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Open Life Sciences

formerly Central European Journal of Biology

Editor-in-Chief: Ratajczak, Mariusz

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Volume 5, Issue 1


Volume 10 (2015)

Anti-inflammatory effect of chitosan oligosaccharides in RAW 264.7 cells

Eun-Jin Yang
  • Jeju Biodiversity Research Institute (JBRI), Jeju Hi-Tech Industry Development Institute (HiDI), Jeju, 699-943, Korea
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/ Jong-Gwan Kim / Ji-Young Kim
  • Jeju Biodiversity Research Institute (JBRI), Jeju Hi-Tech Industry Development Institute (HiDI), Jeju, 699-943, Korea
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/ Seong Kim / Nam Lee
  • Research Group for Beauty and Cosmetics, Cheju National University, Jeju, 690-756, Korea
  • Department of Chemistry, Cheju National University, Jeju, 690-756, Korea
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/ Chang-Gu Hyun
  • Jeju Biodiversity Research Institute (JBRI), Jeju Hi-Tech Industry Development Institute (HiDI), Jeju, 699-943, Korea
  • Department of Chemistry, Cheju National University, Jeju, 690-756, Korea
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Published Online: 2010-01-30 | DOI: https://doi.org/10.2478/s11535-009-0066-5


We examined the effects of chitosan oligosaccharides (COSs) with different molecular weights (COS-A, 10 kDa < MW < 20 kDa; COS-C, 1 kDa < MW < 3 kDa) on the lipopolysaccharide (LPS)-induced production of prostaglandin E2 and nitric oxide and on the expression of cyclooxygenase-2 and inducible nitric oxide synthase in RAW264.7 macrophages. COS-A (0.4%) and COS-C (0.2%) significantly inhibited PGE2 production in LPS-stimulated macrophages without cytotoxicity. The effect of COS-A and COS-C on COX-2 expression in activated macrophages was also investigated by immunoblotting. The inhibition of PGE2 by COS-A and COS-C can be attributed to the blocking of COX-2 protein expression. COS-A (0.4%) and COS-C (0.2%) also markedly inhibited the LPS-induced NO production of RAW 264.7 cells by 50.2% and 44.1%, respectively. The inhibition of NO by COSs was consistent with decreases in inducible nitric oxide synthase (iNOS) protein expression. To test the inhibitory effects of COS-A and COS-C on other cytokines, we also performed ELISA assays for IL-1β in LPS-stimulated RAW 264.7 macrophage cells, but only a dose-dependent decrease in the IL-1β production exerted by COS-A was observed. In order to test for irritation and the potential sensitization of COS-A and COS-C for use as cosmetic materials, human skin primary irritation tests were performed on 32 volunteers; no adverse reactions of COSs usage were observed. Based on these results, we suggest that COS-A and COS-C be considered possible anti-inflammatory candidates for topical application.

Keywords: Chitosan oligosaccharides; COX-2; Inflammation; PGE2; Skin irritation test

  • [1] Paños I., Acosta N., Heras A., New drug delivery systems based on chitosan, Curr. Drug Discov. Technol., 2008, 5, 333–341 http://dx.doi.org/10.2174/157016308786733528CrossrefGoogle Scholar

  • [2] Hayes M., Carney B., Slater J., Brück W., Mining marine shellfish wastes for bioactive molecules: chitin and chitosan-Part B: applications, Biotechnol. J., 2008, 3, 878–889 http://dx.doi.org/10.1002/biot.200800027CrossrefGoogle Scholar

  • [3] No H.K., Meyers S.P., Prinyawiwatkul W., Xu Z., Applications of chitosan for improvement of quality and shelf life of foods: a review, J. Food Sci., 2007, 72, R87–R100 http://dx.doi.org/10.1111/j.1750-3841.2007.00383.xCrossrefGoogle Scholar

  • [4] Liu B., Liu W.S., Han B.Q., Sun Y.Y., Antidiabetic effects of chitooligosaccharides on pancreatic islet cells in streptozotocin-induced diabetic rats, World J. Gastroenterol., 2007, 13, 725–731 Google Scholar

  • [5] Felt O., Buri P., Gurny R., Chitosan: a unique polysaccharide for drug delivery, Drug Dev. Ind. Pharm., 1998, 24, 979–993 http://dx.doi.org/10.3109/03639049809089942CrossrefGoogle Scholar

  • [6] Mitchell J.A., Larkin S., Williams T.J., Cyclooxygenase 2: regulation and relevance in inflammation, Biochem. Pharmacol., 1995, 50, 1535–1542 http://dx.doi.org/10.1016/0006-2952(95)00212-XCrossrefGoogle Scholar

  • [7] Smith W.L., Garavito R.M., Dewitt D.L., Prostaglandin endoperoxide H synthases (cyclooxygenase)-1 and -2, J. Biol. Chem., 1996, 271, 33157–33160 http://dx.doi.org/10.1074/jbc.271.52.33157CrossrefGoogle Scholar

  • [8] da Cunha E.F., Ramalho T.C., Josa D., Caetano M.S., de Souza T.C., Targeting inhibition of COX-2: a review of patents, 2002–2006, Recent Pat. Inflamm. Allergy Drug Discov., 2007, 1, 108–123 http://dx.doi.org/10.2174/187221307780979928CrossrefGoogle Scholar

  • [9] Guilemany J.M., Roca-Ferrer J., Mullol J., Cyclooxygenases and the pathogenesis of chronic rhinosinusitis and nasal polyposis, Curr. Allergy Asthma Rep., 2008, 8, 219–226 http://dx.doi.org/10.1007/s11882-008-0037-3CrossrefGoogle Scholar

  • [10] Yang H., Chen C., Cyclooxygenase-2 in synaptic signaling, Curr. Pharm. Des., 14, 1443–1451 Google Scholar

  • [11] Yoon H.J., Moon M.E., Park H.S., Im S.Y., Kim Y.H., Chitosan oligosaccharide (COS) inhibits LPS-induced inflammatory effects in RAW 264.7 macrophage cells, Biochem. Biophys. Res. Commun., 2007, 358, 954–959 http://dx.doi.org/10.1016/j.bbrc.2007.05.042CrossrefGoogle Scholar

  • [12] Kim J.Y., Kim K.N., Kim J.G., Kim S.C., Lee W.J., Hyun C.G., In vitro antimicrobial and antioxidant activities of chitosan oligosaccharides, J. Appl. Biol. Chem., 2009, 52, 84–87 http://dx.doi.org/10.3839/jabc.2009.015CrossrefGoogle Scholar

  • [13] Gerlier D., Thomasser N., Use of MTT colorimetric assay to measure cell activation, J. Immunol. Methods, 1986, 94, 57–63 http://dx.doi.org/10.1016/0022-1759(86)90215-2CrossrefGoogle Scholar

  • [14] Liu Y., Understanding the biological activity of amyloid proteins in vitro: from inhibited cellular MTT reduction to altered cellular cholesterol homeostasis, Prog. Neuro-Psychopharmacol. Psychiat., 1999, 23, 377–395 http://dx.doi.org/10.1016/S0278-5846(99)00003-2CrossrefGoogle Scholar

  • [15] Kim S.S., Song G., Oh T.H., Kim K.N., Yang E.J., Kim J.Y., et al., Antimicrobial effect of Lindera erythrocarpa essential oil against antibiotic-resistant skin pathogens, J. Pure Appl. Microbiol., 2009, 3, 429–434 Google Scholar

  • [16] Yang E.J., Kim S.S., Oh T.H., Song G., Kim K.N., Kim J.Y., et al., Peucedanum Japonicum and Citrus unshiu essential oils inhibit the growth of antibiotic-resistant skin pathogens, Ann. Microbiol., 2009, 59, 623–628 http://dx.doi.org/10.1007/BF03175155CrossrefGoogle Scholar

  • [17] Bradford M.M., A rapid and sensitive for the quantitation of microgram quantitites of protein utilizing the principle of protein-dye binding, Anal. Biochem., 1976, 72, 248–254 http://dx.doi.org/10.1016/0003-2697(76)90527-3CrossrefGoogle Scholar

  • [18] Yoon W.J., Ham Y.M., Yoo B.S., Moon J.Y., Koh J., Hyun C.G., Oenothera laciniata inhibits lipopolysaccharide induced production of nitric oxide, prostaglandin E2, and proinflammatory cytokines in RAW264.7 macrophages, J. Biosci. Bioeng., 2009, 107, 429–438 http://dx.doi.org/10.1016/j.jbiosc.2008.11.018Google Scholar

  • [19] Yoon W.J., Kim S.S., Oh T.H., Lee N.H., Hyun C.G., Cryptomeria japonica essential oil inhibits the growth of drug-resistant skin pathogens and LPS-induced nitric oxide and pro-inflammatory cytokine production, Pol. J. Microbiol., 2009, 58, 61–68 Google Scholar

  • [20] Yoon W.J., Kim S.S., Oh T.H., Lee N.H., Hyun C.G., Abies koreana essential oil inhibits drug-resistant skin pathogen growth and LPS-induced inflammatory effects of murine macrophage, Lipids, 2009, 44, 471–476 http://dx.doi.org/10.1007/s11745-009-3297-3CrossrefGoogle Scholar

  • [21] Fernandes J.C., Tavaria F.K., Soares J.C., Ramos O.S., João Monteiro M., Pintado M.E., et al., Antimicrobial effects of chitosans and chitooligosaccharides, upon Staphylococcus aureus and Escherichia coli, in food model systems, Food Microbiol., 2008, 25, 922–928 http://dx.doi.org/10.1016/j.fm.2008.05.003CrossrefGoogle Scholar

  • [22] Seo S., King J.M., Prinyawiwatkul W., Simultaneous depolymerization and decolorization of chitosan by ozone treatment, J. Food Sci., 2007, 72, C522–C526 http://dx.doi.org/10.1111/j.1750-3841.2007.00563.xCrossrefGoogle Scholar

  • [23] Lee H.W., Park Y.S., Jung J.S., Shin W.S., Chitosan oligosaccharides, dp 2–8, have prebiotic effect on the Bifidobacterium bifidium and Lactobacillus sp. Anaerobe, 2002, 8, 319–324 http://dx.doi.org/10.1016/S1075-9964(03)00030-1CrossrefGoogle Scholar

  • [24] Shahidi F., Arachchi J.K.V., Jeon Y.J., Food applications of chitin and chitosans, Trend Food Sci. Technol., 1999, 10, 37–51 http://dx.doi.org/10.1016/S0924-2244(99)00017-5CrossrefGoogle Scholar

  • [25] Jeon Y.J., Park P.J., Kim S.K., Antimicrobial effect of chitooligosaccharides produced by bioreactor, Carbohydr. Polymer, 2001, 44, 71–76 http://dx.doi.org/10.1016/S0144-8617(00)00200-9CrossrefGoogle Scholar

  • [26] Liu X.F., Guan Y.L., Yang D.Z., Li Z., Yao K.D., Antibacterial action of chitosan and carboxymethylated chitosan, J. Appl. Polymer Sci., 2001, 79, 1324–1335 http://dx.doi.org/10.1002/1097-4628(20010214)79:7<1324::AID-APP210>3.0.CO;2-LCrossrefGoogle Scholar

  • [27] Zheng L.Y., Zhu J.F., Study on antimicrobial activity of chitosan with different molecular weights, Carbohydr. Polymer, 2003, 54, 527–530 http://dx.doi.org/10.1016/j.carbpol.2003.07.009CrossrefGoogle Scholar

  • [28] Qin C., Li H., Xiao Q., Liu Y., Zhu J., Du Y., Water-solubility of chitosan and its antimicrobial activity, Carbohydr. Polymer, 2006, 63, 367–374 http://dx.doi.org/10.1016/j.carbpol.2005.09.023CrossrefGoogle Scholar

  • [29] Eaton P., Fernandes J.C., Pereira E., Pintado M.E., Xavier Malcata F., Atomic force microscopy study of the antibacterial effects of chitosans on Escherichia coli and Staphylococcus aureus, Ultramicroscopy, 2008, 108, 1128–1134 http://dx.doi.org/10.1016/j.ultramic.2008.04.015CrossrefGoogle Scholar

  • [30] Alemdaroğlu C., Değim Z., Celebi N., Zor.F, Oztürk S., Erdoğan D., An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor, Burns, 2006, 32, 319–327 http://dx.doi.org/10.1016/j.burns.2005.10.015CrossrefGoogle Scholar

  • [31] Matsunaga T., Yanagiguchi K., Yamada S., Ohara N., Ikeda T., Hayashi Y., Chitosan monomer promotes tissue regeneration on dental pulp wounds, J. Biomed. Mater. Res. A, 2006, 76, 711–720 CrossrefGoogle Scholar

  • [32] Chen R.N., Wang G.M., Chen C.H., Ho H.O., Sheu M.T., Development of N,O-(carboxymethyl)chitosan/collagen matrixes as a wound dressing, Biomacromolecules, 2006, 7, 1058–1064 http://dx.doi.org/10.1021/bm050754bCrossrefGoogle Scholar

  • [33] Hamilton V., Yuan Y., Rigney D.A., Puckett A.D., Ong J.L., Yang Y., et al., Characterization of chitosan films and effects on fibroblast cell attachment and proliferation, J. Mater. Sci. Mater. Med., 2006, 17, 1373–1381 http://dx.doi.org/10.1007/s10856-006-0613-9CrossrefGoogle Scholar

  • [34] Huang M., Berkland C., Controlled release of repifermin from polyelectrolyte complexes stimulates endothelial cell proliferation, J. Pharm. Sci., 2009. 98, 268–280 http://dx.doi.org/10.1002/jps.21412CrossrefGoogle Scholar

About the article

Published Online: 2010-01-30

Published in Print: 2010-02-01

Citation Information: Open Life Sciences, Volume 5, Issue 1, Pages 95–102, ISSN (Online) 2391-5412, DOI: https://doi.org/10.2478/s11535-009-0066-5.

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© 2010 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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