Fucoidans are sulfated polysaccharides that are found in marine algae and have many useful activities, including antitumor effects, promotion of apoptosis of cancer cells, and antiviral, anti-inflammatory, and antiallergic actions. In oral medicine, several case reports have shown that fucoidan-containing creams and tablets markedly improved recurrent aphthous stomatitis, symptomatic inflamed tongue, and recurrent oral herpes labialis. The aim of this study was to examine the properties of fucoidans for use in oral healthcare. The antimicrobial, anti-adhesion, endotoxin-neutralizing, and cyclooxygenase (COX)-1 and COX-2 inhibitory activities of fucoidans were examined. Four key results were obtained: fucoidans showed strong antimicrobial activity against Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis; significantly inhibited the adhesion of S. mutans to bovine teeth and porcelain; were suggested to bind to and neutralize endotoxin (lipopolysaccharide) in an LAL assay; and showed COX-1 and/or COX-2 inhibitory activity. These results suggested that fucoidans may be useful in the field of oral healthcare.
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Kylin H. Zur Biochemie der Meeresalgen. Hoppe-Seyler´s Zeitschrift für physiologische Chemie. 1913. p. 171.
Sakai T, Ishizuka K, Shimanaka K, Ikai K, Kato I. Structures of oligosaccharides derived from Cladosiphon okamuranus fucoidan by digestion with marine bacterial enzymes. Mar Biotechnol. 2003;5(6):536–44.
Berteau O, Mulloy B. Sulfated fucans, fresh perspectives: structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide. Glycobiology. 2003;13(6):29–40.
Usui T, Asari K, Mizuno T. Isolation of highly purified fucoidan from Eisenia bicyclis and its anticoagulant and antitumor activities. Agric Biol Chem. 1980;44(8):1965–6.
Senthilkumar K, Manivasagan P, Venkatesan J, Kim S-K. Brown seaweed fucoidan: biological activity and apoptosis, growth signaling mechanism in cancer. Int J Biol Macromol. 2013;60:366–74.
Dinesh S, Menon T, Hanna LE, Suresh V, Sathuvan M, Manikannan M. In vitro anti-HIV-1 activity of fucoidan from Sargassum swartzii. Int J Biol Macromol. 2016;82:83–8.
Teixeira MM, Hellewell PG. The effect of the selectin binding polysaccharide fucoidin on eosinophil recruitment in vivo. Br J Pharmacol. 1997;120(6):1059–66.
de Jesus Raposo M, de Morais A, de Morais R. Marine polysaccharides from algae with potential biomedical applications. Mar Drugs. 2015;13(5):2967–3028.
Zhang Z, Teruya K, Eto H, Shirahata S. Induction of apoptosis by low-molecular-weight fucoidan through calcium- and caspase-dependent mitochondrial pathways in MDA-MB-231 breast cancer cells. Biosci Biotechnol Biochem. 2013;77(2):235–42.
Zhang Z, Teruya K, Yoshida T, Eto H, Shirahata S. Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in MDA-MB-231 and MCF-7 breast cancer cells. Mar Drugs. 2013;11(1):81.
Takahashi H, Kawaguchi M, Kitamura K, Narumiya S, Kawamura M, Tengan I, et al. An exploratory study on the anti-inflammatory effects of fucoidan in relation to quality of life in advanced cancer patients. Integr Cancer Ther. 2018;17(2):282–91.
Tsubura S, Tsubura T, Waki Y. Recurrent aphthous stomatitis treated with fucoidan. J Cranio-Maxillary Dis. 2012;1(2):105. https://doi.org/10.4103/2278-9588.105699.
Tsubura S, Waki Y, Tsubura T. A case of symptomatic inflammatory tongue treated with fucoidan. Am J Med Case Rep. 2015;3(8):250–4. https://doi.org/10.12691/ajmcr-3-8-8.
Tsubura S, Suzuki A. Case report using 4% fucoidan cream for recurrent oral herpes labialis: patient symptoms markedly improved in terms of time to healing and time to loss of discomfort. Dent Open J. 2017;4(2):19–23. https://doi.org/10.17140/DOJ-4-135.
Black WAP, Dewar ET, Woodward FN. Manufacture of algal chemicals. IV—laboratory-scale isolation of fucoidin from brown marine algae. J Sci Food Agric. 1952;3(3):122–9.
Ye J, Li Y, Teruya K, Katakura Y, Ichikawa A, Eto H, et al. Enzyme-digested fucoidan etracts derived from seaweed Mozuku of Cladosiphon novae-caledoniaekylin inhibit invasion and angiogenesis of tumor cells. Cytotechnology. 2005;47(1):117–26.
Oka S. Potential synergistic effects of a mixture of mineral trioxide aggregate (MTA) cement and Bacillus subtilis in dental caries treatment. Odontology. 2018;106(1):46–55. https://doi.org/10.1007/s10266-017-0305-6.
Kameda T, Ohkuma K, Oka S. Polytetrafluoroethylene (PTFE): a resin material for possible use in dental prostheses and devices. Dent Mater J. 2019;38:136–42.
Sakuma Y, Washio J, Sasaki K, Takahashi N. A high-sensitive and non-radioisotopic fluorescence dye method for evaluating bacterial adhesion to denture materials. Dent Mater J. 2013;32(4):585–91.
Taniguchi M, Ochiai A, Matsushima K, Tajima K, Kato T, Saitoh E, et al. Endotoxin-neutralizing activity and mechanism of action of a cationic alpha-helical antimicrobial octadecapeptide derived from alpha-amylase of rice. Peptides. 2016;75:101–8.
Sridhar KR, Vidyavathi N. Antimicrobial activity of seaweeds. Acta Hydrochim Hydrobiol. 1991;19(5):455–96.
Lee K, Jeong M, Choi S, Na S, Cha J. Synergistic effect of fucoidan with antibiotics against oral pathogenic bacteria. Arch Oral Biol. 2013;58(5):482–92.
Marudhupandi T, Kumar T. Antibacterial effect of fucoidan from Sargassum wightii against the chosen human bacterial pathogens. Int Curr Pharm J. 2013;2(10):156–8.
Marudhupandi T, Kumar T. Effect of fucoidan from Turbinaria ornata against marine ornamental fish pathogens. J Coast Life Med. 2013;1(4):282–6.
Shibata H, Kimura-Takagi I, Nagaoka M, Hashimoto S, Sawada H, Ueyama S, et al. Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori to human gastric cells. J Nutr Sci Vitaminol. 1999;45(3):325–36.
Ale MT, Mikkelsen JD, Meyer AS. Important determinants for fucoidan bioactivity: a critical review of structure-function relations and extraction methods for fucose-containing sulfated polysaccharides from brown seaweeds. Mar Drugs. 2011;9(10):2106–30.
Kantachumpoo A, Chirapart A. Components and antimicrobial activity of polysaccharides extracted from Thai brown seaweeds. Kasetsart J (Natural Science). 2010;44(2):220–33.
Gibbons RJ, Nygaard M. Synthesis of insoluble dextran and its significance in the formation of gelatinous deposits by plaque-forming streptococci. Arch Oral Biol. 1968;13(10):1249-IN31.
Toida T, Chaidedgumjorn A, Linhardt RJ. Structure and bioactivity of sulfated polysaccharides. Trends Glycosci Glycotechnol. 2003;15(81):29–46.
Mourão PAS, Pereira MS, Pavão MSG, Mulloy B, Tollefsen DM, Mowinckel M, et al. Structure and anticoagulant activity of a fucosylated chondroitin sulfate from echinoderm: sulfated fucose branches on the polysaccharide account for its high anticoagulant action. J Biol Chem. 1996;271(39):23973–84.
Vaara M. New polymyxin derivatives that display improved efficacy in animal infection models as compared to polymyxin B and colistin. Med Res Rev. 2018.
Jeong J, Hwang SJ, Han MH, Lee D, Yoo JS, Choi I, et al. Fucoidan inhibits lipopolysaccharide-induced inflammatory responses in RAW 264.7 macrophages and zebrafish larvae. Mol Cell Toxicol. 2017;13(4):405–17.
Park H, Han M, Park C, Jin C, Kim G, Choi IW, et al. Anti-inflammatory effects of fucoidan through inhibition of NF-kappaB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells. Food Chem Toxicol. 2011;49(8):1745–52.
Park J, Cha J, Choi K, Lee K, Han K, Jang Y. Fucoidan inhibits LPS-induced inflammation in vitro and during the acute response in vivo. Int Immunopharmacol. 2017;43:91–8.
Okuda K, Kato T. Hemagglutinating activity of lipopolysaccharides from subgingival plaque bacteria. Infect Immun. 1987;55(12):3192–6.
Dewi L. In silico analysis of the potential of the active compounds fucoidan and alginate derived from Sargassum sp. as inhibitors of COX-1 and COX-2. Med Arch. 2016;70(3):172–6. https://doi.org/10.5455/medarh.2016.70.172-176.
Ferreira SH. Peripheral analgesic sites of action of anti-inflammatory drugs. Int J Clin Pract Suppl. 2002;128:2–10.
Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR. Nonsteroid drug selectivities for cyclooxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci USA. 1999;96(13):7563–8.
Ballou LR, Botting RM, Goorha S, Zhang J, Vane JR. Nociception in cyclooxygenase isozyme-deficient mice. Proc Natl Acad Sci. 2000;97(18):10272–6.
Wallace JL, McKnight W, Reuter BK, Vergnolle N. NSAID-induced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2. Gastroenterology. 2000;119(3):706–14.
Abe S, Hiramatsu K, Ichikawa O, Kawamoto H, Kasagi T, Miki Y, et al. Safety evaluation of excessive ingestion of Mozuku fucoidan in human. J Food Sci. 2013;78(4):T648–51.
Choi J, Raghavendran HRB, Sung N, Kim J, Chun BS, Ahn DH, et al. Effect of fucoidan on aspirin-induced stomach ulceration in rats. Chem Biol Interact. 2010;183(1):249–54.
Shirahata S, Katakura Y, Teruya K, Yamashita M, Eto H, Inventors. Kit for inducing changes in the sugar chain structure of a cancer cell surface. Japan patent. 2007. JP5201499B2.
The authors are grateful to Daiichi Sangyo Corporation (Osaka, Japan) for generously providing the fucoidan extract (Power fucoidan) and Cream (Power fucoidan cream); to Dr. Masayuki Taniguchi and Mr. Ryousuke Aida (Niigata University, Niigata, Japan) for advice on the LAL assay; to Dr. Kenjirou Nakamura (Nippon Dental University, Niigata, Japan) for advice on treatment of C. albicans; to Ms. Linda Stevens (National Institute of Health, Bethesda, USA) for valuable advice. This work was supported by a Research Promotion KAKENHI Grant (15K11063, 19K10369) from JSPS and NDU Grants (N-17010, N-18014) from The Nippon Dental University.
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Oka, S., Okabe, M., Tsubura, S. et al. Properties of fucoidans beneficial to oral healthcare. Odontology 108, 34–42 (2020). https://doi.org/10.1007/s10266-019-00437-3
- Oral healthcare