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      Immune-Enhancing Effects of a High Molecular Weight Fraction of Cynanchum wilfordii Hemsley in Macrophages and Immunosuppressed Mice

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          Abstract

          The objective of this study was to investigate the immune-enhancing activity of a high molecular weight fraction (HMF) of Cynanchum wilfordii in RAW 264.7 macrophages and the cyclophosphamide (CYC)-induced mouse model of immunosuppression. To identify the bioactive substances of HMF, a crude polysaccharide (HMFO) was obtained and treated with sodium periodate (an oxidation agent) or digested with protease. In macrophages, HMF treatment enhanced the production of nitric oxide (NO) and cytokines (tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β)), as well as phagocytic ability. In CYC-immunosuppressed mice, HMF improved relative spleen and thymus weights, natural killer (NK) cell activity, and splenic lymphocyte proliferation. These increases in NO and cytokines were mediated by up-regulation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Periodate treatment, but not protease treatment, decreased the immune-enhancing activity of HMFO, suggesting that polysaccharides are the active ingredients in C. wilfordii extract.

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          Most cited references43

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          Colorimetric Method for Determination of Sugars and Related Substances

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            "Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype.

            In the spleens of young, adult mice there exist naturally occurring killer lymphocytes with specificity for mouse Moloney leukemia cells. The lytic activity was directed against syngeneic or allogeneic Moloney leukemia cells to a similar extent, but was primarily expressed when tested against in vitro grown leukemia cells. Two leukemias of non-Moloney origin were resistant and so was the mastocytoma line P815. Although killer activity varied between different strains of mice, the specificity of lysis was the same as indicated by competition experiments using unlabeled Moloney or other tumor cells as inhibitors in the cytotoxic assays. Capacity to compete and sensitivy to lysis by the killer cells were found to be highly positively correlated. Analysis of the kinetics of the cytotoxic assay revealed a rapid induction of lysis within one to four hours, arguing against any conventional in vitro induction of immune response. No evidence was found of soluble factors playing any role in the cytolytic assay.
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              Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

              Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                27 September 2016
                October 2016
                : 8
                : 10
                : 600
                Affiliations
                [1 ]Traditional Food Research Center, Korea Food Research Institute, Seongnam 13539, Gyeonggi, Korea; jangmi@ 123456kfri.re.kr (M.J.); tglim83@ 123456kfri.re.kr (T.-G.L.); honghd@ 123456kfri.re.kr (H.-D.H.); ykrhee@ 123456kfri.re.kr (Y.K.R.); tack@ 123456kfri.re.kr (K.-T.K.); ejlee@ 123456kfri.re.kr (E.L.)
                [2 ]Department of Oriental Medicinal Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Gyeonggi, Korea; se8688@ 123456gmail.com
                [3 ]Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Chungbuk, Korea; artemisia@ 123456korea.kr (J.H.L.); yoong0625@ 123456korea.kr (Y.J.L.); jung100@ 123456korea.kr (C.S.J.)
                [4 ]Herbal Crop Utilization Research Team, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Chungbuk, Korea; dylee0809@ 123456korea.kr
                Author notes
                [* ]Correspondence: cwcho@ 123456kfri.re.kr ; Tel.: +82-31-780-9312
                [†]

                These authors contributed equally to this work.

                Article
                nutrients-08-00600
                10.3390/nu8100600
                5083988
                27690089
                133c7115-1269-49b8-ad8e-57cc924e25d5
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

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

                History
                : 26 July 2016
                : 13 September 2016
                Categories
                Article

                Nutrition & Dietetics
                cynanchum wilfordii,polysaccharide,immunostimulatory activity,cytokine,nitric oxide,cyclophosphamide

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