β-Glukanlar ve İmmün Sistem

β-glukan, D-glukoz monomerlerinin değişik şekillerde bağlanmasıyla oluşan, bitki, mantar, alg, maya ve bazı bakterilerin hücre duvarının komponenti olan doğal polimerlere verilen genel bir isimdir. Buğday, arpa, yulaf, pirinç gibi çok sık tükettiğimiz tahıllar, Shiitake, Reishi ölümsüzlük mantarı , Maitake, Blazei mantarı gibi yiyecek olarak da tüketilebilen tıbbi mantarlar ve Saccharomyces cerevisiae ekmek mayası başlıca β-glukan kaynaklarıdır. Bunların haricinde Agrobacterium radiobacter, A. rhizogenes gibi bakteriler ve Laminaria sp. gibi algler de β-glukan kaynaklarına örnek olarak verilebilir. β-glukanların bağışıklık stimülanı, antitümoral, antienflamatuvar, kolesterol düşürücü, antidiyabetik, antimikrobiyal, antiviral, hepatoprotektif, antiallerjik, radyoprotektif, antioksidan, antikoagülan etkileri olduğu bilinmektedir. Ayrıca, β-glukan özellikle Japonya’da kanser hastalarında adjuvan olarak kullanılmakta ve oral β-glukan uygulamasının monoklonal antikorların etkisini artırdığı bildirilmektedir. Bu çalışmada çok çeşitli biyolojik etkileri bulunan ve gerek besinlerle gerek gıda desteği olarak kullanılan β-glukanların özellikle bağışıklık sistemindeki ve kanserdeki etkileri ile ilgili çalışmaları ve bu bileşikler üzerinde yapılmış olan toksisite çalışmalarını derlenmiştir. Ülkemizde piyasada bulunan yoğun olarak β-glukan içeren ekstrelerin ve saflaştırılmış β-glukan içeren ticari preparatların β 1→3 ; β 1→6 yapısı taşıması nedeniyle, araştırmamızda daha çok bu tip β-glukanlar üzerindeki çalışmalara yer verilmiştir.

β-glucans and the Immune System

β-glucan is a common name for natural polymers which consist of D-glucose monomers binding to each other at different positions. They are components of cell walls of plants, fungi, algae, yeasts and some bacteria. Grains like wheat, barley, oat, and rice consumed frequently in daily diet; medicinal fungi also consumed as food like Shiitake, Reishi, Maitake, Blazei fungi; and Saccharomyces cerevisiae Baker’s yeast are the most common β-glucan sources. Moreover, some bacteria such as Agrobacterium radiobacter, Agrobacterium rhizogenes and some algae like Laminaria sp. are other examples of β-glucan sources. β-glucans possess immunostimulant, antitumor, antiinflammatory, cholestrol lowering, antidiabetic, antimicrobial, antiviral, hepatoprotective, antiallergic, radioprotective, antioxidant and anticoagulant activities. Furthermore, β-glucans are used as adjuvant for cancer patients, especially in Japan, and it is reported that oral administration of β-glucans enhances effects of monoclonal antibodies. In this study, we reviewed the effects of β-glucans which possess a wide range of biological activities especially on immune system and cancer cells when consumed both in diet and as dietary supplement. We also reviewed the toxicity studies on β-glucans. Because the extensively β-glucan containing extracts and purified β-glucan products on the market in Turkey contain the structure of β 1→3 ; β 1→6 , we mainly reviewed the studies on this type of β-glucans.

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  • Barsanti, L., Passarelli, V., Evangelista, V., Frassanito, A.M., Gualtieri, P.: Chemistry, physico-chemistry and applications linked to biological activitiesof  –glucans. Natural Product Reports, 28, 457-466, (2011).
  • Stone, B.A. ‘Chemistry of  –Glucans’, Bacic, A., Fincher, G.B., Stone, B.A., eds. Chemistry, Biochemistry, and Biology of 1-3 Beta Glucans and Related Polysaccharides. 1st ed. San Diego, CA, Elsevier, (2009), p. 5-46.
  • Zekovic, D.B., S. Kwiatkowski, M.M., Vrvic, D., Jakovljevic, A., Moran, C.A.: Natural and Modified (13)--D-Glucans in Health Promotion and Disease Alleviation. Critical Reviews in Biotechnolgy, 25, 205–230, (2005).
  • Surenjav, U., Zhang, L., Xu, X., Zeng, F.: Effects of molecular structure on antitumor activities of (13)- -D-glucans from different Lentinus edodes. Carbohydrate Polymer, 63, 97-104, (2006).
  • Volman, J.J., Ramakers, J.D., Plat, J.: Dietary modulation of immune function by -glucans. Physiology Behavior, 94, 276–284, (2008).
  • Goodridge, H.S., Reyes, C.N., Becker, C.A., Katsumoto, T.R., Ma, J., Wolf, A.J., Bose, N., Chan, A.S.H., Magee, A.S., Danielson, M.E., Weiss, A., Vasilakos, J.P., Underhill, D.M.: Activation of the innate immune receptor Dectin-1 upon formation of a ‘phagocytic synapse’ Nature, 472, 471–476, (2011).
  • Novak, M., Vetvicka, V.: -Glucans, History, and the Present: Immunomodulatory Aspects and Mechanisms of Action. Journal of Immunotoxicolgy, 5, 47–57, (2008).
  • Brown, G.D., Gordon, S.: Fungal -glucans and mammalian immunity. Immunity, 19, 311– 315, (2003).
  • Hong, F., Yan, J., Baran, J.T., Allendorf, D.J., Hansen, R.D., Ostroff, G.R.: Mechanism by Which Orally Administered - 1,3-Glucans Enhance the Tumoricidal Activity of Antitumor Monoclonal Antibodies in Murine Tumor Models. Journal of Immunology, 173, 797-806, (2004).
  • Cramer, D.E., Wagner, S., Li, B., Liu, J., Hansen, R., Reca, R.: Mobilization of Hematopoietic Progenitor Cells by Yeast-Derived -Glucan Requires Activation of Matrix Metalloproteinase-9. Stem Cells, 26, 1231–1240, (2008).
  • Wagnerova, J., Liskova, A., Navarova, J., Kristofova, A., Trnovec, T., Ferencik, M.: The Effect of Two Glucan Carboxymethyl Derivatives with Various Substitution Degrees on Cyclophosphamide Immunosuppression in Mice. Immunopharmacology and Immunotoxicology, 15, 227–242, (1993).
  • Kernodle, D., Gates, H., Kaiser, A.B.: Prophylactic Anti-Infective Activity of Poly-[1-6]--D Glucopyranosyl-[1-3]--D-Glucopyranose Glucan in a Guinea Pig Model of Staphylococcal Wound Infection. Antimicrobial Agents Chemotheraphy, 42(3), 545-549, (1998).
  • Onderdonk, A.B., Cisrenos, R.L., Hinkson, P., Ostroff, G.: Anti-Infective Effect of Poly-1-6- Glucotriosyl- 1-3-Glucopyranose Glucan In Vivo. Infection and Immunutiy, 60(4), 1642- 1647, (1992).
  • Cook, J.A., Holbrook, T.W.: Immunogenicity of soluble and particulate antigens from Leishmania donovani: effect of glucan as an adjuvant Infection and Immunitiy, 40, 1038– 1043, (1984).
  • Yun, C.H., Estrada, A., Van Kessel, A., Gajadhar, A., Redmond, M., Laarveld, B.: Immunomodulatory effects of oat -glucan administered intragastrically or parenterally on mice infected with Eimeria vermiformis. Microbiolgy Immunology, 42, 457–465, (1998).
  • Brown, G.D., Gordon, S.: A new receptor for  –glucans. Nature, 413, 36-37, (2001).
  • Adams, E.L., Rice, P.J., Graves, B., Ensley, H.E., Yu, H., Brown, G.D.: Differential High- Affinity Interaction of Dectin-1 with Natural or Synthetic Glucans Is Dependent upon Primary Structureand Is Influenced by Polymer Chain Length and Side-Chain Branching Journal of Pharmacology and Experimental Theraphy, 325, 115–123, (2008).
  • Vetvicka, V., Vancikova, Z.: Anti-stress action of several orally given  –Glucans. Biomedical papers of the Medical Faculty of the University Palacký Olomouc Czech Repub 154(3), 235- 238, (2010).
  • Suzuki, I., Sakurai, T., Hashimoto, K., Oikawa, S., Masuda, A., Ohsawa, M.: Inhibition of experimental pulmonary metastasis of Lewis lung carcinoma by orally administered  -glucan in mice. Chemical and Pharmaceutical Bulletin, 39, 1606-8, (1991).
  • Louie, B., Rajamahanty, S., Won, J., Choudhury, M., Konno, S.: Synergistic potentiation of interferon activity with maitake mushroom d-fraction on bladder cancer cells. British Journal of Urology International, 105,1011-5, (2010).
  • Kodama, N., Komuta, K., Sakai, N., Nanba, H.: Effects of D-Fraction, a Polysaccharide from Grifola frondosa on Tumor Growth Involve Activation of NK Cells. Biological and Pharmaceutical Bulletin, 25,1647–1650, (2002).
  • Harnack, U., Eckert, K., Pecher, G.: Beta-(1-3),(1-6)-D-glucan Enhances the Effect of Low-dose Cyclophosphamide Treatment on A20 Lymphoma in Mice. Anticancer Research, 31,1169-1172, (2011).
  • Nanba, H.: Maitake D-fraction: Healing and preventive potential for cancer. Journal of Orthomolecular Medicine, 12, 43-50, (1997).
  • Cheung, N.K., Modak, S.: Oral (1, 3);(1, 4)- -D-glucan synergizes with antiganglioside GD2 monoclonal antibody 3F8 in the therapy of neuroblastoma. Clinical Cancer Research, 8, 1217-1223, (2002).
  • Cheung, N.K., Modak, S., Vickers, A., Knuckles, B.: Orally administered-glucans enhance anti-tumor effects of monoclonal antibodies. Cancer Immunology Immunotheraphy, 51, 557-564, (2002).
  • Sveinbjornsson, B., Rushfeldt, C., Seljelid, R., Smedsrİd, B.: Inhibition of Establishment and Growth of Mouse Liver Metastases After Treatment With Interferon Gamma and -1,3- D-Glucan. Hepatology, 27(5), 1241-1248, (1998).
  • Ghavamia, L., Goliaeia, B., Taghizadeha, B., Nikoofar, A.: Effects of barley -glucan on radiation damage in the humanhepatoma cell line HepG2. Mutation Research- Genetical Toxicology and Environmental Mutagenesis. 775-776, 1-6, (2014).
  • Parzonko, A., Makarewicz-Wujecb, M., Jaszewska, E., Harasym, J., Kozłowska- Wojciechowska, M. Pro-apoptotic properties of (1,3) (1,4) -D-glucan from Avena sativa on human melanoma HTB-140 cells in vitro International Journal of Biological Macromolecules, 72, 757–763, (2015).
  • Fullerton, S.A., Samadi, A.A., Tortorelis, D.G., Choudhury, M.S., Mallouh, C., Tazaki, H., Konno, S.: Induction of apoptosis in human prostatic cancer cells with -glucan (Maitake mushroom polysaccharide) Molecular Urology, 4(1), 7–13, (2000).
  • Ho, J.C.K., Konerding, M.A., Gaumann, A., Groth, M., Liu, W.K.: Fungal polysaccharopeptide inhibits tumor angiogenesis and tumor growth in mice Life Sciences, 75, 1343–1356, (2004).
  • Inoue, M., Tanaka, Y., Sugita, N., Yamasaki, M., Yamanaka, T., Minagawa, J.: Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofiran immunotherapy: a prospective randomized controlled study. Biotherapy, 6(1), 13-18, (1993).
  • Ostadrahimi, A., Esfahani, A., Jafarabadi, M.A., Ziaei, J.E., Movassaghpourakbari, A., Farrin, N.: Effect of Beta Glucan on Quality of Life in Women with Breast Cancer Undergoing Chemotherapy: A Randomized Double-Blind Placebo-Controlled Clinical Trial. Advanced Pharmaceutical Bulletin, 4(Suppl 1), 471-477, (2014).
  • Demir, G., Klein, H.O., Mandel-Molinas, N., Tuzuner, N. Beta glucan induces proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer. International Immunopharmacology, 7(1), 113-116, (2007).
  • Go, P., Chung, CH. Adjuvant PSK immunotherapy in patients with carcinoma of the nasopharynx. The Journal of International Medical Research, 17(2):141-149, (1989).
  • Chen, X., Hu, Z.P., Yang, X.X., Huang, M., Gao, Y., Tang, W., Chan, S.Y., Dai, X., Ye, J., Ho, P.C., Duan, W., Yang, H.Y., Zhu, Y.Z., Zhou, S.F.: Monitoring of immune responses to a herbal immuno-modulator in patients with advanced colorectal cancer. International Immunopharmacology, 6(3), 499-508, (2006).
  • Gaullier, Sleboda, J., Snorre, E.O., Ulvestad, E., Nurminiemi, M., Moe, C.: Supplementation with a soluble - glucan exported from Shiitake medicinal mushroom, Lentinus edodes (Berk.) singer mycelium: a crossover, placebo-controlled study in healthy elderly. International Journal of Medicinal Mushrooms, 13(4), 319-324, (2011).
  • Auinger, A., Riede, L., Bothe, G., Busch, R., Gruenwal, J.: Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: a double blind, randomized, placebo-controlled, multicentric study in healthy subjects. European Journal of Nutrition, 52, 1913–1918, (2013).
  • Carpenter, K.C., Breslin, W.L., Davidson, T., Adams, A., McFarlin, B.K.: Baker’s yeast  -glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk? British Journal of Nutrition 109, 478-486, (2013).
  • Weitberg, A.B.: A phase I/II trial of beta-(1,3)/(1,6) D-glucan in the treatment of patients with advanced malignancies receiving chemotherapy. Journal of Experimental and Clinical Cancer Research, 27, 40, (2008).
  • Maeda, Y.Y., Watanabe, S.T., Chibara, C., Rokutanda, M. Denaturation and Renaturation of a -l,6;l,3-Glucan, Lentinan, Associated with Expression of T-Cell-mediated Responses. Cancer Research, 48(3), 671-675, (1998).
  • Tanriverdi, P., Yuksel, B.C., Rasa, K., Guler, G., Iskit, A.B., Guc, M.O. The effects of selective nitric oxide synthase blocker on survival, mesenteric blood flow and multiple organ failure induced by zymosan. Journal of Surgical Research, 124, 67–73, (2005).
  • Yoshioka, S., Ohno, N., Miura, T., Adachi, Y., Yadomae, T. Immunotoxicity of soluble beta- glucans induced by indomethacin treatment. FEMS Immunolgy and Medical Microbiology, 21(3), 1719, (1998).
  • Zent, C.S., Call, T.G., Bowen, D.A., Conte, M.J., LaPlant, B.R., Witzig, T.E.: Early Treatment of High Risk Chronic LymphocyticLeukemia with Alemtuzumab, Rituximab and PGG Beta Glucan is Well Tolerated and Achieves High Complete Remission Rates. Leukemia& Lymphoma 2015; in press doi: 10.3109/10428194.2015.1016932
  • Richter, J., Svozil, V., Král, V., Dobiášová, L.R., Stiborová, I., Vetvicka, V.: Clinical trials of yeast-derived -(1,3) glucan in children: effects on innate immunity. Annals of Translational Medicine, 2(2), 15, (2014).
  • Tşrmina, J.A., Carraro, E., Alves da Cunha, M.A., Dekker, R.F.H., Barbosa, A.M., Seidel dos Santos, F. Toxicological assessment of-(16)-Glucan (Lasiodiplodan) in mice during a 28-day feeding study by gavage. Molecules 17, 14298-14309, (2012).
  • Üstünes, L. Rx Media Pharma, 14.04.2015.