Therapies from fucoidan: An update

Marine Drugs

Volumn 13, Issue 9, 2015, Pages 5920-5946

  Fitton, Janet Helen ^a   Stringer, Damien N ^a   Karpiniec, Samuel S ^a  

^a Marinova Pty Ltd   (Australia)

Author keywords

Anti bacterial; Anti cancer; Anti inflammatory; Anti viral; Immune modulation; Sulfated carbohydrate

Indexed keywords

AMMONIA; BEVACIZUMAB; CHEMOKINE RECEPTOR CXCR4; CHITOSAN; CISPLATIN; CURCUMIN; DOXORUBICIN; FLUOROURACIL; FOLINIC ACID; FUCOIDIN; GASTRIN; GLUCOSE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLUENZA VACCINE; IRINOTECAN; LACTIC ACID; LETROZOLE; LIPOSOME; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; OXALIPLATIN; PLERIXAFOR; SEROTONIN; STROMAL CELL DERIVED FACTOR 1; TAMOXIFEN; TOLL LIKE RECEPTOR 2; TRIACYLGLYCEROL; UNINDEXED DRUG; VASCULOTROPIN; ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; IMMUNOLOGIC FACTOR; POLYSACCHARIDE;

AMMONIA BLOOD LEVEL; ANTIBACTERIAL ACTIVITY; ANTIBODY RESPONSE; ANTIBODY SPECIFICITY; ANTICOAGULATION; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; APOPTOSIS; ASCOPHYLLUM; ASCOPHYLLUM NODOSUM; BREAST CANCER; CANCER GROWTH; CANCER INHIBITION; CELL MATURATION; CLADOSIPHON OKAMURANUS; COHORT ANALYSIS; COLITIS; DENDRITIC CELL; DIABETES MELLITUS; DIET SUPPLEMENTATION; DOWN REGULATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG DETERMINATION; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG ISOLATION; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG SCREENING; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG UPTAKE; DRUG URINE LEVEL; ELECTROCHEMICAL ANALYSIS; ELECTROSPRAY MASS SPECTROMETRY; EPITHELIUM CELL; FATIGUE; FUCUS VESICULOSUS; GLUCOSE BLOOD LEVEL; HEPATITIS C; HISTOLOGY; HUMAN; HYDROLYSIS; IMMUNOMODULATION; IN VITRO STUDY; IN VIVO STUDY; INFLUENZA A; INFLUENZA A (H5N3); INFLUENZA A (H7N2); INFLUENZA A VIRUS (H5N3); INFLUENZA A VIRUS (H7N2); KIDNEY FUNCTION; KIDNEY INJURY; LACTATE BLOOD LEVEL; LEISHMANIASIS; LIMIT OF QUANTITATION; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER DISEASE; LUNG CANCER; MACROCYSTIS; MACROCYSTIS PYRIFERA; MACULAR DEGENERATION; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; METASTASIS POTENTIAL; MICROWAVE RADIATION; MOLECULAR WEIGHT; MUCOSA INFLAMMATION; NANOENCAPSULATION; NATURAL KILLER CELL; NEUTROPHIL; NEWCASTLE DISEASE; NONHUMAN; OSTEOSARCOMA; REVIEW; SEAWEED; SIZE EXCLUSION CHROMATOGRAPHY; STICHOPUS; STICHOPUS JAPONICAS; T LYMPHOCYTE ACTIVATION; TREND STUDY; TRIACYLGLYCEROL BLOOD LEVEL; UNDARIA PINNATIFIDA; WEIGHT REDUCTION;

ANTI-INFECTIVE AGENTS; ANTINEOPLASTIC AGENTS; IMMUNOLOGIC FACTORS; POLYSACCHARIDES;

EID: 84942859830     PISSN: None     EISSN: 16603397     Source Type: Journal    
DOI: 10.3390/md13095920     Document Type: Review

References (125)

1. 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, 29-40.
2. Kannan, R.R.; Arumugam, R.; Anantharaman, P. Pharmaceutical potential of a fucoidan-like sulphated polysaccharide isolated from Halodule pinifolia. Int. J. Biol. Macromol. 2013, 62, 30-34.
3. Fitton, J. Therapies from fucoidan; multifunctional marine polymers. Mar. Drugs 2011, 9, 1731-1760.
4. Kwak, J.Y. Fucoidan as a marine anticancer agent in preclinical development. Mar. Drugs 2014, 12, 851-870.
5. Pomin, V.H. Fucanomics and galactanomics: Current status in drug discovery, mechanisms of action and role of the well-defined structures. Biochim. Biophys. Acta 2012, 1820, 1971-1979.
6. Pomin, V.H. Fucanomics and galactanomics: Marine distribution, medicinal impact, conceptions, and challenges. Mar. Drugs 2012, 10, 793-811.
7. Ale, M.T.; Mikkelsen, J.D.; Meyer, A.S. 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, 2106-2130.
8. Ermakova, S.; Kusaykin, M.; Trincone, A.; Tatiana, Z. Are multifunctional marine polysaccharides a myth or reality? Front. Chem. 2015, 3, 39, doi:10.3389/fchem.2015.00039.
9. Cumashi, A.; Ushakova, N.A.; Preobrazhenskaya, M.E.; D'Incecco, A.; Piccoli, A.; Totani, L.; Tinari, N.; Morozevich, G.E.; Berman, A.E.; Bilan, M.I.; et al. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology 2007, 17, 541-552.
10. Azuma, K.; Ishihara, T.; Nakamoto, H.; Amaha, T.; Osaki, T.; Tsuka, T.; Imagawa, T.; Minami, S.; Takashima, O.; Ifuku, S.; et al. Effects of oral administration of fucoidan extracted from cladosiphon okamuranus on tumor growth and survival time in a tumor-bearing mouse model. Mar. Drugs 2012, 10, 2337-2348.
11. Lovatelli, A.C.C.; Purcell, S.; Uthicke, S.; Hamel, J.F.; Mercier, A. Food and Agriculture Organization of the United Nations. Advances in Sea Cucumber Aquaculture and Management; FAO Fisheries Department: Rome, Italy, 2004.
12. Kariya, Y.; Mulloy, B.; Imai, K.; Tominaga, A.; Kaneko, T.; Asari, A.; Suzuki, K.; Masuda, H.; Kyogashima, M.; Ishii, T. Isolation and partial characterization of fucan sulfates from the body wall of sea cucumber stichopus japonicus and their ability to inhibit osteoclastogenesis. Carbohydr. Res. 2004, 339, 1339-1346.
13. Le Visage, C.; Chaubet, D.L.F. Autissier, A. Method for Preparing Porous Scaffold for Tissue Engineering. U.S. Patent 9,028,857, 12 May 2015.
14. Dockal, M.; Ehrlich, H.; Scheiflinger, F. Methods and Compositions for Treating Bleeding Disorders. U.S. Patent 8,632,991, 21 January 2014.
15. Abe, S.; Hiramatsu, K.; Ichikawa, O.; Kawamoto, H.; Kasagi, T.; Miki, Y.; Kimura, T.; Ikeda, T. Safety evaluation of excessive ingestion of mozuku fucoidan in human. J. Food Sci. 2013, 78, T648-T651.
16. Irhimeh, M.R.; Fitton, J.H.; Lowenthal, R.M.; Kongtawelert, P. A quantitative method to detect fucoidan in human plasma using a novel antibody. Methods Find. Exp. Clin. Pharmacol. 2005, 27, 705-710.
17. Tokita, Y.; Nakajima, K.; Mochida, H.; Iha, M.; Nagamine, T. Development of a fucoidan-specific antibody and measurement of fucoidan in serum and urine by sandwich elisa. Biosci. Biotechnol. Biochem. 2010, 74, 350-357.
18. Nagamine, T.; Nakazato, K.; Tomioka, S.; Iha, M.; Nakajima, K. Intestinal absorption of fucoidan extracted from the brown seaweed, cladosiphon okamuranus. Mar. Drugs 2015, 13, 48-64.
19. Nagamine, T.; Hayakawa, K.; Nakazato, K.; Iho, M. Determination of the active transport of fucoidan derived from okinawa mozuku across the human intestinal caco-2 cells as assessed by size-exclusion chromatography. J. Chromatogr. B 2015, doi:10.1016/j.jchromb.2015.05.026.
20. Pinheiro, A.C.; Bourbon, A.I.; Cerqueira, M.A.; Maricato, E.; Nunes, C.; Coimbra, M.A.; Vicente, A.A. Chitosan/fucoidan multilayer nanocapsules as a vehicle for controlled release of bioactive compounds. Carbohydr. Polym. 2015, 115, 1-9.
21. Lee, K.W.; Jeong, D.; Na, K. Doxorubicin loading fucoidan acetate nanoparticles for immune and chemotherapy in cancer treatment. Carbohydr. Polym. 2013, 94, 850-856.
22. Kimura, R.; Rokkaku, T.; Takeda, S.; Senba, M.; Mori, N. Cytotoxic effects of fucoidan nanoparticles against osteosarcoma. Mar. Drugs 2013, 11, 4267-4278.
23. Zhang, W.; Oda, T.; Yu, Q.; Jin, J.O. Fucoidan from macrocystis pyrifera has powerful immune-modulatory effects compared to three other fucoidans. Mar. Drugs 2015, 13, 1084-1104.
24. Negishi, H.; Mori, M.; Mori, H.; Yamori, Y. Supplementation of elderly japanese men and women with fucoidan from seaweed increases immune responses to seasonal influenza vaccination. J. Nutr. 2013, 143, 1794-1798.
25. Makarenkova, I.D.; Logunov, D.Y.; Tukhvatulin, A.I.; Semenova, I.B.; Besednova, N.N.; Zvyagintseva, T.N. Interactions between sulfated polysaccharides from sea brown algae and toll-like receptors on hek293 eukaryotic cells in vitro. Bull. Exp. Biol. Med. 2012, 154, 241-244.
26. Baxevanis, C.N.; Voutsas, I.F.; Tsitsilonis, O.E. Toll-like receptor agonists: Current status and future perspective on their utility as adjuvants in improving anticancer vaccination strategies. Immunotherapy 2013, 5, 497-511.
27. Jin, W.; Zhang, Q.; Wang, J.; Zhang, W. A comparative study of the anticoagulant activities of eleven fucoidans. Carbohydr. Polym. 2013, 91, 1-6.
28. Zhang, Z.; Till, S.; Jiang, C.; Knappe, S.; Reutterer, S.; Scheiflinger, F.; Szabo, C.M.; Dockal, M. Structure-activity relationship of the pro- and anticoagulant effects of fucus vesiculosus fucoidan. Thromb. Haemost. 2014, 111, 429-437.
29. Clement, M.J.; Tissot, B.; Chevolot, L.; Adjadj, E.; Du, Y.; Curmi, P.A.; Daniel, R. NMR characterization and molecular modeling of fucoidan showing the importance of oligosaccharide branching in its anticomplementary activity. Glycobiology 2010, 20, 883-894.
30. Pereira, M.S.; Mulloy, B.; Mourão, P.A.S. Structure and anticoagulant activity of sulfated fucans. Comparison between the regular, repetitive, and linear fucans from echinoderms with the more heterogeneous and branched polymers from brown algae. J. Biol. Chem. 1999, 274, 7656-7667.
31. Mulloy, B.; Ribeiro, A.C.F.; Alves, A.P.; Vieira, R.P.; Mourão, P.A.S. Sulfated fucans from echinoderms have a regular tetrasaccharide repeating unit defined by specific patterns of sulfation at the 0-2 and 0-4 positions. J. Biol. Chem. 1994, 269, 22113-22123.
32. Synytsya, A.; Kim, W.J.; Kim, S.M.; Pohl, R.; Synytsya, A.; Kvasnicka, F.; Copíková, J.; Park, Y., II. Structure and antitumour activity of fucoidan isolated from sporophyll of korean brown seaweed undaria pinnatifida. Carbohydr. Polym. 2010, 81, 41-48.
33. Black, W.A.P.; Dewar, E.T.; Woodward, F.N. Manufacture of algal chemicals. IV.-Laboratory scale isolation of fucoidin from brown marine algae. J. Sci. Food Agric. 1952, 3, 122-129.
34. Kusaykin, M.I.; Burtseva, Y.V.; Svetasheva, T.G.; Sova, V.V.; Zvyagintseva, T.N. Distribution of o-glycosylhydrolases in marine invertebrates. Enzymes of the marine mollusk littorina kurila that catalyze fucoidan transformation. Biochemistry (Mosc.) 2001, 68, 317-324.
35. Silchenko, A.S.; Kusaykin, M.I.; Kurilenko, V.V.; Zakharenko, A.M.; Isakov, V.V.; Zaporozhets, T.S.; Gazha, A.K.; Zvyagintseva, T.N. Hydrolysis of fucoidan by fucoidanase isolated from the marine bacterium, formosa algae. Mar. Drugs 2013, 11, 2413-2430.
36. Rodriguez-Jasso, R.M.; Mussatto, S.I.; Pastrana, L.; Aguilar, C.N.; Teixeira, J.A. Fucoidan-degrading fungal strains: Screening, morphometric evaluation, and influence of medium composition. Appl. Biochem. Biotechnol. 2010, 162, 2177-2188.
37. Rodriguez-Jasso, R.M.; Mussatto, S.I.; Pastrana, L.; Aguilar, C.N.; Teixeira, J.A. Microwave-assisted extraction of sulfated polysaccharides (fucoidan) from brown seaweed. Carbohydr. Polym. 2011, 86, 1137-1144.
38. Yang, C.; Chung, D.; Shin, I.S.; Lee, H.; Kim, J.; Lee, Y.; You, S. Effects of molecular weight and hydrolysis conditions on anticancer activity of fucoidans from sporophyll of undaria pinnatifida. Int. J. Biol. Macromol. 2008, 43, 433-437.
39. Yuan, Y.; Macquarrie, D. Microwave assisted extraction of sulfated polysaccharides (fucoidan) from ascophyllum nodosum and its antioxidant activity. Carbohydr. Polym. 2015, 129, 101-107.
40. Morvai-Vitányi, M.; Molnár-Perl, I.; Knausz, D.; Sass, P. Simultaneous GC derivatization and quantification of acids and sugars. Chromatographia 1993, 36, 204-206.
41. Filisetti-Cozzi, T.M.C.C.; Carpita, N.C. Measurement of uronic acids without interference from neutral sugars. Anal. Biochem. 1991, 197, 157-162.
42. Dodgson, K.S.; Price, R.G. A note on the determination of the ester sulphate content of sulphated polysaccharides. Biochem. J. 1962, 84, 106-110.
43. Dogson, K.S. Determination of inorganic sulphate in studies on the enzymic and non-enzymic hydrolysis of carbohydrate and other sulphate esters. Biochem. J. 1961, 78, 312-319.
44. Zoecklein, B.W.; Fugelsang, K.C.; Gump, B.H.; Nury, F.S. (Eds.) Phenolic compounds and wine color. Wine Analysis and Production; Chapman & Hall: NewYork, NY, USA, 1995; pp. 115-151.
45. Nagaoka, M.; Shibata, H.; Kimura-Takagi, I.; Hashimoto, S.; Kimura, K.; Makino, T.; Aiyama, R.; Ueyama, S.; Yokokura, T. Structural study of fucoidan from cladosiphon okamuranus tokida. Glycoconj. J. 1999, 16, 19-26.
46. Anastyuk, S.D.; Imbs, T.I.; Dmitrenok, P.S.; Zvyagintseva, T.N. Rapid mass spectrometric analysis of a novel fucoidan, extracted from the brown alga coccophora langsdorfii. Sci. World J. 2014, 2014, 972450, doi:10.1155/2014/972450.
47. Anastyuk, S.D.; Shevchenko, N.M.; Gorbach, V.I. Fucoidan analysis by tandem maldi-tof and esi mass spectrometry. Methods Mol. Biol. 2015, 1308, 299-312.
48. Kadam, S.U.; O'Donnell, C.P.; Rai, D.K.; Hossain, M.B.; Burgess, C.M.; Walsh, D.; Tiwari, B.K. Laminarin from irish brown seaweeds ascophyllum nodosum and laminaria hyperborea: Ultrasound assisted extraction, characterization and bioactivity. Mar. Drugs 2015, 13, 4270-4280.
49. Zaragoza, M.C.; Lopez, D.; Saiz, M.P.; Poquet, M.; Perez, J.; Puig-Parellada, P.; Marmol, F.; Simonetti, P.; Gardana, C.; Lerat, Y.; et al. Toxicity and antioxidant activity in vitro and in vivo of two fucus vesiculosus extracts. J. Agric. Food Chem. 2008, 56, 7773-7780.
50. Parys, S.; Rosenbaum, A.; Kehraus, S.; Reher, G.; Glombitza, K.W.; König, G.M. Evaluation of quantitative methods for the determination of polyphenols in algal extracts. J. Nat. Prod. 2007, 70, 1865-1870.
51. Jiménez-Escrig, A.; Jiménez-Jiménez, I.; Pulido, R.; Saura-Calixto, F. Antioxidant activity of fresh and processed edible seaweeds. J. Sci. Food Agric. 2001, 81, 530-534.
52. Zhang, Q.; Zhang, J.; Shen, J.; Silva, A.; Dennis, D.; Barrow, C. A simple 96-well microplate method for estimation of total polyphenol content in seaweeds. J. Appl. Phycol. 2006, 18, 445-450.
53. Nakazato, K.; Takada, H.; Iha, M.; Nagamine, T. Attenuation of n-nitrosodiethylamine-induced liver fibrosis by high-molecular-weight fucoidan derived from cladosiphon okamuranus. J. Gastroenterol. Hepatol. 2010, 25, 1692-1701.
54. Lee, J.M.; Shin, Z.U.; Mavlonov, G.T.; Abdurakhmonov, I.Y.; Yi, T.H. Solid-phase colorimetric method for the quantification of fucoidan. Appl. Biochem. Biotechnol. 2012, 168, 1019-1024.
55. Kim, J.M.; Nguyen, L.; Barr, M.F.; Morabito, M.; Stringer, D.; Fitton, J.H.; Mowery, K.A. Quantitative determination of fucoidan using polyion-sensitive membrane electrodes. Anal. Chim. Acta 2015, 877, 1-8.
56. Atashrazm, F.; Lowenthal, R.M.; Woods, G.M.; Holloway, A.F.; Dickinson, J.L. Fucoidan and cancer: A multifunctional molecule with anti-tumor potential. Mar. Drugs 2015, 13, 2327-2346.
57. Chen, S.; Zhao, Y.; Zhang, Y.; Zhang, D. Fucoidan induces cancer cell apoptosis by modulating the endoplasmic reticulum stress cascades. PLoS ONE 2014, 9, e108157.
58. Esmaeelian, B.; Abbott, C.A.; Le Leu, R.K.; Benkendorff, K. 6-bromoisatin found in muricid mollusc extracts inhibits colon cancer cell proliferation and induces apoptosis, preventing early stage tumor formation in a colorectal cancer rodent model. Mar. Drugs 2014, 12, 17-35.
59. Zuo, T.; Li, X.; Chang, Y.; Duan, G.; Yu, L.; Zheng, R.; Xue, C.; Tang, Q. Dietary fucoidan of acaudina molpadioides and its enzymatically degraded fragments could prevent intestinal mucositis induced by chemotherapy in mice. Food Funct. 2015, 6, 415-422.
60. Song, M.Y.; Ku, S.K.; Kim, H.J.; Han, J.S. Low molecular weight fucoidan ameliorating the chronic cisplatin-induced delayed gastrointestinal motility in rats. Food Chem. Toxicol. 2012, 50, 4468-4478.
61. Lean, Q.Y.; Eri, R.D.; Fitton, J.H.; Patel, R.P.; Gueven, N. Fucoidan extracts ameliorate acute colitis. PLoS ONE 2015, 10, e0128453.
62. Oh, B.; Kim, J.; Lu, W.; Rosenthal, D. Anticancer effect of fucoidan in combination with tyrosine kinase inhibitor lapatinib. Evid. Based Complement. Altern. Med. 2014, 2014, 865375, doi:10.1155/2014/865375.
63. 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, 81-98.
64. Philchenkov, A.; Zavelevich, M.; Imbs, T.; Zvyagintseva, T.; Zaporozhets, T. Sensitization of human malignant lymphoid cells to etoposide by fucoidan, a brown seaweed polysaccharide. Exp. Oncol. 2007, 29, 181-185.
65. Ikeguchi, M.; Yamamoto, M.; Arai, Y.; Maeta, Y.; Ashida, K.; Katano, K.; Miki, Y.; Kimura, T. Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer. Oncol. Lett. 2011, 2, 319-322.
66. Chen, Y.M.; Tsai, Y.H.; Tsai, T.Y.; Chiu, Y.S.; Wei, L.; Chen, W.C.; Huang, C.C. Fucoidan supplementation improves exercise performance and exhibits anti-fatigue action in mice. Nutrients 2015, 7, 239-252.
67. Tocaciu, S.O.L.; Lowenthal, R.; Peterson, G.M.; Patel, R.; Shastri, M.; McGuinness, G.; Olesen, I.; Fitton, J.H. The effect of undaria pinnatifida fucoidan on the pharmacokinetics of letrozole and tamoxifen in patients with breast cancer. PLoS ONE 2015, submitted for publication.
68. Sweeney, E.A.; Lortat-Jacob, H.; Priestley, G.V.; Nakamoto, B.; Papayannopoulou, T. Sulfated polysaccharides increase plasma levels of sdf-1 in monkeys and mice: Involvement in mobilization of stem/progenitor cells. Blood 2002, 99, 44-51.
69. Fermas, S.; Gonnet, F.; Sutton, A.; Charnaux, N.; Mulloy, B.; Du, Y.; Baleux, F.; Daniel, R. Sulfated oligosaccharides (heparin and fucoidan) binding and dimerization of stromal cell-derived factor-1 (sdf-1/cxcl 12) are coupled as evidenced by affinity ce-ms analysis. Glycobiology 2008, 18, 1054-1064.
70. Schneider, T.; Ehrig, K.; Liewert, I.; Alban, S. Interference with the cxcl12/cxcr4 axis as potential antitumor strategy: Superiority of a sulfated galactofucan from the brown alga saccharina latissima and fucoidan over heparins. Glycobiology 2015, 25, 812-824.
71. Carvalho, A.C.; Sousa, R.B.; Franco, A.X.; Costa, J.V.; Neves, L.M.; Ribeiro, R.A.; Sutton, R.; Criddle, D.N.; Soares, P.M.; de Souza, M.H. Protective effects of fucoidan, a p- and l-selectin inhibitor, in murine acute pancreatitis. Pancreas 2014, 43, 82-87.
72. Delma, C.R.; Somasundaram, S.T.; Srinivasan, G.P.; Khursheed, M.; Bashyam, M.D.; Aravindan, N. Fucoidan from turbinaria conoides: A multifaceted 'deliverable' to combat pancreatic cancer progression. Int. J. Biol. Macromol. 2015, 74, 447-457.
73. Saur, D.; Seidler, B.; Schneider, G.; Algul, H.; Beck, R.; Senekowitsch-Schmidtke, R.; Schwaiger, M.; Schmid, R.M. Cxcr4 expression increases liver and lung metastasis in a mouse model of pancreatic cancer. Gastroenterology 2005, 129, 1237-1250.
74. Huang, T.H.; Chiu, Y.H.; Chan, Y.L.; Chiu, Y.H.; Wang, H.; Huang, K.C.; Li, T.L.; Hsu, K.H.; Wu, C.J. Prophylactic administration of fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor (vegf) and matrix metalloproteinases (mmps) in lewis tumor-bearing mice. Mar. Drugs 2015, 13, 1882-1900.
75. Li, J.; Zhou, L.; Chen, X.; Ba, Y. Addition of bevacizumab to chemotherapy in patients with ovarian cancer: A systematic review and meta-analysis of randomized trials. Clin. Transl. Oncol. 2015, 17, 673-683.
76. Dithmer, M.; Fuchs, S.; Shi, Y.; Schmidt, H.; Richert, E.; Roider, J.; Klettner, A. Fucoidan reduces secretion and expression of vascular endothelial growth factor in the retinal pigment epithelium and reduces angiogenesis in vitro. PLoS ONE 2014, 9, e89150.
77. Kawaguchi, T.; Hayakawa, M.; Koga, H.; Torimura, T. Effects of fucoidan on proliferation, amp-activated protein kinase, and downstream metabolism- and cell cycle-associated molecules in poorly differentiated human hepatoma hlf cells. Int. J. Oncol. 2015, 46, 2216-2222.
78. Min, E.Y.; Kim, I.H.; Lee, J.; Kim, E.Y.; Choi, Y.H.; Nam, T.J. The effects of fucodian on senescence are controlled by the p16ink4a-prb and p14arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines. Int. J. Oncol. 2014, 45, 47-56.
79. Lee, H.E.; Choi, E.S.; Shin, J.A.; Lee, S.O.; Park, K.S.; Cho, N.P.; Cho, S.D. Fucoidan induces caspase-dependent apoptosis in mc3 human mucoepidermoid carcinoma cells. Exp. Ther. Med. 2014, 7, 228-232.
80. Gibson, A.; Edgar, J.D.; Neville, C.E.; Gilchrist, S.E.; McKinley, M.C.; Patterson, C.C.; Young, I.S.; Woodside, J.V. Effect of fruit and vegetable consumption on immune function in older people: A randomized controlled trial. Am. J. Clin. Nutr. 2012, 96, 1429-1436.
81. Jin, J.O.; Zhang, W.; Du, J.Y.; Wong, K.W.; Oda, T.; Yu, Q. Fucoidan can function as an adjuvant in vivo to enhance dendritic cell maturation and function and promote antigen-specific t cell immune responses. PLoS ONE 2014, 9, e99396.
82. Zhang, W.; Du, J.Y.; Jiang, Z.; Okimura, T.; Oda, T.; Yu, Q.; Jin, J.O. Ascophyllan purified from ascophyllum nodosum induces th1 and tc1 immune responses by promoting dendritic cell maturation. Mar. Drugs 2014, 12, 4148-4164.
83. Kar, S.; Sharma, G.; Das, P.K. Fucoidan cures infection with both antimony-susceptible and -resistant strains of leishmania donovani through th1 response and macrophage-derived oxidants. J. Antimicrob. Chemother. 2011, 66, 618-625.
84. Sharma, G.; Kar, S.; Basu Ball, W.; Ghosh, K.; Das, P.K. The curative effect of fucoidan on visceral leishmaniasis is mediated by activation of map kinases through specific protein kinase c isoforms. Cell. Mol. Immunol. 2014, 11, 263-274.
85. Hayashi, K.; Lee, J.B.; Nakano, T.; Hayashi, T. Anti-influenza a virus characteristics of a fucoidan from sporophyll of undaria pinnatifida in mice with normal and compromised immunity. Microbes Infect./Inst. Pasteur 2013, 15, 302-309.
86. Synytsya, A.; Bleha, R.; Synytsya, A.; Pohl, R.; Hayashi, K.; Yoshinaga, K.; Nakano, T.; Hayashi, T. Mekabu fucoidan: Structural complexity and defensive effects against avian influenza a viruses. Carbohydr. Polym. 2014, 111, 633-644.
87. Hayashi, T.; Hayashi, K.; Kanekiyo, K.; Ohta, Y.; Lee, J.-B. Promising antiviral glyco-molecules from an edible alga. In Combating the Threat of Pandemic Infl Uenza: Drug Discovery Approaches; Torrence, P.F., Ed.; John Wiley & Sons: Hoboken, NJ, USA, 2007; pp. 166-182.
88. Trejo-Avila, L.M.; Morales-Martinez, M.E.; Ricque-Marie, D.; Cruz-Suarez, L.E.; Zapata-Benavides, P.; Moran-Santibanez, K.; Rodriguez-Padilla, C. In vitro anti-canine distemper virus activity of fucoidan extracted from the brown alga cladosiphon okamuranus. VirusDisease 2014, 25, 474-480.
89. Elizondo-Gonzalez, R.; Cruz-Suarez, L.E.; Ricque-Marie, D.; Mendoza-Gamboa, E.; Rodriguez-Padilla, C.; Trejo-Avila, L.M. In vitro characterization of the antiviral activity of fucoidan from cladosiphon okamuranus against newcastle disease virus. Virol. J. 2012, 9, 307, doi:10.1186/1743-422X-9-307.
90. Lee, K.Y.; Jeong, M.R.; Choi, S.M.; Na, S.S.; Cha, J.D. Synergistic effect of fucoidan with antibiotics against oral pathogenic bacteria. Arch. Oral Biol. 2013, 58, 482-492.
91. Kandasamy, S.; Khan, W.; Kulshreshtha, G.; Evans, F.; Critchley, A.T.; Fitton, J.H.; Stringer, D.N.; Gardiner, V.A.; Prithiviraj, B. The fucose containing polymer (fcp) rich fraction of ascophyllum nodosum (l.) le jol. Protects caenorhabditis elegans against pseudomonas aeruginosa by triggering innate immune signaling pathways and suppression of pathogen virulence factors. Algae 2015, 30, 147-161.
92. Besednova, N.N.; Zaporozhets, T.S.; Somova, L.M.; Kuznetsova, T.A. Review: Prospects for the use of extracts and polysaccharides from marine algae to prevent and treat the diseases caused by helicobacter pylori. Helicobacter 2015, 20, 89-97.
93. Kallio, K.A.; Hatonen, K.A.; Lehto, M.; Salomaa, V.; Mannisto, S.; Pussinen, P.J. Endotoxemia, nutrition, and cardiometabolic disorders. Acta Diabetol. 2015, 52, 395-404.
94. Kelly, C.J.; Colgan, S.P.; Frank, D.N. Of microbes and meals: The health consequences of dietary endotoxemia. Nutr. Clin. Pract. 2012, 27, 215-225.
95. Kuznetsova, T.A.; Besednova, N.N.; Somova, L.M.; Plekhova, N.G. Fucoidan extracted from fucus evanescens prevents endotoxin-induced damage in a mouse model of endotoxemia. Mar. Drugs 2014, 12, 886-898.
96. Alsac, J.M.; Delbosc, S.; Rouer, M.; Journe, C.; Louedec, L.; Meilhac, O.; Michel, J.B. Fucoidan interferes with porphyromonas gingivalis-induced aneurysm enlargement by decreasing neutrophil activation. J. Vasc. Surg. 2013, 57, 796-805.
97. Kambhampati, S.; Park, W.; Habtezion, A. Pharmacologic therapy for acute pancreatitis. World J. Gastroenterol. 2014, 20, 16868-16880.
98. Fitton, J.H.; Dell'Acqua, G.; Gardiner, V.A.; Karpiniec, S.S.; Stringer, D.N.; Davis, E. Topical benefits of two fucoidan-rich extracts from marine macroalgae. Cosmetics 2015, 2, 66-81.
99. Iwamoto, K.; Hiragun, T.; Takahagi, S.; Yanase, Y.; Morioke, S.; Mihara, S.; Kameyoshi, Y.; Hide, M. Fucoidan suppresses ige production in peripheral blood mononuclear cells from patients with atopic dermatitis. Arch. Dermatol. Res. 2010, 303, 425-431.
100. Yang, J.H. Topical application of fucoidan improves atopic dermatitis symptoms in nc/nga mice. Phytother. Res. 2012, 26, 1898-1903.
101. Iraha, A.; Chinen, H.; Hokama, A.; Yonashiro, T.; Kinjo, T.; Kishimoto, K.; Nakamoto, M.; Hirata, T.; Kinjo, N.; Higa, F.; et al. Fucoidan enhances intestinal barrier function by upregulating the expression of claudin-1. World J. Gastroenterol. 2013, 19, 5500-5507.
102. Lee, S.H. Intestinal permeability regulation by tight junction: Implication on inflammatory bowel diseases. Intest. Res. 2015, 13, 11-18.
103. Wang, J.; Liu, H.; Li, N.; Zhang, Q.; Zhang, H. The protective effect of fucoidan in rats with streptozotocin-induced diabetic nephropathy. Mar. Drugs 2014, 12, 3292-3306.
104. Sanyal, A.J. Novel therapeutic targets for steatohepatitis. Clin. Res. Hepatol. Gastroenterol. 2015, doi:10.1016/j.clinre.2015.05.012.
105. Kim, M.J.; Jeon, J.; Lee, J.S. Fucoidan prevents high-fat diet-induced obesity in animals by suppression of fat accumulation. Phytother. Res. 2014, 28, 137-143.
106. Lim, J.D.; Lee, S.R.; Kim, T.; Jang, S.A.; Kang, S.C.; Koo, H.J.; Sohn, E.; Bak, J.P.; Namkoong, S.; Kim, H.K.; et al. Fucoidan from fucus vesiculosus protects against alcohol-induced liver damage by modulating inflammatory mediators in mice and hepg2 cells. Mar. Drugs 2015, 13, 1051-1067.
107. Meenakshi, S.; Umayaparvathi, S.; Saravanan, R.; Manivasagam, T.; Balasubramanian, T. Hepatoprotective effect of fucoidan isolated from the seaweed turbinaria decurrens in ethanol intoxicated rats. Int. J. Biol. Macromol. 2014, 67, 367-372.
108. Mori, N.; Nakasone, K.; Tomimori, K.; Ishikawa, C. Beneficial effects of fucoidan in patients with chronic hepatitis c virus infection. World J. Gastroenterol. 2012, 18, 2225-2230.
109. Pomin, V.H. Sea, carbohydrates and clotting: A triad on the road of drug discovery. Mini Rev. Med. Chem. 2014, 14, 717-724.
110. Min, S.K.; Kwon, O.C.; Lee, S.; Park, K.H.; Kim, J.K. An antithrombotic fucoidan, unlike heparin, does not prolong bleeding time in a murine arterial thrombosis model: A comparative study of undaria pinnatifida sporophylls and fucus vesiculosus. Phytother. Res. 2011, 26, 752-757.
111. Manne, B.K.; Getz, T.M.; Hughes, C.E.; Alshehri, O.; Dangelmaier, C.; Naik, U.P.; Watson, S.P.; Kunapuli, S.P. Fucoidan is a novel platelet agonist for the c-type lectin-like receptor 2 (clec-2). J. Biol. Chem. 2013, 288, 7717-7726.
112. Dürig, J.; Bruhn, T.; Zurborn, K.-H.; Gutensohn, K.; Bruhn, H.D.; Béress, L. Anticoagulant fucoidan fractions from fucus vesiculosus induce platelet activation in vitro. Thromb. Res. 1997, 85, 479-491.
113. Rouzet, F.; Bachelet-Violette, L.; Alsac, J.M.; Suzuki, M.; Meulemans, A.; Louedec, L.; Petiet, A.; Jandrot-Perrus, M.; Chaubet, F.; Michel, J.B.; et al. Radiolabeled fucoidan as a p-selectin targeting agent for in vivo imaging of platelet-rich thrombus and endothelial activation. J. Nuclear Med. 2011, 52, 1433-1440.
114. Saboural, P.; Chaubet, F.; Rouzet, F.; Al-Shoukr, F.; Azzouna, R.B.; Bouchemal, N.; Picton, L.; Louedec, L.; Maire, M.; Rolland, L.; et al. Purification of a low molecular weight fucoidan for spect molecular imaging of myocardial infarction. Mar. Drugs 2014, 12, 4851-4867.
115. Yanagibayashi, S.K.S.; Ishihara, M.; Murakami, K.; Aoki, H.; Takikawa, M.; Fujita, M.; Sekido, M.; Kiyosawa, T. Novel hydrocolloid-sheet as wound dressing to stimulate healing-impaired wound healing in diabetic db/db mice. Biomed. Mater. Eng. 2012, 22, 301-310.
116. Ho, T.T.; Bremmell, K.E.; Krasowska, M.; Stringer, D.N.; Thierry, B.; Beattie, D.A. Tuning polyelectrolyte multilayer structure by exploiting natural variation in fucoidan chemistry. Soft Matter 2015, 11, 2110-2124.
117. Kim, Y.W.; Baek, S.H.; Lee, S.H.; Kim, T.H.; Kim, S.Y. Fucoidan, a sulfated polysaccharide, inhibits osteoclast differentiation and function by modulating rankl signaling. Int. J. Mol. Sci. 2014, 15, 18840-18855.
118. Park, S.J.; Lee, K.W.; Lim, D.S.; Lee, S. The sulfated polysaccharide fucoidan stimulates osteogenic differentiation of human adipose-derived stem cells. Stem Cells Dev. 2012, 21, 2204-2211.
119. Pereira, J.; Portron, S.; Dizier, B.; Vinatier, C.; Masson, M.; Sourice, S.; Galy-Fauroux, I.; Corre, P.; Weiss, P.; Fischer, A.M.; et al. The in vitro and in vivo effects of a low-molecular-weight fucoidan on the osteogenic capacity of human adipose-derived stromal cells. Tissue Eng. Part A 2014, 20, 275-284.
120. Lee, J.S.; Jin, G.H.; Yeo, M.G.; Jang, C.H.; Lee, H.; Kim, G.H. Fabrication of electrospun biocomposites comprising polycaprolactone/fucoidan for tissue regeneration. Carbohydr. Polym. 2012, 90, 181-188.
121. Venkatesan, J.; Bhatnagar, I.; Kim, S.K. Chitosan-alginate biocomposite containing fucoidan for bone tissue engineering. Mar. Drugs 2014, 12, 300-316.
122. Jeong, H.S.; Venkatesan, J.; Kim, S.K. Hydroxyapatite-fucoidan nanocomposites for bone tissue engineering. Int. J. Biol. Macromol. 2013, 57, 138-141.
123. Hamidi, S.; Letourneur, D.; Aid-Launais, R.; di Stefano, A.; Vainchenker, W.; Norol, F.; le Visage, C. Fucoidan promotes early step of cardiac differentiation from human embryonic stem cells and long-term maintenance of beating areas. Tissue Eng. Part A 2014, 20, 1285-1294.
124. Han, Y.S.; Lee, J.H.; Jung, J.S.; Noh, H.; Baek, M.J.; Ryu, J.M.; Yoon, Y.M.; Han, H.J.; Lee, S.H. Fucoidan protects mesenchymal stem cells against oxidative stress and enhances vascular regeneration in a murine hindlimb ischemia model. Int. J. Cardiol. 2015, 198, 187-195.
125. Huang, Y.C.; Liu, T.J. Mobilization of mesenchymal stem cells by stromal cell-derived factor-1 released from chitosan/tripolyphosphate/fucoidan nanoparticles. Acta Biomater. 2012, 8, 1048-1056.