenic plasminogen activator inhibitor-1 (PAI-1). However, hesperetin metabolites did not counteract the TNF-α-induced production of pro-inflammatory interleukin-6 (IL-6) and IL-8. We also study here for the first time, the metabolism of hesperetin and its derived metabolites by HAEC with and without a pro-inflammatory stimulus. All these results reinforce the concept according to which circulating phase-II hesperetin metabolites are critical molecules contributing to the cardioprotective effects upon consumption of citrus fruits such as orange.

  14. A fucosylated chondroitin sulfate from echinoderm modulates in vitro fibroblast growth factor 2-dependent angiogenesis.

    PubMed

    Tapon-Bretaudière, Jacqueline; Chabut, Delphine; Zierer, Maximiliano; Matou, Sabine; Helley, Dominique; Bros, Andrée; Mourão, Paulo A S; Fischer, Anne-Marie

    2002-12-01

    Fucosylated chondroitin sulfate (FucCS), a glycosaminoglycan obtained from sea cucumber, has the same structure as mammalian chondroitin sulfate, but some of the glucuronic acid residues display sulfated fucose branches. This new polysaccharide has a more favorable effect than heparin on vascular cell growth. It inhibits smooth muscle cell proliferation as heparin, and it has a potent enhancing effect on endothelial cell proliferation and migration in the presence of heparin-binding growth factors. We now extend our studies to the effect of this glycosaminoglycan on endothelial cells to an in vitro angiogenesis model on Matrigel. FucCS, in the presence of fibroblast growth factor-2 (FGF-2), strongly increases the capacity of endothelial cells to form vascular tubes on Matrigel with a well-organized capillary-like network and typical closed structures. Comparison between the activity of native and chemically modified chondroitin sulfate from sea cucumber reveals that the sulfated fucose branches are the structural motif for the proangiogenic activity. Heparin does not induce angiogenesis in this experimental model. We also have evidence for the proposition that endothelial cell proliferation is not the sole event involved in the in vitro FGF-2-induced angiogenesis. It implies a variety of other modifications of the endothelial cells and of their interaction with the extracellular matrix, such as integrin expression and actin cytoskeleton reorganization. Finally, the proangiogenic effect of FucCS, concomitant with its capacity to prevent venous and arterial thrombosis, in animal models makes this new glycosaminoglycan a promising molecule with possible beneficial effects in pathological conditions affecting blood vessels such as the neovascularization of ischemic areas.

  15. 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

  16. Immunogenicity of meningococcal B polysaccharide conjugated to tetanus toxoid or CRM197 via adipic acid dihydrazide.

    PubMed

    Bartoloni, A; Norelli, F; Ceccarini, C; Rappuoli, R; Costantino, P

    1995-04-01

    Vaccine development against Group B Neisseria meningitidis is complicated by the nature of the capsular polysaccharide, which is alpha 2-8-linked poly-sialic acid, identical in structure to the poly-sialic acid found in many mammalian tissues during development. To test the feasibility of a vaccine based on this polysaccharide, we synthesized several conjugates of meningococcal B polysaccharide linked to a carrier protein (tetanus toxoid or diphtheria CRM197), via an adipic acid dihydrazide (ADH) spacer. All conjugates induced a strong immune response. However, most of the antibodies were not directed against the Meningococcus B polysaccharide and could not be inhibited by the purified polysaccharide alone. Further investigations showed that the antibodies recognized an epitope composed by the junction between the spacer and the polysaccharide and protein, that is not present in the native polysaccharide and is generated during the coupling reaction. This epitope becomes immunodominant with respect to the poorly immunogenic polysaccharide. While the majority of the immune response is directed against the above epitope, the conjugates induced also an immune response against the Meningococcus B polysaccharide. The anti-Meningococcus B antibodies elicited are of the IgM and IgG class and are inhibitable by the polysaccharide. Moreover, they are bactericidal, thus suggesting that they would induce protection against disease. PMID:7543714

  17. 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

  18. 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.

  19. 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

    2015-04-01

    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

  20. 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

    2016-06-01

    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. PMID:27083372

  1. 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...

  2. 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.

  3. Selectin blocking activity of a fucosylated chondroitin sulfate glycosaminoglycan from sea cucumber. Effect on tumor metastasis and neutrophil recruitment.

    PubMed

    Borsig, Lubor; Wang, Lianchun; Cavalcante, Moises C M; Cardilo-Reis, Larissa; Ferreira, Paola L; Mourão, Paulo A S; Esko, Jeffrey D; Pavão, Mauro S G

    2007-05-18

    Heparin is an excellent inhibitor of P- and L-selectin binding to the carbohydrate determinant, sialyl Lewis(x). As a consequence of its anti-selectin activity, heparin attenuates metastasis and inflammation. Here we show that fucosylated chondroitin sulfate (FucCS), a polysaccharide isolated from sea cucumber composed of a chondroitin sulfate backbone substituted at the 3-position of the beta-D-glucuronic acid residues with 2,4-disulfated alpha-L-fucopyranosyl branches, is a potent inhibitor of P- and L-selectin binding to immobilized sialyl Lewis(x) and LS180 carcinoma cell attachment to immobilized P- and L-selectins. Inhibition occurs in a concentration-dependent manner. Furthermore, FucCS was 4-8-fold more potent than heparin in the inhibition of the P- and L-selectin-sialyl Lewis(x) interactions. No inhibition of E-selectin was observed. FucCS also inhibited lung colonization by adenocarcinoma MC-38 cells in an experimental metastasis model in mice, as well as neutrophil recruitment in two models of inflammation (thioglycollate-induced peritonitis and lipopolysaccharide-induced lung inflammation). Inhibition occurred at a dose that produces no significant change in plasma activated partial thromboplastin time. Removal of the sulfated fucose branches on the FucCS abolished the inhibitory effect in vitro and in vivo. Overall, the results suggest that invertebrate FucCS may be a potential alternative to heparin for blocking metastasis and inflammatory reactions without the undesirable side effects of anticoagulant heparin.

  4. 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.

  5. Increased calcium affinity of a fucosylated chondroitin sulfate from sea cucumber.

    PubMed

    Ruggiero, J; Vieira, R P; Mourão, P A

    1994-04-01

    Calcium binding and charge distribution on a fucosylated chondroitin sulfate and a standard chondroitin 6-sulfate have been studied using a metallochromic indicator and conductimetric titrations. The fucosylated chondroitin sulfate has a approximately 5-fold greater affinity for calcium ions than the standard chondroitin 6-sulfate. Possibly, this increased affinity for calcium ions is due to the branches on the fucosylated chondroitin sulfate, since the calcium affinity of an unbranched, sulfated fucan is similar to that of the standard chondroitin 6-sulfate. More charged groups per disaccharide unit (and a shorter distance between these groups) also distinguish the fucosylated chondroitin sulfate from standard chondroitin 6-sulfate. Comparison between native and chemically modified (desulfated or carboxyl-reduced) polysaccharides suggests that the sulfate esters are responsible for the increased charge density of the fucosylated chondroitin sulfate and that the presence of the fucose branches does not alter the length of the repetitive units which compose the central core of chondroitin from sea cucumber. These results are consistent with the chemical studies of these two polysaccharides.

  6. 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

  7. Structural analysis of sulfated fucans by high-field NMR.

    PubMed

    Mulloy, B; Ribeiro, A C; Vieira, R P; Mourão, P A

    1994-02-01

    The structures of several sulfated polysaccharides isolated from marine organisms have been determined by a combination of degradative and spectroscopic techniques. For two sulphated fucans, one isolated from the sea cucumber L. grisea, and one from the sea urchin L. variegatus, a novel type of polysaccharide structure is proposed based on the analysis of one- and two-dimensional nuclear magnetic resonance (NMR) spectra. Both polysaccharides are linear, 1-->3 linked alpha-L-fucans in which a four-residue repeating unit is defined by specific patterns of sulfation at the 2- and 4-positions. The four residues give rise to spin systems which may be identified by 2-dimensional 1H-1H correlated spectroscopy (COSY), and the sequence of the residues is deduced from inter-residue nuclear Overhauser enhancements which produce cross-peaks in the NOESY spectrum. To the best of our knowledge, these are the first polysaccharides for which a regular repeating unit is defined by the pattern of sulfate substitution alone.

  8. Microbial extracellular polysaccharides and plagioclase dissolution

    NASA Astrophysics Data System (ADS)

    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 ≈ 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 ≈ 3, below the pK 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.

  9. 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.

  10. 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. PMID:26595186

  11. 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.

  12. Different antithrombotic mechanisms among glycosaminoglycans revealed with a new fucosylated chondroitin sulfate from an echinoderm.

    PubMed

    Pacheco, R G; Vicente, C P; Zancan, P; Mourão, P A

    2000-09-01

    The antithrombotic activity of a fucosylated chondroitin sulfate extracted from the body wall of a sea cucumber was assessed using a stasis thrombosis model in rats. Intravenous administration of the polysaccharide reduced thrombosis in a dose-dependent manner. We also compared the antithrombotic action of the sea cucumber chondroitin sulfate with that of standard mammalian glycosaminoglycans, mainly heparin and dermatan sulfate. Intravascular injection of fucosylated chondroitin sulfate at the dose totally preventing thrombus formation produced a much more intense modification of the plasma anticoagulant activity than antithrombotic doses of unfractionated heparin, low-molecular-weight heparin and mammalian dermatan sulfate. Thus, it is possible that the mechanism of antithrombotic action of these polysaccharides are different. For fucosylated chondroitin sulfate, it depends mostly on modifications of the plasma anticoagulant activity, but it may involve additional effects in the case of mammalian glycosaminoglycans, perhaps modifications induced in the cells of the vessel wall. The anticoagulant and possibly the antithrombotic actions of fucosylated chondroitin sulfate are mostly dependent on heparin cofactor II activity, and both are markedly reduced with the decrease of the chain size of the polymer. Overall, the sulfated polysaccharide from the invertebrate revealed an unequivocal effect in preventing experimental venous thrombosis, is a useful tool to investigate the antithrombotic action in mammals and may offer an alternative for future development of a new therapeutic agent. PMID:10997797

  13. Different antithrombotic mechanisms among glycosaminoglycans revealed with a new fucosylated chondroitin sulfate from an echinoderm.

    PubMed

    Pacheco, R G; Vicente, C P; Zancan, P; Mourão, P A

    2000-09-01

    The antithrombotic activity of a fucosylated chondroitin sulfate extracted from the body wall of a sea cucumber was assessed using a stasis thrombosis model in rats. Intravenous administration of the polysaccharide reduced thrombosis in a dose-dependent manner. We also compared the antithrombotic action of the sea cucumber chondroitin sulfate with that of standard mammalian glycosaminoglycans, mainly heparin and dermatan sulfate. Intravascular injection of fucosylated chondroitin sulfate at the dose totally preventing thrombus formation produced a much more intense modification of the plasma anticoagulant activity than antithrombotic doses of unfractionated heparin, low-molecular-weight heparin and mammalian dermatan sulfate. Thus, it is possible that the mechanism of antithrombotic action of these polysaccharides are different. For fucosylated chondroitin sulfate, it depends mostly on modifications of the plasma anticoagulant activity, but it may involve additional effects in the case of mammalian glycosaminoglycans, perhaps modifications induced in the cells of the vessel wall. The anticoagulant and possibly the antithrombotic actions of fucosylated chondroitin sulfate are mostly dependent on heparin cofactor II activity, and both are markedly reduced with the decrease of the chain size of the polymer. Overall, the sulfated polysaccharide from the invertebrate revealed an unequivocal effect in preventing experimental venous thrombosis, is a useful tool to investigate the antithrombotic action in mammals and may offer an alternative for future development of a new therapeutic agent.

  14. Anti-oxidation and Antiapoptotic Effects of Chondroitin Sulfate on 6-Hydroxydopamine-Induced Injury Through the Up-Regulation of Nrf2 and Inhibition of Mitochondria-Mediated Pathway.

    PubMed

    Ju, Chuanxia; Hou, Lin; Sun, Fusheng; Zhang, Li; Zhang, Zheng; Gao, Hua; Wang, Lei; Wang, Dachao; Lv, Yuqiang; Zhao, Xiaodan

    2015-07-01

    The purpose of the study was to investigate the protective effect and molecular mechanism of chondroitin sulfate (CS) against 6-hydroxydopamine (6-OHDA) induced toxicity in the human neuroblastoma cell line SH-SY5Y. The results showed that CS could protect SH-SY5Y cells against 6-OHDA-induced injury. The subsequent mechanism study showed that the anti-oxidation of CS may partly be mediated through inhibiting the intracellular reactive oxygen species overproduction, recovering the reduction of nuclear NF-E2-related factor-2 (Nrf2) expression and the reduction of antioxidants activity induced by 6-OHDA. Furthermore, CS pretreatment significantly attenuated 6-OHDA-induced cell apoptosis and nuclear condensation. 6-OHDA-induced dysfunctions, including the decrease of mitochondrial membrane potential (ΔΨm), increase of intracellular free Ca(2+), imbalance of Bcl-2/Bax ratio, release of Cyt-c from the mitochondria and activation of caspase-3 and caspase-9 were attenuated by CS pretreatment, which demonstrated that CS suppressed 6-OHDA-induced apoptosis in SH-SY5Y cells possibly through mitochondria protection. These results suggest that CS exhibits anti-oxidation through the up-regulation of Nrf2 along with endogenous antioxidant, and reduces apoptosis via inhibiting the mitochondrial pathway to protect SH-SY5Y cells damaged by 6-OHDA.

  15. Sulfated Galactofucan from the Brown Alga Saccharina latissima—Variability of Yield, Structural Composition and Bioactivity

    PubMed Central

    Ehrig, Karina; Alban, Susanne

    2014-01-01

    The fucose-containing sulfated polysaccharides (SP) from brown algae exhibit a wide range of bioactivities and are, therefore, considered promising candidates for health-supporting and medicinal applications. A critical issue is their availability in high, reproducible quality. The aim of the present study was to fractionate and characterize the SP extracted from Saccharina latissima (S.l.-SP) harvested from two marine habitats, the Baltic Sea and North Atlantic Ocean, in May, June and September. The fractionation of crude S.l.-SP by anion exchange chromatography including analytical investigations revealed that S.l.-SP is composed of a homogeneous fraction of sulfated galactofucan (SGF) and a mixture of low-sulfated, uronic acid and protein containing heteropolysaccharides. Furthermore, the results indicated that S.l. growing at an intertidal zone with high salinity harvested at the end of the growing period delivered the highest yield of S.l.-SP with SGF as the main fraction (67%). Its SGF had the highest degree of sulfation (0.81), fucose content (86.1%) and fucose/galactose ratio (7.8) and was most active (e.g., elastase inhibition: IC50 0.21 μg/mL). Thus, S.l. from the North Atlantic harvested in autumn proved to be more appropriate for the isolation of S.l.-SP than S.l. from the Baltic Sea and S.l. harvested in spring, respectively. In conclusion, this study demonstrated that habitat and harvest time of brown algae should be considered as factors influencing the yield as well as the composition and thus also the bioactivity of their SP. PMID:25548975

  16. 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.

  17. 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

  18. mTOR Inhibition Attenuates Dextran Sulfate Sodium-Induced Colitis by Suppressing T Cell Proliferation and Balancing TH1/TH17/Treg Profile.

    PubMed

    Hu, Shurong; Chen, Mengmeng; 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

  19. Oral versus postingestive origin of polysaccharide appetite in the rat.

    PubMed

    Sclafani, A; Nissenbaum, J W

    1987-01-01

    Previous studies have revealed that rats consume substantial amounts of polysaccharide solutions, even if the solutions are made bitter with the addition of sucrose octa acetate (SOA). The present experiment used the gastric sham-feeding preparation to determine if it is the orosensory or postingestive properties of polysaccharides that motivate rats to consume polysaccharide (Polycose) solutions. In Experiment 1, food deprived rats sham fed less of a 0.05% SOA + 32% Polycose solution than they did of a 32% glucose solution, but their SOA-Polycose intake was still considerable (44 ml/hr). The same rats refused to sham feed SOA-gum and SOA-sugar solutions that were similar to the SOA-Polycose solution in bitter taste, viscosity and free sugar content. In Experiment 2, rats sham fed as much of a 32% Polycose solution as they did of a 32% sucrose solution. Despite the gastric fistula, some of the ingested Polycose was absorbed as evidenced by an increase in the rats' blood glucose levels. The addition of acarbose, a drug that inhibits polysaccharide digestion, to the Polycose solution blocked the increase in blood glucose, but did not reduce the rats' sham feeding of the solution. These findings indicate that it is the orosensory (presumably taste) properties of polysaccharide solutions, not their postingestive effects, that initially attract rats to the solutions. The results question the assumption that polysaccharides are "tasteless" to animals.

  20. Sulfate adsorption on goethite

    SciTech Connect

    Rietra, R.P.J.J.; Hiemstra, T.; Riemsdijk, W.H. van

    1999-10-15

    Recent spectroscopic work has suggested that only one surface species of sulfate is dominant on hematite. Sulfate is therefore a very suitable anion to test and develop adsorption models for variable charge minerals. The authors have studied sulfate adsorption on goethite covering a large range of sulfate concentrations, surface coverages, pH values, and electrolyte concentrations. Four different techniques were used to cover the entire range of conditions. For characterization at low sulfate concentrations, below the detection limit of sulfate with ICP-AES, the authors used proton-sulfate titrations at constant pH. Adsorption isotherms were studied for the intermediate sulfate concentration range. Acid-base titrations in sodium sulfate and electromobility were used for high sulfate concentrations. All the data can be modeled with one adsorbed species if it is assumed that the charge of adsorbed sulfate is spatially distributed in the interface. The charge distribution of sulfate follows directly from modeling the proton-sulfate adsorption stoichoimemtry sine this stoichiometry is independent of the intrinsic affinity constant of sulfate. The charge distribution can be related to the structure of the surface complex by use of the Pauling bond valence concept and is in accordance with the microscopic structure found by spectroscopy. The intrinsic affinity constant follows from the other measurements. Modeling of the proton-ion stoichoimetry with the commonly used 2-pK models, where adsorbed ions are treated as point charges, is possible only if at least two surface species for sulfate are used.

  1. Polysaccharides: Occurrence, Significance, and Properties

    NASA Astrophysics Data System (ADS)

    Bemiller, James N.

    Polysaccharides are properties present significance in all living organisms where they carry out one or more of their diverse functions. While there is no specific category or definition of a complex polysaccharide, most are structurally complex. Polysaccharides contain 1-5 different monosaccharide (sugar) units. The different sugar units may have different anomeric configurations and/or be joined by different glycosidic linkages. Polysaccharides may be linear or branched. Branches may be short saccharide units on a linear backbone or the molecule may have a branch-on-branch structure; in either case, the branches may be isolated or clustered. Polysaccharides may contain non-carbohydrate groups. Esters or cyclic acetal groups, when present, can be removed by appropriate treatments. All polysaccharides are polydisperse, i. e., are present in a range of molecular weights rather than having a single molecular weight. Most are polymolecular, i. e., differ in fine structure from molecule to molecule. So most polysaccharides can be said to be structurally complex. They may be attached to protein molecules or to other polysaccharide molecules. They are solvated by water. Most dissolve in aqueous systems, especially if they are alkaline. Polysaccharides can be depolymerized by acids and heat, specific enzymes, and high pH systems following oxidation. Their hydroxyl groups can be esterified (acylated), etherified (alkylated), and oxidized. Amino groups can be acylated (and deacylated). Carboxyl groups can be converted into esters, amides, and amines. Structural modification makes the molecules even more complex and polymolecular and, perhaps, polydisperse.

  2. Endothelial Heparan Sulfate in Angiogenesis

    PubMed Central

    Fuster, Mark M.; Wang, Lianchun

    2013-01-01

    Heparan sulfate (HS) is a linear polysaccharide composed of 50–200 glucosamine and uronic acid (glucuronic acid or iduronic acid) disaccharide repeats with epimerization and various sulfation modifications. HS is covalently attached to core proteins to form HS-proteoglycans. Most of the functions of HS-proteoglycans are mediated by their HS moieties. The biosynthesis of HS is initiated by chain polymerization and is followed by stepwise modification reactions, including sulfation and epimerization. These modifications generate ligand-binding sites that modulate cell functions and activities of proteinases and/or proteinase inhibitors. HS is abundantly expressed in developing and mature vasculature, and understanding its roles in vascular biology and related human diseases is an area of intense investigation. In this chapter, we summarize the significant recent advances in our understanding of the roles of HS in developmental and pathological angiogenesis with a major focus on studies using transgenic as well as gene knockout/knockdown models in mice and zebrafish. These studies have revealed that HS critically regulates angiogenesis by playing a proangiogenic role, and this regulatory function critically depends on HS fine structure. The latter is responsible for facilitating cell-surface binding of various proangiogenic growth factors that in turn mediate endothelial growth signaling. In cancer, mouse studies have revealed important roles for endothelial cell-surface HS as well as matrix-associated HS, wherein signaling by multiple growth factors as well as matrix storage of growth factors may be regulated by HS. We also discuss important mediators that may fine-tune such regulation, such as heparanase and sulfatases; and models wherein targeting HS (or core protein) biosynthesis may affect tumor growth and vascularization. Finally, the importance of targeting HS in other human diseases wherein angiogenesis may play pathophysiologic (or even therapeutic) roles

  3. In vivo immunological activity of carboxymethylated-sulfated (1→3)-β-D-glucan from sclerotium of Poria cocos.

    PubMed

    Wang, Haili; Mukerabigwi, Jean Felix; Zhang, Yuannian; Han, Lin; Jiayinaguli, Telieke; Wang, Qing; Liu, Lina; Cao, Yu; Sun, Renqiang; Huang, Xueying

    2015-08-01

    β-Glucans are one of the polysaccharides known as biological response modifiers extracted from the sclerotium of Poria cocos which has been used for several decades as Traditional Chinese Medicine. Due to its ability to activate immune system, it can be applied in chemotherapy after being chemically modified. In this study, sulfated (1→3)-β-D-glucan (S-P), carboxymethyl (1→3)-β-D-glucan (CMP), and carboxymethylated-sulfated (1→3)-β-D-glucan (S-CMP), which are (1→3)-β-D-glucan derivatives were synthesized. The current study was aimed to investigate in vivo potential immunological activity of S-CMP in mice. In addition, mice were separately treated with S-P, CMP and S-CMP to evaluate the relationship between single and multiple functional groups. Interestingly, S-CMP exhibited the best in vivo immunological activities and the highest inhibition rate against the implanted HepG2 tumor in BALB/c mice, with significant increase in serum hemolysin antibody titer, spleen antibody production as well as delayed type hypersensitivity compared with S-P and CMP. Furthermore, it was assumed that simultaneous introduction of carboxymethyl and sulfate groups also had great potential effect on antioxidant activity, as substantial decrease in malondialdehyde (MDA) content was remarked. Therefore, it may suggest that S-CMP has better immunological and anti-tumor effects on mice in vivo.

  4. Embryos of the sea urchin Strongylocentrotus purpuratus synthesize a dermatan sulfate enriched in 4-O- and 6-O-disulfated galactosamine units.

    PubMed

    Vilela-Silva, A C; Werneck, C C; Valente, A P; Vacquier, V D; Mourão, P A

    2001-06-01

    Unfertilized eggs of the sea urchin Strongylocentrotus purpuratus are surrounded by a gelatinous layer rich in sulfated fucan. Shortly after fertilization this polysaccharide disappears, but 24 h later the embryos synthesize high amounts of dermatan sulfate concomitantly with the mesenchyme blastula-early gastrula stage when the larval gut is forming. This glycosaminoglycan has the same backbone structure [4-alpha-L-IdoA-1-->3-beta-D-GalNAc-1](n) as the mammalian counterpart but possesses a different sulfation pattern. It has a high content of 4-O- and 6-O-disulfated galactosamine units. In addition, chains of this dermatan sulfate are considerable longer than those of vertebrate tissues. Adult sea urchin tissues contain high concentrations of sulfated polysaccharides, but dermatan sulfate is restricted to the adult body wall where it accounts for approximately 20% of the total sulfated polysaccharides. In addition, sulfation at the 4-O-position decreases markedly in the dermatan sulfate from adult sea urchin when compared with the glycan from larvae. Overall, these results demonstrate the occurrence of dermatan sulfates with unique sulfation patterns in this marine invertebrate. The physiological implication of these oversulfated dermatan sulfates is unclear. One hypothesis is that interactions between components of the extracellular matrix in marine invertebrates occur at higher salt concentrations than in vertebrates and therefore require glycosaminoglycans with increased charge density.

  5. 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.

  6. Modulating Inhibitors of Transthyretin Fibrillogenesis via Sulfation: Polychlorinated Biphenyl Sulfates as Models1

    PubMed Central

    Grimm, Fabian A.; Lehmler, Hans-Joachim; He, Xianran; Robertson, Larry W.; Duffel, Michael W.

    2015-01-01

    Small molecules that bind with high affinity to thyroxine (T4) binding sites on transthyretin (TTR) kinetically stabilize the protein’s tetrameric structure, thereby efficiently decreasing the rate of tetramer dissociation in TTR related amyloidoses. Current research efforts aim to optimize the amyloid inhibiting properties of known inhibitors, such as derivatives of biphenyls, dibenzofurans and benzooxazoles, by chemical modification. In order to test the hypothesis that sulfate group substituents can improve the efficiencies of such inhibitors, we evaluated the potential of six polychlorinated biphenyl sulfates to inhibit TTR amyloid fibril formation in vitro. In addition, we determined their binding orientations and molecular interactions within the T4 binding site by molecular docking simulations. Utilizing this combined experimental and computational approach, we demonstrated that sulfation significantly improves the amyloid inhibiting properties as compared to both parent and hydroxylated PCBs. Importantly, several PCB sulfates were of equal or higher potency than some of the most effective previously described inhibitors. PMID:25595224

  7. Spheciosterol Sulfates, PKCζ Inhibitors from a Philippine Sponge Spheciospongia sp.

    PubMed Central

    2008-01-01

    Three new sterol sulfates, spheciosterol sulfates A−C (1−3), and the known sterol sulfate topsentiasterol sulfate E (4) have been isolated from the sponge Spheciospongia sp., collected in the Philippines. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1−4 inhibited PKCζ with IC50 values of 1.59, 0.53, 0.11, and 1.21 μM, respectively. In a cell-based assay, 1−4 also inhibited NF-κB activation with EC50 values of 12−64 μM. PMID:18558742

  8. 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

  9. A Unique 2-Sulfated β-Galactan from the Egg Jelly of the Sea Urchin Glyptocidaris crenularis

    PubMed Central

    Castro, Michelle O.; Pomin, Vitor H.; Santos, Livia L.; Vilela-Silva, Ana-Cristina E. S.; Hirohashi, Noritaka; Pol-Fachin, Laércio; Verli, Hugo; Mourão, Paulo A. S.

    2009-01-01

    Sulfated polysaccharides from the egg jelly of sea urchins act as species-specific inducers of the sperm acrosome reaction, which is a rare molecular mechanism of carbohydrate-induced signal-transduction event in animal cells. The sea urchin polysaccharides differ in monosaccharide composition (l-fucose or l-galactose), glycosylation, and sulfation sites, but they are always in the α-anomeric configuration. Herein, structural analysis of the polysaccharide from the sea urchin Glyptocidaris crenularis surprisingly revealed a unique sulfated β-d-galactan composed by (3-β-d-Galp-2(OSO3)-1→3-β-d-Galp-1)n repeating units. Subsequently, we used the G. crenularis galactan to compare different 2-sulfated polysaccharides as inducers of the acrosome reaction using homologous and heterologous sperm. We also tested the effect of chemically over-sulfated galactans. Intriguingly, the anomeric configuration of the glycosidic linkage rather than the monosaccharide composition (galactose or fucose) is the preferential structural requirement for the effect of these polysaccharides on sea urchin fertilization. Nuclear magnetic resonance and molecular dynamics indicate that sulfated α-galactan or α-fucan have less dynamic structural behavior, exhibiting fewer conformational populations, with an almost exclusive conformational state with glycosidic dihedral angles Φ/Ψ = −102°/131°. The preponderant conformer observed in the sulfated α-galactan or α-fucan is not observed among populations in the β-form despite its more flexible structure in solution. Possibly, a proper spatial arrangement is required for interaction of the sea urchin-sulfated polysaccharides with the specific sperm receptor. PMID:19403528

  10. 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.

  11. 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. PMID:26974373

  12. 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...

  13. Occurrence of a unique fucose-branched chondroitin sulfate in the body wall of a sea cucumber.

    PubMed

    Vieira, R P; Mourão, P A

    1988-12-01

    The sulfated polysaccharides in the body wall of the sea cucumber occur as three fractions that differ markedly in molecular mass and chemical composition. The fraction containing a high molecular mass component has a high proportion of fucose and small amounts of galactose and amino sugars, whereas another fraction contains primarily a sulfated fucan. The third fraction (F-2), which represents the major portion of the sea cucumber-sulfated polysaccharides, contains approximately equimolar quantities of glucuronic acid, N-acetyl galactosamine, and fucose, and has a sulfate content higher than that in the other two fractions. The structure of fraction F-2 was examined in detail. This polysaccharide has an unusual structure composed of a chondroitin sulfate-like core, containing side chain disaccharide units of sulfated fucopyranosyl linked to approximately half of the glucuronic acid moieties through the O-3 position of the acid. These unusual fucose branches obstruct the access of chondroitinases to the chondroitin sulfate core of F-2. However, after partial acid hydrolysis, which removes the sulfated fucose residues from the polymer, fraction F-2 is degraded by chondroitinases into 6-sulfated and nonsulfated disaccharides.

  14. 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. PMID:24863354

  15. 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.

  16. 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.

  17. 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

  18. The interaction of boar sperm proacrosin with its natural substrate, the zona pellucida, and with polysulfated polysaccharides.

    PubMed

    Urch, U A; Patel, H

    1991-04-01

    Boar sperm acrosin is an acrosomal protease with trypsin-like specificity, and it functions in fertilization by assisting sperm passage through the zona pellucida by limited hydrolysis of this extracellular matrix. In addition to a proteolytic active site domain, acrosin binds the zona pellucida at a separate binding domain that is lost during proacrosin autolysis. In this study, we quantitate the binding of proacrosin to the physiological substrate for acrosin, the zona pellucida, and to a non-substrate, the polysulfated polysaccharide fucoidan. Binding was analogous to sea urchin sperm bindin that binds egg jelly fucan and the vitelline envelope of sea urchin eggs. Proacrosin was found to bind to fucoidan and to the zona pellucida with binding affinities similar to bindin interaction with egg jelly fucan. These interactions were competitively inhibited by similar relative molecular mass polysulfated polymers. Since bindin and proacrosin have distinctly different amino acid sequences, their interaction with acidic sulfate esters demonstrates an example of convergent evolution wherein different macromolecules localized in analogous sperm compartments have the same biological function. From cDNA sequence analysis of proacrosin, this binding may be mediated through a consensus sequence for binding sulfated glycoconjugates. Proacrosin binding to the zona pellucida may serve as both a recognition or primary sperm receptor, as well as maintaining the sperm on the zona pellucida once the acrosome reaction has occurred.

  19. 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.

  20. Cations modulate polysaccharide structure to determine FGF-FGFR signaling: a comparison of signaling and inhibitory polysaccharide interactions with FGF-1 in solution.

    PubMed

    Guimond, Scott E; Rudd, Timothy R; Skidmore, Mark A; Ori, Alessandro; Gaudesi, Davide; Cosentino, Cesare; Guerrini, Marco; Edge, Ruth; Collison, David; McInnes, Eric; Torri, Giangiacomo; Turnbull, Jeremy E; Fernig, David G; Yates, Edwin A

    2009-06-01

    For heparan sulfate (HS) to bind and regulate the activity of proteins, the polysaccharide must present an appropriate sequence and adopt a suitable conformation. The conformations of heparin derivatives, as models of HS, are altered via a change in the associated cations, and this can drastically modify their FGF signaling activities. Here, we report that changing the cations associated with an N-acetyl-enriched heparin polysaccharide, from sodium to copper(II), converted it from supporting signaling through the fibroblast growth factor receptor (FGF-1-FGFR1c) tyrosine kinase signaling system to being inhibitory in a cell-based BaF3 assay. Nuclear magnetic resonance and synchrotron radiation circular dichroism (SRCD) spectroscopy demonstrated that the polysaccharide conformation differed in the presence of sodium or copper(II) cations. Electron paramagnetic resonance confirmed the environment of the copper(II) ion on the N-acetyl-enriched polysaccharide was distinct from that previously observed with intact heparin, which supported signaling. Secondary structures in solution complexes of polysaccharides with FGF-1 (which either supported signaling through FGFR1c or were inhibitory) were determined by SRCD. This allowed direct comparison of the two FGF-1-polysaccharide complexes in solution, containing identical molecular components and differing only in their cation content. Subtle structural differences were revealed, including a reduction in the level of disordered structure in the inhibitory complex. PMID:19400583

  1. The bacteriophage kh receptor of Lactococcus lactis subsp. cremoris KH is the rhamnose of the extracellular wall polysaccharide.

    PubMed Central

    Valyasevi, R; Sandine, W E; Geller, B L

    1990-01-01

    A receptor for bacteriophages of lactic acid bacteria, including Lactococcus lactis subsp. cremoris KH, was found on the cell wall and not on the cell membrane, as determined by a phage-binding assay of sodium dodecyl sulfate- and mutanolysin-treated cell walls. The cell wall carbohydrates of L. lactis subsp. cremoris KH were analyzed by gas chromatography and mass spectrometry and found to contain rhamnose, galactose, glucose and N-acetylglucosamine. Similar analysis of mutants that were reduced in the ability to bind phages kh, 643, c2, ml3, and 1 indicated that galactose was essential for binding all phages. In addition, rhamnose was required for binding phages kh and ml3. Inhibition studies of phage binding by using two different lectins with a specificity for galactose indicated that phage kh may not bind directly to galactose. Rather, galactose may be an essential structural component located in the vicinity of the receptor. Incubation of any of the five phages with rhamnose or of phage kh with purified cell walls inactivated the phages. Inactivation required divalent cations and was irreversible. Inactivation of phages was stereospecific for rhamnose, as neither L-(+)- nor D-(-)-fucose (the stereoisomers of rhamnose) inhibited the phage. Furthermore, phage infection of a culture was completely inhibited by the addition of rhamnose to the medium. Therefore, the receptor for phage kh appears to be a rhamnose component of the extracellular wall polysaccharide. PMID:2116761

  2. 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

  3. 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

    2015-09-01

    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.

  4. A sulfated alpha-L-fucan from sea cucumber.

    PubMed

    Ribeiro, A C; Vieira, R P; Mourão, P A; Mulloy, B

    1994-03-01

    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.

  5. 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

  6. The molecular basis of polysaccharide cleavage by lytic polysaccharide monooxygenases.

    PubMed

    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; Lo Leggio, Leila; Walton, Paul H

    2016-04-01

    Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes that 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 a 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.

  7. Development of affinity-based delivery of NGF from a chondroitin sulfate biomaterial.

    PubMed

    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

  8. Mediating chemical reactions using polysaccharides

    NASA Astrophysics Data System (ADS)

    Tyler, Lauren E.

    We have studied the NaBH4-mediated hydrogenation of select alkenes catalyzed by polysaccharide-stabilized nanoparticles. We compared the catalytic properties of Ni-based nanoparticles or Au/Co-based nanoparticles on the hydrogenation of cinnamic acid, cinnamide, cinnamyl alcohol, and ethyl cinnamate. We evaluated the possibility that the type of stabilizing polysaccharide surrounding the nanoparticle may affect the selectivity towards the alkene compounds that undergo the hydrogenation reaction. We found that the hydrogenation of cinnamide or ethyl cinnamate proceeded readily to 100% completion independent of the type of polysaccharide stabilizing the nanoparticle. However, the extent of the hydrogenation of cinnamyl alcohol and cinnamic acid varied greatly depending on the type of polysaccharide stabilizing the nanoparticle. In the course of these studies, we observed that some polysaccharides by themselves promoted the hydrolysis of ethyl cinnamate. Thus, we have raised the hypothesis that some polysaccharides may act as "esterases" and explored the interaction between select polysaccharides and a variety of ester compounds.

  9. 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

  10. Sulfated fucans from echinoderms have a regular tetrasaccharide repeating unit defined by specific patterns of sulfation at the 0-2 and 0-4 positions.

    PubMed

    Mulloy, B; Ribeiro, A C; Alves, A P; Vieira, R P; Mourão, P A

    1994-09-01

    Sulfated fucans from echinoderms (sea cucumber and sea urchin) have a linear backbone of 1-->3-linked alpha-L-fucopyranose with some sulfate substitution at the 2- and 4-positions. NMR spectroscopy indicates that both polysaccharides have a tetrasaccharide repeat unit in which the separate residues differ only in the extent and position of their sulfate substitution. The sea urchin fucan has the structure, [formula: see text] This type of regular structure has not previously been described, and is in contrast with the random arrangement of substituents on the similar 1-->3-linked alpha-L-fucopyranose backbone of the fucoidans from brown algae.

  11. Biological functions of iduronic acid in chondroitin/dermatan sulfate

    PubMed Central

    Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

    2013-01-01

    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. PMID:23441919

  12. 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.

  13. ERK Activation by Fucoidan Leads to Inhibition of Melanogenesis in Mel-Ab Cells.

    PubMed

    Song, Yu Seok; Balcos, Marie Carmel; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Kim, Myo-Kyoung; Kim, Dong-Seok

    2015-01-01

    Fucoidan, a fucose-rich sulfated polysaccharide derived from brown seaweed in the class Phaeophyceae, has been widely studied for its possible health benefits. However, the potential of fucoidan as a possible treatment for hyperpigmentation is not fully understood. This study investigated the effects of fucoidan on melanogenesis and related signaling pathways using Mel-Ab cells. Fucoidan significantly decreased melanin content. While fucoidan treatment decreased tyrosinase activity, it did not do so directly. Western blot analysis indicated that fucoidan downregulated microphthalmia-associated transcription factor and reduced tyrosinase protein expression. Further investigation showed that fucoidan activated the extracellular signal-regulated kinase (ERK) pathway, suggesting a possible mechanism for the inhibition of melanin synthesis. Treatment with PD98059, a specific ERK inhibitor, resulted in the recovery of melanin production. Taken together, these findings suggest that fucoidan inhibits melanogenesis via ERK phosphorylation.

  14. Sulfated heterorhamnans from the green seaweed Gayralia oxysperma: partial depolymerization, chemical structure and antitumor activity.

    PubMed

    Ropellato, Juliana; Carvalho, Mariana M; Ferreira, Luciana G; Noseda, Miguel D; Zuconelli, Cristiane R; Gonçalves, Alan G; Ducatti, Diogo R B; Kenski, Juliana C N; Nasato, Pauline L; Winnischofer, Sheila M B; Duarte, Maria E R

    2015-03-01

    Sulfated heterorhamnans produced by Gayralia oxysperma were utilized for the preparation of two homogeneous and highly sulfated Smith-degraded products (M(w) of 109 and 251 kDa), which were constituted principally by 3-linked α-L-rhamnosyl units 2- or 4-sulfate and 2-linked α-L-rhamnosyl units 4- or 3,4-sulfate, in different percentages. The homogeneous products and the crude extracts containing the sulfated heterorhamnans showed cytotoxic effect against U87MG cells. These sulfated polysaccharides induced an increase in the number of cells in G1 phase with concomitant increase of the mRNA levels of p53 and p21. The presence of 2-linked disulfated rhamnose residues together with the molecular weight could be important factors to be correlated with the inhibitory effect on human glioblastoma cells.

  15. Sulfated heterorhamnans from the green seaweed Gayralia oxysperma: partial depolymerization, chemical structure and antitumor activity.

    PubMed

    Ropellato, Juliana; Carvalho, Mariana M; Ferreira, Luciana G; Noseda, Miguel D; Zuconelli, Cristiane R; Gonçalves, Alan G; Ducatti, Diogo R B; Kenski, Juliana C N; Nasato, Pauline L; Winnischofer, Sheila M B; Duarte, Maria E R

    2015-03-01

    Sulfated heterorhamnans produced by Gayralia oxysperma were utilized for the preparation of two homogeneous and highly sulfated Smith-degraded products (M(w) of 109 and 251 kDa), which were constituted principally by 3-linked α-L-rhamnosyl units 2- or 4-sulfate and 2-linked α-L-rhamnosyl units 4- or 3,4-sulfate, in different percentages. The homogeneous products and the crude extracts containing the sulfated heterorhamnans showed cytotoxic effect against U87MG cells. These sulfated polysaccharides induced an increase in the number of cells in G1 phase with concomitant increase of the mRNA levels of p53 and p21. The presence of 2-linked disulfated rhamnose residues together with the molecular weight could be important factors to be correlated with the inhibitory effect on human glioblastoma cells. PMID:25498661

  16. 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.

  17. 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. PMID:21419855

  18. Chondroitin / dermatan sulfate modification enzymes in zebrafish development.

    PubMed

    Habicher, Judith; Haitina, Tatjana; Eriksson, Inger; Holmborn, Katarina; Dierker, Tabea; Ahlberg, Per E; Ledin, Johan

    2015-01-01

    Chondroitin/dermatan sulfate (CS/DS) proteoglycans consist of unbranched sulfated polysaccharide chains of repeating GalNAc-GlcA/IdoA disaccharide units, attached to serine residues on specific proteins. The CS/DS proteoglycans are abundant in the extracellular matrix where they have essential functions in tissue development and homeostasis. In this report a phylogenetic analysis of vertebrate genes coding for the enzymes that modify CS/DS is presented. We identify single orthologous genes in the zebrafish genome for the sulfotransferases chst7, chst11, chst13, chst14, chst15 and ust and the epimerase dse. In contrast, two copies were found for mammalian sulfotransferases CHST3 and CHST12 and the epimerase DSEL, named chst3a and chst3b, chst12a and chst12b, dsela and dselb, respectively. Expression of CS/DS modification enzymes is spatially and temporally regulated with a large variation between different genes. We found that CS/DS 4-O-sulfotransferases and 6-O-sulfotransferases as well as CS/DS epimerases show a strong and partly overlapping expression, whereas the expression is restricted for enzymes with ability to synthesize di-sulfated disaccharides. A structural analysis further showed that CS/DS sulfation increases during embryonic development mainly due to synthesis of 4-O-sulfated GalNAc while the proportion of 6-O-sulfated GalNAc increases in later developmental stages. Di-sulfated GalNAc synthesized by Chst15 and 2-O-sulfated GlcA/IdoA synthesized by Ust are rare, in accordance with the restricted expression of these enzymes. We also compared CS/DS composition with that of heparan sulfate (HS). Notably, CS/DS biosynthesis in early zebrafish development is more dynamic than HS biosynthesis. Furthermore, HS contains disaccharides with more than one sulfate group, which are virtually absent in CS/DS.

  19. Finely dispersed single-walled carbon nanotubes for polysaccharide hydrogels.

    PubMed

    Yan, Liang Yu; Chen, Hailan; Li, Peng; Kim, Dong-Hwan; Chan-Park, Mary B

    2012-09-26

    Here we demonstrate a polysaccharide hydrogel reinforced with finely dispersed single-walled carbon nanotubes (SWNTs) using biocompatible dispersants O-carboxymethylchitosan (OC) and chondroitin sulfate A (CS-A) as a structural support. Both of the dispersants can disperse SWNTs in aqueous solutions and hydrogel matrix as individual tubes or small bundles. Additionally, we have found that compressive modulus and strain of the hydrogels reinforced with SWNTs were enhanced as much as two times by the addition of a few weight percent of SWNTs. Moreover, the SWNT-incorporated hydrogels exhibited lower impedance and higher charge capacity than the alginate/dispersant hydrogel without SWNTs. The OC and the CS-A demonstrated much higher reinforcing enhancement than a commercially available dispersant, sodium dodecyl sulfate. Combined with the experimental data on the mechanical and electrical properties, the biocompatibility of OC and CS-A can provide the possibility of biomedical application of the SWNT-reinforced hydrogels. PMID:22909447

  20. Adherence of Candida albicans to a cell surface polysaccharide receptor on Streptococcus gordonii.

    PubMed Central

    Holmes, A R; Gopal, P K; Jenkinson, H F

    1995-01-01

    Candida albicans ATCC 10261 and CA2 bound to cells of the oral bacteria Streptococcus gordonii, Streptococcus oralis, and Streptococcus sanguis when these bacteria were immobilized onto microtiter plate wells, but they did not bind to cells of Streptococcus mutans or Streptococcus salivarius. Cell wall polysaccharide was extracted with alkali from S. gordonii NCTC 7869, the streptococcal species to which C. albicans bound with highest affinity, and was effective in blocking the coaggregation of C. albicans and S. gordonii cells in the fluid phase. When fixed to microtiter plate wells, the S. gordonii polysaccharide was bound by all strains of C. albicans tested. The polysaccharide contained Rha, Glc, GalNAc, GlcNAc, and Gal and was related compositionally to previously characterized cell wall polysaccharides from strains of S. oralis and S. sanguis. The adherence of yeast cells to the immobilized polysaccharide was not inhibitable by a number of saccharides. Antiserum raised to the S. gordonii NCTC 7869 polysaccharide blocked adherence of C. albicans ATCC 10261 to the polysaccharide. The results identify a complex cell wall polysaccharide of S. gordonii as the coaggregation receptor for C. albicans. Adherent interactions of yeast cells with streptococci and other bacteria may be important for colonization of both hard and soft oral surfaces by C. albicans. PMID:7729891

  1. 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

  2. Computer simulation and experimental study of the polysaccharide-polysaccharide interaction in the bacteria Azospirillum brasilense Sp245

    NASA Astrophysics Data System (ADS)

    Arefeva, Oksana A.; Kuznetsov, Pavel E.; Tolmachev, Sergey A.; Kupadze, Machammad S.; Khlebtsov, Boris N.; Rogacheva, Svetlana M.

    2003-09-01

    We have studied the conformational properties and molecular dynamics of polysaccharides by using molecular modeling methods. Theoretical and experimental results of polysaccharide-polysaccharide interactions are described.

  3. 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.

  4. 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

  5. Actinobacillus actinomycetemcomitans Y4 capsular-polysaccharide-like polysaccharide promotes osteoclast-like cell formation by interleukin-1 alpha production in mouse marrow cultures.

    PubMed Central

    Nishihara, T; Ueda, N; Amano, K; Ishihara, Y; Hayakawa, H; Kuroyanagi, T; Ohsaki, Y; Nagata, K; Noguchi, T

    1995-01-01

    The mechanism of osteoclast-like cell formation induced by periodontopathic bacterium Actinobacillus actinomycetemcomitans Y4 (serotype b) capsular-polysaccharide-like polysaccharide (capsular-like polysaccharide) was examined in a mouse bone marrow culture system. When mouse bone marrow cells were cultured with A. actinomycetemcomitans Y4 capsular-like polysaccharide for 9 days, many multinucleated cells were formed. The multinucleated cells showed several characteristics of osteoclasts, including tartrate-resistant acid phosphatase (TRACP) and the ability to resorb the calcified dentine. In this study, we examined the effects of antisera to interleukins on the formation of osteoclast-like cells induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. Monospecific anti-mouse recombinant interleukin-1 alpha (rIL-1 alpha) serum completely inhibited the formation of osteoclast-like cells in the presence of A. actinomycetemcomitans Y4 capsular-like polysaccharide. However, anti-mouse rIL-1 beta and anti-mouse rIL-6 sera showed no effect on osteoclast-like cell formation. IL-1 receptor antagonist significantly inhibited the osteoclast-like cell formation mediated by A. actinomycetemcomitans Y4 capsular-like polysaccharide in mouse marrow cultures. The bioactive IL-1 was detected in the culture media of mouse bone marrow cells stimulated with A. actinomycetemcomitans Y4 capsular-like polysaccharide. These results indicate that IL-1 alpha is involved in the mechanism of the formation of osteoclast-like cells induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. We sought to determine whether osteoclast-like cell formation induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide could be modulated by the protein kinase inhibitors H8 and HA1004. The formation of osteoclast-like cells was suppressed by H8 and HA1004. These findings suggest that the signals by protein kinases may regulate osteoclast-like cell formation induced by A

  6. 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.

  7. Diverse Roles of Heparan Sulfate and Heparin in Wound Repair

    PubMed Central

    Olczyk, Pawel; Mencner, Łukasz; Komosinska-Vassev, Katarzyna

    2015-01-01

    Heparan sulfate (HS) and heparin (Hp) are linear polysaccharide chains composed of repeating (1→4) linked pyrosulfuric acid and 2-amino-2-deoxy glucopyranose (glucosamine) residue. Mentioned glycosaminoglycans chains are covalently O-linked to serine residues within the core proteins creating heparan sulfate/heparin proteoglycans (HSPG). The latter ones participate in many physiological and pathological phenomena impacting both the plethora of ligands such as cytokines, growth factors, and adhesion molecules and the variety of the ECM constituents. Moreover, HS/Hp determine the effective wound healing process. Initial growth of HS and Hp amount is pivotal during the early phase of tissue repair; however heparan sulfate and heparin also participate in further stages of tissue regeneration. PMID:26236728

  8. Characterization, Anti-Inflammatory and Antiproliferative Activities of Natural and Sulfonated Exo-Polysaccharides from Streptococcus thermophilus ASCC 1275.

    PubMed

    Li, Siqian; Shah, Nagendra P

    2016-05-01

    Exo-polysaccharides (EPS) isolated from Streptococcus thermophilus ASCC 1275 were sulfated (31%). High-performance liquid chromatography identified that EPS was composed of mannose (30.19%), galactose (20.10%), glucose (18.05%), glucosamine (16.04%), galactosamine (9.06%), glucuronic acid (3.55%), and ribose (3.01%). Pro-/anti-inflammatory cytokine secretion ratios (IL-1β/IL-10, IL-6/IL-10, and TNF-α/IL-10) of lipopolysaccharide stimulated RAW 264.7 macrophages were significantly decreased by EPS and S.EPS treatments in a dose dependent manner. Furthermore, anti-inflammatory activities of S.EPS improved 49.3% and 24.0% than those of EPS before or after LPS treatment. The reactive oxygen species were inhibited by EPS and S.EPS by 49.6% and 55.1% at 50 μg/mL, respectively. Inhibition activities of S.EPS on nitric oxide production were 12.9% and 55.4% higher than those of EPS at 10 and 50 μg/mL. Additionally, S.EPS exhibited stronger antiproliferative activity on Caco-2 and HepG2 cells. Our results indicated that anti-inflammatory and antiproliferative activities of EPS were significantly (P < 0.01) improved by sulfonation. PMID:27010963

  9. 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.

  10. Sulfate metabolism in mycobacteria.

    PubMed

    Schelle, Michael W; Bertozzi, Carolyn R

    2006-10-01

    Pathogenic bacteria have developed numerous mechanisms to survive inside a hostile host environment. The human pathogen Mycobacterium tuberculosis (M. tb) is thought to control the human immune response with diverse biomolecules, including a variety of exotic lipids. One prevalent M. tb-specific sulfated metabolite, termed sulfolipid-1 (SL-1), has been correlated with virulence though its specific biological function is not known. Recent advances in our understanding of SL-1 biosynthesis will help elucidate the role of this curious metabolite in M. tb infection. Furthermore, the study of SL-1 has led to questions regarding the significance of sulfation in mycobacteria. Examples of sulfated metabolites as mediators of interactions between bacteria and plants suggest that sulfation is a key modulator of extracellular signaling between prokaryotes and eukaryotes. The discovery of novel sulfated metabolites in M. tb and related mycobacteria strengthens this hypothesis. Finally, mechanistic and structural data from sulfate-assimilation enzymes have revealed how M. tb controls the flux of sulfate in the cell. Mutants with defects in sulfate assimilation indicate that the fate of sulfur in M. tb is a critical survival determinant for the bacteria during infection and suggest novel targets for tuberculosis drug therapy.

  11. A unique 2-sulfated {beta}-galactan from the egg jelly of the sea urchin Glyptocidaris crenularis: conformation flexibility versus induction of the sperm acrosome reaction.

    PubMed

    Castro, Michelle O; Pomin, Vitor H; Santos, Livia L; Vilela-Silva, Ana-Cristina E S; Hirohashi, Noritaka; Pol-Fachin, Laércio; Verli, Hugo; Mourão, Paulo A S

    2009-07-10

    Sulfated polysaccharides from the egg jelly of sea urchins act as species-specific inducers of the sperm acrosome reaction, which is a rare molecular mechanism of carbohydrate-induced signal-transduction event in animal cells. The sea urchin polysaccharides differ in monosaccharide composition (l-fucose or l-galactose), glycosylation, and sulfation sites, but they are always in the alpha-anomeric configuration. Herein, structural analysis of the polysaccharide from the sea urchin Glyptocidaris crenularis surprisingly revealed a unique sulfated beta-d-galactan composed by (3-beta-d-Galp-2(OSO(3))-1-->3-beta-d-Galp-1)(n) repeating units. Subsequently, we used the G. crenularis galactan to compare different 2-sulfated polysaccharides as inducers of the acrosome reaction using homologous and heterologous sperm. We also tested the effect of chemically over-sulfated galactans. Intriguingly, the anomeric configuration of the glycosidic linkage rather than the monosaccharide composition (galactose or fucose) is the preferential structural requirement for the effect of these polysaccharides on sea urchin fertilization. Nuclear magnetic resonance and molecular dynamics indicate that sulfated alpha-galactan or alpha-fucan have less dynamic structural behavior, exhibiting fewer conformational populations, with an almost exclusive conformational state with glycosidic dihedral angles Phi/Psi = -102 degrees /131 degrees . The preponderant conformer observed in the sulfated alpha-galactan or alpha-fucan is not observed among populations in the beta-form despite its more flexible structure in solution. Possibly, a proper spatial arrangement is required for interaction of the sea urchin-sulfated polysaccharides with the specific sperm receptor.

  12. 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.

  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. 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.

  16. 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.

  17. Extracellular polysaccharide production by thraustochytrid protists.

    PubMed

    Jain, Ruchi; Raghukumar, Seshagiri; Tharanathan, R; Bhosle, N B

    2005-01-01

    Four strains of marine stramenopilan protists, the thraustochytrids, were studied for their ability to produce extracellular polysaccharides (EPSs). Observations by light and scanning electron microscopy revealed the production of a matrix of EPS around groups of cells in stationary cultures. EPS in shake culture filtrates ranged from 0.3 to 1.1 g/L. EPS production, which was studied in greater detail in 2 isolates, SC-1 and CW1, increased with age of cultures, reaching a peak in the stationary phase. Anion exchange chromatography yielded a single fraction of the EPS of both species. The EPS contained 39% to 53% sugars, besides proteins, lipids, uronic acids, and sulfates. Molecular weight of the EPS produced by SC-1 was approximately 94 kDa, and that of CW1, 320 kDa. Glucose formed the major component in the EPS of both isolates-galactose, mannose, and arabinose being the other components. Cultures of both isolates survived air-drying up to a period of 96 hours, suggesting a role for EPS in preventing desiccation of cells.

  18. Silage supports sulfate reduction in the treatment of metals- and sulfate-containing waste waters.

    PubMed

    Wakeman, Kathryn D; Erving, Leena; Riekkola-Vanhanen, Marja L; Puhakka, Jaakko A

    2010-09-01

    Silage was used as source of carbon and electrons for enrichment of silage-degrading and sulfate reducing bacteria (SRB) from boreal, acidic, metals-containing peat-bog samples and to support their use in batch and semi-batch systems in treatment of synthetic waste water. Sulfidogenic silage utilization resulted in a rapid decrease in lactate concentrations; concentrations of acetate, butyrate and propionate increased concomitantly. Synthetic waste water consisting of Mn, Mg and Fe (II) ions inhibited sulfate reduction at concentrations of 6 g/l, 8 g/l and 1 g/l respectively. During treatment, Mn and Mg ions remained in solution while Fe ions partially precipitated. Up to 87 mg sulfate was reduced per gram of silage. Sulfate reduction rates of 34, 22 and 6 mg/l/day were obtained at temperatures of 30, 20 and 9 °C respectively. In semi-batch reactors operated at low pH, the iron precipitation capacity was controlled by sulfate reduction rates and by partial loss of hydrogen sulfide to the gas phase. Passive reactor systems should, therefore, be operated at neutral pH. Metals tolerant, silage-fermenting (predominantly species belonging to genus Clostridium) and sulfate reducing bacteria (including a species similar to the psychrotolerant Desulfovibrio arcticus) were obtained from the peat bog samples. This work demonstrates that silage supports sulfate reduction and can be used as a low cost carbon and electron source for SRB in treatment of metals-containing waste water.

  19. 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.

  20. Bacterial polysaccharide which binds Rhizobium trifolii to clover root hairs.

    PubMed Central

    Dazzo, F B; Brill, W J

    1979-01-01

    Immunofluorescence, quantitative immunoprecipitation, and inhibition of bacterial agglutination and passive hemagglutination indicate that cross-reactive antigenic determinants are present on the surface of Rhizobium trifolii and clover roots. These determinants are immunochemically unique to this Rhizobium-legume cross-inoculation group. The multivalent lectin trifoliin and antibody to the clover root antigenic determinants bind competitively to two acidic heteropolysaccharides isolated from capsular material of R. Trifolii 0403. The major polysaccharide is an antigen which lacks heptose, 2-keto-3-deoxyoctulosonic acid, and endotoxic lipid A. The minor polysaccharide in the capsular material of R. Trifolii 0403 contains the same antigen in addition to heptose, 2-keto-3-deoxyoctonate, and lipid A. The acidic polysaccharides of two strains of R. trifolii share the clover r-ot cross-reactive antigenic determinant despite other differences in their carbohydrate composition. Studies with monovalent antigen-binding fragments of anti-clover root antibody and Azotobacter vinelandii hybrid transformants carrying the unique antigenic determinant suggest that these polysaccharides bind R. trifolii to the clover root hair tips which contain trifoliin. Images PMID:86535

  1. 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. PMID:22408421

  2. Mitochondrial Protection and Anti-aging Activity of Astragalus Polysaccharides and Their Potential Mechanism

    PubMed Central

    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 Fe2+–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 (O2•−) and hydroxyl radical (•OH), which were produced by reduced nicotinamide adenine dinucleotide (NADH)—N-Methylphenazonium methyl sulfate (PMS) and hydrogen peroxide (H2O2)–Fe2+ system respectively, were measured by 4-nitrobluetetrazolium chloride (NBT) reduction and Fenton reaction colorimetry respectively. The Na2S2O3 titration method was used to measure the scavenging activities of APS on H2O2. APS could inhibit TBARS production, protect mitochondria from PT, and scavenge O2•−, •OH and H2O2 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. PMID:22408421

  3. 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

  4. Expression of two different sulfated fucans by females of Lytechinus variegatus may regulate the seasonal variation in the fertilization of the sea urchin.

    PubMed

    Cinelli, Leonardo P; Castro, Michelle O; Santos, Livia L; Garcia, Clarice R; Vilela-Silva, Ana-Cristina E S; Mourão, Paulo A S

    2007-08-01

    The egg jellies of sea urchins contain sulfated polysaccharides with unusual structures, composed of linear chains of l-fucose or l-galactose with well-defined repetitive units. The specific pattern of sulfation and the position of the glycosidic bond vary among sulfated polysaccharides from different species. These polysaccharides show species specificity in inducing the acrosome reaction, which is a critical event for fertilization. Females of the sea urchin Lytechinus variegatus spawn eggs containing a sulfated fucan with the repetitive sequence [3-alpha-L-Fucp-2(OSO(3))-1 --> 3-alpha-L-Fucp-4(OSO(3))-1 --> 3-alpha-L-Fucp-2,4(OSO(3))-1 --> 3-alpha-L-Fucp-2(OSO(3))-1](n). We now observe that, close to winter, a period of decreased fertility for the sea urchin, the females synthesize a distinct sulfated fucan with a simple structure, composed of 4-sulfated, 3-linked alpha-fucose residues. This sulfated fucan is inactive when tested in vitro for the acrosome reaction using homologous sperm. The amount of egg jellies spawned by females (and their constituent sulfated polysaccharides) varied greatly throughout the year. Apparently, there is a correlation between the temperature of the sea water and the expression of the 4-sulfated, 3-linked sulfated fucan. Overall, we described the occurrence of two isotypes of sulfated fucan in the egg jelly of the sea urchin L. variegatus, which differ in their biological activity and may be involved in the periodicity of the reproductive cycle of the invertebrate.

  5. 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.

  6. Anticoagulant Activity and Structural Characterization of Polysaccharide from Abalone (Haliotis discus hannai Ino) Gonad.

    PubMed

    Zhao, Jun; Yang, Jingfeng; Song, Shuang; Zhou, Dayong; Qiao, Weizhou; Zhu, Ce; Liu, Shuyin; Zhu, Beiwei

    2016-01-01

    In this study, we aimed at characterizing the structure and the anticoagulant activity of a polysaccharide fraction (AGP33) isolated from the gonads of Haliotis discus hannai Ino. AGP33 was extracted by enzymatic hydrolysis and purified by ion-exchange and gel-filtration chromatography. The backbone fraction of AGP33 (BAGP33), which appeared to contain of mannose, glucose and galactose, was prepared by partial acid hydrolysis. According to methylation and nuclear magnetic resonance (NMR) spectroscopy, the backbone of AGP33 was identified as mainly consisting of 1→3-linked, 1→4-linked, and 1→6-linked monosaccharides. AGP33 is a sulfated polysaccharide with sulfates occur at 3-O- and 4-O-positions. It prolonged thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) compared to a saline control solution in a dosage-dependent manner. AGP33 exhibited an extension (p < 0.01) of APTT compared to the saline group at concentrations higher than 5 μg/mL. AGP33 exhibited higher anticoagulant activity than its desulfated product (AGP33-des) and BAGP33. The results showed that polysaccharide with higher molecular weight and sulfate content demonstrated greater anticoagulant activity. PMID:27338320

  7. Anticoagulant Activity and Structural Characterization of Polysaccharide from Abalone (Haliotis discus hannai Ino) Gonad.

    PubMed

    Zhao, Jun; Yang, Jingfeng; Song, Shuang; Zhou, Dayong; Qiao, Weizhou; Zhu, Ce; Liu, Shuyin; Zhu, Beiwei

    2016-06-08

    In this study, we aimed at characterizing the structure and the anticoagulant activity of a polysaccharide fraction (AGP33) isolated from the gonads of Haliotis discus hannai Ino. AGP33 was extracted by enzymatic hydrolysis and purified by ion-exchange and gel-filtration chromatography. The backbone fraction of AGP33 (BAGP33), which appeared to contain of mannose, glucose and galactose, was prepared by partial acid hydrolysis. According to methylation and nuclear magnetic resonance (NMR) spectroscopy, the backbone of AGP33 was identified as mainly consisting of 1→3-linked, 1→4-linked, and 1→6-linked monosaccharides. AGP33 is a sulfated polysaccharide with sulfates occur at 3-O- and 4-O-positions. It prolonged thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) compared to a saline control solution i