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

PubMed

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

2016-07-30

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

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Sulfated modification and anticoagulant activity of pumpkin (Cucurbita pepo, Lady Godiva) polysaccharide.

PubMed

Liang, Li; Ao, Le; Ma, Tao; Ni, Yuanying; Liao, Xiaojun; Hu, Xiaosong; Song, Yi

2018-01-01

Sulfated modification of pumpkin polysaccharide using CAS with pyridines as catalysts under different conditions was conducted to obtain different degrees of sulfation on a laboratory scale. Anticoagulant activities of pumpkin polysaccharide and its sulfated derivatives were also investigated employing various established in vitro systems. Results showed that addition of high ratio of CAS/pyridine under constant conditions could increase the degree of substitution. Sulfate substitution was further confirmed by the FT-IR and 13 C NMR analysis. The d f values between 2.11-2.73 indicated the relatively expanded conformation of the sulfated derivatives. The sulfated polysaccharides showed higher anticoagulant activities through activated partial thrombosis time (aPTT), thrombin time (TT), prothrombin time (PT) and anti-Xa activity assay, which revealed that better anticoagulant activities could be obtained when DS remained higher and M w maintained in a moderate range. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-03-01

Sulfated derivatives of polysaccharide from Momordica charantia L. (MCPS) with different degree of sulfation (DS) were synthesized by chlorosulfonic acid method with ionic liquids as solvent. Fourier transform infrared spectra and 13C nuclear magnetic resonance spectra indicated that C-6 substitution was predominant in MCPS compared with the C-2 position. Compared with the native polysaccharide from Momordica charantia L. (MCP), MCPS exhibited more excellent antioxidant activities in vitro, which indicated that sulfated modification could enhance antioxidant activities of MCP. Furthermore, high DS and moderate molecular weight could improve the antioxidant activities of polysaccharide. Copyright © 2013 Wiley Periodicals, Inc.

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

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

PubMed

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

2016-07-01

Polysaccharides purified from rice bran show antitumor activity against tumor cells, yet the mechanism of this action remains poorly understood. To address this issue, our study evaluated the effect of rice bran polysaccharides on mouse melanoma cell line B16, and Raw264.7 macrophages. Rice bran polysaccharides (RBP) failed to inhibit B16 cell growth in vitro. However, Raw264.7 macrophages treated by RBP enhancement of cytotoxic effects. The cytotoxicity was confirmed by the stimulation of nitric oxide (NO) production and tumor necrosis factor-α (TNF-α) secretion on Raw264.7 macrophages in a dose-dependent manner. RBP2, a fraction of RBP, notably enhanced the inhibition of B16 cells and boosted the immunepotentiation effect compared with RBP. To further enhance the inhibition of B16 cell growth, sulfated polysaccharides (SRBP) was derived using the chlorosulfonic acid-pyridine method. SRBP2 was found to suppress B16 cell growth, reduce B16 cell survival and stimulate NO and TNF-α production. However, SRBP2 displayed a cytotoxic effect on Raw264.7 macrophages. These results suggest that the antitumor activity of RBP and RBP2 is mediated mainly through the activation of macrophages. SRBP2 exerts its antitumor activity by inducing apoptosis in tumor cells and the secretion of NO and TNF-α. Copyright © 2016 Elsevier B.V. All rights reserved.

Sulfated Polysaccharides in the Freshwater Green Macroalga Cladophora surera Not Linked to Salinity Adaptation

PubMed Central

Arata, Paula X.; Alberghina, Josefina; Confalonieri, Viviana; Errea, María I.; Estevez, José M.; Ciancia, Marina

2017-01-01

The presence of sulfated polysaccharides in cell walls of seaweeds is considered to be a consequence of the physiological adaptation to the high salinity of the marine environment. Recently, it was found that sulfated polysaccharides were present in certain freshwater Cladophora species and some vascular plants. Cladophora (Ulvophyceae, Chlorophyta) is one of the largest genera of green algae that are able to grow in both, seas and freshwater courses. Previous studies carried out on the water-soluble polysaccharides of the marine species C. falklandica established the presence of sulfated xylogalactoarabinans constituted by a backbone of 4-linked β-L-arabinopyranose units partially sulfated mainly on C3 and also on C2 with partial glycosylation, mostly on C2, with terminal β-D-xylopyranose or β-D-galactofuranose units. Besides, minor amounts of 3-, 6- and/or 3,6-linked β-D-galactan structures, with galactose in the pyranosic form were detected. In this work, the main water soluble cell wall polysaccharides from the freshwater alga Cladophora surera were characterized. It was found that this green alga biosynthesizes sulfated polysaccharides, with a structure similar to those found in marine species of this genus. Calibration of molecular clock with fossil data suggests that colonization of freshwater environments occurred during the Miocene by its ancestor. Therefore, the presence of sulfated polysaccharides in the freshwater green macroalga C. surera could be, in this case, an adaptation to transient desiccation and changes in ionic strength. Retention of sulfated polysaccharides at the cell walls may represent a snapshot of an evolutionary event, and, thus constitutes an excellent model for further studies on the mechanisms of sulfation on cell wall polysaccharides and environmental stress co-evolution. PMID:29181012

Sulfated Polysaccharides in the Freshwater Green Macroalga Cladophora surera Not Linked to Salinity Adaptation.

PubMed

Arata, Paula X; Alberghina, Josefina; Confalonieri, Viviana; Errea, María I; Estevez, José M; Ciancia, Marina

2017-01-01

The presence of sulfated polysaccharides in cell walls of seaweeds is considered to be a consequence of the physiological adaptation to the high salinity of the marine environment. Recently, it was found that sulfated polysaccharides were present in certain freshwater Cladophora species and some vascular plants. Cladophora (Ulvophyceae, Chlorophyta) is one of the largest genera of green algae that are able to grow in both, seas and freshwater courses. Previous studies carried out on the water-soluble polysaccharides of the marine species C. falklandica established the presence of sulfated xylogalactoarabinans constituted by a backbone of 4-linked β-L-arabinopyranose units partially sulfated mainly on C3 and also on C2 with partial glycosylation, mostly on C2, with terminal β-D-xylopyranose or β-D-galactofuranose units. Besides, minor amounts of 3-, 6- and/or 3,6-linked β-D-galactan structures, with galactose in the pyranosic form were detected. In this work, the main water soluble cell wall polysaccharides from the freshwater alga Cladophora surera were characterized. It was found that this green alga biosynthesizes sulfated polysaccharides, with a structure similar to those found in marine species of this genus. Calibration of molecular clock with fossil data suggests that colonization of freshwater environments occurred during the Miocene by its ancestor. Therefore, the presence of sulfated polysaccharides in the freshwater green macroalga C. surera could be, in this case, an adaptation to transient desiccation and changes in ionic strength. Retention of sulfated polysaccharides at the cell walls may represent a snapshot of an evolutionary event, and, thus constitutes an excellent model for further studies on the mechanisms of sulfation on cell wall polysaccharides and environmental stress co-evolution.

Structural analysis and anticoagulant activities of two sulfated polysaccharides from the sea cucumber Holothuria coluber.

PubMed

Yang, Wenjiao; Cai, Ying; Yin, Ronghua; Lin, Lisha; Li, Zhongkun; Wu, Mingyi; Zhao, Jinhua

2018-05-01

Sulfated polysaccharides such as fucosylated glycosaminoglycan and fucan sulfate from echinoderm possess complex chemical structure and various biological activities. The two sulfated polysaccharides were purified from the low-value sea cucumber Holothuria coluber. Their physicochemical properties and chemical structures were analyzed and characterized by chemical and instrumental methods. Structural analysis clarified that the sea cucumber fucosylated glycosaminoglycan contains a chondroitin sulfate-like backbone and fucosyl branches with four various sulfation patterns. The fucan sulfate with molecular weight of 64.6 kDa comprises a central core of regular α(1 → 4)-linked tetrasaccharide repeating units, each of which is linked by a 4-O-sulfated fucose residue. Anticoagulant assays indicated that these sulfated polysaccharides possessed strong APTT prolonging activities and intrinsic factor Xase inhibitory activities, both of which decreased with the reduction of their molecular weights. Our results expand knowledge on the structural types of sulfated polysaccharides from sea cucumbers and further illustrate their functionality. Copyright © 2018. Published by Elsevier B.V.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

A review of chemical methods for the selective sulfation and desulfation of polysaccharides.

PubMed

Bedini, Emiliano; Laezza, Antonio; Parrilli, Michelangelo; Iadonisi, Alfonso

2017-10-15

Sulfated polysaccharides are known to possess several biological activities, with their sulfation pattern acting as a code able to transmit functional information. Due to their high biological and biomedical importance, in the last two decades many reports on the chemical modification of their sulfate distribution as well as on the regioselective insertion of sulfate groups on non-sulfated polysaccharides appeared in literature. In this Review we have for the first time collected these reports together, categorizing them into three different classes: i) regioselective sulfation reactions, ii) regioselective desulfation reactions, iii) regioselective insertion of sulfate groups through multi-step strategies, and discussing their scope and limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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.

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

PubMed

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

2015-11-01

-initiated hepatocarcinogenesis through inhibition of abnormal cell proliferation and induction of apoptosis. A modest inhibition rat liver carcinogenesis was observed with the aqueous extract. The sulfated polysaccharides altered serum parameters of hepatic damage and modulated various components of the hepatic enzymatic and nonenzymatic antioxidant defense systems. The sulfated polysaccharides from U. lactuca may have unique properties of providing protection against DENA-induced oxidative stress which could contribute to chemoprevention of experimental hepatocarcinogenesis. U. lactuca sulfated polysaccharides could be developed as chemopreventive and therapeutic drug against human HCC. © The Author(s) 2015.

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

PubMed

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

2012-02-13

The extraction from natural sources of Chondroitin sulfate (CS), a polysaccharide used for management of osteoarthritis, leads to very complex mixtures. The synthesis of CS by chemical modification of other polysaccharides has seldom been reported due to the intrinsic complexity that arises from fine chemical modifications of the polysaccharide structure. In view of the growing interest in expanding the application of CS to pharmacological fields other than osteoarthritis treatment, we launched a program to find new sources of known or even unprecedented CS polysaccharides. As part of this program, we report herein on an investigation of the use of a cyclic orthoester group to selectively protect the 4,6-diol of N-acetyl-galactosamine residues in chondroitin (obtained from a microbial source), thereby facilitating its transformation into CSs. In particular, three CS polysaccharides were obtained and demonstrated to possess rare or hitherto unprecedented sulfation patterns by 2D NMR spectroscopy characterization. Two of them contained disaccharide subunits characterized by glucuronic acid residues selectively sulfated at position 3 (GlcA(3S)), the biological functions of which are known but have yet to be fully investigated. This first semi-synthetic access to GlcA(3S)-containing CS could greatly expedite such studies, since it can easily furnish considerable amounts of these polysaccharides, which are usually isolated with difficulty and in very low quantity from natural sources. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure and in vitro anticancer activity of sulfated O-polysaccharide from marine bacterium Poseidonocella pacifica KMM 9010T.

PubMed

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

2017-12-15

We presented the structure of the sulfated polysaccharide moiety and anticancer activity in vitro of the О-deacylated lipopolysaccharide (DPS) isolated from the marine bacterium Poseidonocella pacifica KMM 9010 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 sulfated disaccharide repeating units consisted of d-rhamnose (d-Rhaр) and 3-deoxy-d-manno-oct-2-ulosonic acid (Kdop): →7)-β-Kdoр4Ac5S-(2→3)-β-d-Rhaр2S-(1→. We demonstrated that the DPS from P. pacifica KMM 9010 T non-toxic for normal mouse epidermal cells (JB6 Cl41 cell line) and inhibited colony formation of human colorectal carcinoma HT-29, breast adenocarcinoma MCF-7 and melanoma SK-MEL-5 cells in a dose-dependent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

Seaweed as a source of novel nutraceuticals: sulfated polysaccharides and peptides.

PubMed

Jiménez-Escrig, A; Gómez-Ordóñez, E; Rupérez, P

2011-01-01

Seaweeds and seaweed-derived products are underexploited marine bioresources and a source of natural ingredients for functional foods. Nutritional studies on seaweeds indicate that brown and red seaweeds possess a good nutritional quality and could be used as an alternative source of dietary fiber, protein, and minerals. Moreover, bioactive sulfated polysaccharides are the main components of soluble fiber in seaweeds and also bioactive peptides can be prepared from seaweed protein. This chapter gives an overview of the main biological properties of sulfated polysaccharides and peptides from brown and red seaweeds. Recent studies have provided evidence that sulfated polysaccharides from seaweeds can play a vital role in human health and nutrition. Besides, peptides derived from algal protein are most promising as antihypertensive agents. Further research work, especially in vivo studies, are needed in order to gain a better knowledge of the relation structure-function by which bioactive compounds from seaweeds exert their bioactivity. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

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

PubMed

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

2016-12-12

Fucosylated chondroitin sulfate (fCS)-a glycosaminoglycan (GAG) found in sea cucumbers-has recently attracted much attention owing to its biological properties. In particular, a low molecular mass fCS polysaccharide has very recently been suggested as a strong candidate for the development of an antithrombotic drug that would be safer and more effective than heparin. To avoid the use of animal sourced drugs, here we present the chemical transformation of a microbial sourced unsulfated chondroitin polysaccharide into a small library of fucosylated (and sulfated) derivatives thereof. To this aim, a modular approach based on the different combination of only five reactions was employed, with an almost unprecedented polysaccharide branching by O-glycosylation as the key step. The library was differentiated for sulfation patterns and/or positions of the fucose branches, as confirmed by detailed 2D NMR spectroscopic analysis. These semi-synthetic polysaccharides will allow a wider and more accurate structure-activity relationship study with respect to those reported in literature to date. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2012-09-01

Sulfated polysaccharides (SPSs) from two edible fungal species, including two strains of Antrodia cinnamomea and Poria cocos, were isolated. Fucose, glucosamine, galactose, glucose, and mannose were the major sugars in the SPSs, and these SPSs had a high sulfate content. The area percentage of low-molecular-weight SPSs (1-100 kDa) covered almost half of the SPS mixture of the A. cinnamomea strains. In contrast, high-molecular-weight SPSs (>1000 kDa) of P. cocos covered a large proportion of the area at 30.06%. SPSs from A. cinnamomea B86 showed stronger inhibition of endothelial cell (EC) tube formation in an in vitro assay of angiogenesis, than did A. cinnamomea 35396 or P. cocos. The degree of sulfation paralleled their antiangiogenic activity. When tumor cells were concurrently exposed to doxorubicin (DOX) and fungal SPSs, SPSs synergistically increased the cytotoxicity of DOX to different degree up to 50-fold. Fungal SPSs may offer new applications for combinational-therapy drugs. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-10-01

Ulva prolifera can protect human skin fibroblast from being injured by hydrogen peroxide. This work studied the composition of Ulva prolifera polysaccharide and identified its physicochemical properties. The results showed that the cell proliferation of 0.5mg/mL crude polysaccharide was 154.4% of that in negative control group. Moreover, ROS detection indices, including DCFH-DA, GSH-PX, MDA and CAT, indicated that crude polysaccharide could improve cellular ability to scavenge free radical and decrease the injury on human skin fibroblast by hydrogen peroxide. In purified polysaccharide, the activity of fraction P1-1 was the highest, with 174.6% of that in negative control group. The average molecular weight of P1-1 was 137kD with 18.0% of sulfate content. This work showed the inhibition of hydrogen peroxide induced injuries on human skin fibroblast by Ulva prolifera polysaccharide, which may further evaluate the application of U. prolifera on cosmetics. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of Content of Sulfate Groups in Seaweed Polysaccharides on Antioxidant Activity and Repair Effect of Subcellular Organelles in Injured HK-2 Cells

PubMed Central

Ma, Xiao-Tao; Sun, Xin-Yuan; Yu, Kai; Gui, Qin

2017-01-01

This study aims to investigate the repair effect of subcellular structure injuries of the HK-2 cells of four degraded seaweed polysaccharides (DSPs), namely, the degraded Porphyra yezoensis, Gracilaria lemaneiformis, Sargassum fusiform, and Undaria pinnatifida polysaccharides. The four DSPs have similar molecular weight, but with different content of sulfate groups (i.e., 17.9%, 13.3%, 8.2%, and 5.5%, resp.). The damaged model was established using 2.8 mmol/L oxalate to injure HK-2 cells, and 60 μg/mL of various DSPs was used to repair the damaged cells. With the increase of sulfate group content in DSPs, the scavenging activity of radicals and their reducing power were all improved. Four kinds of DSPs have repair effect on the subcellular organelles of damaged HK-2 cells. After being repaired by DSPs, the release amount of lactate dehydrogenase was decreased, the integrity of cell membrane and lysosome increased, the Δψm increased, the cell of G1 phase arrest was inhibited, the proportion of S phase increased, and cell apoptotic and necrosis rates were significantly reduced. The greater the content of sulfate group is, the stronger is the repair ability of the polysaccharide. These DSPs, particularly the polysaccharide with higher sulfate group content, may be a potential drug for the prevention and cure of kidney stones. PMID:28785372

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

PubMed

Burg, Ariela; Oshrat, Levy-Ontman

2015-10-20

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

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Compositional analysis of sulfated polysaccharides from sea cucumber (Stichopus japonicus) released by autolysis reaction.

PubMed

Song, Shuang; Wu, Sufeng; Ai, Chunqing; Xu, Xin; Zhu, Zhenjun; Cao, Chunyang; Yang, Jingfeng; Wen, Chengrong

2018-07-15

Autolysis is not only a major reason for postharvest quality deterioration of sea cucumber, but also a promising alternative for exogenous protease to produce peptides or polysaccharides. However, little has been known about the effects of autolysis on bioactive polysaccharides of sea cucumber. Concerning the quality and safety of sea cucumber products involved autolysis reaction, the present study focused on the chemical composition of sulfated polysaccharides (SPs) released by autolysis reaction. Chemical analysis indicated that after 3-day autolysis 63% of sulfated polysaccharides were liberated but with protein chains at their reducing ends. Then the composition of SP obtained by autolysis (A-SP) was compared with that of total SPs (T-SP) via a series of analysis techniques, including FTIR, 1 H NMR, HPLC and mass spectroscopy. As indicated by the results, fucan to fucosylated chondroitin sulfate ratio was found high in A-SP compared to T-SP, fucan with a lower molecular weight was the major fraction in A-SP, and the di-sulfated Fuc residue observed in T-SP was absent in A-SP. To conclude, A-SP differed greatly from T-SP in the chemical composition, suggesting possible changes on their bioactivities. Copyright © 2018. Published by Elsevier B.V.

Bush Sophora Root polysaccharide and its sulfate can scavenge free radicals resulted from duck virus hepatitis.

PubMed

Chen, Yun; Xiong, Wen; Zeng, Ling; Wang, Yu; Zhang, Shuaibing; Xu, Meiyun; Song, Meiyun; Wang, Yixuan; Du, Hongxu; Liu, Jiaguo; Wang, Deyun; Wu, Yi; Hu, Yuanliang

2014-05-01

In order to study the antioxidant effect of Bush Sophora Root polysaccharide (BSRPS) and its sulfate on anti-duck virus hepatitis (DVH), sulfated Bush Sophora Root polysaccharide (sBSRPS) was prepared by chlorosulfonic acid-pyridine method. Ducklings were fed with BSRPS and sBSRPS after challenged DHAV. Death was monitored, evaluation indexes of peroxidative and hepatic injury at the initial (4th and 8th hour) and later (54th hour) stages were detected. The results showed a fine treatment effect of BSRPS and sBSRPS. Visual hepatic pathological injury severities were less serious after the treatment. At the initial stage, free radical levels in all groups were the same, and BSRPS and sBSRPS reduced the hepatic injury through inhibiting virus replication. At the later stage, mass free radicals were detected in VC group while free radical levels in BSRPS and sBSRPS groups were significantly lower than VC group. The antioxidant effect of BSRPS and sBSRPS might alleviate the hepatic injury. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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

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

PubMed

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

2012-01-01

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

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

Antiangiogenic activity of semisynthetic biotechnological heparins: low-molecular-weight-sulfated Escherichia coli K5 polysaccharide derivatives as fibroblast growth factor antagonists.

PubMed

Presta, Marco; Oreste, Pasqua; Zoppetti, Giorgio; Belleri, Mirella; Tanghetti, Elena; Leali, Daria; Urbinati, Chiara; Bugatti, Antonella; Ronca, Roberto; Nicoli, Stefania; Moroni, Emanuela; Stabile, Helena; Camozzi, Maura; Hernandez, German Andrés; Mitola, Stefania; Dell'Era, Patrizia; Rusnati, Marco; Ribatti, Domenico

2005-01-01

Low-molecular-weight heparin (LMWH) exerts antitumor activity in clinical trials. The K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor. Chemical and enzymatic modifications of K5 polysaccharide lead to the production of biotechnological heparin-like compounds. We investigated the fibroblast growth factor-2 (FGF2) antagonist and antiangiogenic activity of a series of LMW N,O-sulfated K5 derivatives. Surface plasmon resonance analysis showed that LMW-K5 derivatives bind FGF2, thus inhibiting its interaction with heparin immobilized to a BIAcore sensor chip. Interaction of FGF2 with tyrosine-kinase receptors (FGFRs), heparan sulfate proteoglycans (HSPGs), and alpha(v)beta3 integrin is required for biological response in endothelial cells. Similar to LMWH, LMW-K5 derivatives abrogate the formation of HSPG/FGF2/FGFR ternary complexes by preventing FGF2-mediated attachment of FGFR1-overexpressing cells to HSPG-bearing cells and inhibit FGF2-mediated endothelial cell proliferation. However, LMW-K5 derivatives, but not LMWH, also inhibit FGF2/alpha(v)beta3 integrin interaction and consequent FGF2-mediated endothelial cell sprouting in vitro and angiogenesis in vivo in the chick embryo chorioallantoic membrane. LMW N,O-sulfated K5 derivatives affect both HSPG/FGF2/FGFR and FGF2/alpha(v)beta3 interactions and are endowed with FGF2 antagonist and antiangiogenic activity. These compounds may provide the basis for the design of novel LMW heparin-like angiostatic compounds.

Large-scale preparation of sulfated polysaccharides with anti-angionenic and anti-inflammatory properties from Antrodia cinnamomia.

PubMed

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

2018-07-01

Sulfated polysaccharides (SPSs) were isolated from 0.5mM potassium-sulfate fed Antrodia cinnamomea. We investigated the chemical properties and bio-activities of the five different fractions (SPS-K1, SPS-K2, SPS-K3, SPS-K4, and SPS-K5) with molecular weights ranging from 0.51 to 523.48kDa. SPS-K3 was consisted mainly of glucose, galactose and sulfate in a molar ratio of 15:1:30 with Mn value of 6.82kDa. It showed maximal inhibition of the tumor necrosis factor (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) on bacterial LPS-induced inflammation in RAW264.7 macrophage and the production was recorded as 26.19 and 51.06%, respectively. SPS-K2 showed inhibition of endothelial cell tube formation in an in vitro assay of angiogenesis, and IC 50 was determined to be 160.92μg/ml. Large-scale preparation of SPS was performed in the 3-L fermentation of A. cinnamomea and the yield of the SPS was 5.38%. The area percentage of high-molecular-weight SPSs (1470-1590kDa) covered almost half of the SPSs mixture characterized by size exclusion column chromatography. The SPSs from fermented A. cinnamomea had significant inhibition on TNF-α, IL-1β and IL-6 production. This study is the first report to large-scale produce SPSs and demonstrates sulfated galactoglucan with strong anti-inflammatory activity. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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

PubMed Central

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

2014-01-01

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

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

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

Polysaccharides and their depolymerized fragments from Costaria costata: Molecular weight and sulfation-dependent anticoagulant and FGF/FGFR signal activating activities.

PubMed

Hou, Ningning; Zhang, Meng; Xu, Yingjie; Sun, Zhongmin; Wang, Jing; Zhang, Lijuan; Zhang, Quanbin

2017-12-01

Crude polysaccharides from Costaria costata were extracted by hot water and further fractionated by anion exchange chromatography into three polysaccharide fractions. Three low molecular weight fragments were then prepared by degradation of the polysaccharides with hydrogen peroxide and ascorbic acid. The structural features of the polysaccharides and their low molecular weight fragments were elucidated for the first time based on the HGPC, FT-IR, NMR, MS, monosaccharide composition, and other chemical analyses. Their anticoagulant and FGF-1, -2, -7, -8, -9, -10/FGFR1c signaling activation activities in BaF3 cells were also examined. Our studies showed that the polysaccharides were sulfated at different positions of galactose and fucose residues. The APTT-, PT- and TT-based anticoagulant assay results indicated that a high molecular weight and a higher degree of sulfation were essential for their anticoagulant activities. In contrast, not only the polysaccharides but also the depolymerized fragments showed significant FGF/FGFR signal activating activities in a FGF-, molecular weight-, and sulfation-dependent manner. The results presented in current study demonstrated the potential use of the polysaccharides and their fragments as anticoagulants and FGF signal regulators. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular characteristics of sulfated polysaccharides from Monostroma nitidum and their in vitro anticancer and immunomodulatory activities.

PubMed

Karnjanapratum, Supatra; You, SangGuan

2011-03-01

We investigated water-soluble sulfated polysaccharides isolated from Monostroma nitidum using ion-exchange chromatography to determine their molecular characteristics and biological activities. The crude and fractionated polysaccharides (F(1), F(2), and F(3)) consisted mostly of carbohydrates (58.3-91.9%), uronic acids (0-21.8%) and sulfates (1.8-17.7%) as well as varying amounts of proteins (1.6-9.4%). Their monosaccharide levels were significantly different including rhamnose (0-95.7%) and glucose (0-98.6%) content with small amounts of xylose (0.8-4.3%). These polysaccharides contained one or two subfractions with average molecular weights (M(w)) ranging from 94.4 to 1387×10(3) g/mol. The in vitro inhibitory activity (≤75%) of the polysaccharides on a human cancer cell line (AGS) suggested that the polysaccharides had direct cytotoxic effects on the cancer cells. In addition, these hetero-polysaccharides (from the crude and F(1) and F(2) fractions) stimulated a macrophage cell line, Raw 264.7 cells, inducing considerable NO and PGE(2), production, which suggested that they could be strong immunomodulators. Copyright © 2010 Elsevier B.V. All rights reserved.

Sulfated polysaccharide from the leaves of Artemisia Princeps activates heparin cofactor II independently of the Lys173 and Arg189 residues of heparin cofactor II.

PubMed

Hayashi, T; Hayakawa, Y; Hayashi, T; Sasaki, H; Sakuragawa, N

1997-07-01

A sulfated polysaccharide (AFE-HCD) purified from the leaves of Artemisia princeps Pamp selectively accelerated the rate of thrombin inhibition by heparin cofactor II (HCII). By using plasma derived HCII and bacterial expressed recombinant HCII molecules, the interaction between each HCII molecule and AFE-HCD was analyzed. AFE-HCD accelerated thrombin inhibition by plasma derived HCII or bacterial expressed wild type HCII to the same extent (IC50: 0.056 micrograms/ml for plasma derived HCII and 0.066 micrograms/ml for recombinant HCII under the experimental condition). The recombinant HCII (rHCII) molecule with Lys173-->Leu or Arg189-->His substitution, which is defective in interactions with heparin and dermatan sulfate, respectively, is activated by AFE-HCD to inhibit thrombin in a manner similar to wild type rHCII. These results suggested that activation of HCII was independent of its Lys173 or Arg189 residue. Although AFE-HCD is a selective activator of HCII like dermatan sulfate, the amino acid residue required for the activation of HCII was distinct form that of dermatan sulfate as well as heparin.

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

PubMed

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

2016-11-05

The cell-wall sulfated polysaccharide of the marine red microalga Porphyridium sp. is a high molecular weight biopolymer that has potential for use as a platform for metal complexation for various applications. This paper describes the structural and rheological characterization and antibacterial activity of the polysaccharide in combination with Zn(2+) (Zn-PS). SAXS and rheology studies indicate that with the addition of ZnCl2 to the sulfated polysaccharide the only change was the increase in viscosity in the entangled regime. The antibacterial activity of Zn-PS solutions was more potent than that of the native polysaccharide against Gram-negative and Gram-positive bacteria. The synergy between the bioactivities of Zn(2+) (which is a key player in wound healing and is active against variety of pathogens) and the unique bioactivities of the polysaccharide (e.g., anti-inflammatory) indicates promising potential for the development of novel products for the pharmaceutical and cosmetics industries. Copyright © 2016. Published by Elsevier Ltd.

Medicinal benefits of sulfated polysaccharides from sea vegetables.

PubMed

Kim, Se-Kwon; Li, Yong-Xin

2011-01-01

The cell walls of sea vegetables or marine algae are rich in sulfated polysaccharides (SPs) such as fucoidans in brown algae, carrageenans in red algae, and ulvans in green algae. These SPs exhibit various biological activities such as anticoagulant, antiviral, antioxidative, and anticancer activities with potential health benefits. Therefore, SPs derived from sea vegetables have great potential in further development as nutraceuticals and medicinal foods. This chapter presents an overview of biological activities and potential medicinal benefits of SPs derived from sea vegetables. Copyright © 2011 Elsevier Inc. All rights reserved.

Herpes Simplex Virus Type 2 Glycoprotein G Is Targeted by the Sulfated Oligo- and Polysaccharide Inhibitors of Virus Attachment to Cells▿

PubMed Central

Adamiak, Beata; Ekblad, Maria; Bergström, Tomas; Ferro, Vito; Trybala, Edward

2007-01-01

Variants of herpes simplex virus type 2 (HSV-2) generated by virus passage in GMK-AH1 cells in the presence of the sulfated oligosaccharide PI-88 were analyzed. Many of these variants were substantially resistant to PI-88 in their initial infection of cells and/or their cell-to-cell spread. The major alteration detected in all variants resistant to PI-88 in the initial infection of cells was a frameshift mutation(s) in the glycoprotein G (gG) gene that resulted in the lack of protein expression. Molecular transfer of the altered gG gene into the wild-type background confirmed that the gG-deficient recombinants were resistant to PI-88. In addition to PI-88, all gG-deficient variants of HSV-2 were resistant to the sulfated polysaccharide heparin. The gG-deficient virions were capable of attaching to cells, and this activity was relatively resistant to PI-88. In addition to having a drug-resistant phenotype, the gG-deficient variants were inefficiently released from infected cells. Purified gG bound to heparin and showed the cell-binding activity which was inhibited by PI-88. Many PI-88 variants produced syncytia in cultured cells and contained alterations in gB, including the syncytium-inducing L792P amino acid substitution. Although this phenotype can enhance the lateral spread of HSV in cells, it conferred no virus resistance to PI-88. Some PI-88 variants also contained occasional alterations in gC, gD, gE, gK, and UL24. In conclusion, we found that glycoprotein gG, a mucin-like component of the HSV-2 envelope, was targeted by sulfated oligo- and polysaccharides. This is a novel finding that suggests the involvement of HSV-2 gG in interactions with sulfated polysaccharides, including cell surface glycosaminoglycans. PMID:17928351

NKG2D and CD94 bind to heparin and sulfate-containing polysaccharides.

PubMed

Higai, Koji; Imaizumi, Yuzo; Suzuki, Chiho; Azuma, Yutaro; Matsumoto, Kojiro

2009-09-04

Killer lectin-like receptors NKG2D and CD94 on natural killer cells trigger cytotoxicity through binding of glycans on target cells including sialyl Lewis X antigen. We previously reported that NKG2D and CD94 recognize alpha2,3-linked NeuAc on multi-antennary N-glycans. Here we further investigated polysaccharide binding by these receptors, using glutathione-S-transferase-fused extracellular domains of NKG2D AA 73-216 (rNKG2Dlec) and CD94 AA 68-179 (rCD94lec). We found that rNKG2Dlec and rCD94lec bind in a dose-dependent manner to plates coated with heparin-conjugated bovine serum albumin (heparin-BSA). Binding to heparin-BSA was suppressed by soluble sulfate-containing polysaccharides, but minimally impacted by 2-O-, 6-O-, and 2-N-desulfated heparin. Mutagenesis revealed that (152)Y and (199)Y of NKG2D and (144)F, (160)N, and (166)C of CD94 were critical for binding to heparin-BSA. The present manuscript provides the first evidence that NKG2D and CD94 bind to heparin and sulfate-containing polysaccharides.

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

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

PubMed

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

2014-02-01

Water-soluble sulfated polysaccharides from the red seaweed Nemalion helminthoides: two xylomannan fractions (N3 and N4) and a mannan fraction (N6) were investigated to determine their in vitro and in vivo immunomodulatory activities. N3 and N4 induced in vitro proliferation of macrophages of the murine cell line RAW 264.7 and significantly stimulated the production of nitric oxide (NO) and cytokines (IL-6 and TNF-α) in the same cells, whereas this response was not observed with the mannan N6. The cytokine production was also stimulated by sulfated xylomannans in vivo in BALB/c mice inoculated intravenously with these polysaccharides. Remarkably, when mice were treated with N3 and N4 for 1 h before being infected with Herpes simplex virus type 2, they remained asymptomatic with no signs of disease. The in vitro and in vivo results suggest that sulfated xylomannans could be strong immunomodulators. Copyright © 2013 Elsevier B.V. All rights reserved.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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. © 2016 Federation of European Biochemical Societies.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

2017-07-01

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 EC50 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.

The role of the conformational profile of polysaccharides on skin penetration: the case of hyaluronan and its sulfates.

PubMed

Cilurzo, Francesco; Vistoli, Giulio; Gennari, Chiara G M; Selmin, Francesca; Gardoni, Fabrizio; Franzè, Silvia; Campisi, Monica; Minghetti, Paola

2014-04-01

The literature data suggest the capacity of biomacromolecules to permeate the human skin, even though such a transdermal permeation appears to be governed by physicochemical parameters which are significantly different compared to those ruling the skin permeation of small molecules. On these grounds, the present study was undertaken to investigate the in vitro diffusion properties through the human epidermis of hyaluronic acid and their sulfates. Low- and medium-molecular-weight hyaluronic acids and the corresponding derivatives at two degrees of sulfation were then tested. In vitro studies evidenced that the sulfated polymers permeate better than the corresponding hyaluronic acid, despite their vastly greater polarity, while the observed permeation markedly decreases when increasing the polymer's molecular weight regardless of the sulfation degree. Using a fluorescent-labeled polysaccharide, it was also evidenced that hyaluronans have a great affinity for corneocytes and likely cross the stratum corneum mainly through a transcellular route. The molecular-dynamics study revealed how the observed permeations for the investigated polysaccharides can be rationalized by monitoring their conformational profiles, since the permeation was found to be directly related to their capacity to assume extended and flexible conformations. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

In vitro prebiotic effects of seaweed polysaccharides

NASA Astrophysics Data System (ADS)

Chen, Xiaolin; Sun, Yuhao; Hu, Linfeng; Liu, Song; Yu, Huahua; Xing, Rong'e.; Li, Rongfeng; Wang, Xueqin; Li, Pengcheng

2017-09-01

Although prebiotic activities of alginate and agar oligosaccharides isolated from seaweeds have been reported, it remains unknown whether seaweed polysaccharides have prebiotic activity. In this study, we isolated polysaccharides from four species of seaweeds, such as Grateloupia filicina (GFP), Eucheuma spinosum (ESP), Ulva pertusa (UPP), and Ascophyllum nodosum (ANP), and characterized their structures and prebiotic effects in vitro. The results showed that these polysaccharides were different in total sugar and sulfate contents as well as monosaccharide composition. GFP and ESP significantly promoted bifidobacterium proliferation and 0.1% ESP and 0.4% GFP resulted in the highest proliferation rates of beneficial bacteria, whereas UPP and ANP inhibited the growth of beneficial bacteria at all tested concentrations (0.1%-0.5%). The different behaviors of the four seaweed-originated polysaccharides might be reflected by differences in monosaccharide composition and structure. Therefore, polysaccharides isolated from GFP and ESP could be utilized as prebiotics. However, more studies must be carried out in vivo.

High molecular weight polysaccharide that binds and inhibits virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konowalchuk, Thomas W.; Konowalchuk, Jack

This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods of inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further includes 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.

High molecular weight polysaccharide that binds and inhibits virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konowalchuk, Thomas W

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.

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.

Synthesis and catalytic activity of polysaccharide templated nanocrystalline sulfated zirconia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sherly, K. B.; Rakesh, K.

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 themore » 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.« less

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

PubMed

Zhang, Sheng; Li, Xiang-Zhou

2015-01-22

We isolated and purified polysaccharides from the Camellia oleifera Abel. fruit hull and studied its hypoglycemic potential. Our results revealed six polysaccharides (CFPA-1-5 & CFPB) from the aqueous extract from the defatted C. oleifera fruit hull. Purified polysaccharides (purity >90%) were investigated for the inhibition of α-glucosidase activity in vitro. Two polysaccharides, CFPB and CFPA-3 were present in high concentration in the fruit hull and showed a dose-dependent inhibition of α-glucosidase activity, with IC50 concentrations of 11.80 and 10.95 μg/mL, respectively. This result suggests that polysaccharides (CFP) extracted from the fruit hull of C. oleifera may have potential as functional foods with featuring a hypoglycemic effect. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2012-01-01

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

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.

Influence of bioactive sulfated polysaccharide-protein complexes on hepatocarcinogenesis, angiogenesis and immunomodulatory activities.

PubMed

Matloub, Azza A; Aglan, Hadeer A; Mohamed El Souda, Sahar Salah; Aboutabl, Mona Elsayed; Maghraby, Amany Sayed; Ahmed, Hanaa H

2016-12-01

antitumor activity of sulfated polysaccharide-protein complexes of JCEM and EHEM is due to direct cytotoxic activity, anti-hepatocarcinogenesis, and anti-angiogenesis. In addition, JCEM, PCEM and EHEM had an immunostimulatory response and improved the humoral immune response in HCC induced rats. Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Kinetics of corrosion inhibition of aluminum in acidic media by water-soluble natural polymeric chondroitin-4-sulfate as anionic polyelectrolyte inhibitor.

PubMed

Hassan, Refat M; Ibrahim, Samia M; Takagi, Hideo D; Sayed, Suzan A

2018-07-15

Corrosion inhibition of aluminum (Al) in hydrochloric acid by anionic polyelectrolyte chondroitin-4-sulfate (CS) polysaccharide has been studied using both gasometrical and weight-loss techniques. The results drawn from these two techniques are comparable and exhibit negligible differences. The inhibition efficiency was found to increase with increasing the inhibitor concentration and decreased with increasing temperature. The inhibition action of CS on Al metal surface was found to obey both of Langmuir and Freundlich isotherms. The factors affecting the corrosion rates such as the concentration and geometrical structure of the inhibitor, concentration of the corrosive medium, and the temperature were examined. The kinetic parameters were evaluated and a suitable corrosion mechanism consistent with the results obtained is discussed. Copyright © 2018. Published by Elsevier Ltd.

Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.

PubMed

Powers, Jacquelyn M; Buchanan, George R; Adix, Leah; Zhang, Song; Gao, Ang; McCavit, Timothy L

2017-06-13

Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral iron despite iron polysaccharide complex possibly being better tolerated. To compare the effect of ferrous sulfate with iron polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Three mg/kg of elemental iron once daily as either ferrous sulfate drops or iron polysaccharide complex drops for 12 weeks. Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total iron-binding capacity <425 μg/dL at the 12-week visit), changes in serum ferritin level and total iron-binding capacity, adverse effects. Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in iron polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P < .001) with ferrous sulfate (based on a linear mixed model). Proportion with a complete resolution of IDA was higher in the ferrous sulfate group (29% vs 6%; P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (iron complex) over

A polysaccharide from Dictyophora indusiata inhibits the immunosuppressive function of cancer-associated fibroblasts.

PubMed

Han, Shuyu; Ma, Chaoxiong; Hu, Minghua; Wang, Yuanyuan; Ma, Fangli; Tao, Ning; Qin, Zhihai

2017-10-01

Reversing the function of cancer-associated fibroblasts (CAFs) may improve the efficacy of cancer therapy. Here, we isolated a novel polysaccharide from Dictyophora indusiata (ZSP4) and examined its effects on the function of prostate CAFs. The supernatant of prostate CAFs can stimulate the proliferation of immune cells and inhibit the growth of CD4+/CD8+ T cells. However, after ZSP4 stimulation, the functions of prostate CAFs were inhibited. The mechanism experiment shows that ZSP4 can stimulate prostate CAFs by down-regulating the expression of α-smooth muscle actin. Polysaccharides extracted from Dictyophora indusiata stimulate the proliferation of immune cells and reverse the immune-suppressive functions of prostate CAFs, shedding new light on the development of novel anticancer strategies. The endocrine therapy used to treat prostate cancer aims to eliminate androgenic activity from prostatic tissue; these therapies are painful and of poor therapeutic effect. In this study, we found that polysaccharides extracted from Dictyophora indusiata may affect the micro-environment of tumours and inhibit the growth of the tumours. Our results suggest that polysaccharides may modulate negative immune regulation and enhance antitumour immunity, which is important for clinical therapy. Copyright © 2017 John Wiley & Sons, Ltd.

Polysaccharide structure of tetrasporic red seaweed Tichocarpus crinitus.

PubMed

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

2013-10-15

Sulfated polysaccharide isolated from tetrasporic plants of Tichocarpus crinitus was investigated. The polysaccharide was isolated by two methods: with water extraction at 80 °C (HT) and with a mild alkaline extraction (AE). The extracted polysaccharides were presented by non-gelling ones only, while galactose and 3,6-AG were the main monosaccharides, at the same time amount of 3,6-AG in AE polysaccharides was the similar to that of HT. According to methods of spectroscopy and mass spectrometry, the polysaccharide from tetrasporic T. crinitus contains main blocks of 1,3-linked β-D-galactopyranosyl-2,4-disulfates and 1,4-linked 3,6-anhydro-α-D-galactopyranosyl while 6-sulfated 4-linked galactopyranosyl resudies are randomly distributed along the polysaccharide chain. The alkaline treatment of HT polysaccharide results in obtaining polysaccharide with regular structure that composed of alternating 1,3-linked β-D-galactopyranosyl-2,4-disulfates and 1,4-linked 3,6-anhydro-α-D-galactopyranosyl residues. Native polysaccharide (HT) possessed both high anticoagulant and antiplatelet activity measured by fibrin clotting and platelet aggregation induced by collagen. This activity could be connected with peculiar chemical structure of HT polysaccharide which has high sulfation degree and contains also 3,6-anhydrogalactose in the polymer chain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides.

PubMed

Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S

2010-05-01

We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

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.

Chondroitin-4-sulfation negatively regulates axonal guidance and growth

PubMed Central

Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas E.; Unsworth, Edward; Goldsmith, Paul; Yu, Zu-Xi; Tan, Fei; Santiago, Lizzie; Mills, Edward M.; Wang, Yu; Symes, Aviva J.; Geller, Herbert M.

2008-01-01

Summary Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition, and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate (CS) mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated CS GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings provide the evidence showing that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function. PMID:18768934

Scutellaria polysaccharide inhibits the infectivity of Newcastle disease virus to chicken embryo fibroblast.

PubMed

Xiaona, Zhao; Jianzhu, Liu

2014-03-15

To select the antiviral active site of Scutellaria polysaccharide (SPS), safe concentrations of crude total Scutellaria polysaccharide (SPS(t)) and fractional polysaccharide SPS₅₀, SPS₆₀, SPS₇₀ and SPS₈₀ on chicken embryo fibroblast (CEF) were first compared using the MTT method. Then, SPS(t), SPS₅₀, SPS₆₀, SPS₇₀, and SPS₈₀ at five concentrations within the safe concentration, together with Newcastle disease virus (NDV), were added to the cultivating system of CEF in three models: pre-addition of polysaccharide, post-addition of polysaccharide, and simultaneous addition of polysaccharides and NDV after mixing. The effects of SPS on the cellular infectivity of NDV (A₅₇₀ value and the highest viral inhibitory rate) were compared using the MTT method. At appropriate concentrations, the five polysaccharides could significantly inhibit the infectivity of NDV on CEF. Among the five polysaccharide groups, the SPS₈₀ group exhibited the highest viral inhibitory rate in the three sample-addition modes. This finding indicates that SPS₈₀ possesses the best efficacy as a component of antiviral polysaccharide drug. © 2013 Society of Chemical Industry.

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

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

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

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

PubMed

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

2014-11-04

Microbial-sourced unsulfated chondroitin could be converted into chondroitin sulfate (CS) polysaccharide by a multi-step strategy relying upon benzylidenation and acetylation reactions as key-steps for its regioselective protection. By conducting the two reactions one- or two-pots, CSs with different sulfation patterns could be obtained at the end of the semi-synthesis. In particular, a CS polysaccharide possessing sulfate groups randomly distributed between positions 4 and 6 of N-acetyl-galactosamine (GalNAc) units could be obtained through the two-pots route, whereas the one-pot pathway allowed an additional sulfation at position 3 of some glucuronic acid (GlcA) units. This difference was ascribed to the stabilization of a labile interglycosidic benzylidene acetal involving positions O-3 and O-6 of some GlcA and GalNAc, respectively, when the benzylidene-acetylation reactions were conducted in a one-pot fashion. Isolation and characterization of a polysaccharide intermediate showing interglycosidic acetal moieties was accomplished. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vitro and in vivo anti-inflammatory activities of high molecular weight sulfated polysaccharide; containing fucose separated from Sargassum horneri: Short communication.

PubMed

Sanjeewa, K K Asanka; Fernando, I P S; Kim, Seo-Young; Kim, Hyun-Soo; Ahn, Ginnae; Jee, Youngheun; Jeon, You-Jin

2018-02-01

Recent studies on crude and pure compounds from Sargassum horneri have shown promising bioactive properties. However, anti-inflammatory potentials of fucose-rich sulfated polysaccharides from S. horneri have not yet been discovered. In the present study, we evaluated the in vitro and in vivo anti-inflammatory activities of four polysaccharide fractions separated from membrane filters according to their molecular weights (<5kDa (f1), 5-10kDa (f2), 10-30kDa (f3), and >30kDa (f4)). According to the results, F4 fraction inhibited the lipopolysaccharides (LPS)-induced nitric oxide (NO) (IC 50 =87.12μg/mL) and prostaglandin E 2 production as well as pro-inflammatory cytokine production in RAW 264.7 cells through down-regulating nuclear factor-κB signaling cascade. According to the results, f4 has a potential to down-regulate LPS-induced toxicity, cell death and NO production levels in LPS-induced in vivo zebrafish embryo model. These results suggest that f4 fraction has the potential to develop functional materials or drugs to treat inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Preparation, characterization, and α-glycosidase inhibition activity of a carboxymethylated polysaccharide from the residue of Sarcandra glabra (Thunb.) Nakai.

PubMed

Liu, Wei; Hu, Cheng; Liu, Yameng; Dai, Shijie; Lu, Weisheng; Lv, Xing; Yao, Wenbing; Gao, Xiangdong

2017-06-01

A carboxymethylated polysaccharide (CMSERP) was prepared from the residue of Sarcandra glabra (Thunb.) Nakai. CMSERP was mainly composed of galacturonic acid (GalA), glucose (Glc), galactose (Gal), glucuronic acid (GlcA), arabinose (Ara), rhamnose (Rha), xylose (Xyl), ribose (Rib), and fucose (Fuc) at the ratio of 29.79:19.30:11.92:6.32:4.68:3.95:3.39:2.31:1.00. The primary structure features of CMSERP were determined to be a pectin like polysaccharide according to FT-IR, NMR, and HPAEC-PAD. The results of HPSEC-MALLS-RID and DLS indicated the Mw, Mn, Mz, and S2Z1/2 of CMSERP were 5.515×10 4 g/mol, 1.566×10 4 g/mol, 1.510×10 6 g/mol, and 62.8 (±1.2%) nm, respectively. TEM and AFM revealed CMSERP was dispersed in 0.05M sodium sulfate but aggregated in water. Moreover, a high α-glucosidase inhibition activity (83.38%±2.30% at 1000μg/mL) of CMSERP which is higher than that of acarbose was observed. The results proved the effects of carboxymethylation on poor water-soluble polysaccharides and explore a potential α-glucosidase inhibitor which from abandoned extracted residue for the functional foods and pharmaceutical industries. Copyright © 2017 Elsevier B.V. All rights reserved.

Phosphatidylcholine nanovesicles coated with chitosan or chondroitin sulfate as novel devices for bacteriocin delivery

NASA Astrophysics Data System (ADS)

da Silva, Indjara Mallmann; Boelter, Juliana Ferreira; da Silveira, Nádya Pesce; Brandelli, Adriano

2014-07-01

There is increased interest on the use of natural antimicrobial peptides in biomedicine and food preservation technologies. In this study, the antimicrobial activity of nisin encapsulated into nanovesicles containing polyanionic polysaccharides was investigated. Nisin was encapsulated in phosphatidylcholine (PC) liposomes containing chitosan or chondroitin sulfate by the thin-film hydration method and tested for antimicrobial activity against Listeria spp. The mean particle size of PC liposomes was 145 nm and varied to 210 and 134 nm with the incorporation of chitosan and chondroitin sulfate, respectively. Nisin-containing nanovesicles with and without incorporation of polysaccharides had a zeta potential values around -20 mV, showing mostly spherical structures when observed by transmission electron microscopy. Encapsulated nisin had similar efficiency as free nisin in inhibiting Listeria spp. isolated from bovine carcass, and greater efficiency in inhibiting Listeria monocytogenes. The formulation containing chitosan was more stable and more efficient in inhibiting L. monocytogenes when compared to the other nanovesicles tested. After 24 h, the viable cell counts were 2 log lower as compared with the other treatments and 7 log comparing to controls.

Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects.

PubMed

Cipriani, Thales R; Gracher, Ana Helena P; de Souza, Lauro M; Fonseca, Roberto J C; Belmiro, Celso L R; Gorin, Philip A J; Sassaki, Guilherme L; Iacomini, Marcello

2009-05-01

Evaluated were the anticoagulant and antithrombotic activities, and bleeding effect of two chemically sulfated polysaccharides, obtained from citric pectin, with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600 g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had essentially the same structure, consisting of a (1-->4)-linked alpha-D-GalpA chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more potent antithrombotic agent in vivo, giving rise to total inhibition of venous thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with heparin, Pec-HWS and Pec-LWS are able to directly inhibit alpha-thrombin and factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co-factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than heparin at a dose of 100% effectiveness against venous thrombosis, indicating it to be a promising antithrombotic agent.

The structure-activity relationship between polysaccharides from Sargassum thunbergii and anti-tumor activity.

PubMed

Jin, Weihua; Zhang, Wenjing; Liu, Ge; Yao, Jianting; Shan, Tifeng; Sun, Chaomin; Zhang, Quanbin

2017-12-01

Polysaccharides derived from Sargassum thunbergii were prepared to investigate the structure-activity relationship between polysaccharides and anti-tumor activity in vitro. Many factors were examined. Overall, STW (polysaccharide extracted by hot water) had the best activity, followed by STJ (polysaccharide extracted by dilute alkali), and then STA (polysaccharide extracted by dilute acid). Location of algae had no effect at 500μg/mL and 1000μg/mL, while STW-QD (algae collected from Qingdao, China) had the best activity, followed by STW-WZ (algae collected from Wenzhou, China) and STW-LJ (algae collected from Lianjiang, China) and then STW-DL (algae collected from Dalian, China) and STW-RC (algae collected from Rongcheng, China) at 250μg/mL. Moreover, molecular weight had no effect at 1000μg/mL, while higher molecular weights were associated with better activities at 250μg/mL and 500μg/mL. Sulfate content had no effect at 1000μg/mL, while anti-tumor activities decreased accompanying with the changes of sulfate content. Uronic acid content was an important factor influencing activity. The fractions of STW showed little anti-tumor activity; however, the mixture of the fractions of STW showed approximately 60% inhibition. Overall, these findings suggested that the anti-tumor activity of polysaccharides required multilateral cooperation and that some of the effective components were lost. Copyright © 2017 Elsevier B.V. All rights reserved.

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. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Hepatoprotective and inhibiting HBV effects of polysaccharides from roots of Sophora flavescens.

PubMed

Yang, Hua; Zhou, Zhenhua; He, Lifang; Ma, Hao; Qu, Wensheng; Yin, Jiye; Jia, Mengfan; Zhao, Xiunan; Shan, Junjie; Gao, Yueqiu

2018-03-01

Roots of Sophora flavescens is an important herbal medicine for treatment of HBV and hepatic carcinoma in China. Alkaloids in the root were well known for exhibiting good hepato-protective and anti-HBV effects. However, polysaccharides as main components in the root remained unknown. In the studies, we investigated the chemical features and hepatoprotective effects of Sophora flavescens polysaccharides (SFP-100 and its active fractions) with ConA-induced hepatitis mice, human liver LO2 cells and HepG2.2.15 cells. The results showed that SFP-100 was composed of arabinose, glucose, galactose and galacturonic acid, SFP-100-A mainly contained glucose. SFP-100-B and SFP-100-C were acidic polysaccharides. SFP-100 significantly decreased hepatocytes apoptosis, inhibited the infiltration of neutrophils and macrophages into liver, and improved the production of IFN-γ and IL-6 of splenocytes in ConA-induced hepatitis mice. SFP-100 and its two sugar fractions increased LO2 cell proliferation and reduced cell apoptosis induced by ConA. SFP-100, SFP-100-A and SFP-100-C remarkedly inhibited the secretion of HBsAg and HBeAg by HepG2.2.15 cells.These results suggested Sophora flavescens polysaccharides exerts significant hepatoprotective and anti-HBV roles, and further is used for treatment of immune-mediated liver disease in the future. Copyright © 2017. Published by Elsevier B.V.

Structural analysis of a sulfated galactan from the tunic of the ascidian Microcosmus exasperatus and its inhibitory effect of the intrinsic coagulation pathway.

PubMed

Restrepo-Espinosa, Diana C; Román, Yony; Colorado-Ríos, Jhonny; de Santana-Filho, Arquimedes Paixão; Sassaki, Guilherme Lanzi; Cipriani, Thales R; Martínez, Alejandro; Iacomini, Marcello; Pavão, Mauro S G

2017-12-01

Several bioactive sulfated galactans have been isolated from the tunic of different species of ascidians. The biological activity of this kind of polysaccharides has been related with the presence and position of sulfate groups, and by the chemical composition of this kind of polysaccharides. A sulfated galactan (1000RS) was isolated from the tunic of the Brazilian ascidia Microcosmus exasperatus through proteolytic digestion, ethanol precipitation, dialysis and freeze-thaw cycles. Homogeneity and molecular weight were estimated by using size exclusion chromatography. Monosaccharide composition and type of linkage were assessed by Gas chromatography coupled to mass spectrometry and the sulfate content was quantified through gelatin/BaCl 2 method. These experiments along with NMR and FTIR analysis allowed to claim that the galactan backbone is mainly composed of 4-linked α-l-Galp units. In addition, they permitted to establish that some of the galactose residues are sulfated at the 3-position. This sulfated polysaccharide, which has an average molecular mass of 439.5kDa, presents anticoagulant effect in a dose-dependent manner through the inhibition of the intrinsic coagulation pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical modification, antioxidant and α-amylase inhibitory activities of corn silk polysaccharides.

PubMed

Chen, Shuhan; Chen, Haixia; Tian, Jingge; Wang, Yanwei; Xing, Lisha; Wang, Jia

2013-10-15

Water-soluble corn silk polysaccharides (CSPS) were chemically modified to obtain their sulfated, acetylated and carboxymethylated derivatives. Chemical characterization and bioactivities of CSPS and its derivatives were comparatively investigated by chemical methods, gas chromatography, gel filtration chromatography, scanning electron microscope, infrared spectroscopy and circular dichroism spectroscopy, scavenging DPPH free radical assay, scavenging hydroxyl radical assay, ferric reducing power assay, lipid peroxidation inhibition assay and α-amylase activity inhibitory assay, respectively. Among the three derivatives, carboxylmethylated polysaccharide (C-CSPS) demonstrated higher solubility, narrower molecular weight distribution, lower intrinsic viscosity, a hyperbranched conformation, significantly higher antioxidant and α-amylase inhibitory abilities compared with the native polysaccharide and other derivatives. C-CSPS might be used as a novel nutraceutical agent for human consumption. Copyright © 2013 Elsevier Ltd. All rights reserved.

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. © 2014 Wiley Periodicals, Inc.

Mucopolysaccharide and Protein—Polysaccharide of a Transplantable Rat Chondrosarcoma

PubMed Central

Choi, Haing Ug; Meyer, Karl; Swarm, Richard

1971-01-01

Two mucopolysaccharides, chondroitin 4-sulfate (97.8%) and hyaluronic acid (1.2%), were isolated after exhaustive proteolysis of a transplantable chondrosarcoma of the rat. The chondroitin 4-sulfate was fractionated into three fractions of varying degrees of sulfation and chain length. Keratan sulfate and chondroitin 6-sulfate were absent. Extraction of the fresh tumor gave two protein—polysaccharides of similar carbohydrate composition, one soluble in 0.5 M NaCl, the other insoluble. The latter was solubilized in 4 M guanidine·HCl. A dialyzable fraction from the 4 M guanidine solution may be responsible for the insolubility. Both protein—polysaccharides were antigenic and cross-reacted with similar fractions of bovine and human cartilage. PMID:4252539

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.

Enhanced Differentiation of Human Preosteoblasts on Electrospun Blend Fiber Mats of Polydioxanone and Anionic Sulfated Polysaccharides

PubMed Central

2017-01-01

The viability and differentiation of SaOS-2 preosteoblasts on fiber mats of blends comprising of the biodegradable poly(ester-ether) polydioxanone (PDX) and the sulfate-containing anionic polysaccharides kappa-carrageenan (KCG) and fucoidan (FUC) were investigated for a range of different blend compositions. The detailed analysis of the blend nanofiber properties revealed a different degree of miscibility of PDX and the polysaccharide leading to a different enrichment at the surface of the blend nanofibers, which were observed to be stable in phosphate buffer solution (PBS) for up to 5 weeks. The fibrous mats of PDX/FUC led to the highest osteogenic differentiation with very good cell viability. The electrospun blend fibers also supported human-induced pluripotent stem (iPS) cells and iPS cell-derived embryoid bodies with high cell viability, which underlines the potential of these novel blend fiber systems for optimized performance in bone tissue engineering applications. PMID:29285521

Sulfated Glycopeptide Nanostructures for Multipotent Protein Activation

PubMed Central

Lee, Sungsoo S.; Fyrner, Timmy; Chen, Feng; Álvarez, Zaida; Sleep, Eduard; Chun, Danielle S.; Weiner, Joseph A.; Cook, Ralph W.; Freshman, Ryan D.; Schallmo, Michael S.; Katchko, Karina M.; Schneider, Andrew D.; Smith, Justin T.; Yun, Chawon; Singh, Gurmit; Hashmi, Sohaib Z.; McClendon, Mark T.; Yu, Zhilin; Stock, Stuart R.; Hsu, Wellington K.; Hsu, Erin L.; Stupp, Samuel I.

2017-01-01

Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with very different polysaccharide binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signaling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than expected. These super-bioactive nanostructures may enable many therapies in the horizon involving proteins. PMID:28650443

Sulfated glycopeptide nanostructures for multipotent protein activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Sungsoo S.; Fyrner, Timmy; Chen, Feng

Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptidemore » nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.« less

Decoration of Chondroitin Polysaccharide with Threonine: Synthesis, Conformational Study, and Ice-Recrystallization Inhibition Activity.

PubMed

Laezza, Antonio; Casillo, Angela; Cosconati, Sandro; Biggs, Caroline I; Fabozzi, Antonio; Paduano, Luigi; Iadonisi, Alfonso; Novellino, Ettore; Gibson, Matthew I; Randazzo, Antonio; Corsaro, Maria M; Bedini, Emiliano

2017-08-14

Several threonine (Thr)- and alanine (Ala)-rich antifreeze glycoproteins (AFGPs) and polysaccharides act in nature as ice recrystallization inhibitors. Among them, the Thr-decorated capsular polysaccharide (CPS) from the cold-adapted Colwellia psychrerythraea 34H bacterium was recently investigated for its cryoprotectant activity. A semisynthetic mimic thereof was here prepared from microbial sourced chondroitin through a four-step strategy, involving a partial protection of the chondroitin polysaccharide as a key step for gaining an unprecedented quantitative amidation of its glucuronic acid units. In-depth NMR and computational analysis suggested a fairly linear conformation for the semisynthetic polysaccharide, for which the antifreeze activity by a quantitative ice recrystallization inhibition assay was measured. We compared the structure-activity relationships for the Thr-derivatized chondroitin and the natural Thr-decorated CPS from C. psychrerythraea.

Structure and anticoagulant activity of a sulfated galactan from the red alga, Gelidium crinale. Is there a specific structural requirement for the anticoagulant action?

PubMed

Pereira, Maria G; Benevides, Norma M B; Melo, Marcia R S; Valente, Ana Paula; Melo, Fábio R; Mourão, Paulo A S

2005-09-05

Marine red algae are an abundant source of sulfated galactans with potent anticoagulant activity. However, the specific structural motifs that confer biological activity remain to be elucidated. We have now isolated and purified a sulfated galactan from the marine red alga, Gellidium crinale. The structure of this polysaccharide was determined using NMR spectroscopy. It is composed of the repeating structure -4-alpha-Galp-(1-->3)-beta-Galp1--> but with a variable sulfation pattern. Clearly 15% of the total alpha-units are 2,3-di-sulfated and another 55% are 2-sulfated. No evidence for the occurrence of 3,6-anhydro alpha-galactose units was observed in the NMR spectra. We also compared the anticoagulant activity of this sulfated galactan with a polysaccharide from the species, Botryocladia occidentalis, with a similar saccharide chain but with higher amounts of 2,3-di-sulfated alpha-units. The sulfated galactan from G. crinale has a lower anticoagulant activity on a clotting assay when compared with the polysaccharide from B. occidentalis. When tested in assays using specific proteases and coagulation inhibitors, these two galactans showed significant differences in their activity. They do not differ in thrombin inhibition mediated by antithrombin, but in assays where heparin cofactor II replaces antithrombin, the sulfated galactan from G. crinale requires a significantly higher concentration to achieve the same inhibitory effect as the polysaccharide from B. occidentalis. In contrast, when factor Xa instead of thrombin is used as the target protease, the sulfated galactan from G. crinale is a more potent anticoagulant. These observations suggest that the proportion and/or the distribution of 2,3-di-sulfated alpha-units along the galactan chain may be a critical structural motif to promote the interaction of the protease with specific protease and coagulation inhibitors.

Structural elucidation of polysaccharide fractions from the brown alga Coccophora langsdorfii and in vitro investigation of their anticancer activity.

PubMed

Imbs, Tatiana I; Ermakova, Svetlana P; Malyarenko Vishchuk, Olesya S; Isakov, Vladimir V; Zvyagintseva, Tatiana N

2016-01-01

Laminaran, fucoidan, and alginate were isolated from the brown alga Coccophora langsdorfii collected in the Japan Sea. The structural characteristics of polysaccharides were investigated by NMR spectroscopy. The laminaran was determined as β-d-glucan, which consisted of 80% of 1,3- and 20% of 1,6-linked residues and was terminated with mannitol. The alginate was a guluronic acid-rich polysaccharide (M/G=0.85). Fucoidan, sulfated α-l-fucan, contained a linear backbone of alternating (1→3)- and (1→4)- linked α-l-fucopyranose residues with sulfate at C2 and C4 of (1→3)-α-l-fucopyranose residues. Anticancer activity of this fucoidan was investigated in comparison with activity of fucoidan having similar linear backbone from the brown alga Fucus evanescens. The fucoidan from C. langsdorfii significantly inhibited colony formation of SK-MEL-5 and SK-MEL-28 melanoma cells (the percentage of inhibition was 28 and 76, respectively) and weakly inhibited colony formation of breast adenocarcinoma cells MDA-MB-231 (the percentage of inhibition was about 5). Similar results were obtained for fucoidan from F. evanescens; the percentage of inhibition of colony formation of SK-MEL-5 and SK-MEL-28 melanoma cells was 54 and 56, respectively. The inhibition of colony formation of breast adenocarcinoma cells MDA-MB-231 was weak. We suppose that other sulfated and partially acetylated fucoidans consisting of (1→3)- and (1→4)-linked α-l-fucopyranose residues may suppress progression of melanoma cell colony formation similar to fucoidans of C. langsdorfii and F. evanescens. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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.

Anti-food allergic activity of sulfated polysaccharide from gracilaria lemaneiformis is dependent on immunosuppression and inhibition of p38 mapk

USDA-ARS?s Scientific Manuscript database

Polysaccharides from marine sources offer diverse therapeutic functions due to their multifarious biological nature. Polysaccharide from Gracilaria lemaneiformis possesses various bioactive functions, but its anti-allergic activity remains incompletely defined. Objective: This study aimed to extract...

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.

Mechanism by which ammonium bicarbonate and ammonium sulfate inhibit mycotoxigenic fungi.

PubMed Central

DePasquale, D A; Montville, T J

1990-01-01

In this study we examined the mechanism by which ammonium bicarbonate inhibits mycotoxigenic fungi. Elevated extracellular pH, alone, was not responsible for the antifungal activity. Although conidia of Penicillium griseofulvum and Fusarium graminearum had internal pH (pHi) values as high as 8.0 in buffer at an external pH (pHo) of 9.5, their viability was not markedly affected. The pHi values from conidia equilibrated in glycine-NaOH-buffered treatments without ammonium bicarbonate or ammonium sulfate were similar to values obtained from buffered treatments containing the ammonium salts. Thus, inhibition did not appear to be directly related to increased pHi. Ammonium sulfate in buffered media at pH greater than or equal to 8.7 was as inhibitory as ammonium bicarbonate, but was completely ineffective at pH less than or equal to 7.8. The hypothesis that free ammonia caused the fungal inhibition was tested by using ammonium sulfate as a model for ammonium bicarbonate. Viability, expressed as log CFU/ml, and percent germination of P. griseofulvum and F. graminearum decreased dramatically as the free ammonia concentration increased. Germination rate ratios (the germination rate in buffered ammonium sulfate divided by the germination rate in buffer alone) decreased linearly as the free ammonia concentration increased, further establishing NH3 as the toxic agent. Ammonium bicarbonate inhibits fungi because the bicarbonate anion supplies the alkalinity necessary to establish an antifungal concentration of free ammonia. PMID:2082821

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

PubMed

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

1998-07-01

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

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

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

PubMed

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

2016-02-01

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

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

Physicochemical properties, immunomodulation and antitumor activities of polysaccharide from Pavlova viridis.

PubMed

Sun, Liqin; Chu, Jinling; Sun, Zhongliang; Chen, Lihong

2016-01-01

Polysaccharides synthesized by microalgae can be used as the functional ingredients of food or drugs. Here, we investigated the physicochemical properties and bioactivities of the polysaccharide from microalgae Pavlova viridis, and indicated the structure-activity relationship. The polysaccharides (PPS0) were degraded with H2O2-vitamin C assisted by ultrasonic waves. The functional group content, monosaccharide composition, and average molecular weight (avg-MW) were detected by chemical or chromatographic method. The immunomodulatory activities were evaluated in vitro by detecting nitric oxide (NO) emission, neutral red uptake and macrophage proliferation. Antitumor activities of degraded fragments were detected using S180-tumor-bearing mouse model by intragastric administration. Degraded polysaccharides PPS1 and PPS2 were obtained at avg-MW of 386.96 and 54.99 kDa. The sulfate group content of polysaccharide was 16%, and the uronic acid content was 5.88 and 8.48%. PPS mainly consisted of fructose, glucose and mannose. All the degraded PPSs could increase phagocytosis and proliferation of macrophages, and stimulated NO emission in a dose-dependently way. PPS2 in Low-MW fragments had the strongest immunoenhancing activities. Different doses of PPS all could inhibit the growth of implanted S180 tumor. At dose of 200 mg/kg/day, the tumor inhibition rate of PPS2 was 57.06%, about 23.6% less than that of CTX-treated group. Different-MW PPS significantly increased lymphocyte proliferation. At 200 mg/L, the proliferation index of PPS2 was 1.37, 2.03 times higher than that of CTX-treated group. The polysaccharides of Pavlova viridis had potential antitumor activities by improving immune response. Moreover, the bioactivities depend on their molecular weight. Copyright © 2015 Elsevier Inc. All rights reserved.

Fucoidan and Fucosylated Chondroitin Sulfate Stimulate Hematopoiesis in Cyclophosphamide-Induced Mice.

PubMed

Anisimova, Natalia; Ustyuzhanina, Nadezhda; Bilan, Maria; Donenko, Fedor; Usov, Anatolii; Kiselevskiy, Mikhail; Nifantiev, Nikolay

2017-09-30

Application of cytostatics in cancer patients' chemotherapy results in a number of side effects, including the inhibition of various parts of hematopoiesis. Two sulfated polysaccharides, fucoidan from the seaweed Chordaria flagelliformis ( PS-Fuc ) and fucosylated chondroitin sulfate from the sea cucumber Massinium magnum ( PS-FCS ), were studied as stimulators of hematopoiesis after cyclophosphamide immunosuppression in mice. Recombinant granulocyte colony-stimulating factor ( r G-CSF ) was applied as a reference. Both tested polysaccharides PS-Fuc and PS-FCS have a similar activity to r G-CSF , causing pronounced neutropoiesis stimulation in animals with myelosuppression induced by cyclophosphamide ( CPh ). Moreover, these compounds are also capable to enhance thrombopoiesis and erythropoiesis. It should be noted that PS-FCS demonstrated a greater activity than r G-CSF . The results indicate the perspective of further studies of PS-Fuc and PS-FCS , since these compounds can be considered as potentially promising stimulators of hematopoiesis. Such drugs are in demand for the accompanying treatment of cancer patients who suffer from hematological toxicity during chemo and/or radiation therapy.

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

PubMed

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

2014-06-01

In this study, we employed a one-step method to prepare selenium nanoparticles (SeNPs) decorated by the water-soluble derivative of Ganoderma lucidum polysaccharides (SPS). The SeNPs-SPS complexes were stable, and the diameter of the SeNPs was homogeneous at around 25 nm. We investigated the anti-inflammatory activity of SeNPs-SPS against murine Raw 264.7 macrophage cells induced by LPS. SeNPs-SPS were found to significantly inhibit LPS-stimulated nitric oxide (NO) production against Raw 264.7 macrophages. RT-PCR results reveal the down-regulation of mRNA gene expressions for pro-inflammatory cytokines, including inducible NO synthase (iNOS), interleukin (IL)-1 and TNF-α in a dose-dependent manner. However, the anti-inflammation cytokine IL-10 was markedly increased. In the NF-κB signal pathway, SeNPs-SPS significantly inhibited the phosphorylation of Iκ-Bα. Similar results were observed for inhibition of the phosphorylation of JNK1/2 and p38 mitogen-activated protein kinase(MAPKs), whereas ERK1/2 MAPK was not apparently affected by SeNPs-SPS. All of these results suggest that SeNPs-SPS complexes have anti-inflammatory potential modulating pro-/anti-inflammation cytokine secretion profiles, and that the mechanism is partially due to inhibition of activations of NF-κB, JNK1/2 and p38 MAPKs. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Phosphorylated Codonopsis pilosula polysaccharide could inhibit the virulence of duck hepatitis A virus compared with Codonopsis pilosula polysaccharide.

PubMed

Ming, Ke; Chen, Yun; Yao, Fangke; Shi, Jintong; Yang, Jingjing; Du, Hongxu; Wang, Xunyi; Wang, Yixuan; Liu, Jiaguo

2017-01-01

To screen effective anti-duck hepatitis A virus (DHAV) drugs, we applied STMP-STPP method to prepare phosphorylated Codonopsis pilosula polysaccharide (pCPPS), the phosphorylation-modified product of Codonopsis pilosula polysaccharide (CPPS). The IR spectrum and field emission scanning electron microscope (FE-SEM) were subsequently used to analyze the structure of pCPPS. Several tests were conducted to compare the anti-DHAV activities of CPPS and pCPPS. The MTT method was used to compare the effect of the drugs on DHAV-infected duck embryonic hepatocytes (DEHs), and the Reed-Muench assay was employed to observe changes in the virulence of DHAV. We also applied real-time PCR to examine the relationship between virus replication and the expression of IFN-β. The results indicated that CPPS could not inhibit the replication of DHAV. In contrast, pCPPS increased the virus TCID 50 , inhibited viral replication and, accordingly, increased the survival rate of DEHs infected with DHAV. Because DHAV induced the expression of IFN-β, and the IFN-β expression level was positively associated with the number of DHAV, the reduction of IFN-β expression levels after pCPPS treatment demonstrated a decrease in the number of virus particles. These results indicated that pCPPS, which reduces the number of DHAV, was more effective than CPPS in anti-DHAV activity. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-06-25

Polysaccharides were extracted from the barks of Geoffroea spinosa, purified using anion exchange chromatography and characterized by chemical and methylation analysis, complemented by infrared and NMR spectroscopies. These polysaccharides were tested for their anticoagulant, antithrombotic and antiplatelet activities and also for their effects on bleeding. Unfractionated polysaccharide contains low levels of protein and high levels of carbohydrate (including hexuronic acid). The purified polysaccharides (fractions FII and FIII) are composed of arabinose (Ara), rhamnose (Rha), hexuronic acid, small amounts of galactose, but no sulfate ester. They have highly complex structure, which was partially characterized. NMR and methylation analysis indicate that the polysaccharides have a core of α-Rhap and branches of 5-linked α-Araf. Residues of 4-linked α-GalpA are also found in the structure. The unfractionated (TPL) and fraction FIII, but not fractions FI and FII, prolonged the activated partial thromboplastin time (aPTT). TPL, FII and FIII inhibited the platelet aggregation induced by ADP. More significantly, both unfractionated and purified fractions exhibited potent antithrombotic effect (31-60%) and the fractions did not modify the bleeding tendency. These plant polysaccharides could be alternative source of new anticoagulant, antiplatelet and antithrombotic compounds devoid of the undesirable risk of hemorrhage. Copyright © 2015 Elsevier Ltd. All rights reserved.

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. © 2015 Wiley Periodicals, Inc.

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

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

2014-04-10

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.

Extracts from the edible seaweed, Ascophyllum nodosum, inhibit lipase activity in vitro: contributions of phenolic and polysaccharide components.

PubMed

Austin, Ceri; Stewart, Derek; Allwood, J William; McDougall, Gordon J

2018-01-24

A polyphenol-rich extract (PRE) from the edible seaweed, Ascophyllum nodosum, inhibited pancreatic lipase activity in an oil-based turbidimetric assay with an IC 50 of 200 μg gallic acid equivalents (GAE) perassay) [∼230 μg DW] whereas the known inhibitor, Orlistat, gave an IC 50 at 0.4 μg per assay. A phlorotannin-enriched fraction (TRF) purified from the PRE was more potent with an IC 50 = 60 μg GAE per assay (∼65 μg DW). When the assay was started by the addition of lipase, both Orlistat and TRF were much less effective which suggests that pre-incubation of enzyme and inhibitor improved inhibition. Based on phenol content, water extracts from Ascophyllum were more potent lipase inhibitors than PRE (IC 50 ∼ 150 μg GAE per assay). However, this was equivalent to ∼580 μg DW and these extracts contained polysaccharides (e.g. alginate content = 110 μg mL -1 ) which may also contribute to inhibition. Indeed, a polysaccharide-enriched fraction obtained by ethanol precipitation gave an IC 50 of 1000 μg DW which was equivalent to 130 μg GAE and 420 μg alginate per assay. Therefore a >3 fold increase in alginate content did not markedly improve inhibition. Re-precipitation increased alginate content and reduced polyphenol content but lipase inhibition was markedly reduced (i.e. IC 50 at ∼1100 μg DW per assay, 700 μg alginate and 25 μg GAE). Purifying the polysaccharide fraction by ion exchange removed all phenolics but the IC 50 increased to >2500 μg DW, equivalent to >1970 μg alginate per assay. In conclusion, polysaccharides and phlorotannins may inhibit lipase in an additive fashion, with phlorotannins apparently more effective in vitro. However, interactions between these components may be important when food products containing this edible seaweed are consumed.

Nucleotide Intermediates in the Biosynthesis of Heteropolymeric Polysaccharides

PubMed Central

Strominger, Jack L.

1964-01-01

The role of nucleotides as “carriers” of small molecules for biosynthetic reactions is discussed. Following this introduction, the particular problem of nucleotide intermediates in chondroitin sulfate synthesis is presented. The egg shell of the hen contains a form of chondroitin sulfate and particular emphasis is placed on the biosynthesis of sulfated polysaccharides in the hen oviduct, which has been studied in the author's laboratory. ImagesFigure 16Figure 19 PMID:14104074

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

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. Copyright © 2016 Elsevier

Digestibility of sulfated polysaccharide from the brown seaweed Ascophyllum nodosum and its effect on the human gut microbiota in vitro.

PubMed

Chen, Ligen; Xu, Wei; Chen, Dan; Chen, Guijie; Liu, Junwei; Zeng, Xiaoxiong; Shao, Rong; Zhu, Hongjun

2018-06-01

Sulfated polysaccharides from marine algae exhibit various bioactivities with potential benefits for human health and well-being. In this study, the in vitro digestibility and fermentability of polysaccharides from the brown seaweed Ascophyllum nodosum (AnPs) were examined, and the effects of AnPs on gut microbiota were determined using high-throughput sequencing technology. Salivary amylase, artificial gastric juice, and intestinal juice had no effect on AnPs, but the molecular weight of AnPs and reducing sugar decreased significantly after fermentation by gut microbiota. AnPs significantly modulated the composition of the gut microbiota; in particular, they increased the relative abundance of Bacteroidetes and Firmicutes, suggesting the potential for AnPs to decrease the risk of obesity. Furthermore, the total SCFA content after fermentation increased significantly. These results suggest that AnPs have potential uses as functional food components to improve human gut health. Copyright © 2018. Published by Elsevier B.V.

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.

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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential inhibition of hepatic and duodenal sulfation of (-)-salbutamol and minoxidil by mefenamic acid.

PubMed

Vietri, M; Pietrabissa, A; Spisni, R; Mosca, F; Pacifici, G M

2000-09-01

The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. Sulfotransferase activities were measured for 10 mM (-)-salbutamol and 5 mM minoxidil, and the concentration of 3'-phosphoadenosine-5'-phosphosulphate-[35S] was 0.4 microM. The IC50 estimates for (-)-salbutamol and minoxidil sulfation of mefenamic acid were 72 +/- 5.4 nM and 1.5 +/- 0.6 microM (liver), respectively, and 161 + 23 microM and 420 +/- 18 microM (duodenum), respectively. The figures for the liver were significantly lower (P < 0.0001) than those for the duodenum. The IC50 estimates for (-)-salbutamol sulfation of salicylic acid were 93 +/- 11 microM (liver) and 705 +/- 19 microM (duodenum, P < 0.0001). Salicylic acid was a poor inhibitor of minoxidil sulfation. The IC50 estimates for (-)-salbutamol sulfation of mefenamic acid and salicylic acid are lower than their unbound plasma concentrations after standard dosing, suggesting that mefenamic acid and salicylic acid should inhibit the hepatic sulfation of (-)-salbutamol in vivo.

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.

A characteristic chondroitin sulfate trisaccharide unit with a sulfated fucose branch exhibits neurite outgrowth-promoting activity: Novel biological roles of fucosylated chondroitin sulfates isolated from the sea cucumber Apostichopus japonicus.

PubMed

Shida, Miharu; Mikami, Tadahisa; Tamura, Jun-Ichi; Kitagawa, Hiroshi

2017-06-03

Chondroitin sulfate (CS) is a class of sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide unit composed of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc). CS chains are found throughout the pericellular and extracellular spaces and contribute to the formation of functional microenvironments for numerous biological events. However, their structure-function relations remain to be fully characterized. Here, a fucosylated CS (FCS) was isolated from the body wall of the sea cucumber Apostichopus japonicus. Its promotional effects on neurite outgrowth were assessed by using isolated polysaccharides and the chemically synthesized FCS trisaccharide β-D-GalNAc(4,6-O-disulfate) (1-4)[α-l-fucose (2,4-O-disulfate) (1-3)]-β-D-GlcA. FCS polysaccharides contained the E-type disaccharide unit GlcA-GalNAc(4,6-O-disulfate) as a CS major backbone structure and carried distinct sulfated fucose branches. Despite their relatively lower abundance of E unit, FCS polysaccharides exhibited neurite outgrowth-promoting activity comparable to squid cartilage-derived CS-E polysaccharides, which are characterized by their predominant E units, suggesting potential roles of the fucose branch in neurite outgrowth. Indeed, the chemically synthesized FCS trisaccharide was as effective as CS-E tetrasaccharide in stimulating neurite elongation in vitro. In conclusion, FCS trisaccharide units with 2,4-O-disulfated fucose branches may provide new insights into understanding the structure-function relations of CS chains. Copyright © 2017 Elsevier Inc. All rights reserved.

Preparation of chondroitin sulfate libraries containing disulfated disaccharide units and inhibition of thrombin by these chondroitin sulfates.

PubMed

Numakura, Mario; Kusakabe, Noriko; Ishige, Kazuya; Ohtake-Niimi, Shiori; Habuchi, Hiroko; Habuchi, Osami

2010-07-01

Chondroitin sulfate (CS) containing GlcA-GalNAc(4,6-SO(4)) (E unit) and CS containing GlcA(2SO(4))-GalNAc(6SO(4)) (D unit) have been implicated in various physiological functions. However, it has been poorly understood how the structure and contents of disulfated disaccharide units in CS contribute to these functions. We prepared CS libraries containing E unit or D unit in various proportions by in vitro enzymatic reactions using recombinant GalNAc 4-sulfate 6-O-sulfotransferase and uronosyl 2-O-sulfotransferase, and examined their inhibitory activity toward thrombin. The in vitro sulfated CSs containing disulfated disaccharide units showed concentration-dependent direct inhibition of thrombin when the proportion of E unit or D unit in the CSs was above 15-17%. The CSs containing both E unit and D unit exhibited higher inhibitory activity toward thrombin than the CSs containing either E unit or D unit alone, if the proportion of the total disulfated disaccharide units of these CSs was comparable. The thrombin-catalyzed degradation of fibrinogen, a physiological substrate for thrombin, was also inhibited by the CS containing both E unit and D unit. These observations indicate that the enzymatically prepared CS libraries containing various amounts of disulfated disaccharide units appear to be useful for elucidating the physiological function of disulfated disaccharide units in CS.

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

PubMed

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

2016-05-01

In our previous study, we found that the acidic polysaccharides of Ephedra sinica had immunosuppressive effect to treat rheumatoid arthritis and the pure polysaccharide ESP-B4 was the main composition of the acidic polysaccharides. At present, the exact molecular mechanism of ESP-B4 on treating arthritis is unclear. We are thus evaluating the properties of ESP-B4 on LPS-induced THP-1 pro-monocytic cells and adjuvant-induced arthritis in Wistar rats via TLR4. In vitro, ESP-B4 decreased the production of cytokines induced by LPS. In addition, ESP-B4 reduced the LPS-stimulated nuclear translocation of p65 subunit of NF-κB. Pretreatment with ESP-B4 significantly down-regulated the phosphorylation of MAPKs induced by LPS. Furthermore, in vivo, after 12 days of disease induced by adjuvant, rats were treated with ESP-B4 for 16 days. ESP-B4 significantly improved all parameters of inflammation. ESP-B4 reduced the release of inflammatory factors and cytokines by inhibiting the TLR4 signaling pathway to treat rheumatoid arthritis. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-02-01

We investigated the renal protective effect of low-molecular-weight sulfated polysaccharide (LMWSP) fractions extracted from Laminaria japonica on glycerol-induced acute kidney injury (AKI) in rats. Glycerol treatment significantly increased serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Intraperitoneal injection of LMWSP fractions markedly decreased SCr and BUN levels and reduced renal swelling. The fraction of 1.0M NaCl displayed the best renal protective effect of all fractions in attenuating AKI and maintaining blood glucose. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2013-01-30

Intracellular polysaccharides (iPs) were separated and purified from Coriolus versicolor LH1 mycelia and characterized for their α-glucosidase inhibitory properties. Three iP fractions (iPL-F5-2-1, iPL-F5-4-1, and iPL-F5-5-1) were extracted, separated, and purified from LH1 mycelia using microwave extraction technology, a DEAE-Sepharose CL-6B column, a Diaion HP20 macroporous adsorption column, and a Sephadex™ G-50 gel-permeation column. The principal constituents of iPL-F5-2-1, iPL-F5-4-1, and iPL-F5-5-1 were saponins and polyphenoic compound mixtures. The enzyme inhibition activity, IC(50) values, of these three fractions were 1.7, 1.8, and 0.8 mg/mL, respectively. The α-glucosidase inhibitory properties were related to the presence of α-(1,4) glycosidic linkages in the polysaccharide structure and the total relative percentage of d-glucose and d-galactose in the structure of polysaccharides, other than triterpenoids. Copyright © 2012 Elsevier Ltd. All rights reserved.

Magnesium sulfate provides neuroprotection in lipopolysaccharide-activated primary microglia by inhibiting NF-κB pathway.

PubMed

Gao, Feng; Ding, Baozhong; Zhou, Longan; Gao, Xueshan; Guo, Huiguang; Xu, Hong

2013-10-01

Magnesium sulfate has been used as an anticonvulsant in severe preeclamptic or eclamptic women prior to surgical trauma, but its effects on neuroinflammation is not well defined. In the present study, we investigated the neuroprotective effects of magnesium sulfate in lipopolysaccharide (LPS)-induced microglia and explored the underlying mechanism. Microglia was incubated with LPS in the presence or absence of various concentrations of magnesium sulfate, or L-type calcium channel activator BAY-K8644. The levels of inflammatory mediators, such as nitric oxide, prostaglandin E2, interleukin 1β, and tumor necrosis factor α, were measured using enzyme-linked immunosorbent assay. The expression of inducible nitric oxide synthase mRNA was detected by reverse-transcription polymerase chain reaction. Nuclear factor κB (NF-κB) activity in the nuclear extract of microglia was detected by NF-κB p50/p65 transcription factor assay kit. Magnesium sulfate at 5 and 10 mmol/L significantly inhibited the release of nitric oxide, prostaglandin E2, interleukin 1β, and tumor necrosis factor α, and the expression of inducible nitric oxide synthase mRNA in LPS-activated microglia. Furthermore, magnesium sulfate inhibited the translocation of NF-κB from the cytoplasm to the nucleus in a dose-dependent manner. Notably, these effects were significantly reversed by L-type calcium channel activator BAY-K8644. Magnesium sulfate protects microglia against LPS-induced release of inflammatory mediators, and these effects may be mediated by inhibiting L-type calcium channels and NF-κB signaling. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Coptis chinensis Polysaccharides Inhibit Advanced Glycation End Product Formation.

PubMed

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

2016-06-01

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

Chemically engineered sulfated glucans from rice bran exert strong antiviral activity at the stage of viral entry.

PubMed

Ray, Bimalendu; Hutterer, Corina; Bandyopadhyay, Shruti S; Ghosh, Kanika; Chatterjee, Udipta R; Ray, Sayani; Zeitträger, Isabel; Wagner, Sabrina; Marschall, Manfred

2013-12-27

Attachment and entry of many viruses are mediated by their affinity for polysaccharides present on the surface of target cells. In this paper, we demonstrate that sulfated glucans isolated from rice (Oryza sativa) can be utilized as experimental drugs exerting strong antiviral activity. In particular, oleum-DMF-based extraction is described as a procedure for the generation of chemically engineered glucans from commercially available rice bran. The one-step procedure has the potential to provide a spectrum of related glucans with varying molecular masses and modifications, including sulfation. The sulfated glucans P444, P445, and P446 possess increased antiviral activity compared to a previously described glucan (S1G). P444, P445, and P446 were highly active against human cytomegalovirus (HCMV), moderately active against other members of the family Herpesviridae, while not active against unrelated viruses. Specific experimentation with HCMV-infected cells provided evidence that antiviral activity was based on inhibition of viral entry and that inhibition occurred in the absence of drug-induced cytotoxicity. These findings underline the high potential of sulfated glucans for antiviral research and drug development. In addition, the procedure described for the efficient transformation of glucan hydroxy groups to sulfate groups may be similarly beneficial for the chemical alteration of other natural products.

Genotoxicity and osteogenic potential of sulfated polysaccharides from Caulerpa prolifera seaweed.

PubMed

Chaves Filho, Gildácio Pereira; de Sousa, Angélica Fernandes Gurgel; Câmara, Rafael Barros Gomes; Rocha, Hugo Alexandre Oliveira; de Medeiros, Silvia Regina Batistuzzo; Moreira, Susana Margarida Gomes

2018-07-15

Marine algae are sources of novel bioactive molecules and present a great potential for biotechnological and biomedical applications. Although green algae are the least studied type of seaweed, several of their biological activities have already been described. Here, we investigated the osteogenic potential of Sulfated Polysaccharide (SP)-enriched samples extracted from the green seaweed Caulerpa prolifera on human mesenchymal stem cells isolated from Wharton jelly (hMSC-WJ). In addition, the potential genotoxicity of these SPs was determined by cytokinesis-block micronucleus (CBMN) assay. SP-enriched samples did not show significant cytotoxicity towards hMSCs-WJ at a concentration of up to 10μg/mL, and after 72h of exposure. SP enrichment also significantly increased alkaline phosphatase (ALP) activity, promoting calcium accumulation in the extracellular matrix. Among the SP-enriched samples, the CP0.5 subfraction (at 5μg/mL) presented the most promising results. In this sample, ALP activity was increased approximately by 60%, and calcium accumulation was approximately 6-fold above the negative control, indicating high osteogenic potential. This subfraction also proved to be non-genotoxic, according to the CBMN assay, as it did not induce micronuclei. The results of this study highlight, for the first time, the potential of these SPs for the development of new therapies for bone regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

A Murine Model of Inflammatory Bladder Disease: Cathelicidin Peptide Induced Bladder Inflammation and Treatment With Sulfated Polysaccharides

PubMed Central

Oottamasathien, Siam; Jia, Wanjian; McCoard, Lindsi; Slack, Sean; Zhang, Jianxing; Skardal, Aleksander; Job, Kathleen; Kennedy, Thomas P.; Dull, Randal O.; Prestwich, Glenn D.

2013-01-01

Purpose Studies show that LL-37 is a naturally occurring urinary defensin peptide that is up-regulated during urinary tract infections. Although normal urinary LL-37 levels are antimicrobial, we propose that increased LL-37 may trigger bladder inflammation. We further suggest that anti-inflammatory sulfated polysaccharides known as semi-synthetic glycosaminoglycan ether compounds can treat/prevent LL-37 mediated bladder inflammation. Materials and Methods C57BL/6 mice were catheterized/instilled with LL-37 (320 μM at 150 μl) for 45 minutes. Animals were sacrificed at 12 and 24 hours, and tissues were examined using hematoxylin and eosin. Separate experiments were performed for myeloperoxidase to quantify inflammation. GM-1111 semi-synthetic glycosaminoglycan ether treatments involved instillation of 10 mg/ml for 45 minutes directly before or after LL-37. Tissues were harvested at 24 hours. To compare semi-synthetic glycosaminoglycan ether efficacy experiments were performed using 10 mg/ml heparin. Finally, tissue localization of semi-synthetic glycosaminoglycan ether was examined using a fluorescent GM-1111-Alexa Fluor® 633 conjugate. Results Profound bladder inflammation developed after LL-37. Greater tissue inflammation occurred after 24 hours compared to that at 12 hours. Myeloperoxidase assays revealed a 21 and 61-fold increase at 12 and 24 hours, respectively. Semi-synthetic glycosaminoglycan ether treatment after LL-37 showed mild attenuation of inflammation with myeloperoxidase 2.5-fold below that of untreated bladders. Semi-synthetic glycosaminoglycan ether treatment before LL-37 demonstrated almost complete attenuation of inflammation. Myeloperoxidase results mirrored those in controls. In heparin treated bladders minimal attenuation of inflammation occurred. Finally, instillation of GM-1111-Alexa Fluor 633 revealed urothelial coating, significant tissue penetration and binding to endovasculature. Conclusions We developed what is to our knowledge a new

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

PubMed

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

2015-05-20

Sulfated and pyruvylated galactans were isolated from three tropical species of the Bryopsidales, Penicillus capitatus, Udotea flabellum, and Halimeda opuntia. They represent the only important sulfated polysaccharides present in the cell walls of these highly calcified seaweeds of the suborder Halimedineae. Their structural features were studied by chemical analyses and NMR spectroscopy. Their backbone comprises 3-, 6-, and 3,6-linkages, constituted by major amounts of 3-linked 4,6-O-(1'-carboxy)ethylidene-d-galactopyranose units in part sulfated on C-2. Sulfation on C-2 was not found in galactans from other seaweeds of this order. In addition, a complex sulfation pattern, comprising also 4-, 6-, and 4,6-disulfated galactose units was found. A fraction from P. capitatus, F1, showed a moderate anticoagulant activity, evaluated by general coagulation tests and also kinetics of fibrin formation was assayed. Besides, preliminary results suggest that one of the possible mechanisms involved is direct thrombin inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tea Polysaccharide Prevents Colitis-Associated Carcinogenesis in Mice by Inhibiting the Proliferation and Invasion of Tumor Cells

PubMed Central

Liu, Li-Qiao; Li, Hai-Shan; Shen, Ming-Yue; Hu, Jie-Lun; Xie, Ming-Yong

2018-01-01

The imbalance between cell proliferation and apoptosis can lead to tumor progression, causing oncogenic transformation, abnormal cell proliferation and cell apoptosis suppression. Tea polysaccharide (TPS) is the major bioactive component in green tea, it has showed antioxidant, antitumor and anti-inflammatory bioactivities. In this study, the chemoprophylaxis effects of TPS on colitis-associated colon carcinogenesis, especially the cell apoptosis activation and inhibition effects on cell proliferation and invasion were analyzed. The azoxymethane/dextran sulfate sodium (AOM/DSS) was used to induce the colorectal carcinogenesis in mice. Results showed that the tumor incidence was reduced in TPS-treated AOM/DSS mice compared to AOM/DSS mice. TUNEL staining and Ki-67 immunohistochemistry staining showed that the TPS treatment increased significantly the cell apoptosis and decreased cell proliferation among AOM/DSS mice. Furthermore, TPS reduced the expression levels of the cell cycle protein cyclin D1, matrix metalloproteinase (MMP)-2, and MMP-9. In addition, in vitro studies showed that TPS, suppressed the proliferation and invasion of the mouse colon cancer cells. Overall, our findings demonstrated that TPS could be a potential agent in the treatment and/or prevention of colon tumor, which promoted the apoptosis and suppressed the proliferation and invasion of the mouse colon cancer cells via arresting cell cycle progression. PMID:29419740

Interaction of antithrombin with sulfated, low molecular weight lignins: opportunities for potent, selective modulation of antithrombin function.

PubMed

Henry, Brian L; Connell, Justin; Liang, Aiye; Krishnasamy, Chandravel; Desai, Umesh R

2009-07-31

Antithrombin, a major regulator of coagulation and angiogenesis, is known to interact with several natural sulfated polysaccharides. Previously, we prepared sulfated low molecular weight variants of natural lignins, called sulfated dehydrogenation polymers (DHPs) (Henry, B. L., Monien, B. H., Bock, P. E., and Desai, U. R. (2007) J. Biol. Chem. 282, 31891-31899), which have now been found to exhibit interesting antithrombin binding properties. Sulfated DHPs represent a library of diverse noncarbohydrate aromatic scaffolds that possess structures completely different from heparin and heparan sulfate. Fluorescence binding studies indicate that sulfated DHPs bind to antithrombin with micromolar affinity under physiological conditions. Salt dependence of binding affinity indicates that the antithrombin-sulfated DHP interaction involves a massive 80-87% non-ionic component to the free energy of binding. Competitive binding studies with heparin pentasaccharide, epicatechin sulfate, and full-length heparin indicate that sulfated DHPs bind to both the pentasaccharide-binding site and extended heparin-binding site of antithrombin. Affinity capillary electrophoresis resolves a limited number of peaks of antithrombin co-complexes suggesting preferential binding of selected DHP structures to the serpin. Computational genetic algorithm-based virtual screening study shows that only one sulfated DHP structure, out of the 11 present in a library of plausible sequences, bound in the heparin-binding site with a high calculated score supporting selectivity of recognition. Enzyme inhibition studies indicate that only one of the three sulfated DHPs studied is a potent inhibitor of free factor VIIa in the presence of antithrombin. Overall, the chemo-enzymatic origin and antithrombin binding properties of sulfated DHPs present novel opportunities for potent and selective modulation of the serpin function, especially for inhibiting the initiation phase of hemostasis.

Inhibitory activity of Sargassum hemiphyllum sulfated polysaccharide in arachidonic acid-induced animal models of inflammation.

PubMed

Hwang, Pai-An; Hung, Yu-Lan; Chien, Shih-Yung

2015-03-01

Sargassum hemiphyllum is a common plant found on the coasts of Taiwan; it has been used as an anti-inflammatory agent in traditional herbal medicine. This study aimed to evaluate the anti-inflammatory effects of S. hemiphyllum sulfated polysaccharide (SHSP) using two different mouse models. In both arachidonic acid-induced ear inflammatory gavage and paint models, SHSP decreased ear swelling and erythema. In addition, SHSP decreased the production of myeloperoxidase, nitric oxide, interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α in a dose-dependent manner. Histological examination results showed that SHSP reduced the area of neutrophilic infiltration in inflamed ears. The anti-inflammatory activity of SHSP has already been demonstrated in vitro. In this study, SHSP extracted from the same species of brown seaweed exhibited anti-inflammatory activity in both oral and topical applications in vivo. Therefore, SHSP may play a role in the treatment of inflammatory diseases. Copyright © 2014. Published by Elsevier B.V.

Polysaccharides from Tricholoma matsutake and Lentinus edodes enhance 5-fluorouracil-mediated H22 cell growth inhibition.

PubMed

Ren, Ming; Ye, Lingyan; Hao, Xiaoshi; Ren, Zhixing; Ren, Shuping; Xu, Kun; Li, Juan

2014-06-01

Few studies have investigated the effects produced by combinations of polysaccharides and chemotherapeutic drugs in cancer treatment. We hypothesized that a combination of polysaccharides (COP) from Lentinus edodes and Tricholoma matsutake would improve the efficacy of 5-fluorouracil (5-FU)-mediated inhibition of H22 cell growth. Mice were injected H22 cells and then treated with either 5-FU, polysaccharides from Tricholoma matsutake (PTM), polysaccharides from Lentinus edodes (PL), PTM+PL, 5-FU+PTM, 5-FU+ PL, or 5-FU + COP. The tumor weight and volume, and splenic CD4 + and CD8 + T cell frequencies, were determined. Additionally, splenic natural killer (NK) cell and cytotoxic T lymphocyte (CTL) activities were assessed and the serum levels of tumor necrosis factor-alpha (TNF-alpha), Interleukin-2 (IL-2), and Interferon-gamma (IFN-gamma) were measured. Compared with mice from the control, 5-FU, PL, PTM, PTM + PL, 5-FU + PL, and 5-FU + PTM groups, mice treated with 5-FU + COP showed: (a) significantly reduced tumor weight and volume (P < 0.05); (b) significantly higher serum levels of TNF-alpha, IL-2, and IFN-gamma (P < 0.05); (c) significantly increased CD4+ and CD8+ T cell frequencies in the spleen (P < 0.05); and (d) significantly increased splenic NK cell and CTL activities (P < 0.05). The tumor weight and volume in mice treated with 5-FU+PL or 5-FU+PTM were significantly reduced compared with mice treated with 5-FU alone (P < 0.05). Serum levels of TNF-alpha, IL-2, and IFN-gamma, frequencies of CD4 + and CD8+ T cells in the spleen, and splenic NK and CTL activities were also significantly increased in mice treated with 5-FU+PL or 5-FU+PTM compared with mice treated with 5-FU alone (P < 0.05). Polysaccharides from Lentinus edodes and Tricholoma matsutake could enhance the efficacy of 5-FU-mediated H22 cell growth inhibition.

Synthesis of Fucosylated Chondroitin Sulfate Glycoclusters: A Robust Route to New Anticoagulant Agents.

PubMed

Zhang, Xiao; Yao, Wang; Xu, Xiaojiang; Sun, Huifang; Zhao, Jinhua; Meng, Xiangbao; Wu, Mingyi; Li, Zhongjun

2018-02-01

Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan with excellent anticoagulant activity. Studies show that FuCS and its depolymerized fragments exhibit a different anticoagulant mechanism from that of heparin derivatives, with decreased risks of adverse effects and bleeding. However, further exploitation has been hindered by the scarcity of structurally defined oligosaccharides. Herein, facile method is reported for the synthesis of the repeating trisaccharide unit of FuCS based on the degradation of chondroitin sulfate polymers. A series of simplified FuCS glycomimetics that have highly tunable structures, controllable branches, and defined sulfation motifs were generated by copper-catalyzed alkyne-azide cycloaddition. Remarkable improvement in activated partial thromboplastin time (APTT) assay activities was observed as the branches increased, but no significant influences were observed for prothrombin time (PT) and thrombin time (TT) assay activities. Further FXase inhibition tests suggested that glycoclusters 33 b-40 b selectively inhibited intrinsic anticoagulant activities, but had little effect on the extrinsic and common coagulation pathways. Notably, glycoclusters with the 2,4-di-O-sulfated fucosyl residue displayed the most potency, which was in consistent with that of natural polysaccharides. These FuCS clusters demonstrated potency to mimic linear glycosaminoglycans and offer a new framework for the development of novel anticoagulant agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Salinity-Induced Anti-Angiogenesis Activities and Structural Changes of the Polysaccharides from Cultured Cordyceps Militaris

PubMed Central

Zeng, Yangyang; Han, Zhangrun; Qiu, Peiju; Zhou, Zijing; Tang, Yang; Zhao, Yue; Zheng, Sha; Xu, Chenchen; Zhang, Xiuli; Yin, Pinghe; Jiang, Xiaolu; Lu, Hong; Yu, Guangli; Zhang, Lijuan

2014-01-01

Cordyceps is a rare and exotic mushroom that grows out of the head of a mummified caterpillar. Many companies are cultivating Cordyceps to meet the increased demand for its medicinal applications. However, the structures and functions of polysaccharides, one of the pharmaceutical active ingredients in Cordyceps, are difficult to reproduce in vitro. We hypothesized that mimicking the salty environment inside caterpillar bodies might make the cultured fungus synthesize polysaccharides with similar structures and functions to that of wild Cordyceps. By adding either sodium sulfate or sodium chloride into growth media, we observed the salinity-induced anti-angiogenesis activities of the polysaccharides purified from the cultured C. Militaris. To correlate the activities with the polysaccharide structures, we performed the 13C-NMR analysis and observed profound structural changes including different proportions of α and β glycosidic bonds and appearances of uronic acid signals in the polysaccharides purified from the culture after the salts were added. By coupling the techniques of stable 34S-sulfate isotope labeling, aniline- and D5-aniline tagging, and stable isotope facilitated uronic acid-reduction with LC-MS analysis, our data revealed for the first time the existence of covalently linked sulfate and the presence of polygalacuronic acids in the polysaccharides purified from the salt added C. Militaris culture. Our data showed that culturing C. Militaris with added salts changed the biosynthetic scheme and resulted in novel polysaccharide structures and functions. These findings might be insightful in terms of how to make C. Militaris cultures to reach or to exceed the potency of wild Cordyceps in future. PMID:25203294

Fibrosterol sulfates from the Philippine sponge Lissodendoryx (Acanthodoryx) fibrosa: sterol dimers that inhibit PKCzeta.

PubMed

Whitson, Emily L; Bugni, Tim S; Chockalingam, Priya S; Concepcion, Gisela P; Feng, Xidong; Jin, Guixian; Harper, Mary Kay; Mangalindan, Gina C; McDonald, Leonard A; Ireland, Chris M

2009-08-21

Three new sulfated sterol dimers, fibrosterol sulfates A-C (1-3), have been isolated from the sponge Lissodendoryx (Acanthodoryx) fibrosa, collected in the Philippines. The structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1 and 2 inhibited PKCzeta with IC(50) values of 16.4 and 5.6 microM, respectively.

Bioresponsive cancer-targeted polysaccharide nanosystem to inhibit angiogenesis.

PubMed

Yang, Fang; Fang, Xueyang; Jiang, Wenting; Chen, Tianfeng

2017-01-01

With many desirable features, such as being more effective and having multiple effects, antiangiogenesis has become one of the promising cancer treatments. The aim of this study was to design and synthesize a new targeted bioresponsive nanosystem with antiangiogenesis properties. The mUPR@Ru(POP) nanosystem was constructed by the polymerization of Ulva lactuca polysaccharide and N -isopropyl acrylamide, decorated with methoxy polyethylene glycol and Arg-Gly-Asp peptide, and encapsulated with anticancer complex [Ru(phen)2p-MOPIP](PF 6 ) 2 ·2H 2 O. The nanosystem was both pH responsive and targeted. Therefore, the cellular uptake of the drug was greatly improved. Moreover, the mUPR@Ru(POP) had strong suppressive effects against vascular endothelial growth factor (VEGF)-induced angiogenesis through apoptosis. The mUPR@Ru(POP) significantly inhibited VEGF-induced human umbilical vein endothelial cell migration, invasion, and tube formation. These findings have presented new insights into the development of antiangiogenesis drugs.

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

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

Additionally sulfated xylomannan sulfates from Scinaia hatei and their antiviral activities.

PubMed

Ray, Sayani; Pujol, Carlos A; Damonte, Elsa B; Ray, Bimalendu

2015-10-20

Herpes simplex viruses (HSVs) display affinity for cell-surface heparan sulfate proteoglycans with biological relevance in virus entry. This study demonstrates the potential of chemically engineered sulfated xylomannans from Scinaia hatei as antiHSV drug candidate. Particularly, a dimethylformamide -SO3/pyridine based procedure has been employed for the generation of anionic polysaccharides. This one-step procedure has the power of providing a spectrum of xylomannans with varying molecular masses (<12-74kDa), sulfate content (1-50%) and glycosyl composition. Especially, the sulfated xylomannans S1F1 and S2F1 possessed altered activity against HSV-1 and HSV-2 compared to the parental compound (F1) and that too in the absence of drug-induced cytotoxicity. Regarding methodological facet, the directive decoration of hydroxyl functionality with sulfate group plus changes in the molecular mass and sugar composition during isolation by the used reagent opens a door for the production of new molecular entity with altered biological activity from other natural sources. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sulfated modification and anti-tumor activity of laminarin.

PubMed

Ji, Chen-Feng; Ji, Yu-Bin; Meng, DE-You

2013-11-01

The aim of this study was to investigate the sulfated modification of laminarin and the changes in structure and antitumor activity. The chlorosulfonic acid-pyridine method was applied for sulfated modification. The molecular weights of laminarin and laminarin sulfate (LAMS) were measured by high-performance liquid chromatography (HPLC), and IR and NMR spectra were also recorded. The surface conformations of laminarin and LAMS were observed with a scanning electron microscope. The antitumor activities of the two polysaccharides were also evaluated using an MTT assay. LAMS with a sulfate content of 45.92% and a molecular weight of 16,000 was synthesized. The IR spectra of laminarin and LAMS showed the characteristic absorption peaks of a polysaccharide, and LAMS also had the characteristic absorption peaks of sulfate moieties. The NMR spectra showed that laminarin and LAMS had β-(1→3) glycosidic bonds forming the main chain, and sulfate substitution was at the hydroxyl groups of C 2 and C 6 . Under the scanning electron microscope, there were clear differences in surface conformation between laminarin and LAMS; laminarin was cloud-like and spongy, while LAMS was block-like and flaky. The MTT results showed that laminarin and LAMS had inhibitory effects on LoVo cell growth, and the antitumor activity of LAMS was higher than that of laminarin at the same concentration. This suggests that sulfated modification was able to change the laminarin structure and markedly enhance the antitumor activity.

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. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Polysaccharides from Sargassum thunbergii: Monthly variations and anti-complement and anti-tumour activities.

PubMed

Jin, Weihua; Liu, Ge; Zhong, Weihong; Sun, Chaomin; Zhang, Quanbin

2017-12-01

Monthly variations of polysaccharides from Sargassum thunbergii and their anti-complement and anti-tumour activities were investigated. It was observed that an increase in fucose and total sugar contents occurred during the growth period (from early April to mid-June), accompanied by a decrease in molar ratios of other monosaccharides to fucose. The highest yields were obtained from early July to early September, which was in accordance with the significant increase in molar ratio of glucose to fucose and decrease in molar ratio of other monosaccharides to fucose. And the above results suggested that S. Thunbergii synthesized large amount of laminaran, the storage substance of brown algae, during the senescence period. However, sulfate contents were relatively stable in the life cycle of S. thunbergii. These results suggested that S. thunbergii synthesized complex sulfated heteropolysacchairdes during inactive period, while during other periods, it synthesized more sulfated galactofucan. All polysaccharides showed anti-complement activity, suggesting that the harvesting time did not influence the anti-complement activities. In the anti-tumour assay in vitro, the polysaccharides taken during the senescence period had much lower anti-tumour activity, suggesting that fucoidan, but not laminaran, determined the anti-tumour activities. Therefore, polysaccharides from S. thunbergii might have great potential in anti-complement and anti-tumour application. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of chondroitin sulfate glycosaminoglycans incorporation affected odontoblast differentiation in cultured embryonic mouse molars.

PubMed

Liu, Lipei; Chen, Weiting; Li, Lefeng; Xu, Fangfang; Jiang, Beizhan

2017-12-01

Chondroitin sulfate proteoglycan (CSPG) is an important component of extracellular matrix (ECM), it is composed of a core protein and one or more chondroitin sulfate glycosaminoglycan side chains (CS-GAGs). To investigate the roles of its CS-GAGs in dentinogenesis, the mouse mandibular first molar tooth germs at early bell stage were cultivated with or without β-xyloside. As expected, the CS-GAGs were inhibited on their incorporation to CSPGs by β-xyloside, accompanied by the change of morphology of the cultured tooth germs. The histological results and the transmission electron microscopy (TEM) investigation indicated that β-xyloside exhibited obvious inhibiting effects on odontoblasts differentiation compared with the control group. Meanwhile the results of immunohistochemistry, in situ hybridization and quantitative RT-PCR for type I collagen, dentin matrix acidic phosphoprotein 1 and dentin sialophosphoprotein, the products of differentiated odontoblasts, further proved that odontoblasts differentiation was inhibited. Collagen fibers detected in TEM decreased and arranged in disorder as well. Thus we conclude that the inhibition of CS-GAGs incorporation to CSPGs can affect odontoblast differentiation in cultured embryonic mouse molars.

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

Study on extraction process and activity of plant polysaccharides

NASA Astrophysics Data System (ADS)

Ma, Xiaogen; Wang, Xiaojing; Fan, Shuangli; Chen, Jiezhong

2017-10-01

Recent studies have shown that plant polysaccharides have many pharmacological activities, such as hypoglycemic, anti-inflammatory and tumor inhibition. The pharmacological activities of plant polysaccharides were summarized. The extraction methods of plant polysaccharides were discussed. Finally, the extraction process of Herba Taraxaci polysaccharides was optimized by ultrasonic assisted extraction. Through single factor experiments and orthogonal experiment to optimize the optimum extraction process from dandelion polysaccharide, optimum conditions of dandelion root polysaccharide by ultrasonic assisted extraction method for ultrasonic power 320W, temperature 80°C, extraction time 40min, can get higher dandelion polysaccharide extract.

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

PubMed

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

2016-01-01

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

Phospholipids Polysaccharide and Its Application as Inhibitive Drilling Fluid Additive

NASA Astrophysics Data System (ADS)

Gu, Xue-Fan; Hu, Wei-Min; Zhang, Fan; Du, Wei-Chao; Zhang, Qiang; Zhang, Jie; Zhang, Yong-Ming; Chen, Gang

2018-03-01

For the improvement of solubility and the performance of the sample that derived plant polysaccharide(SJ) in drilling fluid based on water, which was improved by phosphoric esterification with phospholipids reagent. The conditions of the reaction were discussed by orthogonal ways in four factors and three levels, and the optimization of handling approaches were found out: With pH=12 at the temperature of 80°C, the mass ratio between phospholipids agent and SJ is 0.1g/1g. The viscosity about the system added by sulfonated SJ (SJP) was extremely increased and below 120°, rheological properties had a slight change. The inhibitive ability of SJP is assessed by the mud ball immersing tests and clay-swelling experiments, that is apparently better than SJ and even 4wt% KCl in free water.

Fenobam Sulfate Inhibits Cocaine-Taking and Cocaine-Seeking Behavior in Rats: Implications for Addiction Treatment in Humans

PubMed Central

Keck, Thomas M.; Yang, Hong-Ju; Bi, Guo-Hua; Huang, Yong; Zhang, Hai-Ying; Srivastava, Ratika; Gardner, Eliot L.; Newman, Amy Hauck; Xi, Zheng-Xiong

2014-01-01

Rationale The metabotropic glutamate receptor subtype 5 (mGluR5) has been reported to be critically involved in drug reward and addiction. Because the mGluR5 negative allosteric modulators (NAMs) MPEP and MTEP significantly inhibit addictive-like behaviors of cocaine and other drugs of abuse in experimental animals, it has been suggested that mGluR5 NAMs may have translational potential for treatment of addiction in humans. However, neither MPEP nor MTEP have been evaluated in humans due to their off-target actions and rapid metabolism. Objectives Herein, we evaluate a potential candidate for translational addiction research: a new sulfate salt formulation of fenobam, a selective mGluR5 NAM that has been investigated in humans. Results In rats, fenobam sulfate had superior pharmacokinetics compared to the free base, with improved Cmax (maximal plasma concentration) and longer half life. Oral (p.o.) administration of fenobam sulfate (30 or 60 mg/kg) inhibited intravenous cocaine self-administration, cocaine-induced reinstatement of drug-seeking behavior and cocaine-associated cue-induced cocaine-seeking behavior in rats. Fenobam sulfate also inhibited oral sucrose self-administration and sucrose-induced reinstatement of sucrose-seeking behavior, but had no effect on locomotion. Conclusions This study provides additional support for the role of mGluR5 signaling in cocaine addiction and suggests that fenobam sulfate may have translational potential in medication development for the treatment of cocaine addiction in humans. PMID:23615919

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...

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...

Extraction, Structural Characterization, and Potential Antioxidant Activity of the Polysaccharides from Four Seaweeds

PubMed Central

He, Jinzhe; Xu, Yaoyang; Chen, Hongbo; Sun, Peilong

2016-01-01

Four seaweed polysaccharides were extracted from Sarcodia ceylonensis, Ulva lactuca L., Gracilaria lemaneiformis, and Durvillaea antarctica, respectively, by microwave-assisted extraction. The effect of three significant variables (extraction time, extraction temperature, and the ratio of water to raw material) on the process for extracting polysaccharides was investigated, along with the optimization of the extraction using the response surface method (RSM) with a Box–Behnken design. The polysaccharide structure, monosaccharide composition, degree of sulfation, and molecular weight (MW) distribution were analyzed by infrared (IR) spectrometry, gas chromatography (GC), and high-performance gel permeation chromatography (HPGPC). IR spectrometry showed that Sarcodia ceylonensis polysaccharide (SCP), Ulva lactuca L. polysaccharide (ULLP), and Durvillaea antarctica polysaccharide (DAP) were all sulfated polysaccharides and, except Gracilaria lemaneiformis polysaccharide (GLP), all belong to β-pyranosidic polysaccharides. The average molecular weight (MW) of SCP, ULLP, GLP, and DAP was 466, 404, 591, and 482 kDa, respectively. The quantitative and comparative results with external standards indicated that the main monosaccharide in SCP and ULLP was mannose; and GLP and DAP were mainly composed of galactose and glucose, respectively. Then the in vitro antioxidant activity of all of the polysaccharides was evaluated using different assays—2,2–azino –bis (3-ethylbenzthiazoline-6- sulfonate) (ABTS), hydroxyl radical, nitrite scavenging capacity, and reducing power—and the relationship between their antioxidant activity and chemical characteristics were also examined. ULLP presented the highest ABTS radical scavenging activity; ULLP, SCP and DAP also showed a strong effect on the ABTS radical scavenging activity. SCP and ULLP exhibited excellent hydroxyl radical scavenging activities, about 83.33% ± 2.31% and 80.07% ± 2.17%, respectively, at 4 mg/mL. The

Extraction, Structural Characterization, and Potential Antioxidant Activity of the Polysaccharides from Four Seaweeds.

PubMed

He, Jinzhe; Xu, Yaoyang; Chen, Hongbo; Sun, Peilong

2016-11-28

Four seaweed polysaccharides were extracted from Sarcodia ceylonensis , Ulva lactuca L., Gracilaria lemaneiformis , and Durvillaea antarctica , respectively, by microwave-assisted extraction. The effect of three significant variables (extraction time, extraction temperature, and the ratio of water to raw material) on the process for extracting polysaccharides was investigated, along with the optimization of the extraction using the response surface method (RSM) with a Box-Behnken design. The polysaccharide structure, monosaccharide composition, degree of sulfation, and molecular weight ( M W ) distribution were analyzed by infrared (IR) spectrometry, gas chromatography (GC), and high-performance gel permeation chromatography (HPGPC). IR spectrometry showed that Sarcodia ceylonensis polysaccharide (SCP), Ulva lactuca L. polysaccharide (ULLP), and Durvillaea antarctica polysaccharide (DAP) were all sulfated polysaccharides and, except Gracilaria lemaneiformis polysaccharide (GLP), all belong to β-pyranosidic polysaccharides. The average molecular weight ( M W ) of SCP, ULLP, GLP, and DAP was 466, 404, 591, and 482 kDa, respectively. The quantitative and comparative results with external standards indicated that the main monosaccharide in SCP and ULLP was mannose; and GLP and DAP were mainly composed of galactose and glucose, respectively. Then the in vitro antioxidant activity of all of the polysaccharides was evaluated using different assays-2,2-azino -bis (3-ethylbenzthiazoline-6- sulfonate) (ABTS), hydroxyl radical, nitrite scavenging capacity, and reducing power-and the relationship between their antioxidant activity and chemical characteristics were also examined. ULLP presented the highest ABTS radical scavenging activity; ULLP, SCP and DAP also showed a strong effect on the ABTS radical scavenging activity. SCP and ULLP exhibited excellent hydroxyl radical scavenging activities, about 83.33% ± 2.31% and 80.07% ± 2.17%, respectively, at 4 mg/mL. The reducing

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.

Inhibition on the growth of human MDA-MB-231 breast cancer cells in vitro and tumor growth in a mouse xenograft model by Se-containing polysaccharides from Pyracantha fortuneana.

PubMed

Yuan, Chengfu; Wang, Changdong; Wang, Junjie; Kumar, Vikas; Anwar, Firoz; Xiao, Fangxiang; Mushtaq, Gohar; Liu, Yufei; Kamal, Mohammad Amjad; Yuan, Ding

2016-11-01

Breast cancer is the second cause of cancer-related death among Women. Current therapies for breast cancer have adverse side-effects. Selenium (Se)-containing polysaccharides have multiple health benefits to humans. Pyracantha fortuneana (P. fortuneana) contains rich Se polysaccharides. We hypothesized that Se-containing polysaccharides from P. fortuneana possess anticancer activity on breast cancer via inhibiting growth and inducing apoptosis. This study aimed to assess the anticancer effect of Se-containing polysaccharides from P. fortuneana and the underlying mechanisms. Se-containing polysaccharides were purified. Their properties and monosaccharide compositions were analyzed. Their effects on cell growth, expression of cycle proteins, apoptosis and apoptosis-related protein, and tumor growth in mouse xenograft model were examined. This extract contained 93.7% (w/w) of carbohydrate, 2.1% (w/w) of uronic acid and 3.7μg/g of Se, and was considered as Se-conjugated polysaccharides (Se-PFPs). In vitro studies showed that treatment of triple negative breast cancer (TNBC) MDA-MB-231 cells with Se-PFPs (1) inhibited cell growth dose-dependently by arresting cells at G2 phase via inhibiting CDC25C-CyclinB1/CDC2 pathway; (2) caused apoptosis associated with increased p53, Bax, Puma and Noxa, decreased Bcl2, increased Bax/Bcl2 ratio and increased activities of caspases 3/9, suggesting its effect on p53-mediated cytochrome c-caspase pathway. Treatment of nude mice bearing MDA-MB-231-derived xenograft tumors with Se-PFPs significantly reduced tumor growth without altering body weight, confirming its antitumor activity without toxic side effects. Se-PFPs enhanced doxorubicin cytotoxic effects. It is concluded that Se-containing polysaccharides from P. fortuneana potently inhibit the growth and induce apoptosis of TNBC cells and can be potential anticancer agent for TNBC. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2008-01-01

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

Structure analysis of a novel heteroxylan from the stem of Dendrobium officinale and anti-angiogenesis activities of its sulfated derivative.

PubMed

Yue, Han; Liu, Yanqiu; Qu, Huanhuan; Ding, Kan

2017-10-01

Dendrobium officinale Kimura et Migo (Tie-Pi-Shi-Hu), a precious folk medicine exhibiting multiple bioactivities, including antitumor, immune-enhancing and so on. Although evidences showed polysaccharide is one of the major bioactive substances from this herb, several of them were homogenous with fine structures elucidated. In this study, we showed a novel homogeneous heteroxylan obtained from alkali-extracted crude polysaccharide. It composed of arabinose, xylose, glucose and 4-O-methylglucuronic acid (4-MGA) as well as trace amount of rhamnose and galactose in a ratio of 8.9:62.7:8.5:12.3:3.9:3.7. We further showed that it contained a backbone of 1,4-linked β-d-xylan, with branches of 1,4-linked α-d-glucose, 1,3-linked α-l-rhamnose, and terminal-linked α-l-arabinose, β-d-galactose, 4-MGA, and β-d-xylose directly or indirectly attached to C-2 position of glycosyl residues on backbone. The sulfated derivative with substitution degree about 0.9 was prepared according to the chlorosulfonic acid (CSA)-pyridine method. Bioactivity tests suggested that the sulfated polysaccharide could significantly disrupt tube formation and inhibit the migration of human microvascular endothelial cells (HMEC-1) at a low concentration (0.29μM) in a dose-dependent way without significant cytotoxity. Copyright © 2017 Elsevier B.V. All rights reserved.

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

2016-09-06

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.

Layer-by-layer structured polysaccharides-based multilayers on cellulose acetate membrane: Towards better hemocompatibility, antibacterial and antioxidant activities

NASA Astrophysics Data System (ADS)

Peng, Lincai; Li, Hui; Meng, Yahong

2017-04-01

The development of multifunctional cellulose acetate (CA) membranes with enhanced hemocompatibility and antibacterial and antioxidant activities is extremely important for biomedical applications. In this work, significant improvements in hemocompatibility and antibacterial and antioxidant activities of cellulose acetate (CA) membranes were achieved via layer-by-layer (LBL) deposition of chitosan (CS) and water-soluble heparin-mimicking polysaccharides (i.e., sulfated Cantharellus cibarius polysaccharides, SCP) onto their surface. The surface chemical compositions, growth manner, surface morphologies, and wetting ability of CS/SCP multilayer-modified CA membranes were characterized, respectively. The systematical evaluation of hemocompatibility revealed that CS/SCP multilayer-modified CA membranes significantly improved blood compatibility including resistance to non-specific protein adsorption, suppression of platelet adhesion and activation, prolongation of coagulation times, inhibition of complement activation, as well as reduction in blood hemolysis. Meanwhile, CS/SCP multilayer-modified CA membranes exhibited strong growth inhibition against Escherichia coli and Staphylococcus aureus, as well as high scavenging abilities against superoxide and hydroxyl radicals. In summary, the CS/SCP multilayers could confer CA membranes with integrated hemocompatibility and antibacterial and antioxidant activities, which might have great potential application in the biomedical field.

Bacteria and Acidic Drainage from Coal Refuse: Inhibition by Sodium Lauryl Sulfate and Sodium Benzoate

PubMed Central

Dugan, Patrick R.; Apel, William A.

1983-01-01

The application of an aqueous solution of sodium lauryl sulfate and sodium benzoate to the surface of high-sulfur coal refuse resulted in the inhibition of iron-and sulfur-oxidizing chemoautotrophic bacteria and in the decrease of acidic drainage from the refuse, suggesting that acid drainage can be abated in the field by inhibiting iron- and sulfur-oxidizing bacteria. PMID:16346347

Role of central opioid on the antinociceptive effect of sulfated polysaccharide from the red seaweed Solieria filiformis in induced temporomandibular joint pain.

PubMed

Araújo, Ianna Wivianne Fernandes; Chaves, Hellíada Vasconcelos; Pachêco, José Mário; Val, Danielle Rocha; Vieira, Lorena Vasconcelos; Santos, Rodrigo; Freitas, Raul Sousa; Rivanor, Renata Line; Monteiro, Valdécio Silvano; Clemente-Napimoga, Juliana Trindade; Bezerra, Mirna Marques; Benevides, Norma Maria Barros

2017-03-01

This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225μg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or μ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s.c.). After 30min, the animals were treated with an intra-TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45-min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin- and serotonin-induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor-BNI blocked the antinociceptive effect of F II in the 1.5% formalin-induced TMJ nociception. In addition, F II was able to significantly increase the β-endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti-inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue. Copyright © 2017. Published by Elsevier B.V.

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 Central

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. PMID:23658845

In Vivo Anti-Herpes Simplex Virus Activity of a Sulfated Derivative of Agaricus brasiliensis Mycelial Polysaccharide

PubMed Central

Cardozo, F. T. G. S.; Larsen, I. V.; Carballo, E. V.; Jose, G.; Stern, R. A.; Brummel, R. C.; Camelini, C. M.; Rossi, M. J.; Simões, C. M. O.

2013-01-01

Agaricus brasiliensis (syn. A. subrufescens), a basidiomycete fungus native to the Atlantic forest in Brazil, contains cell walls rich in glucomannan polysaccharides. The β-(1→2)-gluco-β-(1→3)-mannan was isolated from A. brasiliensis mycelium, chemically modified by sulfation, and named MI-S. MI-S has multiple mechanisms of action, including inhibition of herpes simplex virus (HSV) attachment, entry, and cell-to-cell spread (F. T. G. S. Cardozo, C. M. Camelini, A. Mascarello, M. J. Rossi, R. J. Nunes, C. R. Barardi, M. M. de Mendonça, and C. M. O. Simões, Antiviral Res. 92:108–114, 2011). The antiherpetic efficacy of MI-S was assessed in murine ocular, cutaneous, and genital infection models of HSV. Groups of 10 mice were infected with HSV-1 (strain KOS) or HSV-2 (strain 333). MI-S was given either topically or by oral gavage under various pre- and posttreatment regimens, and the severity of disease and viral titers in ocular and vaginal samples were determined. No toxicity was observed in the uninfected groups treated with MI-S. The topical and oral treatments with MI-S were not effective in reducing ocular disease. Topical application of MI-S on skin lesions was also not effective, but cutaneously infected mice treated orally with MI-S had significantly reduced disease scores (P < 0.05) after day 9, suggesting that healing was accelerated. Vaginal administration of MI-S 20 min before viral challenge reduced the mean disease scores on days 5 to 9 (P < 0.05), viral titers on day 1 (P < 0.05), and mortality (P < 0.0001) in comparison to the control groups (untreated and vehicle treated). These results show that MI-S may be useful as an oral agent to reduce the severity of HSV cutaneous and mucosal lesions and, more importantly, as a microbicide to block sexual transmission of HSV-2 genital infections. PMID:23507287

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.

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.

[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.

Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon.

PubMed Central

Salyers, A A; Vercellotti, J R; West, S E; Wilkins, T D

1977-01-01

Ten Bacteroides species found in the human colon were surveyed for their ability to ferment mucins and plant polysaccharides ("dietary fiber"). A number of strains fermented mucopolysaccharides (heparin, hyaluronate, and chondroitin sulfate) and ovomucoid. Only 3 of the 188 strains tested fermented beef submaxillary mucin, and none fermented porcine gastric mucin. Many of the Bacteroides strains tested were also able to ferment a variety of plant polysaccharides, including amylose, dextran, pectin, gum tragacanth, gum guar, larch arabinogalactan, alginate, and laminarin. Some plant polysaccharides such as gum arabic, gum karaya, gum ghatti and fucoidan, were not utilized by any of the strains tested. The ability to utilize mucins and plant polysaccharides varied considerably among the Bacteroides species tested. PMID:848954

[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.

Immunomodulatory and anticancer potential of Gan cao (Glycyrrhiza uralensis Fisch.) polysaccharides by CT-26 colon carcinoma cell growth inhibition and cytokine IL-7 upregulation in vitro.

PubMed

Ayeka, Peter Amwoga; Bian, Yuhong; Mwitari, Peter Githaiga; Chu, Xiaoqian; Zhang, Yanjun; Uzayisenga, Rosette; Otachi, Elick Onyango

2016-07-11

Chinese licorice, (Glycyrrhiza uralensis Fisch.) is one of the commonly prescribed herbs in Traditional Chinese Medicine (TCM). Gancao, as commonly known in China, is associated with immune-modulating and anti-tumor potential though the mechanism of action is not well known. In this study, we investigated the in vitro immunomodulatory and antitumor potential of Glycyrrhiza uralensis polysaccharides fractions of high molecular weight (fraction A), low molecular weight (fraction B) and crude extract (fraction C). Cell proliferation and cytotoxicity was investigated using Cell Counting kit 8 (CCK-8) on Intestinal epithelial cell line (IEC-6) and Colon carcinoma cell line (CT-26). IL-7 gene expression relative to GAPDH was analysed using Real time PCR. The stimulation and viability of T lymphocytes was determined by Trypan blue exclusion assay. G.uralensis polysaccharides did not inhibit proliferation of IEC-6 cells even at high concentration. The ED50 was found to be 100 μg/ml. On the other hand, the polysaccharides inhibited the proliferation of cancer cells (CT-26) at a concentration of ≤50 μg/ml. Within 72 h of treatment with the polysaccharides, expression of IL-7 gene was up-regulated over 2 times. It was also noted that, IEC-6 cells secrete IL-7 cytokine into media when treated with G.uralensis polysaccharides. The secreted IL-7 stimulated proliferation of freshly isolated T lymphocytes within 6 h. The effect of the polysaccharides were found to be molecular weight depended, with low molecular weight having a profound effect compared to high molecular weight and total crude extract. Our findings indicate that G.uralensis polysaccharides especially those of low molecular weight have a potential as anticancer agents. Of great importance, is the ability of the polysaccharides to up-regulate anticancer cytokine IL-7, which is important in proliferation and maturation of immune cells and it is associated with better prognosis in cancer. Therefore

Modulating inhibitors of transthyretin fibrillogenesis via sulfation: polychlorinated biphenyl sulfates as models.

PubMed

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

2015-02-25

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Two structurally similar fucosylated chondroitin sulfates from the holothurian species Stichopus chloronotus and Stichopus horrens.

PubMed

Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Shashkov, Alexander S; Nifantiev, Nikolay E; Usov, Anatolii I

2018-06-01

Two fucosylated chondroitin sulfates SC and SH were isolated from the holothurian species Stichopus chloronotus and Stichopus horrens, respectively. The molar ratio of monosaccharides and sulfate (GalNAc:GlcA:Fuc:SO 3 Na) was suggested as ∼1:1:1:4 for both polysaccharides. Really this theoretical ratio was slightly distorted by the presence of some fucan sulfate in both preparations (about 2% in SH and 10% in SC), which could not be separated probably due to coincidence with the main components in charge density and molecular weight. The 1D and 2D NMR spectroscopic methods were applied for the detailed structural characterization of SC and SH, which were found to have similar structures. The main chain of SC and SH was shown to be composed of the repeating disaccharide units →4)-β-d-GlcA-(1 → 3)-β-d-GalNAc-(1→ sulfated at O-4 or both at O-4 and O-6 of the N-acetyl-galactosaminyl residues. The ratio of mono- and disulfated GalNAc residues was determined as 1:9 for SC and SH. Only one type of branches linked to O-3 of glucuronyl residues, namely fucosyl 2,4-disulfate residues, were found in both polysaccharides. Therefore polysaccharides SC and SH are two new examples of highly regular fucosylated chondroitin sulfates. Copyright © 2018 Elsevier Ltd. All rights reserved.

Structure and anticancer activity of native and modified polysaccharides from brown alga Dictyota dichotoma.

PubMed

Usoltseva, Roza V; Shevchenko, Natalia M; Malyarenko, Olesya S; Ishina, Irina A; Ivannikova, Svetlana I; Ermakova, Svetlana P

2018-01-15

The laminaran DdL and fucoidan DdF were obtained from the brown alga Dictyota dichotoma. DdF was a sulfated (28.9%) and acetylated heteropolysaccharide containing fucose, galactose, mannose and glucose (57.9, 20.4, 12.4 and 9.2mol%, respectively). DdL was a 1,3;1,6-β-d-glucan with the main chain built from 1,3-linked glucose residues and single glucose residue in branches at C6 (one branch on three glucose residues of the main chain). Sulfated (43.7%) laminaran DdLs was obtained from DdL by sulfation. It was determined that sulfates occur at C2, C4 and C6 of glucose residues. The anticancer effect of DdF, DdL, and DdLs (200μg/mL) was studied in vitro on colon cancer cells HCT-116, HT-29, and DLD-1. The effect of polysaccharides (40μg/mL) on colony formation of DLD-1 cancer cells after irradiation (4Gy) was investigated first. All polysaccharides showed a synergistic effect with X-ray irradiation against cancer cells, decreasing the amount and size of cancer cells colonies. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Two fucosylated chondroitin sulfates from the sea cucumber Eupentacta fraudatrix.

PubMed

Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Nifantiev, Nikolay E; Usov, Anatolii I

2017-05-15

Two fucosylated chondroitin sulfates EF1 and EF2 were isolated from the sea cucumber Eupentacta fraudatrix. Separation of the polysaccharides was performed using anion-exchange chromatography on DEAE-Sephacel by elution of 0.75M and 1.0M NaCl solutions. The structures of biopolymers were determined by chemical and NMR spectroscopic methods. The backbone of EF1 was found to be composed of chondroitin sulfate A and E units in a ratio of about 1:1. The core of EF2 along with chondroitin sulfate A and E fragments contained unusual disaccharide repeating units →4)-β-d-GlcpA2S3S-(1→3)-β-d-GalpNAc6S-(1→. The main type of branches in both polysaccharides was α-l-Fucp3S4S unit attached to O-3 of GlcA residues. Another type of branches was found to be the disaccharide fragment α-l-Fucp-(1→2)-α-l-Fucp3S4S-(1→ linked to O-3 of GlcA. The presence of structurally different fucosylated chondroitin sulfates in one species of sea cucumber is rather unusual and has not been described previously. Copyright © 2017 Elsevier Ltd. All rights reserved.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

The structural features of the sulfated heteropolysaccharide (ST-1) from Sargassum thunbergii and its neuroprotective activities.

PubMed

Jin, Weihua; Liu, Bing; Li, Shuai; Chen, Jing; Tang, Hong; Jiang, Di; Zhang, Quanbin; Zhong, Weihong

2018-03-01

Polysaccharide (ST) was prepared from Sargassum thunbergii using hot water. Two fractions (ST-1 and ST-2) were prepared using anion exchange chromatography. One desulfated polysaccharide (ST-1-DS) was also prepared. Electrospray ionization mass spectrometry (ESI-MS) performed on ST-1-DS showed that the desulfated polysaccharides contained methyl glycosides of mono-sulfated and di-sulfated galacto-fucooligosaccharides. This result suggested that ST-1 might contain sulfated galactofucan, which consists of a backbone of alternating (Gal) n and (Fuc) n and sulfated randomly on Gal and mainly on C-2 in Fuc. In addition, ST-1 was degraded in 1M sulfuric acid. The solution was centrifuged, and the supernatant was concentrated and precipitated in ethanol to obtain the precipitate (ST-1-P). ST-1-P was then separated using gel chromatography and anion exchange chromatography to obtain the oligomers. ESI-MS spectra of oligomers indicated that ST-1 mostly contained sulfated glucuronomannan and fucoglucuronan. ESI-MS with collision-induced dissociation tandem mass spectrometry (ESI-CID-MS/MS) suggested that glucuronomannan contained alternating 2-linked Man and 4-linked GlcA, while fucoglucuronan contained 4-linked glucuronan with branched Fuc at C-3. Finally, the neuroprotective activities of ST, ST-1, ST-2 and MIX (a mixture of ST-1 and ST-2) were determined. ST showed the most neuroprotective activity, which indicated that ST might be a good candidate for curing neurodegenerative diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Variations of pH as an additional tool in the analysis of crowded NMR spectra of fucosylated chondroitin sulfates.

PubMed

Ustyuzhanina, Nadezhda E; Dmitrenok, Andrey S; Bilan, Maria I; Shashkov, Alexander S; Gerbst, Alexey G; Usov, Anatolii I; Nifantiev, Nikolay E

2016-03-24

The influence of pH variation on chemical shift values in NMR spectra of fucosylated chondroitin sulfates was studied using polysaccharides isolated from three sea cucumber species Apostichopus japonicus, Actinopyga mauritiana and Cucumaria japonica. The signals of glucuronic acid residues were found to be the most sensitive to pH changes in comparison to the chemical shifts of the sulfated galactosamine and fucosyl units, most of which were altered insignificantly. It was shown that in the presence of imidazole-HCl buffer (pH 7.2) NMR spectra of the polysaccharides from A. japonicus and A. mauritiana were sufficiently resolved, whereas under acidic conditions their (1)H NMR spectra were complicated by overlapping of H-1 signals of GlcA and GalNAc. In the case of polysaccharide from C. japonica bearing 3-O-fucosylated and 3-O-sulfated glucuronic acid residues in the backbone, acidification of the medium led to separation of H-1 signals of GlcA3S and GalNAc. Therefore, the combination of data obtained at different pH values may be useful for interpretation of overcrowded spectra of fucosylated chondroitin sulfates. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2009-08-07

Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype. Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA) and 5 heterozygous (GA) PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses.Gene expression analysis revealed 129 genes significantly modulated (p < 0.05). The following genes were up-regulated over 2 fold: IL18, CTSS, LUM, CD44, FN1, GST01. The most down-regulated genes were the following: mitochondrial tRNA, SLC2A2, PRKCalpha, VEGFalpha. Data mining analysis showed that protein synthesis, apoptosis, cellular movement, growth and proliferation were the main cellular functions significantly associated with the modulated genes (p < 0.05). Several up-regulated genes, especially IL18, revealed a severe muscular inflammation in PSSM muscles. The up-regulation of glycogen synthase kinase-3 (GSK3beta) under its active form could be responsible for glycogen synthase (GYS1) inhibition and hypoxia-inducible factor (HIF1alpha

Fever-range hyperthermia inhibits cells immune response to protein-bound polysaccharides derived from Coriolus versicolor extract.

PubMed

Pawlikowska, Małgorzata; Jędrzejewski, Tomasz; Piotrowski, Jakub; Kozak, Wiesław

2016-12-01

The aim of the study was to explore whether fever-range hyperthermia (FRH) might enhance the anticancer and immunoregulatory activities of protein-bound polysaccharides (PBP), a class of fungus derived immunomodifiers used in the cancer adjuvant therapy. Blood lymphocytes and breast cancer cells (MCF-7) were cultured at 39.5°C in humidified atmosphere containing 5% CO 2 for 2h. After rested at 37°C for 6h, the cells were treated with PBP extract at 100- and 300μg/ml concentration. After indicated time, the proliferative response was analyzed and cytokine mRNA expression assessment was performed by qRT-PCR. In animal model, the FRH was induced by placing rats in the Homeothermic Controller with heating blanket. Animals were heated until Tb reached 39.5°C (±0.2°C) and were maintained at this temperature for 30min. The protein-bound polysaccharides solution was injected i.p. at a dose of 100 mg/kg 6h post FRH. Twenty four hours after treatment, the blood was collected and cytokines expression analysis were performed. The results have shown that fever-range hyperthermia has an inhibitory effect on PBP extract-induced proliferative response of blood lymphocytes, as well as IL-1β and IL-6 mRNA expression. Moreover, the temperature of 39.5°C blocks PBP-induced cytotoxicity against MCF-7 cells, which correlates with significant reduction in TNF-α level. Combined treatment of rats (FRH+PBP) results in decrease of IL-1β, IL-6 and TNF-α mRNA expression in peripheral blood mononuclear cells compared to cells derived from rats treated with protein-bound polysaccharides extract alone. This study demonstrates that fever-range temperature inhibits immunostimulatory as well as anticancer effects mediated by protein-bound polysaccharides. Copyright © 2016. Published by Elsevier Ltd.

Inhibitory effects of Enteromorpha linza polysaccharide on micronucleus of Allium sativum root cells.

PubMed

Zhang, Zhongshan; Wang, Xiaomei; Li, Jingfen; Liu, Chongbin; Zhang, Quanbin

2016-06-01

In this study, the antimutagenic function of the polysaccharide from Enteromorpha linza with the micronucleus test of Allium sativum root cells induced by sulfur dioxide and ultraviolet was studied. The concentration-effect relation of the two inducers was firstly evaluated. The results showed that an increase of genotoxicity damage was demonstrated and micronuclei frequency induced by sulfur dioxide and ultraviolet displayed dose dependent increases. All the doses of polysaccharide did affect the micronuclei frequency formation compared with the negative control. And also, the significant increase in inhibition rate of micronuclei frequency was observed with the increase of the dose of polysaccharide. It was showed maximum inhibition of micronuclei frequency cells (71.74% and 66.70%) at a concentration of 200g/mL in three experiments. The low molecular weight polysaccharide showed higher inhibition rate than raw polysaccharide at the higher concentration (50g/mL) in the absence of sulfur dioxide and ultraviolet. It was confirmed to be a good mutant inhibitor. Copyright © 2016 Elsevier B.V. All rights reserved.

Anticancer properties of polysaccharides isolated from fungi of the Basidiomycetes class.

PubMed

Lemieszek, Marta; Rzeski, Wojciech

2012-01-01

Basidiomycete mushrooms represent a valuable source of biologically active compounds with anticancer properties. This feature is primarily attributed to polysaccharides and their derivatives. The anticancer potential of polysaccharides is linked to their origin, composition and chemical structure, solubility and method of isolation. Moreover, their activity can be significantly increased by chemical modifications. Anticancer effects of polysaccharides can be expressed indirectly (immunostimulation) or directly (cell proliferation inhibition and/or apoptosis induction). Among the wide range of polysaccharides with documented anticancer properties, lentinan, polysaccharide-K (PSK) and schizophyllan deserve special attention. These polysaccharides for many years have been successfully applied in cancer treatment and their mechanism of action is the best known.

Structure of a fucose-branched chondroitin sulfate from sea cucumber. Evidence for the presence of 3-O-sulfo-beta-D-glucuronosyl residues.

PubMed

Vieira, R P; Mulloy, B; Mourão, P A

1991-07-25

The structure of a unique focose-branched chondroitin sulfate isolated from the body wall of a sea cucumber was examined in detail. This glycosaminoglycan contains side chain disaccharide units of sulfated fucopyranosyl units linked to approximately one-half of the glucuronic acid moieties through the O-3 position of the acid. The intact polysaccharide is totally resistant to chondroitinase degradation, whereas, after defucosylation, it is partially degraded by the enzyme. However, only after an additional step of desulfation, the chondroitin from sea cucumber is almost totally degraded by chondroitinase AC or ABC. This result, together with the methylation and NMR studies of the native and chemically modified polysaccharide, suggest that besides the fucose branches, the sea cucumber chondroitin sulfate contains sulfate esters at position O-3 of the beta-D-glucuronic acid units. Furthermore, the proteoglycan from the sea cucumber chondroitin sulfate is recognized by anti-Leu-7 monoclonal antibody, which specifically recognizes 3-sulfoglucuronic acid residues. In analogy with the fucose branched units, the 3-O-sulfo-beta-D-glucuronosyl residues are resistant to chondroitinase degradation. Regarding the position of the glycosidic linkage and site of sulfation in the fucose branches, our results suggest high heterogeneity. Tentatively, it is possible to suggest the preponderance of disaccharide units formed by 3,4-di-O-sulfo-alpha-L-fucopyranosyl units glycosidically linked through position 1----2 to 4-O-sulfo-alpha-L-fucopyranose. Finally, the presence of unusual 4/6-disulfated disaccharide units, together with the common 6-sulfated and non-sulfated units, was detected in the chondroitin sulfate core of this polysaccharide.

Sulfated Hexasaccharides Attenuate Metastasis by Inhibition of P-selectin and Heparanase1

PubMed Central

Borsig, Lubor; Vlodavsky, Israel; Ishai-Michaeli, Rivka; Torri, Giangiacomo; Vismara, Elena

2011-01-01

Development of compounds that target both heparanase and selectins is emerging as a promising approach for cancer therapy. Selectins are vascular cell adhesion molecules that mediate tumor cell interactions with platelets, leukocytes, and the vascular endothelium. Heparanase is an endoglycosidase that degrades heparan sulfate in the tumor microenvironment, cell surfaces, and vessel wall. Acting together, these molecules facilitate tumor cell arrest, extravasation, and metastasis. Here, we report the preparation of novel semisynthetic sulfated tri mannose C-C-linked dimers (STMCs) endowed with heparanase and selectin inhibitory activity. The P-selectin specificity of the STMC was defined by the anomeric linkage of the C-C bond. This STMC hexasaccharide is an effective inhibitor of P-selectin in vivo. We show that selective inhibition of heparanase attenuates metastasis in B16-BL6 melanoma cells, expressing high levels of this endoglycosidase, but has no effect on the metastasis of MC-38 carcinoma cells that express little or no heparanase activity. P-selectin-specific STMC attenuated metastasis in both animal models, indicating that inhibition of tumor cell interaction with the vascular endothelium is critical for cancer dissemination. Thus, the small size, the stability of the C-C bond, and the chemically defined structure of the newly generated STMCs make them superior to heparin derivatives and signify STMCs as valuable candidates for further evaluation. PMID:21532885

Matrix polyelectrolyte capsules based on polysaccharide/MnCO₃ hybrid microparticle templates.

PubMed

Wei, Qingrong; Ai, Hua; Gu, Zhongwei

2011-06-15

An efficient strategy for biomacromolecule encapsulation based on spontaneous deposition into polysaccharide matrix-containing capsules is introduced in this study. First, hybrid microparticles composed of manganese carbonate and ionic polysaccharides including sodium hyaluronate (HA), sodium alginate (SA) and dextran sulfate sodium (DS) with narrow size distribution were synthesized to provide monodisperse templates. Incorporation of polysaccharide into the hybrid templates was successful as verified by thermogravimetric analysis (TGA) and confocal laser scanning microscopy (CLSM). Matrix polyelectrolyte microcapsules were fabricated through layer-by-layer (LbL) self-assembly of oppositely charged polyelectrolytes (PEs) onto the hybrid particles, followed by removal of the inorganic part of the cores, leaving polysaccharide matrix inside the capsules. The loading and release properties of the matrix microcapsules were investigated using myoglobin as a model biomacromolecule. Compared to matrix-free capsules, the matrix capsules had a much higher loading capacity up to four times; the driving force is mostly due to electrostatic interactions between myoglobin and the polysaccharide matrix. From our observations, for the same kind of polysaccharide, a higher amount of polysaccharide inside the capsules usually led to better loading capacity. The release behavior of the loaded myoglobin could be readily controlled by altering the environmental pH. These matrix microcapsules may be used as efficient delivery systems for various charged water-soluble macromolecules with applications in biomedical fields. Copyright © 2010 Elsevier B.V. All rights reserved.

An in vitro assessment of titanium functionalized with polysaccharides conjugated with vascular endothelial growth factor for enhanced osseointegration and inhibition of bacterial adhesion.

PubMed

Hu, Xuefeng; Neoh, Koon-Gee; Shi, Zhilong; Kang, En-Tang; Poh, Chyekhoon; Wang, Wilson

2010-12-01

The long-term success of orthopedic implants may be compromised by defective osseointegration and bacterial infection. An effective approach to minimize implant failure would be to modify the surface of the implant to make it habitable for bone-forming cells and anti-infective at the same time. In this in vitro study, the surfaces of titanium (Ti) substrates were functionalized by first covalently grafting either dopamine followed by carboxymethyl chitosan (CMCS) or hyaluronic acid-catechol (HAC). Vascular endothelial growth factor (VEGF) was then conjugated to the polysaccharide-grafted surface. Antibacterial assay with Staphylococcus aureus (S. aureus) showed that the polysaccharide-modified substrates significantly decrease bacterial adhesion. The CMCS-functionalized Ti demonstrated better antibacterial property than the HAC-functionalized Ti since CMCS is bactericidal while HA only inhibits the adhesion of bacteria without killing them. Osteoblast attachment, as well as alkaline phosphatase (ALP) activity and calcium deposition were enhanced by the immobilized VEGF on the polysaccharide-grafted Ti. Thus, Ti substrates modified with polysaccharides conjugated with VEGF can promote osteoblast functions and concurrently reduce bacterial adhesion. Since VEGF is also known to enhance angiogenesis, the VEGF-polysaccharide functionalized substrates will have promising applications in the orthopedic field. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

Acetate production from oil under sulfate-reducing conditions in bioreactors injected with sulfate and nitrate.

PubMed

Callbeck, Cameron M; Agrawal, Akhil; Voordouw, Gerrit

2013-08-01

Oil production by water injection can cause souring in which sulfate in the injection water is reduced to sulfide by resident sulfate-reducing bacteria (SRB). Sulfate (2 mM) in medium injected at a rate of 1 pore volume per day into upflow bioreactors containing residual heavy oil from the Medicine Hat Glauconitic C field was nearly completely reduced to sulfide, and this was associated with the generation of 3 to 4 mM acetate. Inclusion of 4 mM nitrate inhibited souring for 60 days, after which complete sulfate reduction and associated acetate production were once again observed. Sulfate reduction was permanently inhibited when 100 mM nitrate was injected by the nitrite formed under these conditions. Pulsed injection of 4 or 100 mM nitrate inhibited sulfate reduction temporarily. Sulfate reduction resumed once nitrate injection was stopped and was associated with the production of acetate in all cases. The stoichiometry of acetate formation (3 to 4 mM formed per 2 mM sulfate reduced) is consistent with a mechanism in which oil alkanes and water are metabolized to acetate and hydrogen by fermentative and syntrophic bacteria (K. Zengler et al., Nature 401:266-269, 1999), with the hydrogen being used by SRB to reduce sulfate to sulfide. In support of this model, microbial community analyses by pyrosequencing indicated SRB of the genus Desulfovibrio, which use hydrogen but not acetate as an electron donor for sulfate reduction, to be a major community component. The model explains the high concentrations of acetate that are sometimes found in waters produced from water-injected oil fields.

Chemoenzymatic synthesis and structural characterization of 2-O-sulfated glucuronic acid-containing heparan sulfate hexasaccharides

PubMed Central

Hsieh, Po-Hung; Xu, Yongmei; Keire, David A; Liu, Jian

2014-01-01

Heparan sulfate and heparin are highly sulfated polysaccharides that consist of a repeating disaccharide unit of glucosamine and glucuronic or iduronic acid. The 2-O-sulfated iduronic acid (IdoA2S) residue is commonly found in heparan sulfate and heparin; however, 2-O-sulfated glucuronic acid (GlcA2S) is a less abundant monosaccharide (∼<5% of total saccharides). Here, we report the synthesis of three GlcA2S-containing hexasaccharides using a chemoenzymatic approach. For comparison purposes, additional IdoA2S-containing hexasaccharides were synthesized. Nuclear magnetic resonance analyses were performed to obtain full chemical shift assignments for the GlcA2S- and IdoA2S-hexasaccharides. These data show that GlcA2S is a more structurally rigid saccharide residue than IdoA2S. The antithrombin (AT) binding affinities of a GlcA2S- and an IdoA2S-hexasaccharide were determined by affinity co-electrophoresis. In contrast to IdoA2S-hexasaccharides, the GlcA2S-hexasaccharide does not bind to AT, confirming that the presence of IdoA2S is critically important for the anticoagulant activity. The availability of pure synthetic GlcA2S-containing oligosaccharides will allow the investigation of the structure and activity relationships of individual sites in heparin or heparan sulfate. PMID:24770491

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

Engineering of routes to heparin and related polysaccharides.

PubMed

Bhaskar, Ujjwal; Sterner, Eric; Hickey, Anne Marie; Onishi, Akihiro; Zhang, Fuming; Dordick, Jonathan S; Linhardt, Robert J

2012-01-01

Anticoagulant heparin has been shown to possess important biological functions that vary according to its fine structure. Variability within heparin's structure occurs owing to its biosynthesis and animal tissue-based recovery and adds another dimension to its complex polymeric structure. The structural variations in chain length and sulfation patterns mediate its interaction with many heparin-binding proteins, thereby eliciting complex biological responses. The advent of novel chemical and enzymatic approaches for polysaccharide synthesis coupled with high throughput combinatorial approaches for drug discovery have facilitated an increased effort to understand heparin's structure-activity relationships. An improved understanding would offer potential for new therapeutic development through the engineering of polysaccharides. Such a bioengineering approach requires the amalgamation of several different disciplines, including carbohydrate synthesis, applied enzymology, metabolic engineering, and process biochemistry.

Chondroitin Sulfate (CS) Lyases: Structure, Function and Application in Therapeutics.

PubMed

Rani, Aruna; Patel, Seema; Goyal, Arun

2018-01-01

Glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) are the chief natural polysaccharides which reside in biological tissues mainly in extracellular matrix. These CS along with adhesion molecules and growth factors are involved in central nervous system (CNS) development, cell progression and pathogenesis. The chondroitin lyases are the enzyme that degrade and alter the CS chains and hence modify various signalling pathways involving CS chains. These CS lyases are substrate specific, can precisely manipulate the CS polysaccharides and have various biotechnological, medical and therapeutic applications. These enzymes can be used to produce the unsaturated oligosaccharides, which have immune-modulatory, anti-inflammatory and neuroprotective properties. This review focuses on the major breakthrough of the chondroitin sulfate degrading enzymes, their structures and functioning mechanism. This also provides comprehensive information regarding production, purification, characterization of CS lyases and their major applications, both established as well as emerging ones such as neural development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Biphasic Role of Chondroitin Sulfate in Cardiac Differentiation of Embryonic Stem Cells through Inhibition of Wnt/β-Catenin Signaling

PubMed Central

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. PMID:24667694

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.

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

PubMed Central

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

2012-01-01

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

Structural characterization of fucosylated chondroitin sulfates from sea cucumbers Apostichopus japonicus and Actinopyga mauritiana.

PubMed

Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Tsvetkova, Eugenia A; Shashkov, Alexander S; Stonik, Valentin A; Nifantiev, Nikolay E; Usov, Anatolii I

2016-11-20

Two samples of fucosylated chondroitin sulfate (FCS), AJ and AM, were isolated from holothurian species Apostichopus japonicus and Actinopyga mauritiana, respectively. Purification of FCS was performed by ion exchange chromatography followed by gel filtration. Structure of the biopolymers was elucidated using chemical and NMR spectroscopic methods. Both polysaccharides were shown to contain a typical chondroitin core built up of repeating disaccharide units →3)-β-d-GalNAc-(1→4)-β-d-GlcA-(1→ and decorated by sulfate groups and α-l-Fuc branches. Two polysaccharides were different in pattern of sulfation of GalNAc and fucosyl branches connected to O-3 of GlcA. The ratio of GalNAc4S6S:GalNAc4S for AJ was about 2:1, whereas for AM this value was approximately 1:1. AJ contained Fucp2S4S and Fucp3S4S residues linked to O-3 of GlcA in a ratio of 3:1, while for AM this ratio was 1:4. Small portions of Fucp4S units attached to O-3 of GlcA were also found in both polysaccharides. Moreover, in a structure of AM the presence of Fucp3S residues linked to O-6 of GalNAc were determined using the data of NMR spectra. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interaction of antimicrobial peptides with bacterial polysaccharides from lung pathogens.

PubMed

Herasimenka, Yury; Benincasa, Monica; Mattiuzzo, Maura; Cescutti, Paola; Gennaro, Renato; Rizzo, Roberto

2005-07-01

The interaction of two cathelicidin antimicrobial peptides, LL-37 and SMAP-29, with three bacterial polysaccharides, respectively, produced by Pseudomonas aeruginosa, Burkholderia cepacia and Klebsiella pneumoniae, was investigated to identify possible mechanisms adopted by lung pathogens to escape the action of innate immunity effectors. In vitro assays indicated that the antibacterial activity of both peptides was inhibited to a variable extent by the three polysaccharides. Circular dichroism experiments showed that these induced an alpha-helical conformation in the two peptides, with the polysaccharides from K. pneumoniae and B. cepacia showing, respectively, the highest and the lowest effect. Fluorescence measurements also indicated the presence of peptide-polysaccharide interactions. A model is proposed in which the binding of peptides to the polysaccharide molecules induces, at low polysaccharide to peptide ratios, a higher order of aggregation, due to peptide-peptide interactions. Overall, these results suggest that binding of the peptides by the polysaccharides produced by lung pathogens can contribute to the impairment of peptide-based innate defenses of airway surface.

CHARACTERIZATION OF CELL WALL POLYSACCHARIDES OF THE COENCOCYTIC GREEN SEAWEED BRYOPSIS PLUMOSA (BRYOPSIDACEAE, CHLOROPHYTA) FROM THE ARGENTINE COAST(1).

PubMed

Ciancia, Marina; Alberghina, Josefina; Arata, Paula Ximena; Benavides, Hugo; Leliaert, Frederik; Verbruggen, Heroen; Estevez, Jose Manuel

2012-04-01

Bryopsis sp. from a restricted area of the rocky shore of Mar del Plata (Argentina) on the Atlantic coast was identified as Bryopsis plumosa (Hudson) C. Agardh (Bryopsidales, Chlorophyta) based on morphological characters and rbcL and tufA DNA barcodes. To analyze the cell wall polysaccharides of this seaweed, the major room temperature (B1) and 90°C (X1) water extracts were studied. By linkage analysis and NMR spectroscopy, the structure of a sulfated galactan was determined, and putative sulfated rhamnan structures and furanosidic nonsulfated arabinan structures were also found. By anion exchange chromatography of X1, a fraction (F4), comprising a sulfated galactan as major structure was isolated. Structural analysis showed a linear backbone constituted of 3-linked β-d-galactose units, partially sulfated on C-6 and partially substituted with pyruvic acid forming an acetal linked to O-4 and O-6. This galactan has common structural features with those of green seaweeds of the genus Codium (Bryopsidales, Chlorophyta), but some important differences were also found. This is the first report about the structure of the water-soluble polysaccharides biosynthesized by seaweeds of the genus Bryopsis. These sulfated galactans and rhamnans were in situ localized mostly in two layers, one close to the plasma membrane and the other close to the apoplast, leaving a middle amorphous, unstained cell wall zone. In addition, fibrillar polysaccharides, comprising (1→3)-β-d-xylans and cellulose, were obtained by treatment of the residue from the water extractions with an LiCl/DMSO solution at high temperature. These polymers were also localized in a bilayer arrangement. © 2012 Phycological Society of America.

The role of wine polysaccharides on salivary protein-tannin interaction: A molecular approach.

PubMed

Brandão, Elsa; Silva, Mafalda Santos; García-Estévez, Ignacio; Williams, Pascale; Mateus, Nuno; Doco, Thierry; de Freitas, Victor; Soares, Susana

2017-12-01

Polysaccharides are described to inhibit aggregation between food polyphenols and salivary proteins (SP) and may hence lead to astringency modulation. In this work, the effect of two wine polysaccharides (arabinogalactan proteins-AGPs and rhamnogalacturonan II- RGII) on SP-polyphenol interaction was evaluated. In general, both polysaccharides were effective to inhibit or reduce SP-polyphenol interaction and aggregation. They can act by two different mechanisms (ternary or competitive) depending on the SP-tannin pair. In the case of salivary P-B peptide, AGPs and RGII seem to act by a ternary mechanism, in which they surround this complex, enhancing its solubility. Concerning acidic proline-rich proteins (aPRPs), it was possible to observe both mechanisms, depending on the tannin and the polysaccharide involved. Overall, this work point out for a specific property of wine polysaccharides important to modulate this and other beverages and food astringency perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation of low molecular weight Sargassum fusiforme polysaccharide and its anticoagulant activity

NASA Astrophysics Data System (ADS)

Sun, Yuhao; Chen, Xiaolin; Liu, Song; Yu, Huahua; Li, Rongfeng; Wang, Xueqin; Qin, Yukun; Li, Pengcheng

2017-10-01

Heparin has been used as an anticoagulant drug for many years, but it has significant side effects. In the search for good substitutes, low molecular weight (MW) polysaccharides from Sargassum fusiforme have been examined and confirmed to possess biological activities. Here, S. fusiforme polysaccharides (SFP) were extracted and subjected to a hydrogen peroxide (H2O2) oxidation method for the preparation of low-MW SFP (LSFP). The effects of temperature, pH, and H2O2 concentration on the degradation process were also examined. Several LSFP of 36, 9, 5.7, and 2.7 kDa were obtained under different conditions, and their anticoagulant activities studied in vitro. The results showed that SFP and LSFP prolonged activated partial thromboplastin (APTT), prothrombin (PT) and thrombin times (TT) significantly, indicating that these low MW polysaccharides possessed anticoagulant activity in the intrinsic, extrinsic, and common coagulation pathways. As these effects were related to the MW of the polysaccharides in APTT and TT but not in PT, the contents of the monosaccharide fucose and sulfate and the polysaccharide MW could have exerted combined effects. The details of this mechanism require further verification.

A Repeating Sulfated Galactan Motif Resuscitates Dormant Micrococcus luteus Bacteria.

PubMed

Böttcher, Thomas; Szamosvári, Dávid; Clardy, Jon

2018-07-01

Only a small fraction of bacteria can autonomously initiate growth on agar plates. Nongrowing bacteria typically enter a metabolically inactive dormant state and require specific chemical trigger factors or signals to exit this state and to resume growth. Micrococcus luteus has become a model organism for this important yet poorly understood phenomenon. Only a few resuscitation signals have been described to date, and all of them are produced endogenously by bacterial species. We report the discovery of a novel type of resuscitation signal that allows M. luteus to grow on agar but not agarose plates. Fractionation of the agar polysaccharide complex and sulfation of agarose allowed us to identify the signal as highly sulfated saccharides found in agar or carrageenans. Purification of hydrolyzed κ-carrageenan ultimately led to the identification of the signal as a small fragment of a large linear polysaccharide, i.e., an oligosaccharide of five or more sugars with a repeating disaccharide motif containing d-galactose-4-sulfate (G4S) 1,4-linked to 3,6-anhydro-α-d-galactose (DA), G4S-(DA-G4S) n ≥2 IMPORTANCE Most environmental bacteria cannot initiate growth on agar plates, but they can flourish on the same plates once growth is initiated. While there are a number of names for and manifestations of this phenomenon, the underlying cause appears to be the requirement for a molecular signal indicating safe growing conditions. Micrococcus luteus has become a model organism for studying this growth initiation process, often called resuscitation, because of its apparent connection with the persistent or dormant form of Mycobacterium tuberculosis , an important human pathogen. In this report, we identify a highly sulfated saccharide from agar or carrageenans that robustly resuscitates dormant M. luteus on agarose plates. We identified and characterized the signal as a small repeating disaccharide motif. Our results indicate that signals inherent in or absent from the

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Biological functions of iduronic acid in chondroitin/dermatan sulfate.

PubMed

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

2013-05-01

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease. © 2013 The Authors Journal compilation © 2013 FEBS.

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

A highly regular fucan sulfate from the sea cucumber Stichopus horrens.

PubMed

Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Borodina, Elizaveta Yu; Nifantiev, Nikolay E; Usov, Anatolii I

2018-02-01

A highly regular fucan sulfate SHFS was isolated from the sea cucumber Stichopus horrens by extraction of the body walls in the presence of papain followed by ion-exchange and gel permeation chromatography. SHFS had MW of about 140 kDa and contained fucose and sulfate in the molar ratio of about 1:1. Chemical and NMR spectroscopic methods were applied for the structural characterization of the polysaccharide. SHFS was shown to have linear molecules built up of 3-linked α-l-fucopyranose 2-sulfate residues. Anticoagulant properties of SHFS were assessed in vitro in comparison with the LMW heparin (enoxaparin) and totally sulfated 3-linked α-l-fucan. SHFS was found to have the lowest activity, and hence, both sulfate groups at O-2 and O-4 of fucosyl units seem to be important for anticoagulant effect of sulfated homo-(1 → 3)-α-l-fucans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sequence determination of synthesized chondroitin sulfate dodecasaccharides.

PubMed

Shioiri, Tatsumasa; Tsuchimoto, Jun; Watanabe, Hideto; Sugiura, Nobuo

2016-06-01

Chondroitin sulfate (CS) is a linear acidic polysaccharide composed of repeating disaccharide units of glucuronic acid and N-acetyl-d-galactosamine. The polysaccharide is modified with sulfate groups at different positions by a variety of sulfotransferases. CS chains exhibit various biological and pathological functions by interacting with cytokines and growth factors and regulating their signal transduction. The fine structure of the CS chain defines its specific biological roles. However, structural analysis of CS has been restricted to disaccharide analysis, hampering the understanding of the structure-function relationship of CS chains. Here, we chemo-enzymatically synthesized CS dodecasaccharides having various sulfate modifications using a bioreactor system of bacterial chondroitin polymerase mutants and various CS sulfotransferases. We developed a sequencing method for CS chains using the CS dodecasaccharides. The method consists of (i) labeling a reducing end with 2-aminopyridine (PA), (ii) partial digestion of CS with testicular hyaluronidase, followed by separation of PA-conjugated oligosaccharides with different chain lengths, (iii) limited digestion of these oligosaccharides with chondroitin lyase AC II into disaccharides, followed by labeling with 2-aminobenzamide, (iv) CS disaccharide analysis using a dual-fluorescence HPLC system (reversed-phase ion-pair and ion-exchange chromatography), and (v) estimation of the composition by calculating individual disaccharide ratios. This CS chain sequencing allows characterization of CS-modifying enzymes and provides a useful tool toward understanding the structure-function relationship of CS chains. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Selenylation Modification of Degraded Polysaccharide from Enteromorpha prolifera and Its Biological Activities

NASA Astrophysics Data System (ADS)

Lv, Haitao; Duan, Ke; Shan, Hu

2018-04-01

Polysaccharide extracted from Enteromorpha prolifera possessed excellent biological activities, but its molecular weight was greatly high which influenced the activity. Organic Se had higher biological activities and was safer than inorganic Se species. In the present study, Enteromorpha polysaccharide was degraded to low molecular weight by free-radical degradation method of H2O2 and ascorbic acid. By single factor and orthogonal experiments, the optimal degradation conditions were reaction time of 2 h, reaction temperature of 50°C, H2O2/ascorbic acid (n/n=1:1) concentration of 15 mmol L-1, and solid-liquid ratio of 1:50 (g mL-1). Then, the degraded polysaccharide was chemically modified to obtain its selenide derivatives by nitric acid-sodium selenite method. The selenium content was 1137.29 μg g-1, while the content of sulfate radical had no change. IR spectra indicated that the selenite ester group was formed. Degraded polysaccharide selenide was characterized and evaluated for antioxidant, antifungal and antibacterial activities. The results showed that degraded polysaccharide selenide had strong capacity of scavenging DPPH and ·OH free radical. It had significant antibacterial properties for Escherichia coli, Bacillus subtilis and Salmonella spp., and it also had significant antifungal properties for Apple anthrax. The result ascertained degradation and selenylation modification did not change the main structure of polysaccharides. It was possible that free-radical degradation was an effective way for enhancing antioxidant activity to decrease molecular weight of polysaccharides.

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.

Selenizing astragalus polysaccharide attenuates PCV2 replication promotion caused by oxidative stress through autophagy inhibition via PI3K/AKT activation.

PubMed

Liu, Dandan; Xu, Jing; Qian, Gang; Hamid, Mohammed; Gan, Fang; Chen, Xingxiang; Huang, Kehe

2018-03-01

Our previous studies have shown that oxidative stress could promote the porcine circovirus type 2 (PCV2) replication, and astragalus polysaccharide (APS)/selenium could suppress PCV2 replication. However, whether selenizing astragalus polysaccharide (sAPS) provides protection against oxidative stress-induced PCV2 replication promotion and the mechanism involved remain unclear. The present study aimed to explore the mechanism of the PCV2 replication promotion induced by oxidative stress and a novel pharmacotherapeutic approach involving the regulation of autophagy of sAPS. Our results showed that H 2 O 2 promoted PCV2 replication via enhancing autophagy by using 3-methyladenine (3-MA) and autophagy-related gene 5 (ATG5) knockdown. Sodium selenite, APS, the mixture of sodium selenite and APS, and sAPS significantly inhibited H 2 O 2 -induced PCV2 replication promotion, respectively. Among these, sAPS exerted maximal inhibitory effect. sAPS could also significantly inhibit autophagy activated by H 2 O 2 and increase the Akt and mTOR phosphorylation. Moreover, LY294002, the specific phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor, significantly alleviated the effects of sAPS on autophagy and PCV2 replication. Taken together, we conclude that H 2 O 2 promotes PCV2 replication by inducing autophagy and sAPS attenuates the PCV2 replication promotion through autophagy inhibition via PI3K/AKT activation. Copyright © 2017 Elsevier B.V. All rights reserved.

Site-specific identification of heparan and chondroitin sulfate glycosaminoglycans in hybrid proteoglycans.

PubMed

Noborn, Fredrik; Gomez Toledo, Alejandro; Green, Anders; Nasir, Waqas; Sihlbom, Carina; Nilsson, Jonas; Larson, Göran

2016-10-03

Heparan sulfate (HS) and chondroitin sulfate (CS) are complex polysaccharides that regulate important biological pathways in virtually all metazoan organisms. The polysaccharides often display opposite effects on cell functions with HS and CS structural motifs presenting unique binding sites for specific ligands. Still, the mechanisms by which glycan biosynthesis generates complex HS and CS polysaccharides required for the regulation of mammalian physiology remain elusive. Here we present a glycoproteomic approach that identifies and differentiates between HS and CS attachment sites and provides identity to the core proteins. Glycopeptides were prepared from perlecan, a complex proteoglycan known to be substituted with both HS and CS chains, further digested with heparinase or chondroitinase ABC to reduce the HS and CS chain lengths respectively, and thereafter analyzed by nLC-MS/MS. This protocol enabled the identification of three consensus HS sites and one hybrid site, carrying either a HS or a CS chain. Inspection of the amino acid sequence at the hybrid attachment locus indicates that certain peptide motifs may encode for the chain type selection process. This analytical approach will become useful when addressing fundamental questions in basic biology specifically in elucidating the functional roles of site-specific glycosylations of proteoglycans.

Evaluation of free radicals scavenging and immunity-modulatory activities of Purslane polysaccharides.

PubMed

YouGuo, Chen; ZongJi, Shen; XiaoPing, Chen

2009-12-01

In this study, antioxidant and immunity-modulatory activities of Purslane polysaccharide were estimated. The results revealed that in a dose-dependent manner, Purslane polysaccharides could significantly scavenge superoxide anion, 1,1-diphenyl-2-picrylhydrazyl (DPPH(-)), nitric oxide and hydroxyl radicals. Furthermore, the Purslane polysaccharides could still effectively inhibit the red blood cell (RBC) haemolysis, and increase spleen, thymocyte T and B lymphocyte proliferation, it could be concluded that Purslane polysaccharides could be of considerable preventive and therapeutic significance to some free radical associated health problems such as ovarian cancer, by scavenging accumulating free radicals and enhancing immunity functions.

Preparation, characterization and pharmacokinetics of fluorescence labeled propylene glycol alginate sodium sulfate

NASA Astrophysics Data System (ADS)

Li, Pengli; Li, Chunxia; Xue, Yiting; Zhang, Yang; Liu, Hongbing; Zhao, Xia; Yu, Guangli; Guan, Huashi

2014-08-01

A rapid and sensitive fluorescence labeling method was developed and validated for the microanalysis of a sulfated polysaccharide drug,namely propylene glycol alginate sodium sulfate (PSS), in rat plasma. Fluorescein isothiocyanate (FITC) was selected to label PSS, and 1, 6-diaminohexane was used to link PSS and FITC in order to prepare FITC-labeled PSS (F-PSS) through a reductive amination reaction. F-PSS was identified by UV-Vis, FT-IR and 1H-NMR spectrum. The cell stability and cytotoxicity of F-PSS were tested in Madin-Darby canine kidney (MDCK) cells. The results indicated that the labeling efficiency of F-PSS was 0.522% ± 0.0248% and the absolute bioavailability was 8.39%. F-PSS was stable in MDCK cells without obvious cytotoxicity. The method was sensitive and reliable; it showed a good linearity, precision, recovery and stability. The FITC labeling method can be applied to investigating the absorption and metabolism of PSS and other polysaccharides in biological samples.

Molecular weight distribution of polysaccharides from edible seaweeds by high-performance size-exclusion chromatography (HPSEC).

PubMed

Gómez-Ordóñez, Eva; Jiménez-Escrig, Antonio; Rupérez, Pilar

2012-05-15

Biological properties of polysaccharides from seaweeds are related to their composition and structure. Many factors such as the kind of sugar, type of linkage or sulfate content of algal biopolymers exert an influence in the relationship between structure and function. Besides, the molecular weight (MW) also plays an important role. Thus, a simple, reliable and fast HPSEC method with refractive index detection was developed and optimized for the MW estimation of soluble algal polysaccharides. Chromatogram shape and repeatability of retention time was considerably improved when sodium nitrate was used instead of ultrapure water as mobile phase. Pullulan and dextran standards of different MW were used for method calibration and validation. Also, main polysaccharide standards from brown (alginate, fucoidan, laminaran) and red seaweeds (kappa- and iota-carrageenan) were used for quantification and method precision and accuracy. Relative standard deviation (RSD) of repeatability for retention time, peak areas and inter-day precision was below 0.7%, 2.5% and 2.6%, respectively, which indicated good repeatability and precision. Recoveries (96.3-109.8%) also showed its fairly good accuracy. Regarding linearity, main polysaccharide standards from brown or red seaweeds showed a highly satisfactory correlation coefficient (r>0.999). Moreover, a good sensitivity was shown, with corresponding limits of detection and quantitation in mg/mL of 0.05-0.21 and 0.16-0.31, respectively. The method was applied to the MW estimation of standard algal polysaccharides, as well as to the soluble polysaccharide fractions from the brown seaweed Saccharina latissima and the red Mastocarpus stellatus, respectively. Although distribution of molecular weight was broad, the good repeatability for retention time provided a good precision in MW estimation of polysaccharides. Water- and alkali-soluble fractions from S. latissima ranged from very high (>2400 kDa) to low MW compounds (<6 kDa); this high

Impact of clay minerals on sulfate-reducing activity in aquifers

USGS Publications Warehouse

Wong, D.; Suflita, J.M.; McKinley, J.P.; Krumholz, L.R.

2004-01-01

Previous studies have shown that sulfate-reduction activity occurs in a heterogeneous manner throughout the terrestrial subsurface. Low-activity regions are often observed in the presence of clay minerals. Here we report that clays inhibit sulfate reduction activity in sediments and in a pure culture of Desulfovibriovulgaris. Clay minerals including bentonite and kaolinite inhibited sulfate reduction by 70–90% in sediments. Intact clays and clay colloids or soluble components, capable of passing through a 0.2-µm filter, were also inhibitory to sulfate-reducing bacteria. Other adsorbent materials, including anion or cation exchangers and a zeolite, did not inhibit sulfate reduction in sediments, suggesting that the effect of clays was not due to their cation-exchange capacity. We observed a strong correlation between the Al2O3content of clays and their relative ability to inhibit sulfate reduction in sediments (r2 = 0.82). This suggested that inhibition might be a direct effect of Al3+ (aq) on the bacteria. We then tested pure aluminum oxide (Al2O3) and showed it to act in a similar manner to clay. As dissolved aluminum is known to be toxic to a variety of organisms at low concentrations, our results suggest that the effects of clay on sulfate-reducing bacteria may be directly due to aluminum. Thus, our experiments provide an explanation for the lack of sulfate-reduction activity in clay-rich regions and presents a mechanism for the effect.

Mixed layers of sodium caseinate + dextran sulfate: influence of order of addition to oil-water interface.

PubMed

Jourdain, Laureline S; Schmitt, Christophe; Leser, Martin E; Murray, Brent S; Dickinson, Eric

2009-09-01

We report on the interfacial properties of electrostatic complexes of protein (sodium caseinate) with a highly sulfated polysaccharide (dextran sulfate). Two routes were investigated for preparation of adsorbed layers at the n-tetradecane-water interface at pH = 6. Bilayers were made by the layer-by-layer deposition technique whereby polysaccharide was added to a previously established protein-stabilized interface. Mixed layers were made by the conventional one-step method in which soluble protein-polysaccharide complexes were adsorbed directly at the interface. Protein + polysaccharide systems gave a slower decay of interfacial tension and stronger dilatational viscoelastic properties than the protein alone, but there was no significant difference in dilatational properties between mixed layers and bilayers. Conversely, shear rheology experiments exhibited significant differences between the two kinds of interfacial layers, with the mixed system giving much stronger interfacial films than the bilayer system, i.e., shear viscosities and moduli at least an order of magnitude higher. The film shear viscoelasticity was further enhanced by acidification of the biopolymer mixture to pH = 2 prior to interface formation. Taken together, these measurements provide insight into the origin of previously reported differences in stability properties of oil-in-water emulsions made by the bilayer and mixed layer approaches. Addition of a proteolytic enzyme (trypsin) to both types of interfaces led to a significant increase in the elastic modulus of the film, suggesting that the enzyme was adsorbed at the interface via complexation with dextran sulfate. Overall, this study has confirmed the potential of shear rheology as a highly sensitive probe of associative electrostatic interactions and interfacial structure in mixed biopolymer layers.

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

Boreal pollen contain ice-nucleating as well as ice-binding ‘antifreeze’ polysaccharides

NASA Astrophysics Data System (ADS)

Dreischmeier, Katharina; Budke, Carsten; Wiehemeier, Lars; Kottke, Tilman; Koop, Thomas

2017-02-01

Ice nucleation and growth is an important and widespread environmental process. Accordingly, nature has developed means to either promote or inhibit ice crystal formation, for example ice-nucleating proteins in bacteria or ice-binding antifreeze proteins in polar fish. Recently, it was found that birch pollen release ice-nucleating macromolecules when suspended in water. Here we show that birch pollen washing water exhibits also ice-binding properties such as ice shaping and ice recrystallization inhibition, similar to antifreeze proteins. We present spectroscopic evidence that both the ice-nucleating as well as the ice-binding molecules are polysaccharides bearing carboxylate groups. The spectra suggest that both polysaccharides consist of very similar chemical moieties, but centrifugal filtration indicates differences in molecular size: ice nucleation occurs only in the supernatant of a 100 kDa filter, while ice shaping is strongly enhanced in the filtrate. This finding may suggest that the larger ice-nucleating polysaccharides consist of clusters of the smaller ice-binding polysaccharides, or that the latter are fragments of the ice-nucleating polysaccharides. Finally, similar polysaccharides released from pine and alder pollen also display both ice-nucleating as well as ice-binding ability, suggesting a common mechanism of interaction with ice among several boreal pollen with implications for atmospheric processes and antifreeze protection.

Boreal pollen contain ice-nucleating as well as ice-binding ‘antifreeze’ polysaccharides

PubMed Central

Dreischmeier, Katharina; Budke, Carsten; Wiehemeier, Lars; Kottke, Tilman; Koop, Thomas

2017-01-01

Ice nucleation and growth is an important and widespread environmental process. Accordingly, nature has developed means to either promote or inhibit ice crystal formation, for example ice-nucleating proteins in bacteria or ice-binding antifreeze proteins in polar fish. Recently, it was found that birch pollen release ice-nucleating macromolecules when suspended in water. Here we show that birch pollen washing water exhibits also ice-binding properties such as ice shaping and ice recrystallization inhibition, similar to antifreeze proteins. We present spectroscopic evidence that both the ice-nucleating as well as the ice-binding molecules are polysaccharides bearing carboxylate groups. The spectra suggest that both polysaccharides consist of very similar chemical moieties, but centrifugal filtration indicates differences in molecular size: ice nucleation occurs only in the supernatant of a 100 kDa filter, while ice shaping is strongly enhanced in the filtrate. This finding may suggest that the larger ice-nucleating polysaccharides consist of clusters of the smaller ice-binding polysaccharides, or that the latter are fragments of the ice-nucleating polysaccharides. Finally, similar polysaccharides released from pine and alder pollen also display both ice-nucleating as well as ice-binding ability, suggesting a common mechanism of interaction with ice among several boreal pollen with implications for atmospheric processes and antifreeze protection. PMID:28157236

Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells.

PubMed

Feyerabend, Thorsten B; Li, Jin-Ping; Lindahl, Ulf; Rodewald, Hans-Reimer

2006-04-01

Biosynthesis of heparin, a mast cell-derived glycosaminoglycan with widespread importance in medicine, has not been fully elucidated. In biosynthesis of heparan sulfate (HS), a structurally related polysaccharide, HS glucuronyl C5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) residues. We have generated Hsepi-null mouse mutant mast cells, and we show that the same enzyme catalyzes the generation of IdoA in heparin and that 'heparin' lacking IdoA shows a distorted O-sulfation pattern.

Isolation and chemical characterization of dissolved and particulate polysaccharides in Mikawa Bay

NASA Astrophysics Data System (ADS)

Sakugawa, Hiroshi; Handa, Nobuhiko

1985-05-01

Isolation and chemical elucidation of dissolved and particulate polysaccharides in seawater were conducted. The water samples were collected in Mikawa Bay, Japan during a red tide bloom of the dinoflagellate, Prorocentrum minimum. Dissolved polysaccharides were concentrated from 5-101 of seawater with dialysis followed by separation by gel flitration, and isolation by ethanol precipitation. A heteropolysaccharide consisting of glucose, galactose, mannose, xylose, arabinose, fucose and rhamnose and a glucan were isolated from the polysaccharide component having a molecular weight more than 4,000 Dalton and were characterized by several chemical analyses. The heteropolysaccharide is a mucilaginous polysaccharide having a highly branched structure and a molecular weight of 10 4-5 × 10 6 Daltons and probably contains a sulfate half ester: the glucan is a polysaccharide with β-1,3- and 1,6-linkages (chrysolaminaran type). Concentrations of these were respectively ca. 20 and 67 μg l -1 at 1 m, and 2 and 26 μg l -1 at 6 m. A similar heteropolysaccharide was found in the boiling water extract of the particulate matter, while β-glucan was isolated in a much less purified form than the seawater β-glucan. In addition, a large amount of β-1,4 glucan was found in the strong alkali extract of the particulate matter, indicating that this glucan must be a cell wall polysaccharide derived from phytoplankton. These results strongly suggest that the heteropolysaccharide and chrysolaminaran type polysaccharide dissolved in seawater were derived from water soluble carbohydrates of phytoplankton through extracellular release or cell lysis.

Protective effect of polysaccharides from Sargassum horneri against oxidative stress in RAW264.7 cells.

PubMed

Wen, Zheng-Shun; Liu, Li-Jia; OuYang, Xiao-Kun; Qu, You-Le; Chen, Yin; Ding, Guo-Fang

2014-07-01

This study was designed to investigate chemical composition and the protective effects of polysaccharides isolated from Sargassum horneri against hydrogen peroxide (H2O2)-induced oxidative injury in RAW264.7 cells. Results showed that isolated polysaccharides (SHSc) and the major fractions (SHS1, SHS0.5) contained sulfate ester, and SHS1 was high fucose-containing sulfated polysaccharide. After preincubation with three isolated polysaccharides, RAW264.7 cells viability were significantly restored and decreased in cellular LDH release (P<0.05). SHS1 and SHS0.5 decreased intracellular ROS level, intracellular NO and malonic dialdehyde (MDA) level (P<0.05), restoring activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) (P<0.05), decreasing inducible nitric oxide synthase (iNOS) (P<0.05). Moreover, preincubation of SHS1 with RAW264.7 cells resulted in the increase of the gene expression level of endogenous antioxidant enzymes such as MnSOD and GSH-Px (P<0.05). These results clearly showed that SHSc and its fractions could attenuate H2O2-induced stress injury in RAW264.7 cells, and a similar efficiency in protecting RAW264.7 cells against H2O2-induced oxidative injury between SHS1 and Vitamin C. Taken together, our findings suggested that SHS1 can effectively protect RAW264.7 cells against oxidative stress by H2O2, which might be used as a potential natural antioxidant in the functional food and pharmaceutical industries. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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

PubMed

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

2015-06-01

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

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potential antidiabetic activity of extracellular polysaccharides in submerged fermentation culture of Coriolus versicolor LH1.

PubMed

Yang, John Powen; Hsu, Taihao; Lin, Fangyi; Hsu, Wenkuang; Chen, Yucheng

2012-09-01

The separation and purification of extracellular polysaccharides from Coriolus versicolor LH1 were investigated along with their α-glucosidase inhibition properties. Three polysaccharide fractions (ePS-F2-1, ePS-F3-1, and ePS-F4-1) were separated from the culture medium of LH1 using a DEAE anion-exchange column and a Sephadex™ G-50 gel filtration column. Their chemical compositions was determined. On the basis of an α-glucosidase inhibition assay, the enzyme inhibition activities of ePS-F2-1, ePS-F3-1, and ePS-F4-1 were investigated. Among these, ePS-F4-1 had the highest enzyme inhibition effects on α-glucosidase. According to the results of the chemical component analysis, ePS-F3-1 and ePS-F4-1 are the polysaccharides which are combined with triterpenoides, and ePS-F2-1 is complexed with proteins and triterpenoides. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ferrous Iron Oxidation by Thiobacillus ferrooxidans: Inhibition with Benzoic Acid, Sorbic Acid, and Sodium Lauryl Sulfate

PubMed Central

Onysko, Steven J.; Kleinmann, Robert L. P.; Erickson, Patricia M.

1984-01-01

Benzoic acid, sorbic acid, and sodium lauryl sulfate at low concentrations (5 to 10 mg/liter) each effectively inhibited bacterial oxidation of ferrous iron in batch cultures of Thiobacillus ferrooxidans. The rate of chemical oxidation of ferrous iron in low-pH, sterile batch reactors was not substantially affected at the tested concentrations (5 to 50 mg/liter) of any of the compounds. PMID:16346592

Tandem Mass Spectrometry of Heparan Sulfate Negative Ions: Sulfate Loss Patterns and Chemical Modification Methods for Improvement of Product Ion Profiles

NASA Astrophysics Data System (ADS)

Shi, Xiaofeng; Huang, Yu; Mao, Yang; Naimy, Hicham; Zaia, Joseph

2012-09-01

Heparan sulfate (HS) is a polysaccharide modified with sulfation, acetylation, and epimerization that enable its binding with protein ligands and regulation of important biological processes. Tandem mass spectrometry has been employed to sequence linear biomolecules e.g., proteins and peptides. However, its application in structural characterization of HS is limited due to the neutral loss of sulfate (SO3) during collisional induced dissociation (CID). In this report, we studied the dissociation patterns of HS disaccharides and demonstrate that the N-sulfate (N-S) bond is especially facile during CID. We identified factors that influence the propensities of such losses from precursor ions and proposed a Free Proton Index (FPI) to help select ions that are able to produce meaningful backbone dissociations. We then investigated the thermodynamics and kinetics of SO3 loss from sulfates that are protonated, deprotonated, and metal-adducted using density functional theory computations. The calculations showed that sulfate loss from a protonated site was much more facile than that from a deprotonated or metal-adducted site. Further, the loss of SO3 from N-sulfate was energetically favored by 3-8 kcal/mol in transition states relative to O-sulfates, making it more prone to this process by a substantial factor. In order to reduce the FPI, representing the number of labile sulfates in HS native chains and oligosaccharides, we developed a series of chemical modifications to selectively replace the N-sulfates of the glucosamine with deuterated acetyl group. These modifications effectively reduced the sulfate density on the HS oligosaccharides and generated considerably more backbone dissociation using on-line LC/tandem MS.

Antiviral activity of polysaccharide extract from Laminaria japonica against respiratory syncytial virus.

PubMed

Cao, Yin-Guang; Hao, Yu; Li, Zhi-Hui; Liu, Shun-Tao; Wang, Le-Xin

2016-12-01

This study was designed to investigate the inhibition activity of polysaccharide extract from Laminaria japonica against RSV. The polysaccharide from Laminaria japonica was isolated by ethanol precipitation. HEK293 cells were infected with RVS, and the antiviral activity of polysaccharide extract against RSV in host cells was tested. By using ELISA and western blot assay, the expression level of IFN-α and IRF3 and their functional roles in polysaccharide-mediated antiviral activity against RSV were investigated. The polysaccharide extract from Laminaria japonica had low toxicity to HEK293 cell. The TC50 to HEK293 cells was up to 1.76mg/mL. Furthermore, the EC50 of polysaccharide extract to RSV was 5.27μg/mL, and TI was 334. The polysaccharide extract improved IRF-3 expression which promoted the level of IFN-α. Polysaccharide extract from Laminaria japonica elicits antiviral activity against RSV by up-regulation of IRF3 signaling-mediated IFN-α production. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Enhanced Reduction of Helicobacter pylori Load in Precolonized Mice Treated with Combined Famotidine and Urease-Binding Polysaccharides

PubMed Central

Icatlo, Faustino C.; Kimura, Nobutake; Goshima, Hideo; Kodama, Yoshikatsu

2000-01-01

The present study investigated the effect of a model urease-binding polysaccharide in combination with a histamine H2 receptor antagonist on Helicobacter pylori colonization in vivo. Euthymic hairless mice were treated daily with dextran sulfate via drinking water and/or famotidine via intragastric gavage starting at 1 week postchallenge with a CagA+ VacA+ (type 1) strain of H. pylori. Treatment of precolonized mice for 2 weeks with dextran sulfate combined with famotidine yielded a group mean bacterial load (per 100 mg of gastric tissue) of log10 1.04 CFU, which was significantly lower than those of the famotidine (log10 3.35 CFU, P < 0.01) and dextran sulfate (log10 2.45 CFU, P < 0.05) monotherapy groups and the infected nontreated group (log10 3.64 CFU, P < 0.01). Eradication was achieved after 2 weeks of treatment in 50% or more of the test mice using drug combinations (1 or 2 weeks of famotidine plus 2 weeks of dextran sulfate) versus none in the monotherapy and positive control groups. The enhanced activity of the drug combination may be related to the daily pattern of transient acid suppression by famotidine inducing periodic bacterial convergence to superficial mucus sites penetrated by dextran sulfate from the lumen. Increased urease-dextran sulfate avidity was observed in vitro in the presence of famotidine and may partly account for the enhanced activity. With potential utility in abbreviating treatment time and eradication of antibiotic-resistant strains, the use of urease-targeted polysaccharides concurrently with a gastric acid inhibitor warrants consideration as an additional component of the standard multidrug chemotherapy of H. pylori infection. PMID:10952600

Anti-inflammatory and angiogenic activity of polysaccharide extract obtained from Tibetan kefir.

PubMed

Prado, Maria Rosa Machado; Boller, Christian; Zibetti, Rosiane Guetter Mello; de Souza, Daiany; Pedroso, Luciana Lopes; Soccol, Carlos Ricardo

2016-11-01

The search for new bioactive molecules is a driving force for research pharmaceutical industries, especially those molecules obtained from fermentation. The molecules possessing angiogenic and anti-inflammatory attributes have attracted attention and are the focus of this study. Angiogenic activity from kefir polysaccharide extract, via chorioallantoic membrane assay, exhibited a pro-angiogenic effect compared with vascular endothelial factor (pro-angiogenic) and hydrocortisone (anti-angiogenic) activity as standards with an EC50 of 192ng/mL. In terms of anti-inflammatory activity determined via hyaluronidase enzyme assay, kefir polysaccharide extract inhibited the enzyme with a minimal activity of 2.08mg/mL and a maximum activity of 2.57mg/mL. For pharmaceutical purposes, kefir polysaccharide extract is considered to be safe because it does not inhibit VERO cells in cytotoxicity assays. Copyright © 2016 Elsevier Inc. All rights reserved.

Selective Synthesis and Biological Evaluation of Sulfate-Conjugated Resveratrol Metabolites

PubMed Central

Hoshino, Juma; Park, Eun-Jung; Kondratyuk, Tamara P.; Marler, Laura; Pezzuto, John M.; van Breemen, Richard B.; Mo, Shunyan; Li, Yongchao; Cushman, Mark

2010-01-01

Five resveratrol sulfate metabolites were synthesized and assessed for activities known to be mediated by resveratrol: inhibition of tumor necrosis factor (TNF)-α-induced NFκB activity, cylcooxygenases (COX-1 and COX-2), aromatase, nitric oxide production in endotoxin-stimulated macrophages, and proliferation of KB or MCF7 cells, induction of quinone reductase 1 (QR1), accumulation in the sub-G1 phase of the cell cycle, and quenching of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. Two metabolites showed activity in these assays; the 3-sulfate exhibited QR1 induction, DPPH free radical scavenging, and COX-1 and COX-2 inhibitory activities, and the 4′-sulfate inhibited NFκB induction, as well as COX-1 and COX-2 activities. Resveratrol, as well as its 3′-sulfate and 4-sulfate, inhibit NO production by NO scavenging and down-regulation of iNOS expression in RAW 264.7 cells. Resveratrol sulfates displayed low antiproliferative activity and negligible uptake in MCF7 cells. PMID:20527891

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

Microwave-assisted extraction and pharmacological evaluation of polysaccharides from Posidonia oceanica.

PubMed

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

2017-10-01

Microwave-assisted extraction was employed for the isolation of polysaccharides from Posidonia oceanica (PPO). The extracting parameters were optimized adopting response surface methodology. The highest polysaccharide yield (2.55 ± 0.09%), which is in concordance with the predicted value (2.76%), was obtained under the following conditions: extraction time 60 s, liquid-solid ratio of 50:1 (mL/g) and power of 800 W. This polysaccharide, with molecular weight of 524 KDa, characterized by gas chromatography-mass spectrometry showed that PPO was mainly composed of galactose, glucose, and arabinose with molar percentages 25.38, 24.37, and 21.64%, respectively. The pharmacological evaluation of PPO using animal models at the dose of 100 mg/kg indicated a significant anti-inflammatory activity with a percentage of inhibition of edema of 54.65% and a significant antinociceptive activity with 78.91% inhibition of writhing for peripheral analgesic activity and an increase in the hot plate reaction time for central analgesic activity.

Antiviral Potential of Algae Polysaccharides Isolated from Marine Sources: A Review.

PubMed

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.

[In vitro studies on antioxidant and antimicrobial activities of polysaccharide from Lycoris aurea].

PubMed

Ru, Qiao-Mei; Pei, Zhen-Ming; Zheng, Hai-Lei

2008-10-01

To study the preliminary antioxidant and antimicrobial activities of polysaccharide extracted from Lycoris aurea. The scavenging activities of the polysaccharide in vitro on superoxide radical (O2-*), hydroxyl radical (*OH), alkyl radical (R*) and hydrogen peroxide (H2O2) were investigated by modified chemical systems. Meanwhile, the antimicrobial activities were tested using paper-discagar diffusion method. In general, the antioxidant activities of the polysaccharide were lower compared with Vc. However, the scavenging effects to *OH and H2O2 were parallel to Vc. Meanwhile, polysaccharide from Lycoris aurea had strong antimicrobial activities against Micrococcus luteus, Bacillus pumilus and Staphylococcus aureus. The polysaccharide extracted from L. aurea can scavenge *OH and H2O2 effectively and inhibit Gram-positive bacterias.

Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis.

PubMed

Sun, Xin-Zhi; Liao, Ying; Li, Wei; Guo, Li-Mei

2017-06-01

Ganoderma lucidum polysaccharides have protective effects against apoptosis in neurons exposed to ischemia/reperfusion injury, but the mechanisms are unclear. The goal of this study was to investigate the underlying mechanisms of the effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Hydrogen peroxide (H 2 O 2 ) was used to induce apoptosis in cultured cerebellar granule cells. In these cells, ganoderma lucidum polysaccharides remarkably suppressed H 2 O 2 -induced apoptosis, decreased expression of caspase-3, Bax and Bim and increased that of Bcl-2. These findings suggested that ganoderma lucidum polysaccharides regulate expression of apoptosis-associated proteins, inhibit oxidative stress-induced neuronal apoptosis and, therefore, have significant neuroprotective effects.

Sealing effect of a polysaccharide nanosheet for murine cecal puncture.

PubMed

Fujie, Toshinori; Kinoshita, Manabu; Shono, Satoshi; Saito, Akihiro; Okamura, Yosuke; Saitoh, Daizoh; Takeoka, Shinji

2010-07-01

Recent developments in nanobiotechnology have led us to develop a method of producing a free-standing polymer nanosheet composed of polysaccharides (ie, polysaccharide nanosheet) with a thickness of tens of nanometers. Owing to its enormous aspect ratio, the polysaccharide nanosheet is semi-absorbent and has a physical adhesive strength 7.5-fold greater than that of conventional films of >1 microm thickness. Herein, we have investigated the therapeutic sealing effect of this polysaccharide nanosheet on murine cecal puncture as a wound dressing material. Murine cecum was punctured and then overlapped with the polysaccharide nanosheet. Thereafter, we evaluated its sealing effect on bacterial peritonitis as well as the protection offered by the polysaccharide nanosheet against bacterial permeability using an in vitro transmembrane assay. The 39-nm-thick polysaccharide nanosheet overlapped tightly the perforated cecum. No adhering agents were required because of the ability of the polysaccharide nanosheet to adhere to the tissue surface by physical adsorption (eg, van der Waals interaction). Sealing the perforated cecum with the polysaccharide nanosheet increased survival rate without postoperative adhesion by comparison with untreated mice (90 vs 30%; P < .01). These data were supported by the improvement in peritonitis related to bacterial counts, white blood cell counts, and the serum tumor necrosis factor level. Moreover, using an in vitro transmembrane assay, we showed that the polysaccharide nanosheet inhibited effectively bacterial penetration. We have demonstrated the potential clinical benefits of the nanosheet-type biomaterial that can be used for repairing a cecal colotomy without chemical bonding agents. Copyright 2010 Mosby, Inc. All rights reserved.

Synthesis of the oligosaccharides related to branching sites of fucosylated chondroitin sulfates from sea cucumbers.

PubMed

Ustyuzhanina, Nadezhda E; Fomitskaya, Polina A; Gerbst, Alexey G; Dmitrenok, Andrey S; Nifantiev, Nikolay E

2015-02-02

Natural anionic polysaccharides fucosylated chondroitin sulfates (FCS) from sea cucumbers attract great attention nowadays due to their ability to influence various biological processes, such as blood coagulation, thrombosis, angiogenesis, inflammation, bacterial and viral adhesion. To determine pharmacophore fragments in FCS we have started systematic synthesis of oligosaccharides with well-defined structure related to various fragments of these polysaccharides. In this communication, the synthesis of non-sulfated and selectively O-sulfated di- and trisaccharides structurally related to branching sites of FCS is described. The target compounds are built up of propyl β-d-glucuronic acid residue bearing at O-3 α-l-fucosyl or α-l-fucosyl-(1→3)-α-l-fucosyl substituents. O-Sulfation pattern in the fucose units of the synthetic targets was selected according to the known to date holothurian FCS structures. Stereospecific α-glycoside bond formation was achieved using 2-O-benzyl-3,4-di-O-chloroacetyl-α-l-fucosyl trichloroacetimidate as a donor. Stereochemical outcome of the glycosylation was explained by the remote participation of the chloroacetyl groups with the formation of the stabilized glycosyl cations, which could be attacked by the glycosyl acceptor only from the α-side. The experimental results were in good agreement with the SCF/MP2 calculated energies of such participation. The synthesized oligosaccharides are regarded as model compounds for the determination of a structure-activity relationship in FCS.

Synthesis of the Oligosaccharides Related to Branching Sites of Fucosylated Chondroitin Sulfates from Sea Cucumbers

PubMed Central

Ustyuzhanina, Nadezhda E.; Fomitskaya, Polina A.; Gerbst, Alexey G.; Dmitrenok, Andrey S.; Nifantiev, Nikolay E.

2015-01-01

Natural anionic polysaccharides fucosylated chondroitin sulfates (FCS) from sea cucumbers attract great attention nowadays due to their ability to influence various biological processes, such as blood coagulation, thrombosis, angiogenesis, inflammation, bacterial and viral adhesion. To determine pharmacophore fragments in FCS we have started systematic synthesis of oligosaccharides with well-defined structure related to various fragments of these polysaccharides. In this communication, the synthesis of non-sulfated and selectively O-sulfated di- and trisaccharides structurally related to branching sites of FCS is described. The target compounds are built up of propyl β-d-glucuronic acid residue bearing at O-3 α-l-fucosyl or α-l-fucosyl-(1→3)-α-l-fucosyl substituents. O-Sulfation pattern in the fucose units of the synthetic targets was selected according to the known to date holothurian FCS structures. Stereospecific α-glycoside bond formation was achieved using 2-O-benzyl-3,4-di-O-chloroacetyl-α-l-fucosyl trichloroacetimidate as a donor. Stereochemical outcome of the glycosylation was explained by the remote participation of the chloroacetyl groups with the formation of the stabilized glycosyl cations, which could be attacked by the glycosyl acceptor only from the α-side. The experimental results were in good agreement with the SCF/MP2 calculated energies of such participation. The synthesized oligosaccharides are regarded as model compounds for the determination of a structure-activity relationship in FCS. PMID:25648510

2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall Polysaccharide Fucosylation

PubMed Central

Wallace, Ian S.

2015-01-01

The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall polysaccharides and other plant glycans, including the hemicellulose xyloglucan, pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II), arabinogalactan proteins, and N-linked glycans. Mutations compromising the biosynthesis of many plant cell wall polysaccharides are lethal, and as a result, small molecule inhibitors of plant cell wall polysaccharide biosynthesis have been developed because these molecules can be applied at defined concentrations and developmental stages. In this study, we characterize novel small molecule inhibitors of plant fucosylation. 2-fluoro-L-fucose (2F-Fuc) analogs caused severe growth phenotypes when applied to Arabidopsis seedlings, including reduced root growth and altered root morphology. These phenotypic defects were dependent upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule. The L-Fuc content of cell wall matrix polysaccharides was reduced in plants treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of L-Fuc into these polysaccharides. Additionally, phenotypic defects induced by 2F-Fuc treatment could be partially relieved by the exogenous application of boric acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. Overall, the results presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of plant cellular fucosylation events, and potentially suggest that other 2-fluorinated monosaccharides could serve as useful chemical probes for the inhibition of cell wall polysaccharide biosynthesis. PMID:26414071

The role of novel chitin-like polysaccharides in Alzheimer disease.

PubMed

Castellani, Rudy J; Perry, George; Smith, Mark A

2007-12-01

While controversy over the role of carbohydrates in amyloidosis has existed since the initial recognition of amyloid, current understanding of the role of polysaccharides in the pathogenesis of amyloid deposition of Alzheimer disease and other amyloidoses is limited to studies of glyco-conjugates such as heparin sulfate proteoglycan. We hypothesized that polysaccharides may play a broader role in light of 1) the impaired glucose utilization in Alzheimer disease; 2) the demonstration of amylose in the Alzheimer disease brain; 3) the role of amyloid in Alzheimer disease pathogenesis. Specifically, as with glucose polymers (amyloid), we wanted to explore whether glucosamine polymers such as chitin were being synthesized and deposited as a result of impaired glucose utilization and aberrant hexosamine pathway activation. To this end, using calcofluor histochemistry, we recently demonstrated that amyloid plaques and blood vessels affected by amyloid angiopathy in subjects with sporadic and familial Alzheimer disease elicit chitin-type characteristics. Since chitin is a highly insoluble molecule and a substrate for glycan-protein interactions, chitin-like polysaccharides within the Alzheimer disease brain could provide a scaffolding for amyloid-beta deposition. As such, glucosamine may facilitate the process of amyloidosis, and /or provide neuroprotection in the Alzheimer disease brain.

A sulfated alpha-L-fucan from sea cucumber.

PubMed

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

1994-03-04

A purified sulfated alpha-L-fucan from the sea cucumber body wall was studied, before and after almost complete desulfation, using methylation analysis and NMR spectroscopy. NMR analysis indicates that 2,4-di-O-sulfo-L-fucopyranose and unsubstituted fucopyranose are present in equal proportions, and that 2-O-sulfo-L-fucopyranose is present in twice that proportion. There is some NMR evidence that a regular repeating sequence of four residues comprises most or all of the polysaccharide chain.

Homologous overexpression of rfaH in E. coli K4 improves the production of chondroitin-like capsular polysaccharide

PubMed Central

2013-01-01

Background Glycosaminoglycans, such as hyaluronic acid, heparin, and chondroitin sulfate, are among the top ranked products in industrial biotechnology for biomedical applications, with a growing world market of billion dollars per year. Recently a remarkable progress has been made in the development of tailor-made strains as sources for the manufacturing of such products. The genetic modification of E. coli K4, a natural producer of chondroitin sulfate precursor, is challenging considering the lack of detailed information on its genome, as well as its mobilome. Chondroitin sulfate is currently used as nutraceutical for the treatment of osteoarthritis, and several new therapeutic applications, spanning from the development of skin substitutes to live attenuated vaccines, are under evaluation. Results E. coli K4 was used as host for the overexpression of RfaH, a positive regulator that controls expression of the polysaccharide biosynthesis genes and other genes necessary for the virulence of E. coli K4. Various engineering strategies were compared to investigate different types of expression systems (plasmid vs integrative cassettes) and integration sites (genome vs endogenous mobile element). All strains analysed in shake flasks on different media showed a capsular polysaccharide production improved by 40 to 140%, compared to the wild type, with respect to the final product titer. A DO-stat fed-batch process on the 2L scale was also developed for the best performing integrative strain, EcK4r3, yielding 5.3 g∙L-1 of K4 polysaccharide. The effect of rfaH overexpression in EcK4r3 affected the production of lipopolysaccharide and the expression of genes involved in the polysaccharide biosynthesis pathway (kfoC and kfoA), as expected. An alteration of cellular metabolism was revealed by changes of intracellular pools of UDP-sugars which are used as precursors for polysaccharide biosynthesis. Conclusions The present study describes the identification of a gene target

Homologous overexpression of RfaH in E. coli K4 improves the production of chondroitin-like capsular polysaccharide.

PubMed

Cimini, Donatella; De Rosa, Mario; Carlino, Elisabetta; Ruggiero, Alessandro; Schiraldi, Chiara

2013-05-09

Glycosaminoglycans, such as hyaluronic acid, heparin, and chondroitin sulfate, are among the top ranked products in industrial biotechnology for biomedical applications, with a growing world market of billion dollars per year. Recently a remarkable progress has been made in the development of tailor-made strains as sources for the manufacturing of such products. The genetic modification of E. coli K4, a natural producer of chondroitin sulfate precursor, is challenging considering the lack of detailed information on its genome, as well as its mobilome. Chondroitin sulfate is currently used as nutraceutical for the treatment of osteoarthritis, and several new therapeutic applications, spanning from the development of skin substitutes to live attenuated vaccines, are under evaluation. E. coli K4 was used as host for the overexpression of RfaH, a positive regulator that controls expression of the polysaccharide biosynthesis genes and other genes necessary for the virulence of E. coli K4. Various engineering strategies were compared to investigate different types of expression systems (plasmid vs integrative cassettes) and integration sites (genome vs endogenous mobile element). All strains analysed in shake flasks on different media showed a capsular polysaccharide production improved by 40 to 140%, compared to the wild type, with respect to the final product titer. A DO-stat fed-batch process on the 2L scale was also developed for the best performing integrative strain, EcK4r3, yielding 5.3 g ∙ L(-1) of K4 polysaccharide. The effect of rfaH overexpression in EcK4r3 affected the production of lipopolysaccharide and the expression of genes involved in the polysaccharide biosynthesis pathway (kfoC and kfoA), as expected. An alteration of cellular metabolism was revealed by changes of intracellular pools of UDP-sugars which are used as precursors for polysaccharide biosynthesis. The present study describes the identification of a gene target and the application of a

Acidic Polysaccharide Extracts from Gastrodia Rhizomes Suppress the Atherosclerosis Risk Index through Inhibition of the Serum Cholesterol Composition in Sprague Dawley Rats Fed a High-Fat Diet

PubMed Central

Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

2012-01-01

Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels. PMID:22408412

Acidic polysaccharide extracts from Gastrodia Rhizomes suppress the atherosclerosis risk index through inhibition of the serum cholesterol composition in Sprague Dawley rats fed a high-fat diet.

PubMed

Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

2012-01-01

Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels.

Characterizations and hepatoprotective effect of polysaccharides from Mori Fructus in rats with alcoholic-induced liver injury.

PubMed

Zhou, Xin; Deng, Qingfang; Chen, Huaguo; Hu, Enming; Zhao, Chao; Gong, Xiaojian

2017-09-01

Crude polysaccharides of Mori Fructus (MFPs) were found to have anti-inflammatory antioxidant, and immuno-enhancing activities. However, the structure of the polysaccharides was ambiguous and its holistic hepatic protection evaluation was defective. This study was conducted to illustrate the characterization of MFPs, and evaluate its hepatoprotective activities. The results found that MFPs contained 67.93±1.18% carbohydrates, 31.03±0.54% uronic acid, and little protein and sulfate. The average molecular weight was ranging from 112.2kDa to 181.9kDa. Monosaccharide component analysis indicated that MFPs was mainly composed of glucose, galacturonic acid, rhamnose and galactose. Both the acute and subacute alcoholic-induced liver injury animal models were adopted to evaluate the MFPs's hepatoprotective activity. After administration of MFPs, both serological indexes (aspartate aminotransferase and alanine aminotransferase) and hepatic indicators (glutathione, superoxide dismutase, glutathione peroxidase and malondialdehyde) were improved by comparing with the non-MFPs group. The hepatic histopathology results also showed a prominent lipid degeneration and microvesicular steatosis attenuation in the MFPs groups. These outstanding hepatic protecting activities of MFPs might be related to its activation of ethanol dehydrogenase, elimination of free radicals and/or inhibition of lipid peroxidation capacities. MFPs could be important active substances for preventing and remedying liver injury. Copyright © 2017. Published by Elsevier B.V.

Highly sulfated hexasaccharide sequences isolated from chondroitin sulfate of shark fin cartilage: insights into the sugar sequences with bioactivities.

PubMed

Mizumoto, Shuji; Murakoshi, Saori; Kalayanamitra, Kittiwan; Deepa, Sarama Sathyaseelan; Fukui, Shigeyuki; Kongtawelert, Prachya; Yamada, Shuhei; Sugahara, Kazuyuki

2013-02-01

Chondroitin sulfate (CS) chains regulate the development of the central nervous system in vertebrates and are linear polysaccharides consisting of variously sulfated repeating disaccharides, [-4GlcUAβ1-3GalNAcβ1-](n), where GlcUA and GalNAc represent D-glucuronic acid and N-acetyl-D-galactosamine, respectively. CS chains containing D-disaccharide units [GlcUA(2-O-sulfate)-GalNAc(6-O-sulfate)] are involved in the development of cerebellar Purkinje cells and neurite outgrowth-promoting activity through interaction with a neurotrophic factor, pleiotrophin, resulting in the regulation of signaling. In this study, to obtain further structural information on the CS chains containing d-disaccharide units involved in brain development, oligosaccharides containing D-units were isolated from a shark fin cartilage. Seven novel hexasaccharide sequences, ΔO-D-D, ΔA-D-D, ΔC-D-D, ΔE-A-D, ΔD-D-C, ΔE-D-D and ΔA-B-D, in addition to three previously reported sequences, ΔC-A-D, ΔC-D-C and ΔA-D-A, were isolated from a CS preparation of shark fin cartilage after exhaustive digestion with chondroitinase AC-I, which cannot act on the galactosaminidic linkages bound to D-units. The symbol Δ stands for a 4,5-unsaturated bond of uronic acids, whereas A, B, C, D, E and O represent [GlcUA-GalNAc(4-O-sulfate)], [GlcUA(2-O-sulfate)-GalNAc(4-O-sulfate)], [GlcUA-GalNAc(6-O-sulfate)], [GlcUA(2-O-sulfate)-GalNAc(6-O-sulfate)], [GlcUA-GalNAc(4-O-, 6-O-sulfate)] and [GlcUA-GalNAc], respectively. In binding studies using an anti-CS monoclonal antibody, MO-225, the epitopes of which are involved in cerebellar development in mammals, novel epitope structures, ΔA-D-A, ΔA-D-D and ΔA-B-D, were revealed. Hexasaccharides containing two consecutive D-units or a B-unit will be useful for the structural and functional analyses of CS chains particularly in the neuroglycobiological fields.

[Antivirus effect of polysaccharides of brewer yeast in vitro].

PubMed

Li, F; Shi, Y; Guan, X; Zhang, S; Tian, T

1998-03-01

The antivirus effect of polysaccharides of brewer yeast from yeast mud on 13 kinds of viruses including DNA and RNA virus along with their mechanisms were studied. The result showed that this effect was remarkable on the infections with poliovirus III, adenovirus III, ECHO6 virus, enterovirus 71, vesicular stomatitis virus, herpesvirus I, II, coxsackie A16 virus and coxsackie B3 virus. The polysaccharides of brewer yeast could also inhibit the development of cytopathic effect(CPE) and protect cultural cells from being infected with the above viruses.

Chondroitin sulfate synthase-2 is necessary for chain extension of chondroitin sulfate but not critical for skeletal development.

PubMed

Ogawa, Hiroyasu; Hatano, Sonoko; Sugiura, Nobuo; Nagai, Naoko; Sato, Takashi; Shimizu, Katsuji; Kimata, Koji; Narimatsu, Hisashi; Watanabe, Hideto

2012-01-01

Chondroitin sulfate (CS) is a linear polysaccharide consisting of repeating disaccharide units of N-acetyl-D-galactosamine and D-glucuronic acid residues, modified with sulfated residues at various positions. Based on its structural diversity in chain length and sulfation patterns, CS provides specific biological functions in cell adhesion, morphogenesis, neural network formation, and cell division. To date, six glycosyltransferases are known to be involved in the biosynthesis of chondroitin saccharide chains, and a hetero-oligomer complex of chondroitin sulfate synthase-1 (CSS1)/chondroitin synthase-1 and chondroitin sulfate synthase-2 (CSS2)/chondroitin polymerizing factor is known to have the strongest polymerizing activity. Here, we generated and analyzed CSS2(-/-) mice. Although they were viable and fertile, exhibiting no overt morphological abnormalities or osteoarthritis, their cartilage contained CS chains with a shorter length and at a similar number to wild type. Further analysis using CSS2(-/-) chondrocyte culture systems, together with siRNA of CSS1, revealed the presence of two CS chain species in length, suggesting two steps of CS chain polymerization; i.e., elongation from the linkage region up to Mr ∼10,000, and further extension. There, CSS2 mainly participated in the extension, whereas CSS1 participated in both the extension and the initiation. Our study demonstrates the distinct function of CSS1 and CSS2, providing a clue in the elucidation of the mechanism of CS biosynthesis.

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.

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

PubMed

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

2013-01-15

Inhibition of bacterial oxidation of ferrous iron (Fe(II)) by Pb(NO(3))(2) was investigated with a mixed culture of Acidithiobacillus ferrooxidans. The culture was incubated at 30 °C in ferrous-sulfate medium amended with 0-24.2 mM Pb(II) added as Pb(NO(3))(2). Anglesite (PbSO(4)) precipitated immediately upon Pb addition and was the only solid phase detected in the abiotic controls. Both anglesite and jarosite (KFe(3)(SO(4))(2)(OH)(6)) were detected in inoculated cultures. Precipitation of anglesite maintained dissolved Pb concentrations at 16.9-17.6 μM regardless of the concentrations of Pb(NO(3))(2) added. Fe(II) oxidation was suppressed by 24.2 mM Pb(NO(3))(2) addition even when anglesite was removed before inoculation. Experiments with 0-48 mM KNO(3) demonstrated that bacterial Fe(II) oxidation decreased as nitrate concentration increased. Therefore, inhibition of Fe(II) oxidation at 24.2 mM Pb(NO(3))(2) addition resulted from nitrate toxicity instead of Pb addition. Geochemical modeling that considered the initial precipitation of anglesite to equilibrium followed by progressive oxidation of Fe(II) and the precipitation of jarosite and an amorphous iron hydroxide phase, without allowing plumbojarosite to precipitate were consistent with the experimental time-series data on Fe(II) oxidation under biotic conditions. Anglesite precipitation in mine tailings and other sulfate-rich systems maintains dissolved Pb concentrations below the toxicity threshold of A. ferrooxidans. Copyright © 2012 Elsevier B.V. All rights reserved.

EDTA Inhibits Biofilm Formation, Extracellular Vesicular Secretion, and Shedding of the Capsular Polysaccharide Glucuronoxylomannan by Cryptococcus neoformans

PubMed Central

Robertson, Emma J.; Wolf, Julie M.

2012-01-01

The fungal pathogen Cryptococcus neoformans can grow as a biofilm on a range of synthetic and prosthetic materials. Cryptococcal biofilm formation can complicate the placement of shunts used to relieve increased intracranial pressure in cryptococcal meningitis and can serve as a nidus for chronic infection. Biofilms are generally advantageous to pathogens in vivo, as they can confer resistance to antimicrobial compounds, including fluconazole and voriconazole in the case of C. neoformans. EDTA can inhibit biofilm formation by several microbes and enhances the susceptibility of biofilms to antifungal drugs. In this study, we evaluated the effect of sublethal concentrations of EDTA on the growth of cryptococcal biofilms. EDTA inhibited biofilm growth by C. neoformans, and the inhibition could be reversed by the addition of magnesium or calcium, implying that the inhibitory effect was by divalent cation starvation. EDTA also reduced the amount of the capsular polysaccharide glucuronoxylomannan shed into the biofilm matrix and decreased vesicular secretion from the cell, thus providing a potential mechanism for the inhibitory effect of this cation-chelating compound. Our data imply that the growth of C. neoformans biofilms requires the presence of divalent metals in the growth medium and suggest that cations are required for the export of materials needed for biofilm formation, possibly including extracellular vesicles. PMID:22941091

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

PubMed

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

2017-01-10

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

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

PubMed Central

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

2017-01-01

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

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.

Biosynthesis and function of chondroitin sulfate.

PubMed

Mikami, Tadahisa; Kitagawa, Hiroshi

2013-10-01

Chondroitin sulfate proteoglycans (CSPGs) are principal pericellular and extracellular components that form regulatory milieu involving numerous biological and pathophysiological phenomena. Diverse functions of CSPGs can be mainly attributed to structural variability of their polysaccharide moieties, chondroitin sulfate glycosaminoglycans (CS-GAG). Comprehensive understanding of the regulatory mechanisms for CS biosynthesis and its catabolic processes is required in order to understand those functions. Here, we focus on recent advances in the study of enzymatic regulatory pathways for CS biosynthesis including successive modification/degradation, distinct CS functions, and disease phenotypes that have been revealed by perturbation of the respective enzymes in vitro and in vivo. Fine-tuned machineries for CS production/degradation are crucial for the functional expression of CS chains in developmental and pathophysiological processes. Control of enzymes responsible for CS biosynthesis/catabolism is a potential target for therapeutic intervention for the CS-associated disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

Removing organic matter from sulfate-rich wastewater via sulfidogenic and methanogenic pathways.

PubMed

Vilela, Rogerio Silveira; Damianovic, Márcia Helena Rissato Zamariolli; Foresti, Eugenio

2014-01-01

The simultaneous organic matter removal and sulfate reduction in synthetic sulfate-rich wastewater was evaluated for various chemical oxygen demand (COD)/sulfate ratios applied in a horizontal-flow anaerobic immobilized sludge (HAIS) reactor. At higher COD/sulfate ratios (12.5 and 7.5), the removal of organic matter was stable, likely due to methanogenesis. A combination of sulfate reduction and methanogenesis was clearly established at COD/sulfate ratios of 3.0 and 1.9. At a COD/sulfate ratio of 1.0, the organic matter removal was likely influenced by methanogenesis inhibition. The quantity of sulfate removed at a COD/sulfate ratio of 1.0 was identical to that obtained at a ratio of 1.9, indicating a lack of available electron donors for sulfidogenesis. The sulfate reduction and organic matter removal were not maximized at the same COD/sulfate ratio; therefore, competitive inhibition must be the predominant mechanism in establishing an electron flow.

Wheatgrass-Derived Polysaccharide Has Antiinflammatory, Anti-Oxidative and Anti-Apoptotic Effects on LPS-Induced Hepatic Injury in Mice.

PubMed

Nepali, Sarmila; Ki, Hyeon-Hui; Lee, Ji-Hyun; Lee, Hoon-Yeon; Kim, Dae-Ki; Lee, Young-Mi

2017-07-01

Hepatic injury occurs frequently during sepsis, and polysaccharides isolated from plants have been reported to have antiinflammatory and antioxidant effects in various models. However, the effect of wheatgrass-derived polysaccharide (WGP) has not been previously studied. In the present study, we investigated the effect of WGP on lipopolysaccharide (LPS)-induced hepatic injury in mice. Mice were pre-treated with WGP (100 or 200 mg/kg daily for 2 days) and then challenged with LPS (1 mg/kg, intraperitoneal), and sacrificed after 12 h. Wheatgrass-derived polysaccharide decreased serum aminotransferase levels and histological changes as compared with LPS-challenged mice. Wheatgrass-derived polysaccharide also significantly inhibited LPS-induced pro-inflammatory cytokine up-regulation and improved the oxidative status of liver tissues. Furthermore, these effects were found to be mediated by the suppression of the transcriptional activity of nuclear factor-kappa B (NF-κB), due to inhibitions of transforming growth factor beta (TGF-β)-activated kinase (TAK)-1 phosphorylation and inhibition of kappa B (IκB)-α degradation. In addition, WGP inhibited the activations of mitogen-activated protein kinases (MAPKs). Wheatgrass-derived polysaccharide also attenuated hepatic cell death by modulating caspase-3 and apoptosis associated mitochondrial proteins, such as, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). Taken together, WGP possesses antiinflammatory, anti-oxidant and anti-apoptotic activity and ameliorates LPS-induced liver injury in mice. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Protective effect of Dendrobium officinale polysaccharides on H2O2-induced injury in H9c2 cardiomyocytes.

PubMed

Zhao, Xiaoyan; Dou, Mengmeng; Zhang, Zhihao; Zhang, Duoduo; Huang, Chengzhi

2017-10-01

The preliminary studies have shown that Dendrobium officinale possessed therapeutic effects on hypertension and atherosclerosis. Studies also reported that Dendrobium officinale polysaccharides showed antioxidant capabilities. However, little is known about its effects on myocardial cells under oxidative stress. The present study was designed to study the protective effect of Dendrobium officinale polysaccharides against H 2 O 2 -induced oxidative stress in H9c2 cells. MTT assay was carried out to determine the cell viability of H9c2 cells when pretreated with Dendrobium officinale polysaccharides. Fluorescent microscopy measurements were performed for evaluating the apoptosis in H9c2 cells. Furthermore, effects of Dendrobium officinale polysaccharides on the activities of antioxidative indicators (malondialdehyde, superoxide dismutase), reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) levels were analyzed. Dendrobium officinale polysaccharides attenuated H 2 O 2 -induced cell death, as determined by the MTT assay. Dendrobium officinale polysaccharides decreased malondialdehyde levels, increased superoxide dismutase activities, and inhibited the generation of intracellular ROS. Moreover, pretreatment with Dendrobium officinale polysaccharides also inhibited apoptosis and increased the MMP levels in H9c2 cells. These results suggested the protective effects of Dendrobium officinale polysaccharides against H 2 O 2 -induced injury in H9c2 cells. The results also indicated the anti-oxidative capability of Dendrobium officinale polysaccharides. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Discrepancies in composition and biological effects of different formulations of chondroitin sulfate.

PubMed

Martel-Pelletier, Johanne; Farran, Aina; Montell, Eulàlia; Vergés, Josep; Pelletier, Jean-Pierre

2015-03-06

Osteoarthritis is a common, progressive joint disease, and treatments generally aim for symptomatic improvement. However, SYmptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOAs) not only reduce joint pain, but slow structural disease progression. One such agent is chondroitin sulfate-a complex, heterogeneous polysaccharide. It is extracted from various animal cartilages, thus has a wide range of molecular weights and different amounts and patterns of sulfation. Chondroitin sulfate has an excellent safety profile, and although various meta-analyses have concluded that it has a beneficial effect on symptoms and structure, others have concluded little or no benefit. This may be due, at least partly, to variations in the quality of the chondroitin sulfate used for a particular study. Chondroitin sulfate is available as pharmaceutical- and nutraceutical-grade products, and the latter have great variations in preparation, composition, purity and effects. Moreover, some products contain a negligible amount of chondroitin sulfate and among samples with reasonable amounts, in vitro testing showed widely varying effects. Of importance, although some showed anti-inflammatory effects, others demonstrated weak effects, and some instances were even pro-inflammatory. This could be related to contaminants, which depend on the origin, production and purification process. It is therefore vitally important that only pharmaceutical-grade chondroitin sulfate be used for treating osteoarthritis patients.

Unique Extracellular Matrix Heparan Sulfate from the Bivalve Nodipecten nodosus (Linnaeus, 1758) Safely Inhibits Arterial Thrombosis after Photochemically Induced Endothelial Lesion*

PubMed Central

Gomes, Angélica M.; Kozlowski, Eliene O.; Pomin, Vitor H.; de Barros, Cintia Monteiro; Zaganeli, José L.; Pavão, Mauro S. G.

2010-01-01

Heparin-like glycans with diverse disaccharide composition and high anticoagulant activity have been described in several families of marine mollusks. The present work focused on the structural characterization of a new heparan sulfate (HS)-like polymer isolated from the mollusk Nodipecten nodosus (Linnaeus, 1758) and on its anticoagulant and antithrombotic properties. Total glycans were extracted from the mollusk and fractionated by ethanol precipitation. The main component (>90%) was identified as HS-like glycosaminoglycan, representing ∼4.6 mg g−1 of dry tissue. The mollusk HS resists degradation with heparinase I but is cleaved by nitrous acid. Analysis of the mollusk glycan by one-dimensional 1H, two-dimensional correlated spectroscopy, and heteronuclear single quantum coherence nuclear magnetic resonance revealed characteristic signals of glucuronic acid and glucosamine residues. Signals corresponding to anomeric protons of nonsulfated, 3- or 2-sulfated glucuronic acid as well as N-sulfated and/or 6-sulfated glucosamine were also observed. The mollusk HS has an anticoagulant activity of 36 IU mg−1, 5-fold lower than porcine heparin (180 IU mg−1), as measured by the activated partial thromboplastin time assay. It also inhibits factor Xa (IC50 = 0.835 μg ml−1) and thrombin (IC50 = 9.3 μg ml−1) in the presence of antithrombin. In vivo assays demonstrated that at the dose of 1 mg kg−1, the mollusk HS inhibited thrombus growth in photochemically injured arteries. No bleeding effect, factor XIIa-mediated kallikrein activity, or toxic effect on fibroblast cells was induced by the invertebrate HS at the antithrombotic dose. PMID:20053999

Pectic polysaccharides from Panax ginseng as the antirotavirus principals in ginseng.

PubMed

Baek, Seung-Hoon; Lee, Jin Gyun; Park, Seo Young; Bae, Ok Nam; Kim, Dong-Hyun; Park, Jeong Hill

2010-08-09

To evaluate the antidiarrheal effect of ginseng, the active principals of ginseng were studied in vitro model of rotavirus infection, the leading cause of severe diarrhea. Two pectic polysaccharides, named as GP50-dHR (56.0 kDa) and GP50-eHR (77.0 kDa), were purified from hot water extract of ginseng by bioassay-linked fractionation. Both polysaccharides rescued cell viability from rotavirus infection dose-dependently (IC50 are 15 and 10 microg/mL, respectively). Both polysaccharides had common structural features of homogalacturonan backbone with hairy regions of rhamnogalacturonan type I. Arabinose-rich side chains with abundant branch points were unique in GP50-eHR and may contribute to a greater antirotavirus effect of GP50-eHR than GP50-dHR. Because homogalacturonan itself did not show an antirotavirus effect, hairy regions might be functional sites. Of note, the antirotavirus effect of both polysaccharides resulted from inhibiting rotavirus attachment to cells. Together with a wide range of noncytotoxicity, these findings suggest that ginseng polysaccharides are viable therapeutic options for rotavirus diarrhea.

Fractionation and Characterization of Biologically-active Polysaccharides from Artemisia tripartita

PubMed Central

Xie, Gang; Schepetkin, Igor A.; Siemsen, Daniel W.; Kirpotina, Liliya N.; Wiley, James A.; Quinn, Mark T.

2008-01-01

The leaves of Artemisia species have been traditionally used for prevention and treatment of a number of diseases. In this study, five polysaccharide fractions (designated A-I to A-V) were isolated from the leaves of Artemisia tripartita Rydb. by the sequential use of hot-water extraction, ethanol precipitation, ultra-filtration, and chromatography. The homogeneity and average molecular weight of each fraction were determined by high performance size-exclusion chromatography. Sugar composition analysis revealed that Artemisia polysaccharides consisted primarily of xylose, glucose, arabinose, galactose, and galactosamine. Moreover, all fractions contained at least 3.4% sulfate, and fractions A-II through A-V contained an arabinogalactan type II structure. All fractions exhibited macrophage-activating activity, enhancing production of intracellular reactive oxygen species and release of nitric oxide, interleukin 6, interleukin 10, tumor necrosis factor α, and monocyte chemotactic protein-1. In addition, all fractions exhibited scavenging activity for reactive oxygen species generated enzymatically or produced extracellularly by human neutrophils. Finally, fractions A-I and A-V exhibited complement-fixing activity. Taken together, our results provide a molecular basis to explain at least part of the beneficial therapeutic effects of Artemisia extracts, and suggest the possibility of using Artemisia polysaccharides as an immunotherapeutic adjuvant. PMID:18325553

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. Copyright © 2014 Elsevier B.V. All rights reserved.

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

O-Acetylation of Plant Cell Wall Polysaccharides

PubMed Central

Gille, Sascha; Pauly, Markus

2011-01-01

Plant cell walls are composed of structurally diverse polymers, many of which are O-acetylated. How plants O-acetylate wall polymers and what its function is remained elusive until recently, when two protein families were identified in the model plant Arabidopsis that are involved in the O-acetylation of wall polysaccharides – the reduced wall acetylation (RWA) and the trichome birefringence-like (TBL) proteins. This review discusses the role of these two protein families in polysaccharide O-acetylation and outlines the differences and similarities of polymer acetylation mechanisms in plants, fungi, bacteria, and mammals. Members of the TBL protein family had been shown to impact pathogen resistance, freezing tolerance, and cellulose biosynthesis. The connection of TBLs to polysaccharide O-acetylation thus gives crucial leads into the biological function of wall polymer O-acetylation. From a biotechnological point understanding the O-acetylation mechanism is important as acetyl-substituents inhibit the enzymatic degradation of wall polymers and released acetate can be a potent inhibitor in microbial fermentations, thus impacting the economic viability of, e.g., lignocellulosic based biofuel production. PMID:22639638

The influence of conditioning film on antifouling properties of the polyurethane film modified by chondroitin sulfate in urine

NASA Astrophysics Data System (ADS)

Yuan, Huihui; Qian, Bin; Chen, Huaying; Lan, Minbo

2017-12-01

The encrustation and induced infection severely impact on the therapeutic effectiveness and service life of urinary stents due to the fast formation of conditioning film on urinary stents after implantation. The composition and properties of conditioning film have great influence on antifouling properties of stent materials. In our previous work, we modified polyurethane films by chondroitin sulfate (PU-CS) with different CS grafting densities to verify its anti-fouling properties. To obtain the in-depth understanding of encrustation on urinary stents, we investigated the impact of the composition and properties of conditioning film on the following inorganic salt deposition and bacteria adhesion in urine. The results showed that quantity of proteins and polysaccharides in conditioning films, and the roughness, water contact angle and zeta potential of PU-CSs covered with corresponding conditioning film decreased with the increase of CS grafting density on PU films.PU-CS(3) with highest CS grafting density (3.70 g/cm2) had the highest bacteria inhibition rate and least inorganic salt deposition among the PU-CSs in artificial urine. Moreover, inorganic salts depositing on the PU-CS(3) were less and smaller than those on other films. Bacteria were not detectable until day 21 in real urine. Meanwhile, the pH value was elevated. The results suggested that the component of conditioning films was more important than other surface properties such as hydrophilicity, zeta potential and roughness for inorganic salt deposition and bacteria adhesion. Moreover, the anti-encrustation properties of the surface was promoted by proteins and inhibited by polysaccharides.

[Correlation Between Functional Groups and Radical Scavenging Activities of Acidic Polysaccharides from Dendrobium].

PubMed

Liao, Ying; Yuan, Wen-yu; Zheng, Wen-ke; Luo, Ao-xue; Fan, Yi-jun

2015-11-01

To compare the radical scavenging activity of five different acidic polysaccharides, and to find the correlation with the functional groups. Alkali extraction method and Stepwise ethanol precipitation method were used to extract and concentrate the five Dendrobium polysaccharides, and to determine the contents of sulfuric acid and uronic acid of each kind of acidic polysaccharides, and the scavenging activity to ABTS+ radical and hydroxyl radical. Functional group structures were examined by FTIR Spectrometer. Five kinds of Dendrobium polysaccharides had different ability of scavenging ABTS+ free radical and hydroxyl free radical. Moreover, the study had shown that five kinds of antioxidant activity of acidic polysaccharides had obvious correlation withuronic acid and sulfuric acid. The antioxidant activity of each sample was positively correlated with the content of uronic acid, and negatively correlated with the content of sulfuric acid. Sulfuric acid can inhibit the antioxidant activity of acidic polysaccharide but uronic acid can enhance the free radical scavenging activity. By analyzing the structure characteristics of five acidic polysaccharides, all samples have similar structures, however, Dendrobium denneanum, Dendrobium devonianum and Dendrobium officinale which had β configuration have higher antioxidant activity than Dendrobium nobile and Dendrobium fimbriatum which had a configuration.

The anticancer activity of lytic peptides is inhibited by heparan sulfate on the surface of the tumor cells

PubMed Central

2009-01-01

Background Cationic antimicrobial peptides (CAPs) with antitumor activity constitute a promising group of novel anticancer agents. These peptides induce lysis of cancer cells through interactions with the plasma membrane. It is not known which cancer cell membrane components influence their susceptibility to CAPs. We have previously shown that CAPs interact with the two glycosaminoglycans (GAGs), heparan sulfate (HS) and chondroitin sulfate (CS), which are present on the surface of most cells. The purpose of this study was to investigate the role of the two GAGs in the cytotoxic activity of CAPs. Methods Various cell lines, expressing different levels of cell surface GAGs, were exposed to bovine lactoferricin (LfcinB) and the designer peptide, KW5. The cytotoxic effect of the peptides was investigated by use of the colorimetric MTT viability assay. The cytotoxic effect on wild type CHO cells, expressing normal amounts of GAGs on the cell surface, and the mutant pgsA-745, that has no expression of GAGs on the cell surface, was also investigated. Results We show that cells not expressing HS were more susceptible to CAPs than cells expressing HS at the cell surface. Further, exogenously added heparin inhibited the cytotoxic effect of the peptides. Chondroitin sulfate had no effect on the cytotoxic activity of KW5 and only minor effects on LfcinB cytotoxicity. Conclusion Our results show for the first time that negatively charged molecules at the surface of cancer cells inhibit the cytotoxic activity of CAPs. Our results indicate that HS at the surface of cancer cells sequesters CAPs away from the phospholipid bilayer and thereby impede their ability to induce cytolysis. PMID:19527490

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.

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

PubMed

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

2016-01-01

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

Prognostic significance of highly sulfated chondroitin sulfates in ovarian cancer defined by the single chain antibody GD3A11.

PubMed

van der Steen, Sophieke C H A; van Tilborg, Angela A G; Vallen, Myrtille J E; Bulten, Johan; van Kuppevelt, Toin H; Massuger, Leon F A G

2016-03-01

The extracellular matrix (ECM) of ovarian cancer may provide a number of potential biomarkers. Chondroitin sulfate (CS), a class of sulfated polysaccharides, is abundantly present in the ECM of ovarian cancer. Structural alterations of CS chains (i.e. sulfation pattern) have been demonstrated to play a role in cancer development and progression. In this study we investigate the potential of highly sulfated CS as a biomarker in ovarian cancer using the single chain antibody GD3A11 selected by the phage display technology. The specificity of the antibody was determined by an indirect ELISA. GD3A11 epitope expression was assessed by immunohistochemistry in healthy organs, benign and malignant ovarian tumors (N=359) and correlated to clinical parameters. The CHST15 gene, responsible for the biosynthesis of highly sulfated CS was evaluated for mutation and methylation status. The GD3A11 epitope was minimally expressed in normal organs. Intense expression was observed in the ECM of different ovarian cancer subtypes, in contrast to benign ovarian tumors. Expression was independent of tumor grade, FIGO stage, and the use chemotherapy. For the aggressive ovarian cancer phenotype, intense expression was identified as an independent predictor for poor prognosis. CHST15 gene analysis showed no mutations nor an altered methylation status. Specific highly sulfated CS motifs expressed in the tumoral ECM hold biomarker potential in ovarian cancer patients. These matrix motifs constitute a novel class of biomarkers with prognostic significance and may be instrumental for innovative diagnostic and therapeutic applications (e.g. targeted therapy) in management of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Prospects for the therapeutic application of sulfated polysaccharides of brown algae in diseases of the cardiovascular system: review.

PubMed

Zaporozhets, Tatyana; Besednova, Natalia

2016-12-01

Fucoidans are water-soluble, highly sulfated, branched homo- and hetero-polysaccharides derived from the fibrillar cell walls and intercellular spaces of brown seaweeds of the class Phaeophyceae. Fucoidans possess mimetic properties of the natural ligands of protein receptors and regulate functions of biological systems via key signaling molecules. The aim of this review was to collect and combine all available scientific literature about the potential use of the fucoidans for diseases of cardiovascular system. The review has been compiled using references from major databases such as Web of Science, PubMed, Scopus, Elsevier, Springer and Google Scholar (up to September 2015). After obtaining all reports from database (a total number is about 580), the papers were carefully analyzed in order to find data related to the topic of this review (129 references). An exhaustive survey of literature revealed that fucoidans possess a broad spectrum of biological activity, including anti-coagulant, hypolipidemic, anti-thrombotic, anti-inflammatory, immunomodulatory, anti-tumor, anti-adhesive and anti-hypertensive properties. Numerous investigations of fucoidans in diseases of the cardiovascular system mainly focus on pleiotropic anti-inflammatory effects. Fucoidans also possess pro-angiogenic and pro-vasculogenic properties. A great number of investigations in the past years have demonstrated that fucoidans has great potential for in-depth investigation of their effects on cardiovascular system. Through this review, the authors hope to attract the attention of researchers to use fucoidan as mimetic of natural ligand receptor protein with the view of developing new formulations with an improved therapeutic value.

Effects of sulfate on microcystin production, photosynthesis, and oxidative stress in Microcystis aeruginosa.

PubMed

Chen, Lei; Gin, Karina Y H; He, Yiliang

2016-02-01

Increasing sulfate in freshwater systems, caused by human activities and climate change, may have negative effects on aquatic organisms. Microcystis aeruginosa (M. aeruginosa) is both a major primary producer and a common toxic cyanobacterium, playing an important role in the aquatic environment. This study first investigated the effects of sulfate on M. aeruginosa. The experiment presented here aims at analyzing the effects of sulfate on physiological indices, molecular levels, and its influencing mechanism. The results of our experiment showed that sulfate (at 40, 80, and 300 mg L(-1)) inhibited M. aeruginosa growth, increased both intracellular and extracellular toxin contents, and enhanced the mcyD transcript level. Sulfate inhibited the photosynthesis of M. aeruginosa, based on the decrease in pigment content and the down-regulation of photosynthesis-related genes after sulfate exposure. Furthermore, sulfate decreased the maximum electron transport rate, causing the cell to accumulate surplus electrons and form reactive oxygen species (ROS). Sulfate also increased the malondialdehyde (MDA) content, which showed that sulfate damaged the cytomembrane. This damage contributed to the release of intracellular toxin to the culture medium. Although sulfate increased superoxide dismutase (SOD) activities, expression of sod, and total antioxidant capacity in M. aeruginosa, it still overwhelmed the antioxidant system since the ROS level simultaneously increased, and finally caused oxidative stress. Our results indicate that sulfate has direct effects on M. aeruginosa, inhibits photosynthesis, causes oxidative stress, increases toxin production, and affects the related genes expression in M. aeruginosa.

Osmotic Pressure of Aqueous Chondroitin Sulfate Solution: A Molecular Modeling Investigation

PubMed Central

Bathe, Mark; Rutledge, Gregory C.; Grodzinsky, Alan J.; Tidor, Bruce

2005-01-01

The osmotic pressure of chondroitin sulfate (CS) solution in contact with an aqueous 1:1 salt reservoir of fixed ionic strength is studied using a recently developed coarse-grained molecular model. The effects of sulfation type (4- vs. 6-sulfation), sulfation pattern (statistical distribution of sulfate groups along a chain), ionic strength, CS intrinsic stiffness, and steric interactions on CS osmotic pressure are investigated. At physiological ionic strength (0.15 M NaCl), the sulfation type and pattern, as measured by a standard statistical description of copolymerization, are found to have a negligible influence on CS osmotic pressure, which depends principally on the mean volumetric fixed charge density. The intrinsic backbone stiffness characteristic of polysaccharides such as CS, however, is demonstrated to contribute significantly to its osmotic pressure behavior, which is similar to that of a solution of charged rods for the 20-disaccharide chains considered. Steric excluded volume is found to play a negligible role in determining CS osmotic pressure at physiological ionic strength due to the dominance of repulsive intermolecular electrostatic interactions that maintain chains maximally spaced in that regime, whereas at high ionic-strength steric interactions become dominant due to electrostatic screening. Osmotic pressure predictions are compared to experimental data and to well-established theoretical models including the Donnan theory and the Poisson-Boltzmann cylindrical cell model. PMID:16055525

Heparan Sulfate Modification of the Transmembrane Receptor CD47 Is Necessary for Inhibition of T Cell Receptor Signaling by Thrombospondin-1*

PubMed Central

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

2011-01-01

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 Mr > 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 Mr 230,000) and CD47 (apparent Mr > 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 Ser64 and Ser79. 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 Ser64. PMID:21343308

Cytoprotective effect of polysaccharide isolated from different mushrooms against 7-ketocholesterol induced damage in mouse liver cell line (BNL CL. 2).

PubMed

Kim, Joo-Shin; Chung, Hau Yin; Na, Keun

2007-01-01

Cytoprotective ability of polysaccharides isolated from different edible mushrooms was investigated on the 7-ketocholesterol-induced damaged cell line. Polysaccharide extracts from six different edible mushrooms-Flammulina velutipes, Peurotus ostreatus, Lentinus edodes, Agrocybe aegerita, Agaricus blazei, and Cordyceps militaris- were prepared by hot water extraction and alcohol precipitation. Cytoprotective ability was evaluated by measuring the viable cells of the normal embryonic liver cell line (BNL CL. 2) in the presence of 7-ketocholesterol. At 80 microg/mL of 7-ketocholesterol, cytotoxicity was very high with a loss of 98% of viable cells after 20 h of incubation. With the addition of 200 microg/mL of each polysaccharide isolate to the cell line containing 80 microg/mL of 7-ketocholesterol, polysaccharide isolates from both Flammulina velutipes and Peurotus ostreatus could significantly inhibit the 7-ketochoelsterol-induced cytotoxicity in the cells. But other polysaccharide isolates were not effective in inhibiting cell damage caused by the oxLDL-induced cytotoxicity.

Cytoprotective effect of polysaccharide isolated from different mushrooms against 7-ketocholesterol induced damage in mouse liver cell line (BNL CL. 2)

PubMed Central

Chung, Hau Yin; Na, Keun

2007-01-01

Cytoprotective ability of polysaccharides isolated from different edible mushrooms was investigated on the 7-ketocholesterol-induced damaged cell line. Polysaccharide extracts from six different edible mushrooms-Flammulina velutipes, Peurotus ostreatus, Lentinus edodes, Agrocybe aegerita, Agaricus blazei, and Cordyceps militaris- were prepared by hot water extraction and alcohol precipitation. Cytoprotective ability was evaluated by measuring the viable cells of the normal embryonic liver cell line (BNL CL. 2) in the presence of 7-ketocholesterol. At 80 µg/mL of 7-ketocholesterol, cytotoxicity was very high with a loss of 98% of viable cells after 20 h of incubation. With the addition of 200 µg/mL of each polysaccharide isolate to the cell line containing 80 µg/mL of 7-ketocholesterol, polysaccharide isolates from both Flammulina velutipes and Peurotus ostreatus could significantly inhibit the 7-ketochoelsterol-induced cytotoxicity in the cells. But other polysaccharide isolates were not effective in inhibiting cell damage caused by the oxLDL-induced cytotoxicity. PMID:20368935

Microwave-assisted extraction of polysaccharides from Cyphomandra betacea and its biological activities.

PubMed

C, Senthil Kumar; M, Sivakumar; K, Ruckmani

2016-11-01

Response Surface Methodology (RSM) was used to optimize the parameters for microwave-assisted extraction of polysaccharides from Cyphomandra betacea. The results showed a good fit with a second-order polynomial equation that was statistically acceptable at P<0.05. Optimal conditions for the extraction of polysaccharides were: extraction time, 2h; microwave power, 400W; extraction temperature, 60°C; and ratio of raw material to water 1:40 (g/mL). Under the optimized conditions, the yield of polysaccharides was found to be relatively high (about 36.52%). The in vitro biological activities of antioxidant and antitumor were evaluated. The IC 50 value of polysaccharides was found to be 3mg/mL. The percentage of Cell viability was determined by MTT assay. Our results showed that polysaccharides inhibited proliferation of MCF-7 (Breast carcinoma), A549 (Human lung carcinoma) and HepG2 (Liver carcinoma) with an IC 50 of 0.23mg/mL, 0.17mg/mL and 0.62mg/mL respectively after 48h incubation. Polysaccharides were shown to promote apoptosis as seen in the nuclear morphological examination study using acridine orange (AO) and ethidium bromide (EB) staining. This is the first report on the effects of polysaccharides extracted from Cyphomandra betacea which exhibited stronger antioxidant and antitumor activities. Copyright © 2016 Elsevier B.V. All rights reserved.

Polysaccharide with antioxidant, α-amylase inhibitory and ACE inhibitory activities from Momordica charantia.

PubMed

Tan, Hwee-Feng; Gan, Chee-Yuen

2016-04-01

Functional polysaccharide was isolated from Momordica charantia, with a yield of 36% (w/w). M. charantia bioactive polysaccharide (MCBP) was an acidic and branched heteropolysaccharide with a molecular weight of 92 kDa. Fourier transform infrared spectroscopic analysis indicated that MCBP was a pectin-like polysaccharide with an esterification degree of 53% and it contains numerous monosaccharides, predominantly glucose, galactose, and galaturonic acid. The results also showed that MCBP exhibited free radical scavenging activity (31.9%), ferric reducing antioxidant power (0.95 mM), α-amylase inhibition (89.1%), and angiotensin-converting enzyme inhibition (94.1%). In the terms of functionality, MCBP showed a lower water-holding capacity but higher in oil-holding capacity, emulsifying activity and foaming capacity compared to citrus pectin. Scanning electron microscopy images demonstrated that MCBP formed gels with a porous structure, and flow analysis showed that the gel solution exhibited pseudoplastic shear-thinning behavior. These findings indicated that MCBP is a promising functional macromolecular carbohydrate for the food and nutraceutical industries. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhancement of cordyceps polysaccharide production via biosynthetic pathway analysis in Hirsutella sinensis.

PubMed

Lin, Shan; Liu, Zhi-Qiang; Baker, Peter James; Yi, Ming; Wu, Hui; Xu, Feng; Teng, Yi; Zheng, Yu-Guo

2016-11-01

The addition of various sulfates for enhanced cordyceps polysaccharide (CP) production in submerged cultivation of H. sinensis was investigated, and manganese sulfate was found the most effective. 2mM of manganese sulfate on 0day (d) was investigated as the optimal adding condition, and the CP production reached optimum with 5.33%, increasing by 93.3% compared with the control. Furthermore, the consumption of three main precursors of CP was studied over cultivation under two conditions. Intracellular mannose content decreased by 43.1% throughout 6days cultivation, which corresponded to CP accumulation rate sharply increased from 0 d to 6 d, and mannose was considered as the most preferred precursor for generating CP. Subsequently, mannose biosynthetic pathway was constructed and verified for the first time in H. sinensis, which constituted the important part of CP biosynthesis, and transcriptional levels of the biosynthetic genes were studied. Transcriptional level of gene cpsA was significantly up-regulated 5.35-fold and it was a key gene involved both in mannose and CP biosynthesis. This study demonstrated that manganese sulfate addition is an efficient and simple way to improve CP production. Transcriptional analysis based on biosynthetic pathway was helpful to find key genes and better understand CP biosynthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibitory effect of chondroitin sulfate oligosaccharides on bovine testicular hyaluronidase.

PubMed

Kakizaki, Ikuko; Koizumi, Hideyo; Chen, Fengchao; Endo, Masahiko

2015-05-05

Hyaluronan and chondroitin sulfates are prominent components of the extracellular matrices of animal tissues; however, their functions in relation to their oligosaccharide structures have not yet been fully elucidated. The oligosaccharides of hyaluronan and chondroitin sulfate were prepared and used to investigate their effects on the hydrolysis and transglycosylation reactions of bovine testicular hyaluronidase when hyaluronan was used as a substrate. Hydrolysis and transglycosylation activities were assessed in independent reaction systems by analyzing the products by HPLC. The hydrolysis and transglycosylation reactions of bovine testicular hyaluronidase were dose-dependently inhibited by chondroitin sulfate oligosaccharides, but not by hyaluronan or chondroitin oligosaccharides. A kinetic analysis of the hydrolysis reaction using hyaluronan octasaccharide revealed that the inhibition mode by chondroitin sulfate oligosaccharides was competitive. Copyright © 2015 Elsevier Ltd. All rights reserved.

Receptor for advanced glycation end products (RAGE) functions as receptor for specific sulfated glycosaminoglycans, and anti-RAGE antibody or sulfated glycosaminoglycans delivered in vivo inhibit pulmonary metastasis of tumor cells.

PubMed

Mizumoto, Shuji; Takahashi, Jun; Sugahara, Kazuyuki

2012-06-01

Altered expression of chondroitin sulfate (CS) and heparan sulfate (HS) at the surfaces of tumor cells plays a key role in malignant transformation and tumor metastasis. Previously we demonstrated that a Lewis lung carcinoma (LLC)-derived tumor cell line with high metastatic potential had a higher proportion of E-disaccharide units, GlcUA-GalNAc(4,6-O-disulfate), in CS chains than low metastatic LLC cells and that such CS chains are involved in the metastatic process. The metastasis was markedly inhibited by the pre-administration of CS-E from squid cartilage rich in E units or by preincubation with a phage display antibody specific for CS-E. However, the molecular mechanism of the inhibition remains to be investigated. In this study the receptor molecule for CS chains containing E-disaccharides expressed on LLC cells was revealed to be receptor for advanced glycation end products (RAGE), which is a member of the immunoglobulin superfamily predominantly expressed in the lung. Interestingly, RAGE bound strongly to not only E-disaccharide, but also HS-expressing LLC cells. Furthermore, the colonization of the lungs by LLC cells was effectively inhibited by the blocking of CS or HS chains at the tumor cell surface with an anti-RAGE antibody through intravenous injections in a dose-dependent manner. These results provide the clear evidence that RAGE is at least one of the critical receptors for CS and HS chains expressed at the tumor cell surface and involved in experimental lung metastasis and that CS/HS and RAGE are potential molecular targets in the treatment of pulmonary metastasis.

Inhibition of lipopolysaccharide (LPS)-induced neuroinflammatory response by polysaccharide fractions of Khaya grandifoliola (C.D.C.) stem bark, Cryptolepis sanguinolenta (Lindl.) Schltr and Cymbopogon citratus Stapf leaves in raw 264.7 macrophages and U87 glioblastoma cells.

PubMed

Mediesse, Francine Kengne; Boudjeko, Thaddée; Hasitha, Anantharaju; Gangadhar, Matharasala; Mbacham, Wilfred Fon; Yogeeswari, Perumal

2018-03-12

Khaya grandifoliola (C.D.C.) stem bark, Cymbopogon citratus (Stapf) and Cryptolepis sanguinolenta (Lindl.) Schltr leaves are used in Cameroonian traditional medicine for the treatment of inflammatory diseases. Several studies have been performed on the biological activities of secondary metabolites extracted from these plants. However, to the best of our knowledge, the anti-neuro inflammatory and protective roles of the polysaccharides of these three plants have not yet been elucidated. This study aimed at investigating potential use of K. grandifoliola, C. sanguinolenta and C. citratus polysaccharides in the prevention of chronic inflammation. Firstly, the composition of polysaccharide fractions isolated from K. grandifoliola stem bark (KGF), C. sanguinolenta (CSF) and C. citratus (CCF) leaves was assessed. Secondly, the cytotoxicity was evaluated on Raw 264.7 macrophages and U87-MG glioblastoma cell lines by the MTT assay. This was followed by the in vitro evaluation of the ability of KGF, CSF and CCF to inhibit lipopolysaccharides (LPS) induced overproduction of various pro-inflammatory mediators (NO, ROS and IL1β, TNFα, IL6, NF-kB cytokines). This was done in Raw 264.7 and U87-MG cells. Finally, the in vitro protective effect of KGF, CSF and CCF against LPS-induced toxicity in the U87-MG cells was evaluated. CCF was shown to mostly contain sugar and no polyphenol while KGP and CSP contained very few amounts of these metabolites (≤ 2%). The three polysaccharide fractions were non-toxic up to 100 μg.mL - 1 . All the polysaccharides at 10 μg/mL inhibited NO production, but only KGF and CCF at 12.5 μg/mL down-regulated LPS-induced ROS overproduction. Finally, 100 μg/mL LPS reduced 50% of U87 cell viability, and pre-treatment with the three polysaccharides significantly increased the proliferation. These results suggest that the polysaccharides of K. grandifoliola, C. citratus and C. sanguinolenta could be beneficial in preventing

Partial characterization and antioxidant and antiproliferative activities of the aqueous extracellular polysaccharides from the thermophilic microalgae Graesiella sp.

PubMed

Trabelsi, Lamia; Chaieb, Olfa; Mnari, Amira; Abid-Essafi, Salwa; Aleya, Lotfi

2016-07-12

For thousands of years, Tunisian geothermal water has been used in bathing. Indeed, thermal baths "Hammam" were recommended in the treatment of different type of illnesses as, for instance, for relaxing joints and soothing. The ability of microalgae to sustain at the high temperature makes them potential producers of high value thermostable bio-products. This study aimed to explore the therapeutic potential of the aqueous extracellular polysaccharides (AEPS) of the Tunisian thermophilic microalgae Graesiella sp. and to evaluate its physico-chemical characteristics. Different parameters were used to characterize the AEPS. The dry weight, volatile dry weight, elemental analysis, monosaccharide composition and IR-spectroscopy analysis. Carbohydrate, uronic acid, ester sulfate and protein concentrations were also determined using colorimetric assay. AEPS was analyzed for its antioxidant propriety by means of total antioxidant capacity, DPPH radicals scavenging assay, ferrous chelating ability and hydroxyl and superoxide radical scavenging activity. The antiproliferative activity of AEPS was evaluated for HepG2 and Caco-2 cells using the MTT assay. The Graesiella sp. AEPS is found to be a hetero-sulfated-anionic polysaccharides that contain carbohydrate (52 %), uronic acids (23 %), ester sulfate (11 %) and protein (12 %). The carbohydrate fraction was formed by eight neutral sugars glucose, galactose, mannose, fucose, rhamnose, xylose, arabinose and ribose. The FT-IR revealed the presence of carboxyl, hydroxyl, amine and sulfate groups. AEPS showed high activity as reducing agent, high ferrous chelating capacity and caused a significant decrease in a concentration-dependent manner of hydroxyl radical. A moderate DPPH scavenging activity and a poor superoxide radical scavenging ability were also observed. AEPS treatment (from 0.01 to 2.5 mg/ml) caused also a clear decrease of cell viabilities in a dose-dependent manner. The IC50 values obtained in HepG2 and Caco-2

Lycium barbarum Polysaccharides Protect Rat Corneal Epithelial Cells against Ultraviolet B-Induced Apoptosis by Attenuating the Mitochondrial Pathway and Inhibiting JNK Phosphorylation.

PubMed

Du, Shaobo; Han, Biao; Li, Kang; Zhang, Xuan; Sha, Xueli; Gao, Lan

2017-01-01

Lycium barbarum polysaccharides (LBPs) have been shown to play a key role in protecting the eyes by reducing the apoptosis induced by certain types of damage. However, it is not known whether LBPs can protect damaged corneal cells from apoptosis. Moreover, no reports have focused on the role of LBPs in guarding against ultraviolet B- (UVB-) induced apoptosis. The present study aimed to investigate the protective effect and underlying mechanism of LBPs against UVB-induced apoptosis in rat corneal epithelial (RCE) cells. The results showed that LBPs significantly prevented the loss of cell viability and inhibited cell apoptosis induced by UVB in RCE cells. LBPs also inhibited UVB-induced loss of mitochondrial membrane potential, downregulation of Bcl-2 , and upregulation of Bax and caspase-3. Finally, LBPs attenuated the phosphorylation of c-Jun NH 2 -terminal kinase (JNK) triggered by UVB. In summary, LBPs protect RCE cells against UVB-induced damage and apoptosis, and the underlying mechanism involves the attenuation of the mitochondrial apoptosis pathway and the inhibition of JNK phosphorylation.

The investigation of immunoprotective and sedative hypnotic effect of total polysaccharide from Suanzaoren decoction by serum metabonomics approach.

PubMed

Niu, Xiaoyi; He, Bosai; Du, Yiyang; Sui, Zhenyu; Rong, Weiwei; Wang, Xiaotong; Li, Qing; Bi, Kaishun

2018-06-01

Suanzaoren decoction, as one of the traditional Chinese medicine prescriptions, has been most commonly used in Asian countries and reported to inhibit the process of immunodeficiency insomnia. Polysaccharide is important component which also contributes to the role of immunoprotective and sedative hypnotic effects. This study was aimed to explore the immunoprotective and sedative hypnotic mechanisms of polysaccharide from Suanzaoren decoction by serum metabonomics approach. With this purpose, complex physical and chemical immunodeficiency insomnia models were firstly established according to its multi-target property. Serum samples were analyzed using UHPLC/Q-TOF-MS spectrometry approach to determine endogenous metabolites. Then, principal component analysis was used to distinguish the groups, and partial least squares discriminate analysis was carried out to confirm the important variables. The serum metabolic profiling was identified and pathway analysis was performed after the total polysaccharide administration. The twenty-one potential biomarkers were screened, and the levels were all reversed to different degrees in the total polysaccharide treated groups. These potential biomarkers were mainly related to vitamin, sphingolipid, bile acid, phospholipid and acylcarnitine metabolisms. The result has indicated that total polysaccharide could inhibit insomnia triggered by immunodeficiency stimulation through regulating those metabolic pathways. This study provides a useful approach for exploring the mechanism and evaluating the efficacy of total polysaccharide from Suanzaoren decoction. Copyright © 2018 Elsevier B.V. All rights reserved.

Physico-chemical characterization and pharmacological evaluation of sulfated polysaccharides from three species of Mediterranean brown algae of the genus Cystoseira.

PubMed

Hadj Ammar, Hiba; Lajili, Sirine; Ben Said, Rafik; Le Cerf, Didier; Bouraoui, Abderrahman; Majdoub, Hatem

2015-01-13

Seaweed polysaccharides are highly active natural substances having valuable applications. The present study was conducted to characterize the physico-chemical properties of sulphated polysaccharides from three Mediterranean brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita) and to evaluate their anti-radical, anti-inflammatory and gastroprotective activities. The different rates of neutral sugars, uronic acids, L-fucose and sulphate content were determined by colorimetric techniques. The different macromolecular characteristics of isolated fucoidans were identified by size exclusion chromatography equipped with a triple detection: multiangle light scattering, viscometer and differential refractive index detectors, (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test in comparison to the references drugs Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats and to examine the antioxidant effect of fucoidans in the three species, the free radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl. The pharmacological evaluation of the isolated fucoidans for their anti-inflammatory, and their gastroprotective effect established that these products from C. sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from C. sedoides and C. compressa showed a significant decrease of the intensity of gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan from C. crinita produced a less gastroprotective effect. Furthermore, the isolated fucoidans exhibited a radical scavenging activity. The comparative study of fucoidans isolated from three species of the genus Cystoseira showed that they

Sequencing of chondroitin sulfate oligosaccharides using a novel exolyase from a marine bacterium that degrades hyaluronan and chondroitin sulfate/dermatan sulfate.

PubMed

Wang, Wenshuang; Cai, Xiaojuan; Han, Naihan; Han, Wenjun; Sugahara, Kazuyuki; Li, Fuchuan

2017-11-09

Glycosaminoglycans (GAGs) are a family of chemically heterogeneous polysaccharides that play important roles in physiological and pathological processes. Owing to the structural complexity of GAGs, their sophisticated chemical structures and biological functions have not been extensively studied. Lyases that cleave GAGs are important tools for structural analysis. Although various GAG lyases have been identified, exolytic lyases with unique enzymatic property are urgently needed for GAG sequencing. In the present study, a putative exolytic GAG lyase from a marine bacterium was recombinantly expressed and characterized in detail. Since it showed exolytic lyase activity toward hyaluronan (HA), chondroitin sulfate (CS), and dermatan sulfate (DS), it was designated as HCDLase. This novel exolyase exhibited the highest activity in Tris-HCl buffer (pH 7.0) at 30°C. Especially, it showed a specific activity that released 2-aminobenzamide (2-AB)-labeled disaccharides from the reducing end of 2-AB-labeled CS oligosaccharides, which suggest that HCDLase is not only a novel exolytic lyase that can split disaccharide residues from the reducing termini of sugar chains but also a useful tool for the sequencing of CS chains. Notably, HCDLase could not digest 2-AB-labeled oligosaccharides from HA, DS, or unsulfated chondroitin, which indicated that sulfates and bond types affect the catalytic activity of HCDLase. Finally, this enzyme combined with CSase ABC was successfully applied for the sequencing of several CS hexa- and octasaccharides with complex structures. The identification of HCDLase provides a useful tool for CS-related research and applications. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

PubMed

Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

2017-04-03

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

Antifouling potential of Nature-inspired sulfated compounds

NASA Astrophysics Data System (ADS)

Almeida, Joana R.; Correia-da-Silva, Marta; Sousa, Emília; Antunes, Jorge; Pinto, Madalena; Vasconcelos, Vitor; Cunha, Isabel

2017-02-01

Natural products with a sulfated scaffold have emerged as antifouling agents with low or nontoxic effects to the environment. In this study 13 sulfated polyphenols were synthesized and tested for antifouling potential using the anti-settlement activity of mussel (Mytilus galloprovincialis) plantigrade post-larvae and bacterial growth inhibition towards four biofilm-forming bacterial strains. Results show that some of these Nature-inspired compounds were bioactive, particularly rutin persulfate (2), 3,6-bis(β-D-glucopyranosyl) xanthone persulfate (6), and gallic acid persulfate (12) against the settlement of plantigrades. The chemical precursors of sulfated compounds 2 and 12 were also tested for anti-settlement activity and it was possible to conclude that bioactivity is associated with sulfation. While compound 12 showed the most promising anti-settlement activity (EC50 = 8.95 μg.mL-1), compound 2 also caused the higher level of growth inhibition in bacteria Vibrio harveyi (EC20 = 12.5 μg.mL-1). All the three bioactive compounds 2, 6, and 12 were also found to be nontoxic to the non target species Artemia salina (<10% mortality at 250 μM) and Vibrio fischeri (LC50 > 1000 μg.mL-1). This study put forward the relevance of synthesizing non-natural sulfated small molecules to generate new nontoxic antifouling agents.

Antifouling potential of Nature-inspired sulfated compounds

PubMed Central

Almeida, Joana R.; Correia-da-Silva, Marta; Sousa, Emília; Antunes, Jorge; Pinto, Madalena; Vasconcelos, Vitor; Cunha, Isabel

2017-01-01

Natural products with a sulfated scaffold have emerged as antifouling agents with low or nontoxic effects to the environment. In this study 13 sulfated polyphenols were synthesized and tested for antifouling potential using the anti-settlement activity of mussel (Mytilus galloprovincialis) plantigrade post-larvae and bacterial growth inhibition towards four biofilm-forming bacterial strains. Results show that some of these Nature-inspired compounds were bioactive, particularly rutin persulfate (2), 3,6-bis(β-D-glucopyranosyl) xanthone persulfate (6), and gallic acid persulfate (12) against the settlement of plantigrades. The chemical precursors of sulfated compounds 2 and 12 were also tested for anti-settlement activity and it was possible to conclude that bioactivity is associated with sulfation. While compound 12 showed the most promising anti-settlement activity (EC50 = 8.95 μg.mL−1), compound 2 also caused the higher level of growth inhibition in bacteria Vibrio harveyi (EC20 = 12.5 μg.mL−1). All the three bioactive compounds 2, 6, and 12 were also found to be nontoxic to the non target species Artemia salina (<10% mortality at 250 μM) and Vibrio fischeri (LC50 > 1000 μg.mL−1). This study put forward the relevance of synthesizing non-natural sulfated small molecules to generate new nontoxic antifouling agents. PMID:28205590

Isolation, Structural characterization, and antiproliferative activity of phycocolloids from the red seaweed Laurencia papillosa on MCF-7 human breast cancer cells.

PubMed

Ghannam, Ahmed; Murad, Hossam; Jazzara, Marie; Odeh, Adnan; Allaf, Abdul Wahab

2018-03-01

Hydrocolloids from seaweeds (phycocolloids) have interesting functional properties like antiproliferative activity. Marine algae consumptions are linked to law cancer incidences in countries that traditionally consume marine products. In this study, we have investigated water-soluble sulfated polysaccharides isolated from the red seaweed Laurencia papillosa and determined their chemical characteristics and biological activities on the human breast cancer cell line MCF-7. Total polysaccharides were extracted and fractionated from L. papillosa and characterized using FTIR-ATR and NMR spectrometry. In addition, their approximate molar mass was determined by GPC method. The chemical characterization of purified polysaccharides reveals the presence of sulfated polysaccharides differentially dispersed in the algal cell wall. They are the three types of carrageenan, kappa, iota and lambda carrageenans, named LP-W1, -W2 and -W3 respectively. Biological effects and cytotoxicity of the identified of the three sulfated polysaccharide fractions were evaluated in MCF-7 cell line. Our results showed a significant inhibition of MCF-7 cell viability by dose-dependent manner for cells exposed to LP-W2 and LP-W3 polysaccharides for 24h. The mechanistic of LP fractions-mediated apoptosis in MCF-7 cells was demonstrated. The biological effects of L. papillosa SPs indicate that it may be a promising candidate for breast cancer prevention and therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural elucidation of fucosylated chondroitin sulfates from sea cucumber using FTICR-MS/MS.

PubMed

Agyekum, Isaac; Pepi, Lauren; Yu, Yanlei; Li, Junhui; Yan, Lufeng; Linhardt, Robert J; Chen, Shiguo; Amster, I Jonathan

2018-02-01

Fucosylated chondroitin sulfates are complex polysaccharides extracted from sea cucumber. They have been extensively studied for their anticoagulant properties and have been implicated in other biological activities. While nuclear magnetic resonance spectroscopy has been used to extensively characterize fucosylated chondroitin sulfate oligomers, we herein report the first detailed mass characterization of fucosylated chondroitin sulfate using high-resolution Fourier transform ion cyclotron resonance mass spectrometry. The two species of fucosylated chondroitin sulfates considered for this work include Pearsonothuria graeffei (FCS-Pg) and Isostichopus badionotus (FCS-Ib). Fucosylated chondroitin sulfate oligosaccharides were prepared by N-deacetylation-deaminative cleavage of the two fucosylated chondroitin sulfates and purified by repeated gel filtration. Accurate mass measurements obtained from electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry measurements confirmed the oligomeric nature of these two fucosylated chondroitin sulfate oligosaccharides with each trisaccharide repeating unit averaging four sulfates per trisaccharide. Collision-induced dissociation of efficiently deprotonated molecular ions through Na/H + exchange proved useful in providing structurally relevant glycosidic and cross-ring product ions, capable of assigning the sulfate modifications on the fucosylated chondroitin sulfate oligomers. Careful examination of the tandem mass spectrometry of both species deferring in the positions of sulfate groups on the fucose residue (FCS-Pg-3,4- OS) and (FCS-Ib-2,4- OS) revealed cross-ring products 0,2 A αf and 2,4 X 2αf which were diagnostic for (FCS-Pg-3,4- OS) and 0,2 X 2αf diagnostic for (FCS-Ib-2,4- OS). Mass spectrometry and tandem mass spectrometry data acquired for both species varying in oligomer length (dp3-dp15) are presented.

Enterovirus 71 Uses Cell Surface Heparan Sulfate Glycosaminoglycan as an Attachment Receptor

PubMed Central

Tan, Chee Wah; Poh, Chit Laa; Sam, I-Ching

2013-01-01

Enterovirus 71 (EV-71) infections are usually associated with mild hand, foot, and mouth disease in young children but have been reported to cause severe neurological complications with high mortality rates. To date, four EV-71 receptors have been identified, but inhibition of these receptors by antagonists did not completely abolish EV-71 infection, implying that there is an as yet undiscovered receptor(s). Since EV-71 has a wide range of tissue tropisms, we hypothesize that EV-71 infections may be facilitated by using receptors that are widely expressed in all cell types, such as heparan sulfate. In this study, heparin, polysulfated dextran sulfate, and suramin were found to significantly prevent EV-71 infection. Heparin inhibited infection by all the EV-71 strains tested, including those with a single-passage history. Neutralization of the cell surface anionic charge by polycationic poly-d-lysine and blockage of heparan sulfate by an anti-heparan sulfate peptide also inhibited EV-71 infection. Interference with heparan sulfate biosynthesis either by sodium chlorate treatment or through transient knockdown of N-deacetylase/N-sulfotransferase-1 and exostosin-1 expression reduced EV-71 infection in RD cells. Enzymatic removal of cell surface heparan sulfate by heparinase I/II/III inhibited EV-71 infection. Furthermore, the level of EV-71 attachment to CHO cell lines that are variably deficient in cell surface glycosaminoglycans was significantly lower than that to wild-type CHO cells. Direct binding of EV-71 particles to heparin-Sepharose columns under physiological salt conditions was demonstrated. We conclude that EV-71 infection requires initial binding to heparan sulfate as an attachment receptor. PMID:23097443

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.

In vivo anti-radiation activities of the Ulva pertusa polysaccharides and polysaccharide-iron(III) complex.

PubMed

Shi, Jinming; Cheng, Cuilin; Zhao, Haitian; Jing, Jing; Gong, Ning; Lu, Weihong

2013-09-01

Polysaccharides with different molecular weights were extracted from Ulva pertusa and fractionated by ultrafiltration. Iron(III) complex of the low molecular-weight U. pertusa polysaccharides were synthesized. Atomic absorption spectrum showed that the iron content of iron(III)-polysaccharide complex was 27.4%. The comparison between U. pertusa polysaccharides and their iron(III) complex showed that iron chelating altered the structural characteristics of the polysaccharides. The bioactivity analysis showed that polysaccharide with low molecular weight was more effective than polysaccharide with high molecular weight in protecting mice from radiation induced damages on bone marrow cells and immune system. Results also proved that the anti-radiation and anti-oxidative activity of iron(III) complex of low molecular-weight polysaccharides were not less than that of low molecular-weight polysaccharides. Copyright © 2013 Elsevier B.V. All rights reserved.

Thermoreversible gel formulation containing sodium lauryl sulfate as a potential contraceptive device.

PubMed

Haineault, Caroline; Gourde, Pierrette; Perron, Sylvie; Désormeaux, André; Piret, Jocelyne; Omar, Rabeea F; Tremblay, Roland R; Bergeron, Michel G

2003-08-01

The contraceptive properties of a gel formulation containing sodium lauryl sulfate were investigated in both in vitro and in vivo models. Results showed that sodium lauryl sulfate inhibited, in a concentration-dependent manner, the activity of sheep testicular hyaluronidase. Sodium lauryl sulfate also completely inhibited human sperm motility as evaluated by the 30-sec Sander-Cramer test. The acid-buffering capacity of gel formulations containing sodium lauryl sulfate increased with the molarity of the citrate buffers used for their preparations. Furthermore, experiments in which semen was mixed with undiluted gel formulations in different proportions confirmed their physiologically relevant buffering capacity. Intravaginal application of the gel formulation containing sodium lauryl sulfate to rabbits before their artificial insemination with freshly ejaculated semen completely prevented egg fertilization. The gel formulation containing sodium lauryl sulfate was fully compatible with nonlubricated latex condoms. Taken together, these results suggest that the gel formulation containing sodium lauryl sulfate could represent a potential candidate for use as a topical vaginal spermicidal formulation to provide fertility control in women.

Box-Behnken design for extraction optimization of crude polysaccharides from Tunisian Phormidium versicolor cyanobacteria (NCC 466): Partial characterization, in vitro antioxidant and antimicrobial activities.

PubMed

Belhaj, Dalel; Frikha, Donyez; Athmouni, Khaled; Jerbi, Bouthaina; Ahmed, Mohammad Boshir; Bouallagui, Zouhaier; Kallel, Monem; Maalej, Sami; Zhou, John; Ayadi, Habib

2017-12-01

In this study, response surface methodology (RSM) based on Box-Behnken design (BBD) was employed to optimize the aqueous extraction of crude polysaccharides from Tunisian cyanobacteria Phormidium versicolor (NCC 466). The optimal extraction conditions with an extraction yield of 21.56±0.92% were as follows: extraction temperature at 81.05°C, extraction time of 3.99h, and water to raw material ratio of 21.52mLg -1 . Crude Phormidium versicolor polysaccharides (CPv-PS) are found to be a hetero-sulfated-anionic polysaccharides that contained carbohydrate (79.37±1.58%), protein (0.45±0.11%), uronic acids (4.37±0.19%) and sulfate (6.83±0.28%). The carbohydrate fraction was composed of arabinose, xylose, ribose, rhamnose, N-acetyl glucosamine, galactose, glucose, mannose, glucuronic acid and saccharose with corresponding mole percentages of 2.41, 14.58, 2.18, 6.23, 7.04, 28.21, 26.04, 3.02, 0.86 and 5.07, respectively. Evaluation of the antioxidant activity in vitro suggested that CPv-PS strongly scavenged radicals, prevented bleaching of β-carotene and reduced activity. Furthermore, the CPv-PS exhibited effective antimicrobial properties. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

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. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Method for producing capsular polysaccharides

NASA Technical Reports Server (NTRS)

Richards, Gil F. (Inventor); Kern, Roger G. (Inventor); Petersen, Gene R. (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.

Anti-fibrotic effect of Cordyceps sinensis polysaccharide: Inhibiting HSC activation, TGF-β1/Smad signalling, MMPs and TIMPs.

PubMed

Peng, Jinghua; Li, Xuemei; Feng, Qin; Chen, Liang; Xu, Lili; Hu, Yiyang

2013-06-01

Cordyceps sinensis has been used to treat liver disease in traditional Chinese medicine for thousands of years. Polysaccharide extracted from cultured Cordyceps sinensis mycelia (CS-PS) is the major active components of cordyceps sinensis with anti-liver injury effects. In the present study, the effects of CS-PS on hepatic stellate cell (HSC) activation, transforming growth factor-β1 (TGF-β1)/Smad pathway, as well as matrix metalloproteinase (MMP) 2, MMP9 and tissue inhibitor of metalloproteinase (TIMP) 1, TIMP2, were investigated in liver fibrosis in rats induced by carbon tetrachloride (CCl4). Colchicine was used as a positive control. The effect of CS-PS inhibition liver injury and fibrosis was confirmed by decreasing serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, hepatic hydroxyproline and increasing serum albumin, as well as alleviation of histological changes, which was comparable to that of colchicine. With CS-PS treatment, hepatic α-smooth muscle actin, TGF-β1, TGF-β1 receptor (TβR)-I, TβR-II, p-Smad2, p-Smad3 and TIMP2 proteins expression were down-regulated comparing to that in CCl4 group. The activities of MMP2 and MMP9 in liver tissue were also inhibited in CS-PS-treated group. It is indicated that the effects of CS-PS anti-liver fibrosis are probably associated with the inhibition on HSC activation, TGF-β1/Smads signalling pathway, as well as MMP2, MMP9 activity and TIMP2 expression.

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

PubMed

Sanjeewa, Kalu Kapuge Asanka; Fernando, Ilekkuttige Priyan Shanura; Kim, Eun-A; Ahn, Ginnae; Jee, Youngheun; Jeon, You-Jin

2017-02-01

Sargassum horneri is an edible brown alga that grows in the subtidal zone as an annual species along the coasts of South Korea, China, and Japan. Recently, an extreme amount of S. horneri moved into the coasts of Jeju Island from the east coast of China, which made huge economic and environmental loss to the Jeju Island. Thus, utilization of this biomass becomes a big issue with the local authorities. Therefore, the present study was performed to evaluate the anti-inflammatory potential of crude polysaccharides (CPs) extracted from S. horneri China strain in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. CPs were precipitated from S. horneri digests prepared by enzyme assistant extraction using four food-grade enzymes (AMG, Celluclast, Viscozyme, and Alcalase). The production levels of nitric oxide (NO) and pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured by Griess assay and enzyme-linked immunosorbent assay, respectively. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPKs) were measured by using western blot. The IR spectrums of the CPs were recorded using a fourier transform infrared spectroscopy (FT-IR) spectrometer. The polysaccharides from the Celluclast enzyme digest (CCP) showed the highest inhibition of NO production in LPS-stimulated RAW 264.7 cells (IC 50 value: 95.7 µg/mL). Also, CCP dose-dependently down-regulated the protein expression levels of iNOS and COX-2 as well as the production of inflammatory cytokines, including TNF-α and IL-1β, compared to the only LPS-treated cells. In addition, CCP inhibited the activation of NF-κB p50 and p65 and the phosphorylation of MAPKs, including p38 and extracellular signal-regulated kinase, in LPS-stimulated RAW 264.7 cells. Furthermore, FT-IR analysis showed that the FT-IR spectrum of CCP is similar to that of commercial fucoidan. Our results

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

PubMed Central

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

2017-01-01

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

Characteristics and Antitumor Activity of Morchella esculenta Polysaccharide Extracted by Pulsed Electric Field

PubMed Central

Liu, Chao; Sun, Yonghai; Mao, Qian; Guo, Xiaolei; Li, Peng; Liu, Yang; Xu, Na

2016-01-01

Polysaccharides from Morchella esculenta have been proven to be functional and helpful for humans. The purpose of this study was to investigate the chemical structure and anti-proliferating and antitumor activities of a Morchella esculenta polysaccharide (MEP) extracted by pulsed electric field (PEF) in submerged fermentation. The endo-polysaccharide was separated and purified by column chromatography and Gel permeation chromatography, and analyzed by gas chromatography. The MEP with an average molecular weight of 81,835 Da consisted of xylose, glucose, mannose, rhamnose and galactose at the ratio of 5.4:5.0:6.5:7.8:72.3. Structure of MEP was further analyzed by Fourier-transform infrared spectroscopy and 1H and 13C liquid-state nuclear magnetic resonance spectroscopy. Apoptosis tests proved that MEP could inhibit the proliferation and growth of human colon cancer HT-29 cells in a time- and dose-dependent manner within 48 h. This study provides more information on chemical structure of anti-proliferating polysaccharides isolated from Morchella esculenta. PMID:27338370

Antiviral and Antioxidant Activities of Sulfated Galactomannans from Plants of Caatinga Biome.

PubMed

Marques, Márcia Maria Mendes; de Morais, Selene Maia; da Silva, Ana Raquel Araújo; Barroso, Naiara Dutra; Pontes Filho, Tadeu Rocha; Araújo, Fernanda Montenegro de Carvalho; Vieira, Ícaro Gusmão Pinto; Lima, Danielle Malta; Guedes, Maria Izabel Florindo

2015-01-01

Dengue represents a serious social and economic public health problem; then trying to contribute to improve its control, the objective of this research was to develop phytoterapics for dengue treatment using natural resources from Caatinga biome. Galactomannans isolated from Adenanthera pavonina L., Caesalpinia ferrea Mart., and Dimorphandra gardneriana Tull were chemically sulfated in order to evaluate the antioxidant, and antiviral activities and the role in the inhibition of virus DENV-2 in Vero cells. A positive correlation between the degree of sulfation, antioxidant and antiviral activities was observed. The sulfated galactomannans showed binding to the virus surface, indicating that they interact with DENV-2. The sulfated galactomannans from C. ferrea showed 96% inhibition of replication of DENV-2 followed by D. gardneriana (94%) and A. pavonina (77%) at 25 µg/mL and all sulfated galactomannans also showed antioxidant activity. This work is the first report of the antioxidant and antiviral effects of sulfated galactomannans against DENV-2. The results are very promising and suggest that these sulfated galactomannans from plants of Caatinga biome act in the early step of viral infection. Thus, sulfated galactomannans may act as an entry inhibitor of DENV-2.

Antiviral and Antioxidant Activities of Sulfated Galactomannans from Plants of Caatinga Biome

PubMed Central

Marques, Márcia Maria Mendes; de Morais, Selene Maia; da Silva, Ana Raquel Araújo; Barroso, Naiara Dutra; Pontes Filho, Tadeu Rocha; Araújo, Fernanda Montenegro de Carvalho; Vieira, Ícaro Gusmão Pinto; Lima, Danielle Malta; Guedes, Maria Izabel Florindo

2015-01-01

Dengue represents a serious social and economic public health problem; then trying to contribute to improve its control, the objective of this research was to develop phytoterapics for dengue treatment using natural resources from Caatinga biome. Galactomannans isolated from Adenanthera pavonina L., Caesalpinia ferrea Mart., and Dimorphandra gardneriana Tull were chemically sulfated in order to evaluate the antioxidant, and antiviral activities and the role in the inhibition of virus DENV-2 in Vero cells. A positive correlation between the degree of sulfation, antioxidant and antiviral activities was observed. The sulfated galactomannans showed binding to the virus surface, indicating that they interact with DENV-2. The sulfated galactomannans from C. ferrea showed 96% inhibition of replication of DENV-2 followed by D. gardneriana (94%) and A. pavonina (77%) at 25 µg/mL and all sulfated galactomannans also showed antioxidant activity. This work is the first report of the antioxidant and antiviral effects of sulfated galactomannans against DENV-2. The results are very promising and suggest that these sulfated galactomannans from plants of Caatinga biome act in the early step of viral infection. Thus, sulfated galactomannans may act as an entry inhibitor of DENV-2. PMID:26257815

Preparation, Separation, and Conformational Analysis of Differentially Sulfated Heparin Octasaccharide Isomers using Ion Mobility Mass Spectrometry

PubMed Central

Seo, Youjin; Andaya, Armann; Leary, Julie A.

2012-01-01

Heparin is a linear sulfated polysaccharide widely used in medicine because of its anticoagulant properties. The various sulfation and/or acetylation patterns on heparin impart different degrees of conformational change around the glycosidic bonds and subsequently alter its function as an anticoagulant, anticancer, or antiviral drug. Characterization of these structures is important for eventual elucidation of its function but presents itself as an analytical challenge due to the inherent heterogeneity of the carbohydrates. Heparin octasaccharide structural isomers of various sulfation patterns were investigated using ion mobility mass spectrometry (IMMS). In addition to distinguishing the isomers, we report the preparation and tandem mass spectrometry analysis for multiple sulfated or acetylated oligosaccharides. Herein, our data indicate that heparin octasaccharide isomers were separated based on their structural conformations in the ion mobility cell. Subsequent to this separation, isomers were further distinguished using product ions resulting from tandem mass spectrometry. Overall, IMMS analysis was used to successfully characterize and separate individual isomers and subsequently measure their conformations. PMID:22283665

[Preparation of Ganoderma lucidum polysaccharides and triterpenes microemulsion and its anticancer effect in mice with transplant Heps tumors].

PubMed

Chen, Yan; Lu, Hui; Song, Shihua; Jia, Xiaobin

2010-10-01

To research the microemulsion preparation of Ganoderma lucidum polysaccharides and triterpenes and investigate its properities. Evaluate the effects of polysaccharides and triterpenes microemulsions against transplant tumor growth. The microemulsion formula was optimized by constructing the pseudo-ternary phase diagrams of blank microemulsion. The polysaccharides and triterpenes microemulsions were prepared on the blank microemulsions. The appearance, particle distribution and Zeta potential were investigated by transmission electron microscope and grain size analyzer. The Heps mice were randomly administered with polysaccharides and triterpenes microemulsions (114.5, 57.25 mg x kg(-1) x d(-1)) for 7 days. The effectiveness was assessed based on tumor inhibitory ratio of mice with Heps tumors. The toxicity was evaluated by measurements of the mice weight, immune organ weight. The optimal microemulsion formula was composed of tween 20, dimethyl carbinol, water and 9-octadecenoic acid with the ratio of 14.3: 14.3: 33. 3:2. Polysaccharides and triterpenes microemulsions in transmission electron microscope were consisted of small spherical drop. The average particle size was 32.43 nm and the Zeta potential was -3.41 mV. The polysaccharides and triterpenes microemulsions showed an inhibition rate of 37.66% (57.25 mg x kg(-1) x d(-1)) and 52.34% (114.5 mg x kg(-1) x d(-1)) respectively against Heps tumor growth. The acquired microemulsion with small particle size is stable. It significantly inhibits the tumor growth in Heps mice.

Corrosion inhibition of stainless steel by a sulfate-reducing bacteria biofilm in seawater

NASA Astrophysics Data System (ADS)

Li, Fu-shao; An, Mao-zhong; Duan, Dong-xia

2012-08-01

Corrosion inhibition of stainless steel due to a sulfate-reducing bacteria (SRB) biofilm in seawater was studied. By atomic force microscopy, a layer of fish-scale-like biofilm was found to form as stainless steel coupons were exposed to the culture media with SRB, and this biofilm grew more and more compact. As a result, coupons' surface under the biofilm turned irregular less slowly than that exposed to the sterilized culture media. Then, physicoelectric characteristics of the electrode/biofilm/solution interface were investigated by electrochemical impedance spectroscopy (EIS), and the coverage of the biofilm as well as the relative irregularity of coupons' surface was also recorded by EIS spectra. Finally, anodic cyclic polarization results further demonstrated the protective property of the biofilm. Therefore, in estimation of SRB-implicated corrosion of stainless steel, not only the detrimental SRB metabolites but also the protective SRB biofilm as well should be taken into account.

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.

Antithrombin activity of an algal polysaccharide.

PubMed

Trento, F; Cattaneo, F; Pescador, R; Porta, R; Ferro, L

2001-06-01

In an effort to reduce the risks of a possible iatrogenic transmission of bovine spongiform encephalitis (BSE) through the use of bovine-derived medicinal products, we patented in the USA in 1999 a polysaccharide from brown algae, endowed with interesting pharmacological activities: (a) concentration-dependent inhibition of thromboplastin or cephalin-kaolin-induced thrombin generation from platelets, (b) concentration-dependent inhibition of thrombin-induced platelet aggregation, (c) thrombin has hypotensive effect, which was blunted and zeroed by our fucansulfate in a dose-dependent way, (d) when aortae are stimulated with thrombin, they become stickier for polymorphonucleated leukocytes (PMNs); our fucansulfate decreased concentration-dependently, PMNs sticking to autologous rabbit aortae, (e) dose-dependent inhibition of thrombin-induced thrombosis. All the above data suggest that our fucansulfate could be a heparin substitute endowed with antithrombotic and anti-inflammatory activities, devoid or the problems caused to heparin by its animal origin, i.e., possible prion protein contamination.

Kinetics of nitrate and sulfate removal using a mixed microbial culture with or without limited-oxygen fed.

PubMed

Xu, Xi-Jun; Chen, Chuan; Wang, Ai-Jie; Guo, Hong-Liang; Yuan, Ye; Lee, Duu-Jong; Ren, Nan-Qi

2014-07-01

The biological degradation of nitrate and sulfate was investigated using a mixed microbial culture and lactate as the carbon source, with or without limited-oxygen fed. It was found that sulfate reduction was slightly inhibited by nitrate, since after nitrate depletion the sulfate reduction rate increased from 0.37 mg SO4 (2-)/mg VSS d to 0.71 mg SO4 (2-)/mg VSS d, and the maximum rate of sulfate reduction in the presence of nitrate corresponded to 56 % of the non-inhibited sulfate reduction rate determined after nitrate depleted. However, simultaneous but not sequential reduction of both oxy-anions was observed in this study, unlike some literature reports in which sulfate reduction starts only after depletion of nitrate, and this case might be due to the fact that lactate was always kept above the limiting conditions. At limited oxygen, the inhibited effect on sulfate reduction by nitrate was relieved, and the sulfate reduction rate seemed relatively higher than that obtained without limited-oxygen fed, whereas kept almost constant (0.86-0.89 mg SO4 (2-)/mg VSS d) cross the six ROS states. In contrast, nitrate reduction rates decreased substantially with the increase in the initial limited-oxygen fed, showing an inhibited effect on nitrate reduction by oxygen. Kinetic parameters determined for the mixed microbial culture showed that the maximum specific sulfate utilization rate obtained (0.098 ± 0.022 mg SO4 (2-)/(mg VSS h)) was similar to the reported typical value (0.1 mg SO4 (2-)/(mg VSS h)), also indicating a moderate inhibited effect by nitrate.

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

Preliminary study on the potential of polysaccharide from indigenous Tiger's Milk mushroom (Lignosus rhinocerus) as anti-lung cancer agent

NASA Astrophysics Data System (ADS)

Lai, Wei Hong; Zainal, Zamri; Daud, Fauzi

2014-09-01

Tiger's Milk mushroom is a tropical polypore genus that can be found in the tropical part of the world in Australia, Papua New Guinea, Philippines, Indonesia, Malaysia, Sri Lanka and Vanuatu. In Malaysia, Lignosus rhinocerus is the most sought after medicinal mushroom by Semai aborigine upon request by local herbalist. This priced mushroom has been used traditionally to treat various diseases such as asthma, breast cancer, cough, fever and food poisoning. Current results indicated polysaccharide from sclerotia of indigenous L. rhinocerus extracted through hot water is able to inhibit up to 45% growth of human lung carcinoma. Inhibition is achieved when concentration of polysaccharide are in the range of 4-8 μg/ml. Present preliminary study suggests beta-glucan-rich polysaccharide from sclerotia of indigenous L. rhinocerus has anti-proliferation activity on human lung carcinoma (A549).

Polysaccharide peptides from Coriolus versicolor competitively inhibit model cytochrome P450 enzyme probe substrates metabolism in human liver microsomes.

PubMed

Yeung, John H K; Or, Penelope M Y

2012-03-15

Polysaccharide peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy or health supplement in China. Previous studies have shown that PSP decreased antipyrine clearance and inhibited rat CYP2C11-mediated tolbutamide 4-hydroxylation and in human CYP2C9. In this study, the effects of the water extractable fraction of PSP on the metabolism of model CYP1A2, CYP2D6, CYP2E1 and CYP3A4 probe substrates were investigated in pooled human liver microsomes. PSP (1.25-20μM) dose-dependently decreased CYP1A2-mediated metabolism of phenacetin to paracetamol (IC(50) 19.7μM) and CYP3A4-mediated metabolism of testosterone to 6β-hydroxytestosterone (IC(20) 7.06μM). Enzyme kinetics studies showed the inhibition of CYP1A2 activity was competitive and concentration-dependent (K(i)=18.4μM). Inhibition of testosterone to 6β-hydroxytestosterone was also competitive and concentration-dependent (K(i)=31.8μM). Metabolism of dextromethorphan to dextrorphan (CYP2D6-mediated) and chlorzoxazone to 6-hydroxychlorzoxazone (CYP2E1-mediated) was only minimally inhibited by PSP, with IC(20) values at 15.6μM and 11.9μM, respectively. This study demonstrated that PSP competitively inhibited the CYP1A2- and CYP3A4-mediated metabolism of model probe substrates in human liver microsomes in vitro. The relatively high K(i) values for CYP1A2 and CYP3A4 would suggest a low potential for PSP to cause herb-drug interaction related to these CYP isoforms. Copyright © 2011 Elsevier GmbH. All rights reserved.

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

PubMed

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

2015-07-10

CPS-F, a polysaccharide derived from Cordyceps sinensis, is a potential anti-inflammatory and anti-oxidative agent. We demonstrated that CPS-F not only inhibits platelet-derived growth factor BB (PDGF-BB)-induced intracellular reactive oxygen species (ROS) generation, and up-regulation of tumor necrosis factor-α (TNF-α), TNF-α receptor 1 (TNFR1), and monocyte chemotactic protein-1 (MCP-1), but also acts synergistically in combination with MAPK/ERK inhibitor U0126 and PI3K/Akt inhibitor LY294002. Additionally, up-regulation of pro-inflammatory factors was reversed by use of a combination of CPS-F and NADPH oxidase (NOX) inhibitor diphenyleneiodonium chloride (DPI) or silencing of NOX1. Furthermore, CPS-F prevents the PDGF receptor β (PDGFRβ) promoter activity induced by PDGF-BB in transfected cells and ameliorates increased levels of TNF-α, TNFR1, and MCP-1 when PDGFRβ is silenced, thereby suggesting that CPS-F possesses a bidirectional regulatory function. Our findings suggest CPS-F may exert its therapeutic effect for the treatment of glomerulonephritis related to human mesangial cells (HMCs) through the ERK1/2/Akt pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of elevated nitrate on sulfate-reducing bacteria: A comparative study of Desulfovibrio vulgaris

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Q.; He, Z.; Joyner, D.C.

2010-07-15

Sulfate-reducing bacteria have been extensively studied for their potential in heavy-metal bioremediation. However, the occurrence of elevated nitrate in contaminated environments has been shown to inhibit sulfate reduction activity. Although the inhibition has been suggested to result from the competition with nitrate-reducing bacteria, the possibility of direct inhibition of sulfate reducers by elevated nitrate needs to be explored. Using Desulfovibrio vulgaris as a model sulfate-reducing bacterium, functional genomics analysis reveals that osmotic stress contributed to growth inhibition by nitrate as shown by the upregulation of the glycine/betaine transporter genes and the relief of nitrate inhibition by osmoprotectants. The observation thatmore » significant growth inhibition was effected by 70 mM NaNO{sub 3} but not by 70 mM NaCl suggests the presence of inhibitory mechanisms in addition to osmotic stress. The differential expression of genes characteristic of nitrite stress responses, such as the hybrid cluster protein gene, under nitrate stress condition further indicates that nitrate stress response by D. vulgaris was linked to components of both osmotic and nitrite stress responses. The involvement of the oxidative stress response pathway, however, might be the result of a more general stress response. Given the low similarities between the response profiles to nitrate and other stresses, less-defined stress response pathways could also be important in nitrate stress, which might involve the shift in energy metabolism. The involvement of nitrite stress response upon exposure to nitrate may provide detoxification mechanisms for nitrite, which is inhibitory to sulfate-reducing bacteria, produced by microbial nitrate reduction as a metabolic intermediate and may enhance the survival of sulfate-reducing bacteria in environments with elevated nitrate level.« less

Astragalus polysaccharide enhanced antitumor effects of Apatinib in gastric cancer AGS cells by inhibiting AKT signalling pathway.

PubMed

Wu, Jun; Yu, Junxian; Wang, Jing; Zhang, Chenguang; Shang, Kun; Yao, Xiaojun; Cao, Bangwei

2018-04-01

Apatinib has been proved effective in the treatment of advanced gastric cancer. Traditional Chinese medicine is often considered as adjuvants which could increase the effects and counteract the side effects of chemotherapy. The present study aims to explore the antitumor effects of Astragalus polysaccharide (AsPs) in combination with Apatinib in gastric cancer AGS cells. Our results demonstrated that the expression of VEGFR-2 was observed in human gastric cancer line AGS. Both Apatinib and AsPs could significantly inhibit the proliferation of AGS cells in a dose-dependent manner and Apatinib in combination with AsPs showed enhanced inhibitory effects on cell proliferation, migration and invasion compared with Apatinib monotherapy. Moreover, there was a remarkable increase in apoptosis following Apatinib treatment which could be enhanced by the addition of AsPs. Western blotting showed that the combination of Apatinib and AsPs could inhibit the expression of phosphorylated AKT (p-AKT) and MMP-9 expression. In addition, both Apatinib alone and Apatinib in combination with AsPs induced celluar autophagy which could be attenuated by the autophagy inhibitor 3-MA. The suppression of autophagy leaded to further apoptosis induction and cell proliferation suppression. In conclusion, the current study showed AsPs enhanced antitumor effects of Apatinib on AGS cells by the mechanism which includes inhibition of AKT signaling pathway. Apatinib-induced autophagy could be attenuated by 3-MA, which subsequently increased the apoptosis rate. On the basis of our study, the combination of Apatinib and AsPs could be considered as a potential candidate in the gastric cancer treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Metabolic niche of a prominent sulfate-reducing human gut bacterium

PubMed Central

Rey, Federico E.; Gonzalez, Mark D.; Cheng, Jiye; Ahern, Philip P.; Gordon, Jeffrey I.

2013-01-01

Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger, the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types of carbohydrates and sulfur sources. Diet was a major determinant of functions expressed by this artificial nine-member community and of the genes that impact D. piger fitness; the latter includes high- and low-affinity systems for using ammonia, a limiting resource for D. piger in mice consuming a polysaccharide-rich diet. Although genes involved in hydrogen consumption and sulfate reduction are necessary for its colonization, varying dietary-free sulfate levels did not significantly alter levels of D. piger, which can obtain sulfate from the host in part via cross-feeding mediated by Bacteroides-encoded sulfatases. Chondroitin sulfate, a common dietary supplement, increased D. piger and H2S levels without compromising gut barrier integrity. A chondroitin sulfate-supplemented diet together with D. piger impacted the assemblage’s substrate utilization preferences, allowing consumption of more reduced carbon sources and increasing the abundance of the H2-producing Actinobacterium, Collinsella aerofaciens. Our findings provide genetic and metabolic details of how this H2-consuming SRB shapes the responses of a microbiota to diet ingredients and a framework for examining how individuals lacking D. piger differ from those who harbor it. PMID:23898195

Metabolic niche of a prominent sulfate-reducing human gut bacterium.

PubMed

Rey, Federico E; Gonzalez, Mark D; Cheng, Jiye; Wu, Meng; Ahern, Philip P; Gordon, Jeffrey I

2013-08-13

Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger, the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types of carbohydrates and sulfur sources. Diet was a major determinant of functions expressed by this artificial nine-member community and of the genes that impact D. piger fitness; the latter includes high- and low-affinity systems for using ammonia, a limiting resource for D. piger in mice consuming a polysaccharide-rich diet. Although genes involved in hydrogen consumption and sulfate reduction are necessary for its colonization, varying dietary-free sulfate levels did not significantly alter levels of D. piger, which can obtain sulfate from the host in part via cross-feeding mediated by Bacteroides-encoded sulfatases. Chondroitin sulfate, a common dietary supplement, increased D. piger and H2S levels without compromising gut barrier integrity. A chondroitin sulfate-supplemented diet together with D. piger impacted the assemblage's substrate utilization preferences, allowing consumption of more reduced carbon sources and increasing the abundance of the H2-producing Actinobacterium, Collinsella aerofaciens. Our findings provide genetic and metabolic details of how this H2-consuming SRB shapes the responses of a microbiota to diet ingredients and a framework for examining how individuals lacking D. piger differ from those who harbor it.

Factor h and properdin recognize different epitopes on renal tubular epithelial heparan sulfate.

PubMed

Zaferani, Azadeh; Vivès, Romain R; van der Pol, Pieter; Navis, Gerjan J; Daha, Mohamed R; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A; van den Born, Jacob

2012-09-07

During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope than properdin. Factor H was present on the urinary side of renal tubular cells in proteinuric, but not in normal renal tissues and colocalized with properdin in proteinuric kidneys. Factor H dose-dependently bound to proximal tubular epithelial cells (PTEC) in vitro. Preincubation of factor H with exogenous heparin and pretreatment of PTECs with heparitinase abolished the binding to PTECs. Surface plasmon resonance experiments showed high affinity of factor H for heparin and HS (K(D) values of 32 and 93 nm, respectively). Using a library of HS-like polysaccharides, we showed that chain length and high sulfation density are the most important determinants for glycosaminoglycan-factor H interaction and clearly differ from properdin-heparinoid interaction. Coincubation of properdin and factor H did not hamper HS/heparin binding of one another, indicating recognition of different nonoverlapping epitopes on HS/heparin by factor H and properdin. Finally we showed that certain low anticoagulant heparinoids can inhibit properdin binding to tubular HS, with a minor effect on factor H binding to tubular HS. As a result, these heparinoids can control the alternative complement pathway. In conclusion, factor H and properdin interact with different HS epitopes of PTECs. These interactions can be manipulated with some low anticoagulant heparinoids, which can be important for preventing complement-derived tubular injury in proteinuric renal diseases.

Monofluorophosphate is a selective inhibitor of respiratory sulfate-reducing microorganisms.

PubMed

Carlson, Hans K; Stoeva, Magdalena K; Justice, Nicholas B; Sczesnak, Andrew; Mullan, Mark R; Mosqueda, Lorraine A; Kuehl, Jennifer V; Deutschbauer, Adam M; Arkin, Adam P; Coates, John D

2015-03-17

Despite the environmental and economic cost of microbial sulfidogenesis in industrial operations, few compounds are known as selective inhibitors of respiratory sulfate reducing microorganisms (SRM), and no study has systematically and quantitatively evaluated the selectivity and potency of SRM inhibitors. Using general, high-throughput assays to quantitatively evaluate inhibitor potency and selectivity in a model sulfate-reducing microbial ecosystem as well as inhibitor specificity for the sulfate reduction pathway in a model SRM, we screened a panel of inorganic oxyanions. We identified several SRM selective inhibitors including selenate, selenite, tellurate, tellurite, nitrate, nitrite, perchlorate, chlorate, monofluorophosphate, vanadate, molydate, and tungstate. Monofluorophosphate (MFP) was not known previously as a selective SRM inhibitor, but has promising characteristics including low toxicity to eukaryotic organisms, high stability at circumneutral pH, utility as an abiotic corrosion inhibitor, and low cost. MFP remains a potent inhibitor of SRM growing by fermentation, and MFP is tolerated by nitrate and perchlorate reducing microorganisms. For SRM inhibition, MFP is synergistic with nitrite and chlorite, and could enhance the efficacy of nitrate or perchlorate treatments. Finally, MFP inhibition is multifaceted. Both inhibition of the central sulfate reduction pathway and release of cytoplasmic fluoride ion are implicated in the mechanism of MFP toxicity.

Sulfate transport in apical membrane vesicles isolated from tracheal epithelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elgavish, A.; DiBona, D.R.; Norton, P.

1987-09-01

Sulfate uptake in apical membrane vesicles isolated from bovine tracheal epithelium is shown to occur into an osmotically sensitive intravesicular space, via a carrier-mediated system. This conclusion is based on three lines of evidence: 1) saturation kinetics: 2) substrate specificity; and 3) inhibition by the anion transport inhibitors SITS and DIDS. The affinity of the transport system is highest in low ionic strength media and decreases in the presence of gluconate. Chloride appears to cis-inhibit sulfate uptake and to trans-stimulate sulfate efflux. Cis-inhibition and trans-stimulation studies with a variety of anions indicate that this exchange system may be shared bymore » HCO/sub 3//sup -/, S/sub 2/O/sub 3//sup 2 -/, SeO/sub 4//sup 2 -/, and MoO/sub 4//sup 2 -/ but not by H/sub 2/PO/sub 4//sup -/ or HAsO/sub 4//sup 2/. Studies indicate that protons may play two distinct roles in sulfate transport in this system. These studies show that the carrier-mediated system can function in the absence of chloride. The overshoot observed in the presence of a proton gradient indicates that under those conditions the mechanism of transport may be a SO/sub 4//sup 2 -/-OH/sup -/ exchange.« less

Polysaccharides from brown algae Sargassum duplicatum: the structure and anticancer activity in vitro.

PubMed

Usoltseva, Roza V; Anastyuk, Stanislav D; Shevchenko, Natalia M; Surits, Valerii V; Silchenko, Artem S; Isakov, Vladimir V; Zvyagintseva, Tatiana N; Thinh, Pham Duc; Ermakova, Svetlana P

2017-11-01

The laminaran SdL and fucoidan SdF were isolated from brown algae Sargassum duplicatum. SdL was 1,3;1,6-β-d-glucan (1,3:1,6=6:1) with a main chain, represented by 1,3-linked glucose residues, due to NMR spectroscopy data. Single glucose residues could form branches at C6. Unusual structure of fucoidan SdF was studied by chemical and enzymatic methods, NMR spectroscopy of desulfated and deacetylated polysaccharide and mass spectrometry of fucoidan fragments labeled with 18 O. Fucoidan was sulfated (31.7%) and acetylated galactofucan (Fuc:Gal∼1:1) with a main chain of 1,4-linked alternating α-l-fucose and β-d-galactose residues. Side chains were represented by extensive (DP≥5) 1,3-linked 2,4-disulfated α-l-fucose residues with branching points at C2. Fucose residues in the main chain were sulfated at C2 and less at C3, while galactose residues were sulfated at C2, C3, and less at C4, C6. The fucoidan SdF was effective against colony formation of colon cancer cells in vitro. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

Raish, Mohammad

2017-04-01

The polysaccharide extract of Momordica charantia has various biological activities; however, its effect on endothelial dysfunction in myocardial infarction remains unclear. To elucidate this, myocardial infarction was induced in rats using isoproterenol (ISP). Pretreatment with M. charantia polysaccharides (MCP; 150 or 300mg/kg) for 25days significantly inhibited increases in heart weight, the heart-weight-to-body-weight ratio, and infarction size, and ameliorated the increased serum levels of aspartate transaminase, creatine kinase, lactate dehydrogenase, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. In addition, MCP enhanced the activity of superoxide dismutase, catalase, and non-protein sulfhydryls, and decreased the level of lipid peroxidation. Moreover, MCP pretreatment downregulated the expression of proinflammatory cytokines (tumor necrosis factor alpha, interleukin (IL)-6, and IL-10), inflammatory markers (nitric oxide, myeloperoxidase, and inducible nitric oxide synthase), and apoptotic markers (caspase-3 and BAX), and upregulated Bcl-2 expression. Pretreatment with MCP reduced myonecrosis, edema, and inflammatory cell infiltration, and restored cardiomyocytes architecture. This myocardial protective effect could be related to the enhancement of the antioxidant defense system through the nuclear factor kappa B (NF-kB) pathways, and to anti-apoptosis through regulation of Bax, caspase-3, and Bcl-2. Copyright © 2017 Elsevier B.V. All rights reserved.

Sulfation of LH Does Not Affect Intracellular Trafficking

PubMed Central

Pearl, Christopher A.; Boime, Irving

2009-01-01

LH and FSH are produced by the same gonadotrope cells of the anterior pituitary but differ in their mode of secretion. LH secretion is primarily episodic, or regulated, while FSH secretion is primarily basal, or constitutive. The asparagine (N)-linked oligosaccharides of LH and FSH terminate with sulfate and sialic acid, respectively. TSH also contains sulfated N-linked oligosaccharides and is secreted through the regulated pathway. It has been hypothesized that sulfate plays a role in segregating LH to the regulated pathway. Using a mouse pituitary model, we tested this hypothesis by examining the secretory fate of LH from pituitaries treated with sodium chlorate, a known inhibitor of sulfation. Here we show that mouse LH is sulfated and secreted through the regulated pathway, while FSH is secreted constitutively. LH secretion from chlorate treated pituitaries, which showed complete inhibition of sulfation, was similar to untreated pituitaries. These data suggest that the metabolic role for sulfated N-linked oligosaccharides is not for intracellular trafficking but for the extracellular bioactivity of LH. PMID:19647136

[Super Liquid Crystalline Polysaccharides Produced by Ultimately-ecological Microreactors].

PubMed

Kaneko, Tatsuo; Okajima, Maiko K

2018-01-01

　Cyanobacteria fix carbon dioxide and nitrogen from the atmosphere using solar energy to produce various biomolecules, and thus are regarded as ultimately ecological microreactors. Sacran is a cyanobacterial polysaccharide with a very high molecular weight of 29 Mg/mol, which is extracted from Aphanothece sacrum cyanobacterium mass-cultivated in freshwater environments such as river or spring. Sacran is a water-soluble heteropolysaccharide comprising more than 6 kinds of sugar residues and contains 12% sulfate anionic groups and 27% carboxyls. Sacran has a super-absorbent function of water, which can retain 6000 mL for 1 g specimen, due to very long hydrating chains. The value is much higher than hyaluronic acid or conventional super-absorbent polymers. Sacran exhibits self-orienting behavior in dilute solution at a concentration range over 0.25 wt%, which is quite low when compared with conventional liquid crystalline polysaccharides. Mesogenic helical chains of sacrans have extremely high aspect ratios of 1600 for highly persistent lengths of 32 micrometer. Through the liquid crystallinity, sacran solution shows a shear-thinning behavior and the solution spread over a substrate such as biological skin very efficiently to create a thin layer. Applied on atopic dermatitis skin sacran solution exerts excellent moisturizing effect and anti-itching action.

Structural characterization of an all-aminosugar-containing capsular polysaccharide from Colwellia psychrerythraea 34H

PubMed Central

Casillo, Angela; Ståhle, Jonas; Parrilli, Ermenegilda; Sannino, Filomena; Mitchell, Daniel E.; Pieretti, Giuseppina; Gibson, Matthew I.; Marino, Gennaro; Lanzetta, Rosa; Parrilli, Michelangelo; Widmalm, Göran; Tutino, Maria L.; Corsaro, Maria M.

2017-01-01

Colwellia psychrerythraea strain 34H, a Gram-negative bacterium isolated from Arctic marine sediments, is considered a model to study the adaptation to cold environments. Recently, we demonstrated that C. psychrerythraea 34H produces two different extracellular polysaccharides, a capsular polysaccharide and a medium released polysaccharide, which confer cryoprotection to the bacterium. In this study, we report the structure of an additional capsular polysaccharide produced by Colwellia grown at a different temperature. The structure was determined using chemical methods, and one- and two-dimensional NMR spectroscopy. The results showed a trisaccharide repeating unit made up of only amino-sugar residues: N-acetyl-galactosamine, 2,4-diacetamido-2,4,6-trideoxy-glucose (bacillosamine), and 2-acetamido-2-deoxyglucuronic acid with the following structure: →4)-β-d-GlcpNAcA-(1→3)-β-d-QuipNAc4NAc-(1→3)-β-d-GalpNAc-(1→. The 3D model, generated in accordance with 1H,1H-NOE NMR correlations and consisting of ten repeating units, shows a helical structure. In contrast with the other extracellular polysaccharides produced from Colwellia at 4 °C, this molecule displays only a low ice recrystallization inhibition activity. PMID:28161737

The anti-obesity effect of green tea polysaccharides, polyphenols and caffeine in rats fed with a high-fat diet.

PubMed

Xu, Yan; Zhang, Min; Wu, Tao; Dai, ShengDong; Xu, Jinling; Zhou, Zhongkai

2015-01-01

Beneficial effects of green tea (Camellia sinensis, Theaceae) extracts against obesity have been reported; however, the anti-obesity ability of the major components of green tea, polysaccharides, polyphenols and caffeine is not clear. Therefore, experiments with total green tea extracts, polyphenols, polysaccharides, caffeine, and a complex of polysaccharide and polyphenol at a dose of 400 or 800 mg kg⁻¹ were conducted on high-fat diet fed rats for 6 weeks to investigate their anti-obesity effects. The results indicated that polyphenols and polysaccharides were responsible for the suppressive effect of green tea extracts on body weight increase and fat accumulation. Moreover, polyphenols, polysaccharides, or caffeine can improve blood lipid and antioxidant levels, and effectively reduce rat serum leptin levels, inhibit the absorption of fatty acids, and markedly reduce the expression levels of the IL-6 and TNF-α gene. Furthermore, it was shown that polysaccharides and polyphenols were synergistic in reduction of serum leptin levels and in anti-inflammatory activity. These results suggest that the polysaccharide combination with polyphenols might be a potential therapy against obesity.

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.

Bacterially Induced Dolomite Formation in the Presence of Sulfate Ions under Aerobic Conditions

NASA Astrophysics Data System (ADS)

Sanchez-Roman, M.; McKenzie, J. A.; Vasconcelos, C.; Rivadeneyra, M.

2005-12-01

The origin of dolomite remains a long-standing enigma in sedimentary geology because, although thermodynamically favorable, precipitation of dolomite from modern seawater does not occur. Experiments conducted at elevated temperatures (200 oC) indicated that the presence of small concentrations of sulfate ions inhibits the transformation of calcite to dolomite [1]. Indeed, sulfate ions appeared to inhibit dolomite formation above 2 mM concentration (versus 28 mM in modern seawater). Recently, culture experiments have demonstrated that sulfate-reducing bacteria mediate the precipitation of dolomite at Earth surface conditions in the presence of sustained sulfate ion concentrations [2,3]. Additionally, in a number of modern hypersaline environments, dolomite forms from solutions with high sulfate ion concentrations (2 to 70 times seawater). These observations suggest that the experimentally observed sulfate-ion inhibition [1] may not apply to all ancient dolomite formation. Here, we report aerobic culture experiments conducted at low temperatures (25 and 35 oC) and variable sulfate ion concentrations (0, 0.5, 1 and 2 x seawater values) using moderately halophilic bacteria, Halomonas meridiana. After an incubation period of 15 days, experiments at 35 oC with variable sulfate ion concentrations (0, 0.5 x and seawater values) contained crystals of Ca-dolomite and stochiometric dolomite. The experiment at 35 oC with 2 x seawater sulfate ion concentration produced dolomite crystals after 20 days of incubation. In a parallel set of experiments at 25 oC, precipitation of dolomite was observed after 25 days of incubation in cultures with variable sulfate ion concentrations (0, 0.5 x and seawater values). In the culture with 2 x seawater sulfate ion concentration, dolomite crystals were observed after 30 days. Our study demonstrates that halophilic bacteria (or heterotrophic microorganisms), which do not require sulfate ions for metabolism, can mediate dolomite precipitation

Marine Bacterial Polysaccharide EPS11 Inhibits Cancer Cell Growth via Blocking Cell Adhesion and Stimulating Anoikis

PubMed Central

Cao, Ruobing; Jin, Weihua; Shan, Yeqi; Wang, Ju; Liu, Ge; Kuang, Shan

2018-01-01

Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its cytotoxic effects through affecting cancer cell adhesion and anoikis. Firstly, we found that EPS11 could significantly affect cell proliferation and block cell adhesion in A549 cells. We further demonstrated that the expression of several cell adhesion associated proteins is downregulated and the filiform structures of cancer cells are destroyed after EPS11 treatment. Interestingly, the destruction of filiform structures in A549 cells by EPS11 is in a dose-dependent manner, and the inhibitory tendency is very consistent with that observed in the cell adhesion assay, which confirms that filiform structures play important roles in modulating cell adhesion. Moreover, we showed that EPS11 induces apoptosis of A549 cells through stimulating βIII-tubulin associated anoikis: (i) EPS11 inhibits the expression of βIII-tubulin in both transcription and translation levels; and (ii) EPS11 treatment dramatically decreases the phosphorylation of protein kinase B (PKB or AKT), a critical downstream effector of βIII-tubulin. Importantly, EPS11 evidently inhibits the growth of A549-derived tumor xenografts in vivo. Thus, our results suggest that EPS11 may be a potential candidate for human non-small cell lung carcinoma treatment via blocking filiform structure mediated adhesion and stimulating βIII-tubulin associated anoikis. PMID:29518055

Lycium barbarum polysaccharide protects against LPS-induced ARDS by inhibiting apoptosis, oxidative stress, and inflammation in pulmonary endothelial cells.

PubMed

Chen, Lan; Li, Wen; Qi, Di; Wang, Daoxin

2018-04-01

Acute respiratory distress syndrome (ARDS) is a heterogenous syndrome characterised by diffuse alveolar damage, with an increase in lung endothelial and epithelial permeability. Lycium barbarum polysaccharide (LBP), the most biologically active fraction of wolfberry, possesses antiapoptotic and antioxidative effects in distinct situations. In the present study, the protective effects and potential molecular mechanisms of LBP against lipopolysaccharide (LPS)-induced ARDS were investigated in the mice and in the human pulmonary microvascular endothelial cells (HPMECs). The data indicated that pretreatment with LBP significantly attenuated LPS-induced lung inflammation and pulmonary oedema in vivo. LBP significantly reversed LPS-induced decrease in cell viability, increase in apoptosis and oxidative stress via inhibiting caspase-3 activation and intracellular reactive oxygen species (ROS) production in vitro. Moreover, the scratch assay verified that LBP restored the dysfunction of endothelial cells (ECs) migration induced by LPS stimulation. Furthermore, LBP also significantly suppressed LPS-induced NF-κB activation, and subsequently reversed the release of cytochrome c. These results showed the antiapoptosis and antioxidant LBP could partially protect against LPS-induced ARDS through promoting the ECs survival and scavenging ROS via inhibition of NF-κB signalling pathway. Thus, LBP could be potentially used for ARDS against pulmonary inflammation and pulmonary oedema.

Interactions between acidified dispersions of milk proteins and dextran or dextran sulfate.

PubMed

Pachekrepapol, U; Horne, D S; Lucey, J A

2014-09-01

Polysaccharides are often used to stabilize cultured milk products, although the nature of these interactions is not entirely clear. The objective of this study was to investigate phase behavior of milk protein dispersions with added dextran (DX; molecular weight = 2 × 10(6) Da) or dextran sulfate (DS; molecular weight = 1.4 × 10(6) Da) as examples of uncharged and charged polysaccharides, respectively. Reconstituted skim milk (5-20% milk solids, wt/wt) was acidified to pH 4.4, 4.6, 4.8, or 4.9 at approximately 0°C (to inhibit gelation) by addition of 3 N HCl. Dextran or DS was added to acidified milk samples to give concentrations of 0 to 2% (wt/wt) and 0 to 1% (wt/wt) polysaccharide, respectively. Milk samples were observed for possible phase separation after storage at 0°C for 1 and 24h. Possible gelation of these systems was determined by using dynamic oscillatory rheology. The type of interactions between caseins and DX or DS was probed by determining the total carbohydrate analysis of supernatants from phase-separated samples. At 5.0 to 7.5% milk solids, phase separation of milk samples occurred after 24h even without DX or DS addition, due to destabilization of caseins in these acidic conditions, and a stabilizing effect was observed when 0.7 or 1.0% DS was added. At higher milk solids content, phase separation was not observed without DX or DS addition. Similar results were observed at all pH levels. Gelation occurred in samples containing high milk solids (≥10%) with the addition of 1.0 to 2.0% DX or 0.4 to 1.0% DS. Based on carbohydrate analysis of supernatants, we believe that DX interacted with milk proteins through a type of depletion flocculation mechanism, whereas DS appeared to interact via electrostatic-type interactions with milk proteins. This study helps to explain how uncharged and charged stabilizers influence the texture of cultured dairy products. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All

Endothelial Heparan Sulfate 6-O-Sulfation Levels Regulate Angiogenic Responses of Endothelial Cells to Fibroblast Growth Factor 2 and Vascular Endothelial Growth Factor*

PubMed Central

Ferreras, Cristina; Rushton, Graham; Cole, Claire L.; Babur, Muhammad; Telfer, Brian A.; van Kuppevelt, Toin H.; Gardiner, John M.; Williams, Kaye J.; Jayson, Gordon C.; Avizienyte, Egle

2012-01-01

Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor 165 (VEGF165) are potent pro-angiogenic growth factors that play a pivotal role in tumor angiogenesis. The activity of these growth factors is regulated by heparan sulfate (HS), which is essential for the formation of FGF2/FGF receptor (FGFR) and VEGF165/VEGF receptor signaling complexes. However, the structural characteristics of HS that determine activation or inhibition of such complexes are only partially defined. Here we show that ovarian tumor endothelium displays high levels of HS sequences that harbor glucosamine 6-O-sulfates when compared with normal ovarian vasculature where these sequences are also detected in perivascular area. Reduced HS 6-O-sulfotransferase 1 (HS6ST-1) or 6-O-sulfotransferase 2 (HS6ST-2) expression in endothelial cells impacts upon the prevalence of HS 6-O-sulfate moieties in HS sequences, which consist of repeating short, highly sulfated S domains interspersed by transitional N-acetylated/N-sulfated domains. 1–40% reduction in 6-O-sulfates significantly compromises FGF2- and VEGF165-induced endothelial cell sprouting and tube formation in vitro and FGF2-dependent angiogenesis in vivo. Moreover, HS on wild-type neighboring endothelial or smooth muscle cells fails to restore endothelial cell sprouting and tube formation. The affinity of FGF2 for HS with reduced 6-O-sulfation is preserved, although FGFR1 activation is inhibited correlating with reduced receptor internalization. These data show that 6-O-sulfate moieties in endothelial HS are of major importance in regulating FGF2- and VEGF165-dependent endothelial cell functions in vitro and in vivo and highlight HS6ST-1 and HS6ST-2 as potential targets of novel antiangiogenic agents. PMID:22927437

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.

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.

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

Preparation, characterization and in vitro anticoagulant activity of corn stover xylan sulfates.

PubMed

Cheng, He-Li; Liu, Hao; Feng, Qing-Hua; Xie, Yi-Min; Zhan, Huai-Yu

2017-02-01

A new anticoagulant agent was prepared by introducing sulfate groups into corn stover xylan through homogeneous reactions. Three organic solvents, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and formamide (FA), were adopted as reaction media, with the assistance of LiCl. Structural characterization by FT-IR and 13 CNMR showed that xylan sulfate (XS) could be successfully synthesized with SO 3 ∙Pyridine (SO 3 ∙Py) complexes sulfation reagent in the three media. The effect of sulfation temperature, sulfation time, media type and molar ratio of -SO 3 /-OH on the degree of substitution (DS) and degree of the polymerization (DP) were studied. DMF/LiCl were more effective than DMSO/LiCl and FA/LiCl in preparation of xylan sulfate with high DS. The optimal conditions for sulfation were obtained when SO 3 ∙Py complex was added to DMF/LiCl with -SO 3 /-OH ratio of 1.5:1 and maintained at 50 °C for 3 h. Degree of polymerization of xylan was decreased during the sulfation process and DMF/LiCl offered the least xylan degradation as compared with DMSO/LiCl or FA/LiCl. Anticoagulant activities of the resultant xylan sulfates with different DS were evaluated by using activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). Results indicated that the introducing of sulfate groups into xylan did endow the polysaccharides with anticoagulant activity. The APTT and TT of XS with DS of 1.20 reached 141 and 45.3 s at a dosage of 20 μg/mL, while the APTT and TT values for the blank sample were only 35.5 and 15.6 s. Furthermore, coagulation time was prolonged with the increase of DS and the concentration of XS. Our findings provide new insights into the value-added utilization of agricultural biomass.

Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia.

PubMed

Hermawan, Idam; Furuta, Atsushi; Higashi, Masahiro; Fujita, Yoshihisa; Akimitsu, Nobuyoshi; Yamashita, Atsuya; Moriishi, Kohji; Tsuneda, Satoshi; Tani, Hidenori; Nakakoshi, Masamichi; Tsubuki, Masayoshi; Sekiguchi, Yuji; Noda, Naohiro; Tanaka, Junichi

2017-04-11

Bioassay-guided separation of a lipophilic extract of the crinoid Alloeocomatella polycladia , inhibiting the activity of HCV NS3 helicase, yielded two groups of molecules: cholesterol sulfate and four new aromatic sulfates 1 - 4 . The structures of the aromatics were elucidated by spectroscopic analysis in addition to theoretical studies. The aromatic sulfates 1 - 4 showed moderate inhibition against NS3 helicase with IC 50 values of 71, 95, 7, and 5 μM, respectively.

Hericium erinaceus polysaccharide-protein HEG-5 inhibits SGC-7901 cell growth via cell cycle arrest and apoptosis.

PubMed

Zan, Xinyi; Cui, Fengjie; Li, Yunhong; Yang, Yan; Wu, Di; Sun, Wenjing; Ping, Lifeng

2015-05-01

HEG-5 is a novel polysaccharide-protein purified from the fermented mycelia of Hericium erinaceus CZ-2. The present study aims to investigate the effects of HEG-5 on proliferation, cell cycle and apoptosis of human gastric cancer cells SGC-7901. Here, we first uncover that HEG-5 significantly inhibited the proliferation and colony formation of SGC-7901 cells by promoting apoptosis and cell cycle arrest at S phase. RT-PCR and Western blot analysis suggested that HEG-5 could decrease the expressions of Bcl2, PI3K and AKT1, while increase the expressions of Caspase-8, Caspase-3, p53, CDK4, Bax and Bad. These findings indicated that the Caspase-8/-3-dependent, p53-dependent mitochondrial-mediated and PI3k/Akt signaling pathways involved in the molecular events of HEG-5 induced apoptosis and cell cycle arrest. Thus, our study provides in vitro evidence that HEG-5 may be taken as a potential candidate for treating gastric cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of ammonium sulfate and urea on PCDD/F formation from active carbon and possible mechanism of inhibition.

PubMed

Yan, Mi; Qi, Zhifu; Yang, Jie; Li, Xiaodong; Ren, Jianli; Xu, Zhang

2014-11-01

The effect of ammonium sulfate ((NH4)2SO4) and urea (CO(NH2)2) on polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) formation from active carbon was investigated in this study. Both additives could significantly inhibit PCDD/F formation, and PCDD/F (TEQ) generation was reduced to 98.5% (98%) or 64.5% (77.2%) after 5% (NH4)2SO4 or CO(NH2)2 was added into model ash, respectively. The inhibition efficiency of PCDDs was higher than the value of PCDFs, however, the reduction of PCDD/F yield was mainly from PCDFs decreasing. In addition, the solid-phase products were reduced more than the gas-phase compounds by inhibitors. By the measurement of chlorine emission in the phase of ion (Cl[Cl(-)]) and molecule gas (Cl[Cl2]), it was observed that both Cl[Cl(-)] and Cl[Cl2] were reduced after inhibitors were added into ash. Cl[Cl2] was reduced to 51.0% by urea addition, which was supposed as one possible mechanism of PCDD/F inhibition. Copyright © 2014. Published by Elsevier B.V.

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.

Neutral monosaccharide composition analysis of plant-derived oligo- and polysaccharides by high performance liquid chromatography.

PubMed

Yan, Jun; Shi, Songshan; Wang, Hongwei; Liu, Ruimin; Li, Ning; Chen, Yonglin; Wang, Shunchun

2016-01-20

A novel analytical method for neutral monosaccharide composition analysis of plant-derived oligo- and polysaccharides was developed using hydrophilic interaction liquid chromatography coupled to a charged aerosol detector. The effects of column type, additives, pH and column temperature on retention and separation were evaluated. Additionally, the method could distinguish potential impurities in samples, including chloride, sulfate and sodium, from sugars. The results of validation demonstrated that this method had good linearity (R(2) ≥ 0.9981), high precision (relative standard deviation ≤ 4.43%), and adequate accuracy (94.02-103.37% recovery) and sensitivity (detection limit: 15-40 ng). Finally, the monosaccharide compositions of the polysaccharide from Eclipta prostrasta L. and stachyose were successfully profiled through this method. This report represents the first time that all of these common monosaccharides could be well-separated and determined simultaneously by high performance liquid chromatography without additional derivatization. This newly developed method is convenient, efficient and reliable for monosaccharide analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Controls of Polysaccharide Chemistry on the Kinetics and Thermodynamics of Heterogeneous Calcium Carbonate Nucleation

NASA Astrophysics Data System (ADS)

Giuffre, A. J.; Han, N.; Dove, P. M.

2011-12-01

. Preliminary analyses of the data attribute these differences to changes in both kinetic and thermodynamic barriers to nucleation. These initial findings indicate that polysaccharide chemistry can have active roles in regulating the kinetics of calcite formation. It may be time to reconsider their presumed function as inert framework molecules for mineralized structures. Future work will investigate CaCO3 nucleation on substrates of polysaccharides with more complex functionalization and monomer sequences to decipher the origins of these effects in promoting or inhibiting mineralization.

Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair.

PubMed

Zhou, Feifei; Zhang, Xianzhu; Cai, Dandan; Li, Jun; Mu, Qin; Zhang, Wei; Zhu, Shouan; Jiang, Yangzi; Shen, Weiliang; Zhang, Shufang; Ouyang, Hong Wei

2017-11-01

The demand of favorable scaffolds has increased for the emerging cartilage tissue engineering. Chondroitin sulfate (CS) and silk fibroin have been investigated and reported with safety and excellent biocompatibility as tissue engineering scaffolds. However, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate neo-tissue similar to natural articular cartilage. Meanwhile the silk fibroin is well used as a structural constituent material because its remarkable mechanical properties, long-lasting in vivo stability and hypoimmunity. The application of composite silk fibroin and CS scaffolds for joint cartilage repair has not been well studied. Here we report that the combination of silk fibroin and CS could synergistically promote articular cartilage defect repair. The silk fibroin (silk) and silk fibroin/CS (silk-CS) scaffolds were fabricated with salt-leaching, freeze-drying and crosslinking methodologies. The biocompatibility of the scaffolds was investigated in vitro by cell adhesion, proliferation and migration with human articular chondrocytes. We found that silk-CS scaffold maintained better chondrocyte phenotype than silk scaffold; moreover, the silk-CS scaffolds reduced chondrocyte inflammatory response that was induced by interleukin (IL)-1β, which is in consistent with the well-documented anti-inflammatory activities of CS. The in vivo cartilage repair was evaluated with a rabbit osteochondral defect model. Silk-CS scaffold induced more neo-tissue formation and better structural restoration than silk scaffold after 6 and 12weeks of implantation in ICRS histological evaluations. In conclusion, we have developed a silk fibroin/ chondroitin sulfate scaffold for cartilage tissue engineering that exhibits immuno-inhibition property and can improve the self-repair capacity of cartilage. Severe cartilage defect such as osteoarthritis (OA) is difficult to self-repair because of its avascular, aneural and alymphatic nature

Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia

PubMed Central

Hermawan, Idam; Furuta, Atsushi; Higashi, Masahiro; Fujita, Yoshihisa; Akimitsu, Nobuyoshi; Yamashita, Atsuya; Moriishi, Kohji; Tsuneda, Satoshi; Tani, Hidenori; Nakakoshi, Masamichi; Tsubuki, Masayoshi; Sekiguchi, Yuji; Noda, Naohiro; Tanaka, Junichi

2017-01-01

Bioassay-guided separation of a lipophilic extract of the crinoid Alloeocomatella polycladia, inhibiting the activity of HCV NS3 helicase, yielded two groups of molecules: cholesterol sulfate and four new aromatic sulfates 1–4. The structures of the aromatics were elucidated by spectroscopic analysis in addition to theoretical studies. The aromatic sulfates 1–4 showed moderate inhibition against NS3 helicase with IC50 values of 71, 95, 7, and 5 μM, respectively. PMID:28398249

Sulfated, low-molecular-weight lignins are potent inhibitorsof plasmin, in addition to thrombin and factor Xa: Novel opportunity for controlling complex pathologies.

PubMed

Henry, Brian L; Abdel Aziz, May; Zhou, Qibing; Desai, Umesh R

2010-03-01

Recently we prepared sulfated, low-molecular-weight lignins (LMWLs) to mimic the biological activities of heparin and heparan sulfate. Chemo-enzymatically prepared sulfated LMWLs represent a library of diverse non-sugar, aromatic molecules with structures radically different from the heparins, and have been found to potently inhibit thrombin and factor Xa. To assess their effect on the fibrinolytic system, we studied the interaction of LMWLs with human plasmin. Enzyme inhibition studies indicate that the three sulfated LMWLs studied inhibit plasmin with IC50 values in the range of 0.24 and 1.3 mM, which are marginally affected in the presence of antithrombin. Similarly, plasmin degradation of polymeric fibrin is also inhibited by sulfated LMWLs. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of chromogenic substrates decreases nearly 70% in the presence of LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. Competitive binding studies indicate that the sulfated LMWLs compete with full-length heparin. Comparison with thrombin-heparin crystal structure identifies an anionic region on plasmin as a plausible sulfated LMWL binding site. Overall, the chemo-enzymatic origin coupled with coagulation and fibrinolysis inhibition properties of sulfated LMWLs present novel opportunities for designing new pharmaceutical agents that regulate complex pathologies in which both systems are known to play important roles such as disseminated intravascular coagulation.

Effects of chlorate on the sulfation process of Trypanosoma cruzi glycoconjugates. Implication of parasite sulfates in cellular invasion.

PubMed

Ferrero, Maximiliano R; Soprano, Luciana L; Acosta, Diana M; García, Gabriela A; Esteva, Mónica I; Couto, Alicia S; Duschak, Vilma G

2014-09-01

Sulfation, a post-translational modification which plays a key role in various biological processes, is inhibited by competition with chlorate. In Trypanosoma cruzi, the agent of Chagas' disease, sulfated structures have been described as part of glycolipids and we have reported sulfated high-mannose type oligosaccharides in the C-T domain of the cruzipain (Cz) glycoprotein. However, sulfation pathways have not been described yet in this parasite. Herein, we studied the effect of chlorate treatment on T. cruzi with the aim to gain some knowledge about sulfation metabolism and the role of sulfated molecules in this parasite. In chlorate-treated epimastigotes, immunoblotting with anti-sulfates enriched Cz IgGs (AS-enriched IgGs) showed Cz undersulfation. Accordingly, a Cz mobility shift toward higher isoelectric points was observed in 2D-PAGE probed with anti-Cz antibodies. Ultrastructural membrane abnormalities and a significant decrease of dark lipid reservosomes were shown by electron microscopy and a significant decrease in sulfatide levels was confirmed by TLC/UV-MALDI-TOF-MS analysis. Altogether, these results suggest T. cruzi sulfation occurs via PAPS. Sulfated epitopes in trypomastigote and amastigote forms were evidenced using AS-enriched IgGs by immunoblotting. Their presence on trypomastigotes surface was demonstrated by flow cytometry and IF with Cz/dCz specific antibodies. Interestingly, the percentage of infected cardiac HL-1 cells decreased 40% when using chlorate-treated trypomastigotes, suggesting sulfates are involved in the invasion process. The same effect was observed when cells were pre-incubated with dCz, dC-T or an anti-high mannose receptor (HMR) antibody, suggesting Cz sulfates and HMR are also involved in the infection process by T. cruzi. Copyright © 2014 Elsevier B.V. All rights reserved.

Extraction and characterization of polysaccharides from Semen Cassiae by microwave-assisted aqueous two-phase extraction coupled with spectroscopy and HPLC.

PubMed

Chen, Zhi; Zhang, Wei; Tang, Xunyou; Fan, Huajun; Xie, Xiujuan; Wan, Qiang; Wu, Xuehao; Tang, James Z

2016-06-25

A novel and rapid method for simultaneous extraction and separation of the different polysaccharides from Semen Cassiae (SC) was developed by microwave-assisted aqueous two-phase extraction (MAATPE) in a one-step procedure. Using ethanol/ammonium sulfate system as a multiphase solvent, the effects of MAATPE on the extraction of polysaccharides from SC such as the composition of the ATPS, extraction time, temperature and solvent-to-material ratio were investigated by UV-vis analysis. Under the optimum conditions, the yields of polysaccharides were 4.49% for the top phase, 8.80% for the bottom phase and 13.29% for total polysaccharides, respectively. Compared with heating solvent extraction and ultrasonic assisted extraction, MAATPE exhibited the higher extraction yields in shorter time. Fourier-transform infrared spectra showed that two polysaccharides extracted from SC to the top and bottom phases by MAATPE were different from each other in their chemical structures. Through acid hydrolysis and PMP derivatization prior to HPLC, analytical results by indicated that a polysaccharide of the top phases was a relatively homogeneous homepolysaccharide composed of dominant gucose glucose while that of the bottom phase was a water-soluble heteropolysaccharide with multiple components of glucose, xylose, arabinose, galactose, mannose and glucuronic acid. Molar ratios of monosaccharides were 95.13:4.27:0.60 of glucose: arabinose: galactose for the polysaccharide from the top phase and 62.96:14.07:6.67: 6.67:5.19:4.44 of glucose: xylose: arabinose: galactose: mannose: glucuronic acid for that from the bottom phase, respectively. The mechanism for MAATPE process was also discussed in detail. MAATPE with the aid of microwave and the selectivity of the ATPS not only improved yields of the extraction, but also obtained a variety of polysaccharides. Hence, it was proved as a green, efficient and promising alternative to simultaneous extraction of polysaccharides from SC. Copyright

Polyphenolic-polysaccharide conjugates from plants of Rosaceae/Asteraceae family as potential radioprotectors.

PubMed

Zbikowska, Halina Malgorzata; Szejk, Magdalena; Saluk, Joanna; Pawlaczyk-Graja, Izabela; Gancarz, Roman; Olejnik, Alicja Klaudia

2016-05-01

Polyphenolic-polysaccharide macromolecular, water-soluble glycoconjugates, isolated from the selected medicinal plants of Rosaceae/Asteraceae family: from leaves of Fragaria vesca L., Rubus plicatus Whe. et N. E., and from flowering parts of Sanguisorba officinalis L., and Erigeron canadensis L., were investigated for their ability to protect proteins and lipids of human plasma against γ-radiation-induced oxidative damage. Treatment of plasma with plant conjugates (6, 30, 150 μg/ml) prior exposure to 100 Gy radiation resulted in a significant inhibition of lipid peroxidation, evaluated by TBARS levels; conjugates isolated from E. canadensis and R. plicatus and a reference flavonoid quercetin showed similar high potential (approx. 70% inhibition, at 6 μg/ml). The conjugates prevented radiation-induced oxidation of protein thiols and significantly improved plasma total antioxidant capacity, estimated with Ellman's reagent and ABTS(.+) assay, respectively. The results demonstrate by the first time a significant radioprotective capability of the polyphenolic-polysaccharide conjugates isolated from E. canadensis, R. plicatus, S. officinalis and to the less extent from F. vesca. The abilities of these substances to inhibit radiation-induced lipid peroxidation and thiol oxidation in plasma seems to be mediated, but not limited to ROS scavenging activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Polysaccharides and food processing.

PubMed

Pilnik, W; Rombouts, F M

1985-10-01

The rôle of polysaccharides during processing and for the quality of foods is discussed. Starch is the most important energy source for man. Most other polysaccharides are not metabolized for energy, but play an important rôle as dietary fibres. Pectins, alginates, carrageenans, and galactomannans are discussed as functional food additives in relation to their structure and their rheological behaviour, stability and interactions. Endogenous polysaccharides of fruits and vegetables and in products derived from them are responsible for such phenomena as texture (changes), press yields, ease of filtration and clarification, cloud stability, and mouth feel. To achieve desirable properties, the action of endogenous enzymes on polysaccharides must be inactivated and/or exogenous enzymes added as processing aids. This is also true for overcoming haze phenomena in clear juices or to break down undesirable microbial polysaccharides. Dough properties for bread baking can be improved by enzymic breakdown of a restrictive pentoglycan network. Network formation may come about by oxidative coupling of phenol rings of ferulic acid bound to hemicelluloses by ester links. Gels may be made by inducing oxidative coupling in natural or synthetic systems. Stagnation in development of new polysaccharide food additives is ascribed to difficulties in obtaining government approval for food use.

Uronic polysaccharide degrading enzymes.

PubMed

Garron, Marie-Line; Cygler, Miroslaw

2014-10-01

In the past several years progress has been made in the field of structure and function of polysaccharide lyases (PLs). The number of classified polysaccharide lyase families has increased to 23 and more detailed analysis has allowed the identification of more closely related subfamilies, leading to stronger correlation between each subfamily and a unique substrate. The number of as yet unclassified polysaccharide lyases has also increased and we expect that sequencing projects will allow many of these unclassified sequences to emerge as new families. The progress in structural analysis of PLs has led to having at least one representative structure for each of the families and for two unclassified enzymes. The newly determined structures have folds observed previously in other PL families and their catalytic mechanisms follow either metal-assisted or Tyr/His mechanisms characteristic for other PL enzymes. Comparison of PLs with glycoside hydrolases (GHs) shows several folds common to both classes but only for the β-helix fold is there strong indication of divergent evolution from a common ancestor. Analysis of bacterial genomes identified gene clusters containing multiple polysaccharide cleaving enzymes, the Polysaccharides Utilization Loci (PULs), and their gene complement suggests that they are organized to process completely a specific polysaccharide. Copyright © 2014 Elsevier Ltd. All rights reserved.

Purification, structural characterization and antiproliferative properties of chondroitin sulfate/dermatan sulfate from tunisian fish skins.

PubMed

Krichen, Fatma; Volpi, Nicola; Sila, Assaâd; Maccari, Francesca; Mantovani, Veronica; Galeotti, Fabio; Ellouz-Chaabouni, Semia; Bougatef, Ali

2017-02-01

Chondroitin sulfate/dermatan sulfate GAGs were extracted and purified from the skins of grey triggerfish (GTSG) and smooth hound (SHSG). The disaccharide composition produced by chondroitinase ABC treatment showed the presence of nonsulfated disaccharide, monosulfated disaccharides ΔDi6S and ΔDi4S, and disulfated disaccharides in different percentages. In particular, the nonsulfated disaccharide ΔDi0S of GTSG and SHSG were 3.5% and 5.5%, respectively, while monosulfated disaccharides ΔDi6S and ΔDi4S were evaluated to be 18.2%, 59% and 14.6%, 47.0%, respectively. Capillary elecrophoresis analysis of GTSG and SHSG contained 99.2% and 95.4% of chondroitin sulfate/dermatan sulfate, respectively. PAGE analysis showed a GTSG and SHSG having molecular masses with average values of 41.72KDa and 23.8KDa, respectively. HCT116 cell proliferation was inhibited (p<0.05) by 70.6% and 72.65% at 200μg/mL of GTSG and SHSG respectively. Both GTSG and SHSG demonstrated promising antiproliferative potential, which may be used as a novel, effective agent. Copyright © 2016 Elsevier B.V. All rights reserved.

In vivo growth-inhibition of Sarcoma 180 by an alpha-(1-->4)-glucan-beta-(1-->6)-glucan-protein complex polysaccharide obtained from Agaricus blazei Murill.

PubMed

Gonzaga, Maria Leônia Costa; Bezerra, Daniel Pereira; Alves, Ana Paula Negreiros Nunes; de Alencar, Nylane Maria Nunes; Mesquita, Rodney de Oliveira; Lima, Michael Will; Soares, Sandra de Aguiar; Pessoa, Cláudia; de Moraes, Manoel Odorico; Costa-Lotufo, Letícia Veras

2009-01-01

Agaricus blazei Murrill, a native mushroom of Brazil, has been widely consumed in different parts of the world due to its anticancer potential. This effect is generally attributed to its polysaccharides; however, the precise structure of these has not been fully characterized. To better understand the relationship between polysaccharide structures and antitumor activity, we investigated the effect of the intraperitoneally (i.p.) or orally (p.o.) administered alpha-(1-->4)-glucan-beta-(1-->6)-glucan-protein complex polysaccharide from A. blazei alone or in association with 5-fluorouracil (5-FU) in tumor growth using Sarcoma 180 transplanted mice. Hematological, biochemical, and histopathological analyses were performed in order to evaluate the toxicological aspects of the polysaccharide treatment. The polysaccharide had no direct cytotoxic action on tumor cells in vitro. However, the polysaccharide showed strong in vivo antitumor effect. Thus, the tumor growth-inhibitory effect of the polysaccharide is apparently due to host-mediated mechanisms. The histopathological analysis suggests that the liver and the kidney were not affected by polysaccharide treatment. Neither enzymatic activity of transaminases (AST and ALT) nor urea levels were significantly altered. In hematological analysis, leucopeny was observed after 5-FU treatment, but this effect was prevented when the treatment was associated with the polysaccharide. In conclusion, this polysaccharide probably could explain the ethnopharmacological use of this mushroom in the treatment of cancer.

Polysaccharides as Bacterial Antiadhesive Agents and "Smart" Constituents for Improved Drug Delivery Systems Against Helicobacter pylori Infection.

PubMed

Menchicchi, Bianca; Hensel, Andreas; Goycoolea, Francisco M

2015-01-01

The standard eradication treatment of the hostile Helicobacter pylori (H. pylori) stomach infection is facing increasing alarming antibiotic resistance worldwide and calls for alternative strategies to the use of antibiotics. One new perspective in this direction is cytoprotective compounds for targeted prevention of the adhesion of the bacteria to the stomach host cell and to inhibit the bacterial cell-cell communication via quorum sensing by specific inhibitors. Bacterial adhesion of H. pylori to the host cells is mainly mediated by carbohydrate-protein interactions. Therefore, the use of polyvalent carbohydrates, (e.g. plant-derived polysaccharides), as potential antiadhesive compounds, seems to be a promising tool to prevent the initial docking of the bacterium to the stomach cells. Polysaccharides are common constituents of daily food, either as starch or as dietary fiber and often also function as excipients for galenic drug-delivery formulations. In addition, polysaccharides with defined pharmacodynamics action against bacterial outer membrane proteins can have potential as therapeutic tools in the treatment of bacterial infections. Some polysaccharides are known to possess antibacterial properties against gram-positive bacteria, others to inhibit bacterial colonization by blocking specific carbohydrate receptors involved in host-bacteria interaction. This mode of action is advocated as alternative antiadhesion therapy. Ongoing research is also seeking for polysaccharide-based nanoformulations with potential for local drug delivery at the stomach as novel H. pylori therapies. These approaches pose challenges concerned with the stability of the nanomaterials in the harsh conditions of the gastric environment and their capacity to adhere to the stomach mucosa. In a global scenario, geographical diversity and social habits, namely lifestyle and dietary factors, influence the prevalence of the H. pylori-associated diseases and their severity. In this context

Therapies from Fucoidan: An Update

PubMed Central

Fitton, Janet Helen; Stringer, Damien N.; Karpiniec, Samuel S.

2015-01-01

Fucoidans are a class of sulfated fucose-rich polysaccharides found in brown marine algae and echinoderms. Fucoidans have an attractive array of bioactivities and potential applications including immune modulation, cancer inhibition, and pathogen inhibition. Research into fucoidan has continued to gain pace over the last few years and point towards potential therapeutic or adjunct roles. The source, extraction, characterization and detection of fucoidan is discussed. PMID:26389927

Control of Chondrogenesis in Limb-Bud Cell Cultures by Bromodeoxyuridine

PubMed Central

Levitt, Daniel; Doreman, Albert

1973-01-01

Initial exposure of cultured limb-bud cells (stage 23-24) to 5-bromo-2′-deoxyuridine (BrdU) irreversibly inhibits differentiation to cartilage under three different culture conditions. The inhibition of chondroitin sulfate synthesis is partially reversed by D-xylose in limb-bud cells after treatment with BrdU. The activities of four enzymes involved in chondroitin sulfate production were reduced in BrdU-treated cultures, but the magnitude of decrease was far less than the decrease in glycosaminoglycan synthesis. The slight increase in the turnover rate of sulfated glycosaminoglycans in BrdU-treated mesenchyme was not sufficient to account for the marked decrease in chondroitin sulfate content. The results suggest that BrdU treatment interferes with normal synthesis of chondroitin sulfate core protein in cultured limb-bud cells, but does not greatly diminish enzyme activities or UDP-sugar levels necessary for production of polysaccharide chains. PMID:4275762

Cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii.

PubMed

Yu, Siran; Ye, Xuewei; Chen, Lu; Xie, Xin; Zhou, Qian; Lian, Xiao-Yuan; Zhang, Zhizhen

2015-11-15

Whether sulfated saponins from Holothuria moebii inhibit the proliferation of colorectal cancer cells and have anti-colorectal tumor effects in animal model has not been investigated. To evaluate the cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii. (1) Column chromatography was used to prepare the total and individual saponins and HPLC was applied to define the components of the total saponins; (2) the activity of the total and individual saponins inhibiting the proliferation of human colorectal cancer cells was determined by SRB assay and the apoptosis induced by the saponins was qualified using cytometric analysis with Annexin V-FITC/PI double staining; and (3) the antitumor effects of the sulfated saponins on colorectal CT-26 tumor-bearing Balb/c mice were tested. The total and individual sulfated saponins significantly inhibited the proliferation of four different human colorectal cancer cells with IC50 values ranging from 1.04 to 4.08 μM (or 1.46 to 3.24 μg/ml for total saponins) and induced late apoptosis at an early treatment time in cancer cells. The total saponins (120 mg/kg) had antitumor activity in colorectal CT-26 tumor-bearing Balb/c mice. The sulfated saponins from H. moebii remarkably inhibited the proliferation of different human colorectal cancer cells and had significant anti-colorectal tumor activity in animal model. Copyright © 2015 Elsevier GmbH. All rights reserved.

Two Variants of a High-Throughput Fluorescent Microplate Assay of Polysaccharide Endotransglycosylases.

PubMed

Kováčová, Kristína; Farkaš, Vladimír

2016-04-01

Polysaccharide endotransglycosylases (PETs) are the cell wall-modifying enzymes of fungi and plants. They catalyze random endo-splitting of the polysaccharide donor molecule and transfer of the newly formed reducing sugar residue to the nonreducing end of an acceptor molecule which can be a polysaccharide or an oligosaccharide. Owing to their important role in the cell wall formation, the inhibition of PETs represents an attractive strategy in the fight against fungal infections. We have elaborated two variants of a versatile high-throughput microplate fluorimetric assay that could be used for effective identification of PETs and screening of their inhibitors. Both assays use the respective polysaccharides as the donors and sulforhodamine-labeled oligosaccharides as the acceptors but differ from each other by mode of how the labeled polysaccharide products of transglycosylation are separated from the unreacted oligosaccharide acceptors. In the first variant, the reactions take place in a layer of agar gel laid on the bottoms of the wells of a microtitration plate. After the reaction, the high-Mr transglycosylation products are precipitated with 66 % ethanol and retained within the gel while the low-Mr products and the unreacted acceptors are washed out. In the second variant, the donor polysaccharides are adsorbed to the surface of a microplate well and remain adsorbed there also after becoming labeled in the course of the transglycosylation reaction whereas the unused low-Mr acceptors are washed out. As a proof of versatility, assays of heterologously expressed transglycosylases ScGas1, ScCrh1, and ScCrh2 from the yeast Saccharomyces cerevisiae, CaPhr1 and CaPhr2 from Candida albicans, and of a plant xyloglucan endotransglycosylase (XET) are demonstrated.

Polysaccharide-based antibiofilm surfaces.

PubMed

Junter, Guy-Alain; Thébault, Pascal; Lebrun, Laurent

2016-01-01

Surface treatment by natural or modified polysaccharide polymers is a promising means to fight against implant-associated biofilm infections. The present review focuses on polysaccharide-based coatings that have been proposed over the last ten years to impede biofilm formation on material surfaces exposed to bacterial contamination. Anti-adhesive and bactericidal coatings are considered. Besides classical hydrophilic coatings based on hyaluronic acid and heparin, the promising anti-adhesive properties of the algal polysaccharide ulvan are underlined. Surface functionalization by antimicrobial chitosan and derivatives is extensively surveyed, in particular chitosan association with other polysaccharides in layer-by-layer assemblies to form both anti-adhesive and bactericidal coatings. Bacterial contamination of surfaces, leading to biofilm formation, is a major problem in fields as diverse as medicine, first, but also food and cosmetics. Many prophylactic strategies have emerged to try to eliminate or reduce bacterial adhesion and biofilm formation on surfaces of materials exposed to bacterial contamination, in particular implant materials. Polysaccharides are widely distributed in nature. A number of these natural polymers display antibiofilm properties. Hence, surface treatment by natural or modified polysaccharides is a promising means to fight against implant-associated biofilm infections. The present manuscript is an in-depth look at polysaccharide-based antibiofilm surfaces that have been proposed over the last ten years. This review, which is a novelty compared to published literature, will bring well documented and updated information to readers of Acta Biomaterialia. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of sulfate on anaerobic reduction of nitrobenzene with acetate or propionate as an electron donor.

PubMed

Huang, Jingang; Wen, Yue; Ding, Ning; Xu, Yue; Zhou, Qi

2012-09-15

Sulfate is frequently found in wastewaters that contain nitrobenzene. To reveal the effect of sulfate on the reductive transformation of nitrobenzene to aniline--with acetate or propionate as potential electron donors in anaerobic systems--an acetate series (R1-R5) and a propionate series (R6-R10) were set up. Each of these was comprised of five laboratory-scale sequence batch reactors. The two series were amended with the same amount of nitrobenzene and electron donor electron equivalents, whereas with increasing sulfate concentrations. Results indicated that the presence of sulfate could depress nitrobenzene reduction. Such depression is linked to the inhibition of nitroreductase activity and/or the shift of electron flow. In the acetate series, although sulfate did not strongly compete with nitrobenzene for electron donors, noncompetitive inhibition of specific nitrobenzene reduction rates by sulfate was observed, with an inhibition constant of 0.40 mM. Propionate, which can produce intermediate H₂ as preferred reducing equivalent, is a more effective primary electron donor for nitrobenzene reduction as compared to acetate. In the propionate series, sulfate was found to be a preferential electron acceptor as compared to nitrobenzene, resulting in a quick depletion of propionate and then a likely termination of H₂-releasing under higher sulfate concentrations (R9 and R10). In such a situation, nitrobenzene reduction slowed down, occurring two-stage zero-order kinetics. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Sequence analysis of the pyruvylated galactan sulfate-derived oligosaccharides by negative-ion electrospray tandem mass spectrometry.

PubMed

Li, Na; Mao, Wenjun; Liu, Xue; Wang, Shuyao; Xia, Zheng; Cao, Sujian; Li, Lin; Zhang, Qi; Liu, Shan

2016-10-04

Five sulfated oligosaccharide fragments, F1-F5, were prepared from a pyruvylated galactan sulfate from the green alga Codium divaricatum, by partial depolymerization using mild acid hydrolysis and purification with gel-permeation chromatography. Negative-ion electrospray tandem mass spectrometry with collision-induced dissociation (ES-CID-MS/MS) is attempted for sequence determination of the sulfated oligosaccharides. The sequence of F1 with homogeneous disaccharide composition was first characterized to be Galp-(4SO4)-(1 → 3)-Galp by detailed nuclear magnetic resonance spectroscopic analyses. The fragmentation pattern of F1 in the product ion spectra was established on the basis of negative-ion ES-CID MS/MS, which was then applied to sequence analysis of other sulfated oligosaccharides. The sequences of F2 and F3 were deduced to be Galp-(4SO4)-(1 → 3)-Galp-(1 → 3)-Galp-(1 → 3)-Galp and 3,4-O-(1-carboxyethylidene)-Galp-(6SO4)-(1 → 3)-Galp, respectively. The sequences of major fragments in F4 and F5 were also deduced. The investigation demonstrated that negative-ion ES-CID-MS/MS was an efficient method for the sequence analysis of the pyruvylated galactan sulfate-derived oligosaccharides which revealed the patterns of substitution and glycosidic linkages. The pyruvylated galactan sulfate-derived oligosaccharides were novel sulfated oligosaccharides different from other algal polysaccharide-derived oligosaccharides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Polysulfonate suramin inhibits Zika virus infection.

PubMed

Tan, Chee Wah; Sam, I-Ching; Chong, Wei Lim; Lee, Vannajan Sanghiran; Chan, Yoke Fun

2017-07-01

Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log 10  PFU viral reduction with IC 50 value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of light wavelengths on extracellular and capsular polysaccharide production by Nostoc flagelliforme.

PubMed

Han, Pei-pei; Sun, Ying; Jia, Shi-ru; Zhong, Cheng; Tan, Zhi-lei

2014-05-25

The influences of different wavelengths of light (red 660nm, yellow 590nm, green 520nm, blue 460nm, purple 400nm) and white light on extracellular polysaccharide (EPS) and capsular polysaccharide (CPS) production by Nostoc flagelliforme in liquid culture were demonstrated in this study. The results showed that, compared with white light, red and blue lights significantly increased both EPS and CPS production while yellow light reduced their production; purple and green lights stimulated EPS production but inhibited CPS formation. Nine constituent monosaccharides and one uronic acid were detected in both EPS and CPS, and their ratios showed significant differences among treatment with different light wavelengths. However, the advanced structure of EPS and CPS from various light conditions did not present obvious difference through Fourier transform infrared spectroscopy and X-ray diffraction characterization. These findings establish a basis for development of high-yielding polysaccharide production process and understanding their regulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

The system of sulfated galactans from the red seaweed Gymnogongrus torulosus (Phyllophoraceae, Rhodophyta): Location and structural analysis.

PubMed

Estevez, José M; Ciancia, Marina; Cerezo, Alberto S

2008-09-05

Sulfated polysaccharides were localized in the cuticle, cortex and medulla of the gametophyte thallus, being more concentrated in the intercellular matrix than in the cell walls. During the water extraction sequence, a small percentage of galactan sulfates (5.1% of dry seaweed) with average low Mr (6-11.4kDa) were extracted at room temperature without disturbing the cellular arrangement, while sulfated galactans of average medium Mr (18-45kDa) were obtained by further hot-water extractions (52.4% of dry seaweed), with diorganization of the tissue. The residue (40.0% of dry seaweed) still contained carrageenan-type (major) and agaran-type (minor) galactans. Part of these galactans was extracted with 8.4% LiCl solution in DMSO, from which "pure" κ/ι-carrageenans were isolated. Carrageenans and agarans were extracted in a ratio 1:0.5, showing the highest amount of agaran-structures for a carrageenophyte. The galactans comprise alternating 4-sulfated (major) and non-sulfated (minor) 3-linked β-d-galactopyranose units, and 4-linked α-galactopyranose units with the following substitutions: (i) non-sulfated and 2-sulfated 3,6-anhydro-α-d-galactopyranose residues in the carrageenan-structures, which belong to the κ-family (κ/ι-carrageenans); (ii) 3-sulfated α-l-galactopyranose units and 2-sulfated 3,6-anhydro-α-l-galactopyranose residues in the agaran-structures. Alkaline treatment and alkaline dialysis of the main extracts gave "pure" κ/ι-carrageenans, showing that carrageenan molecules are extracted together with low Mr agarans or agaran-dl-hybrids. Copyright © 2008 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-04-01

Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preparation, characterization, and anti-Helicobacter pylori activity of Bi3+-Hericium erinaceus polysaccharide complex.

PubMed

Zhu, Yang; Chen, Yao; Li, Qian; Zhao, Ting; Zhang, Ming; Feng, Weiwei; Takase, Mohammed; Wu, Xueshan; Zhou, Zhaoxiang; Yang, Liuqing; Wu, Xiangyang

2014-09-22

Two new Bi3+-Hericium erinaceus polysaccharide (BiHEP) complexes were prepared using Bi3+ and two purified polysaccharides from H. erinaceus (HEPs), respectively. The complexes were characterized by elemental analysis, FT-IR, CD, SEM, AFM, XRD, and TG. The anti-Helicobacter pylori (Hp) activities in vitro by agar dilution assay of the complexes were evaluated. The molecular weights of HEPs were 197 and 20 kDa, respectively. All the analyses confirmed the formation of new BiHEP complexes with lower content of Bi3+ compared with colloidal bismuth subcitrate (CBS), the most utilized bismuth preparation clinically. Furthermore, HEPs themselves have definite inhibition effects on Hp, and BiHEP complexes have lower content of Bi exhibited strong inhibition effects on Hp (MIC=20 μg/mL), similar to that of CBS with higher content of Bi. The study provides a basis for further development of multiple treatments of Hp infection or new medicines. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Antitumor and immunomodulating activity of a polysaccharide from Sophora flavescens Ait.

PubMed

Bai, Lu; Zhu, Li-Ying; Yang, Bao-Shan; Shi, Li-Jun; Liu, Yong; Jiang, Ai-Min; Zhao, Li-Li; Song, Guang; Liu, Tie-Fu

2012-12-01

The immunostimulatory activity of Sophora flavescens polysaccharide (SFPW1) was evaluated by using in vitro cell models and in vivo animal models. The results demonstrated that SFPW1 could effectively inhibit the tumor growth in H22 tumor-bearing mice and promote the splenocyte proliferation, thus resulting in a prolonged life survival. For assay in vitro, SFPW1 significantly strengthened peritoneal macrophages to devour H22 tumor cells and stimulated macrophages to produce nitric oxide (NO) via up-regulation of inducible NO synthase (iNOS) activity. However, no direct cytotoxicity against H22 tumor cells was observed in vitro. These results suggest that SFPW1 might be a strong natural immunomodulator and the antitumor effect of this polysaccharide is associated with its potent immunostimulating effect. Copyright © 2012 Elsevier B.V. All rights reserved.

Tyrosine sulfation modulates activity of tick-derived thrombin inhibitors

NASA Astrophysics Data System (ADS)

Thompson, Robert E.; Liu, Xuyu; Ripoll-Rozada, Jorge; Alonso-García, Noelia; Parker, Benjamin L.; Pereira, Pedro José Barbosa; Payne, Richard J.

2017-09-01

Madanin-1 and chimadanin are two small cysteine-free thrombin inhibitors that facilitate blood feeding in the tick Haemaphysalis longicornis. Here, we report a post-translational modification—tyrosine sulfation—of these two proteins that is critical for potent anti-thrombotic and anticoagulant activity. Inhibitors produced in baculovirus-infected insect cells displayed heterogeneous sulfation of two tyrosine residues within each of the proteins. One-pot ligation-desulfurization chemistry enabled access to homogeneous samples of all possible sulfated variants of the proteins. Tyrosine sulfation of madanin-1 and chimadanin proved crucial for thrombin inhibitory activity, with the doubly sulfated variants three orders of magnitude more potent than the unmodified inhibitors. The three-dimensional structure of madanin-1 in complex with thrombin revealed a unique mode of inhibition, with the sulfated tyrosine residues binding to the basic exosite II of the protease. The importance of tyrosine sulfation within this family of thrombin inhibitors, together with their unique binding mode, paves the way for the development of anti-thrombotic drug leads based on these privileged scaffolds.

Fucosylated chondroitin sulfate oligosaccharides exert anticoagulant activity by targeting at intrinsic tenase complex with low FXII activation: Importance of sulfation pattern and molecular size.

PubMed

Li, Junhui; Li, Shan; Yan, Lufeng; Ding, Tian; Linhardt, Robert J; Yu, Yanlei; Liu, Xinyue; Liu, Donghong; Ye, Xingqian; Chen, Shiguo

2017-10-20

Fucosylated chondroitin sulfates (fCSs) are structurally unusual glycosaminoglycans isolated from sea cucumbers that exhibit potent anticoagulant activity. These fCSs were isolated from sea cucumber, Isostichopus badionotus and Pearsonothuria graeffei. Fenton reaction followed by gel filtration chromatography afforded fCS oligosaccharides, with different sulfation patterns identified by mass and NMR spectroscopy, and these were used to clarify the relationship between the structures and the anticoagulant activities of fCSs. In vitro activities were measured by activated partial thromboplastin time (APTT), thrombin time (TT), thrombin and factor Xa inhibition, and activation of FXII. The results showed that free radicals preferentially acted on GlcA residues affording oligosaccharides that were purified from both fCSs. The inhibition of thrombin and factor X activities, mediated through antithrombin III and heparin cofactor II of fCSs oligosaccharides were affected by their molecular weight and fucose branches. Oligosaccharides with different sulfation patterns of the fucose branching had a similar ability to inhibit the FXa by the intrinsic factor Xase (factor IXa-VIIIa complex). Oligosaccharides with 2,4-O-sulfo fucose branches from fCS-Ib showed higher activities than ones with 3,4-O-disulfo branches obtained from fCS-Pg. Furthermore, a heptasaccharide is the minimum size oligosaccharide required for anticoagulation and FXII activation. This activity was absent for fCS oligosaccharides smaller than nonasaccharides. Molecular size and fucose branch sulfation are important for anticoagulant activity and reduction of size can reverse the activation of FXII caused by native fCSs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Tyrosine sulfation in precursors of collagen V.

PubMed

Fessler, L I; Brosh, S; Chapin, S; Fessler, J H

1986-04-15

Radioactive labeling of p-collagens V, collagens V, and, to a small extent, of procollagen V occurred when [35S]sulfate was incubated with tendons or primary tendon cell cultures, or blood vessels and crops of 17- to 19-day-old chick embryos, or with lung slices from neonatal rats. Most or all of this label is in the form of 1 or more sulfated tyrosine residues/chain of p alpha 1(V), alpha 1(V), p alpha 1'(V), alpha 1'(V), p alpha 2(V), and alpha 2(V), and it remains attached through purification by dialysis, ammonium sulfate precipitation, CsCl-GdnCl2 equilibrium buoyant density and velocity sedimentations, ion-exchange chromatography, and sodium dodecyl sulfate gel electrophoresis. Radioactive tyrosine sulfate was identified in alkaline hydrolysates of these collagen V chains, after labeling the tissues with either [35S]sulfate or [3H]tyrosine, by electrophoretic and chromatographic comigration with a tyrosine sulfate standard. Tunicamycin A1, which inhibits the attachment of N-linked complex carbohydrate, did not interfere with the sulfation process. The tyrosine sulfate is located in a noncollagenous domain, which is probably adjacent to the amino end of the collagen helix, and is retained throughout the physiological proteolytic processing of procollagens V. After digestion with Staphylococcus aureus V8 protease, 35S-labeled p alpha 1(V) and alpha 1(V) chains gave the same map of labeled peptides, and this differed from the map given by p alpha 1'(V) and alpha 1'(V) chains. Little sulfation of p alpha 2(V) and alpha 2(V) chains occurs. The implications of these observations for the structure and properties of procollagens V and their derivatives are considered.

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. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Polysaccharide-Based Micelles for Drug Delivery

PubMed Central

Zhang, Nan; Wardwell, Patricia R.; Bader, Rebecca A.

2013-01-01

Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date. PMID:24300453

Antioxidant and antitumor effects of polysaccharides from the fungus Pleurotus abalonus.

PubMed

Ren, Daoyuan; Jiao, Yadong; Yang, Xingbin; Yuan, Li; Guo, Jianjun; Zhao, Yan

2015-07-25

Dietary supplement of edible Pleurotus abalonus (P. abalonus) rich in fungal polysaccharides is associated with anticancer health benefit. We here isolated the polysaccharides (PAP) from the fruiting bodies of P. abalonus, and evaluated the antiproliferative activity of the polysaccharides in human colorectal carcinoma LoVo cells. HPLC analysis showed that PAP consisted of D-mannose, D-ribose, l-rhamnose, D-glucuronic acid, D-glucose and D-galactose, and their corresponding mole percentages were 3.4%, 1.1%, 1.9%, 1.4%, 87.9% and 4.4%, respectively. PAP was shown to exert a high antioxidant activity in vitro and a dose-dependent antiproliferative effect against LoVo cancer cells. Flow cytometry analysis demonstrated that PAP exhibited a stimulatory effect on apoptosis of LoVo cells, and induced the cell-cycle arrest at the S phase. We also found that PAP could increase the generation of intracellular ROS which was a critical mediator in PAP-induced cell growth inhibition. These findings suggest that PAP may serve as a potential novel dietary agent for human colon cancer chemoprevention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

A potential role for chondroitin sulfate/dermatan sulfate in arm regeneration in Amphiura filiformis.

PubMed

Ramachandra, Rashmi; Namburi, Ramesh B; Dupont, Sam T; Ortega-Martinez, Olga; van Kuppevelt, Toin H; Lindahl, Ulf; Spillmann, Dorothe

2017-05-01

Glycosaminoglycans (GAGs), such as chondroitin sulfate (CS) and dermatan sulfate (DS) from various vertebrate and invertebrate sources are known to be involved in diverse cellular mechanisms during repair and regenerative processes. Recently, we have identified CS/DS as the major GAG in the brittlestar Amphiura filiformis, with high proportions of di- and tri-O-sulfated disaccharide units. As this echinoderm is known for its exceptional regeneration capacity, we aimed to explore the role of these GAG chains during A. filiformis arm regeneration. Analysis of CS/DS chains during the regeneration process revealed an increase in the proportion of the tri-O-sulfated disaccharides. Conversely, treatment of A. filiformis with sodium chlorate, a potent inhibitor of sulfation reactions in GAG biosynthesis, resulted in a significant reduction in arm growth rates with total inhibition at concentrations higher than 5 mM. Differentiation was less impacted by sodium chlorate exposure or even slightly increased at 1-2 mM. Based on the structural changes observed during arm regeneration we identified chondroitin synthase, chondroitin-4-O-sulfotransferase 2 and dermatan-4-O-sulfotransferase as candidate genes and sought to correlate their expression with the expression of the A. filiformis orthologue of bone morphogenetic factors, AfBMP2/4. Quantitative amplification by real-time PCR indicated increased expression of chondroitin synthase and chondroitin-4-O-sulfotransferase 2, with a corresponding increase in AfBMP2/4 during regeneration relative to nonregenerating controls. Our findings suggest that proper sulfation of GAGs is important for A. filiformis arm regeneration and that these molecules may participate in mechanisms controlling cell proliferation. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Energy for biologic sulfate reduction in a hydrothermally formed ocean on Europa

NASA Astrophysics Data System (ADS)

Zolotov, Mikhail Y.; Shock, Everett L.

2003-04-01

Formation of a sulfate-bearing ocean on Jupiter's satellite Europa by quenched hydrothermal fluids provides a source of metabolic energy for low-temperature sulfate-reducing organisms that use dissolved H2 as an electron donor. Inhibition of thermodynamically favorable sulfate reduction in cooled hydrothermal fluids creates the potential for biologic reduction. Both high temperature and reduced conditions of ocean-forming hydrothermal solutions favor sulfate reduction in quenched fluids. The maximum amount of energy available to support autotrophic sulfate reduction is on the order of a few kilojoules per kilogram of water and is limited by the low abundances of either H2 or sulfate in ocean-forming fluids. Although this irreplaceable energy source might have supported early life on Europa, maintenance of biologic sulfate reduction throughout the ocean's history would require a supply of organic compounds from endogenic sources or from the satellite's surface.

Multiple Effects of Ginseng Berry Polysaccharides: Plasma Cholesterol Level Reduction and Enteric Neoplasm Prevention.

PubMed

Wan, Jin-Yi; Huang, Wei-Hua; Zheng, Wei; Park, Chan Woong; Kim, Su Hwan; Seo, Dae Bang; Shin, Kwang-Soon; Zeng, Jinxiang; Yao, Haiqiang; Sava-Segal, Clara; Wang, Chong-Zhi; Yuan, Chun-Su

2017-01-01

The root of Asian ginseng (Panax ginseng C.A. Meyer) has been used for centuries in Oriental medicine to improve general well-being and to relieve various medical conditions. It is commonly understood that ginsenosides are responsible for the pharmacological activities of ginseng. Compared to the root of ginseng, studies on the berry are considerably limited. In this study, we evaluated the effects of polysaccharides from Asian ginseng berries on plasma lipid levels, chemically-induced enteric inflammation and neoplasm, and cancer chemoprevention in different experimental models. We tested two polysaccharide preparations: regular ginseng berry polysaccharide extract (GBPE) and ginseng berry polysaccharide portion (GBPP, removed MV [Formula: see text]). We first observed that both oral GBPE and oral GBPP significantly reduced plasma cholesterol and triglycerides levels in a dose-related manner in ob/ob mice, without obvious body weight changes. Then, in AOM/DSS-induced acute colitis mice, GBPE and GBPP significantly ameliorated the increased gut disease activity index and inhibited the reduction of the colon length. Further, the berry polysaccharides significantly suppressed chemically-induced pro-inflammatory cytokine levels. This is consistent with the observation that GBPE and GBPP attenuated tumorigenesis in mice by significantly and dose-dependently reducing tumor load. Finally, in vitro HCT-116 and HT-29 human colon cancer cells were used. While these berry preparations had better antiproliferation effects on the HCT-116 than the HT-29 cells, the GBPE had significantly stronger inhibitory effects than GBPP. The observed in vitro GBPE's effect could contribute to the actions of its small-molecule non-polysaccharide compounds due to their direct antiproliferative activities. Results obtained from the present study suggest that ginseng berry polysaccharides may have a therapeutic role in the management of high lipid levels, enteric inflammation, and colon