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      Structural and Immunological Activity Characterization of a Polysaccharide Isolated from Meretrix meretrix Linnaeus

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          Abstract

          Polysaccharides from marine clams perform various biological activities, whereas information on structure is scarce. Here, a water-soluble polysaccharide MMPX-B2 was isolated from Meretrix meretrix Linnaeus. The proposed structure was deduced through characterization and its immunological activity was investigated. MMPX-B2 consisted of d-glucose and d-galctose residues at a molar ratio of 3.51:1.00. The average molecular weight of MMPX-B2 was 510 kDa. This polysaccharide possessed a main chain of (1→4)-linked-α- d-glucopyranosyl residues, partially substituted at the C-6 position by a few terminal β- d-galactose residues or branched chains consisting of (1→3)-linked β- d-galactose residues. Preliminary immunological tests in vitro showed that MMPX-B2 could stimulate the murine macrophages to release various cytokines, and the structure-activity relationship was then established. The present study demonstrated the potential immunological activity of MMPX-B2, and provided references for studying the active ingredients in M. meretrix.

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          Most cited references31

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          Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock

          Inflammasomes are multi-protein complexes that trigger the activation of caspase-1 and the maturation of interleukin-1β (IL-1β), yet the regulation of these complexes remains poorly characterized. Here we show that nitric oxide (NO) inhibited the NLRP3-mediated ASC pyroptosome formation, caspase-1 activation and IL-1β secretion in myeloid cells from both mice and humans. Meanwhile, endogenous NO derived from iNOS (inducible form of NO synthase) also negatively regulated NLRP3 inflammasome activation. Depletion of iNOS resulted in increased accumulation of dysfunctional mitochondria in response to LPS and ATP, which was responsible for the increased IL-1β production and caspase-1 activation. iNOS deficiency or pharmacological inhibition of NO production enhanced NLRP3-dependent cytokine production in vivo, thus increasing mortality from LPS-induced sepsis in mice, which was prevented by NLRP3 deficiency. Our results thus identify NO as a critical negative regulator of the NLRP3 inflammasome via the stabilization of mitochondria. This study has important implications for the design of new strategies to control NLRP3-related diseases.
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            Structure characterization of a novel polysaccharide from Dictyophora indusiata and its macrophage immunomodulatory activities.

            A novel polysaccharide, here named DP1, was isolated from the fruiting body of Dictyophora indusiata using a water extraction method. Structure characterization revealed that DP1 had an average molecular weight of 1132 kDa and consisted of glucose (56.2%), galactose (14.1%), and mannose (29.7%). The main linkage type of DP1 were proven to be (1 → 3)-linked α-l-Man, (1 → 2,6)-linked α-d-Glc, (1 → 6)-linked β-d-Glc, (1 → 6)-linked β-d-Gal, and (1 → 6)-linked β-d-Man by periodate oxidation-Smith degradation and nuclear magnetic resonance analysis. The immunostimulating assay indicated that DP1 could significantly promote macrophage NO, TNF-α, and IL-6 secretion in murine RAW 264.7 cells involving complement receptor 3 (CR3). The immune activities of DP1 were quite stable under thermal processing (100, 121, and 145 °C). Besides, DP1 retained stability after acidic/alkline treatment (pH 4.0-10.0), which enabled it to be an ideal complementary medicine or functional food for therapeutics of hypoimmunity and immunodeficiency diseases.
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              Immunomodulatory Effects of Alginate Oligosaccharides on Murine Macrophage RAW264.7 Cells and Their Structure-Activity Relationships.

              This study evaluated the immunomodulatory activities, including regulation of nitric oxide (NO), reactive oxygen species (ROS), and tumor necrosis factor (TNF)-α production in RAW264.7 murine macrophages, of alginate oligosaccharides (AOS) and investigated their structure-activity relationships. Our results revealed that unsaturated guluronate oligosaccharide prepared by enzymatic degradation (GOS-ED) induced NO production and inducible nitric oxide synthase (iNOS) expression, dose and time dependently, and stimulated ROS and TNF-α production; however, other AOS prepared by different ways or polymers showed very low and even no such effects. Moreover, GOS-ED induced macrophage activation to release the above-mentioned mediators partly involved in nuclear factor (NF)-κB and mitogen-activated protein (MAP) kinase signaling pathways. We also show that the structural characteristics of AOS, especially the unsaturated terminal structure, molecular size, and M/G ratio, play important roles in determining the macrophage-activating effects. GOS-ED could be applicable for agriculture, drug, and food industry as a potent immune-modulatory agent.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                29 December 2015
                January 2016
                : 14
                : 1
                : 6
                Affiliations
                School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China; li792051095@ 123456163.com (L.L.); eternal83@ 123456163.com (H.L.); jackieqian@ 123456163.com (J.Q.); 15061888901@ 123456163.com (Y.H.); 18262280354@ 123456163.com (J.Z.); zhenming_lu@ 123456163.com (Z.L.); zhenghxu@ 123456jiangnan.edu.cn (Z.X.)
                Author notes
                [* ]Correspondence: shijs@ 123456163.com ; Tel.: +86-510-8532-8177; Fax: +86-510-8591-8206
                [†]

                These authors contributed equally to this work.

                Article
                marinedrugs-14-00006
                10.3390/md14010006
                4728503
                26729136
                511f9bfb-d565-4d2e-b9d4-d5ace6a53641
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 December 2015
                : 21 December 2015
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                meretrix meretrix linnaeus,polysaccharide,structure,immunological activity

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