1. Li B, Lu F, Wei X, et al. (2008) Fucoidan: structure and bioactivity. Molecules 13: 1671–1695. https://doi.org/10.3390/molecules13081671
2. Dobrinčić A, Balbino S, Zorić Z, et al. (2020) Advanced technologies for the extraction of marine brown algal polysaccharides. Mar Drugs 18: 168. https://doi.org/10.3390/md18030168
3. Ale MT, Meyer AS (2013) Fucoidans from brown seaweeds: an update on structures, extraction techniques and use of enzymes as tools for structural elucidation. RSC Adv 3: 8131–8141. https://doi.org/10.1039/C3RA23373A
4. Liu J, Wu SY, Chen L, et al. (2020) Different extraction methods bring about distinct physicochemical properties and antioxidant activities of Sargassum fusiforme fucoidans. Int J Biol Macromol 155: 1385–1392. https://doi.org/10.1016/j.ijbiomac.2019.11.113
5. Ale MT, Mikkelsen JD, Meyer AS (2011) 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 9: 2106–2130. https://doi.org/10.3390/md9102106
6. Zhu Q, Chen J, Li Q, et al. (2016) Antitumor activity of polysaccharide from Laminaria japonica on mice bearing H22 liver cancer. Int J Biol Macromol 92: 156–158. https://doi.org/10.1016/j.ijbiomac.2016.06.090
7. Peng Y, Song Y, Wang Q, et al. (2019) In vitro and in vivo immunomodulatory effects of fucoidan compound agents. Int J Biol Macromol 127: 48–56. https://doi.org/10.1016/j.ijbiomac.2018.12.197
8. Luan F, Zou J, Rao Z (2021) Polysaccharides from Laminaria japonica: an insight into the current research on structural features and biological properties. Food Funct 12: 4254–4283. https://doi.org/10.1039/D1FO00311A
9. Herath KHINM, Kim HJ, Kim A, et al. (2020) The role of fucoidans isolated from the sporophylls of undaria pinnatifida against particulate-matter-induced allergic airway inflammation: Evidence of the attenuation of oxidative stress and inflammatory responses. Molecules 25: 2869. https://doi.org/10.3390/molecules25122869
10. Yang CH, Tian JJ, Ko WS, et al. (2019) Oligo-fucoidan improved unbalance the Th1/Th2 and Treg/Th17 ratios in asthmatic patients: An ex vivo study. Exp Ther Med 17: 3–10. https://doi.org/10.3892/etm.2018.6939
11. Tomori M, Nagamine T, Miyamoto T, et al. (2019) Evaluation of the immunomodulatory effects of fucoidan derived from Cladosiphon okamuranus Tokida in mice. Mar Drugs 17: 547. https://doi.org/10.3390/md17100547
12. Yanase Y, Hiragun T, Uchida K, et al. (2009) Peritoneal injection of fucoidan suppresses the increase of plasma IgE induced by OVA-sensitization. Biochem Biophys Res Commun 387: 435–439. https://doi.org/10.1016/j.bbrc.2009.07.031
13. Vo TS (2020) The role of algal fucoidans in potential anti-allergic therapeutics. Int J Biol Macromol 165: 1093–1098. https://doi.org/10.1016/j.ijbiomac.2020.09.252
14. Tanino Y, Hashimoto T, Ojima T, et al. (2016) F-fucoidan from Saccharina japonica is a novel inducer of galectin-9 and exhibits anti-allergic activity. J Clin Biochem Nutr 59: 25–30. https://doi.org/10.3164/jcbn.15-144
15. Mizuno M, Sakaguchi K, Sakane I (2020) Oral administration of fucoidan can exert anti-allergic activity after allergen sensitization by enhancement of galectin-9 secretion in blood. Biomolecules 10: 258. https://doi.org/10.3390/biom10020258
16. Niki T, Tsutsui S, Hirose S, et al. (2009) Galectin-9 is a high affinity ige-binding lectin with anti-allergic effect by blocking ige-antigen complex formation. J Biol Chem 284: 32344–32352. https://doi.org/10.1074/jbc.M109.035196
17. Nagamine N, Nakazato K, Tomioka S, et al. (2015) Intestinal absorption of fucoidan extracted from the brown seaweed, Cladosiphon okamuranus. Mar Drugs 13: 48–64. https://doi.org/10.3390/md13010048
18. Tokita Y, Nakajima K, Mochida H, et al. (2010) Development of a fucoidan-specific antibody and measurement of fucoidan in serum and urine by sandwich ELISA. Biosci Biotechnol Biochem 74: 350–357. https://doi.org/10.1271/bbb.90705
19. de Kivit S, Saeland E, Kraneveld AD, et al. (2012) Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans. Allergy 67: 343–352. https://doi.org/10.1111/j.1398-9995.2011.02771.x
20. de Kivit S, Kraneveld AD, Knippels LMJ, et al. (2013) Intestinal epithelium-derived galectin-9 is involved in the immunomodulating effects of nondigestible oligosaccharides. J Innate Immun 5: 625–638. https://doi.org/10.1159/000350515
21. de Kivit S, Kostadinova AI, Kerperien J, et al. (2017) Galectin-9 produced by intestinal epithelial cells enhances aldehyde dehydrogenase activity in dendritic cells in a PI3K- and p38- dependent manner. J Innate Immun 9: 609–620. https://doi.org/10.1159/000479817
22. Overbeek SA, Kostadinova AI, Boks MA, et al. (2019) Combined exposure of activated intestinal epithelial cells to nondigestible oligosaccharides and CpG-ODN suppresses Th2- associated CCL22 release while enhancing galectin-9, TGFβ, and Th1 polarization. Mediators Inflamm 2019: 8456829. https://doi.org/10.1155/2019/8456829
23. Ayechu-Muruzabal V, Overbeek SA, Kostadinova AI, et al. (2020) Exposure of intestinal epithelial cells to 2'-fucosyllactose and CpG enhances galectin release and instructs dendritic cells to drive Th1 and regulatory-type immune development. Biomolecules 10: 784. https://doi.org/10.3390/biom10050784
24. Ayechu-Muruzabal V, van de Kaa M, Mukherjee R, et al. (2022) Modulation of the epithelialimmune cell crosstalk and related galectin secretion by DP3-5 galacto-oligosaccharides and β3′galactosyllactose. Biomolecules 12: 384. https://doi.org/10.3390/biom12030384
25. Lee J, Mo JH, Katakura K, et al. (2006) Maintenance of colonic homeostasis by distinctive apical TLR9 signaling in intestinal epithelial cells. Nat Cell Biol 8: 1327–1336. https://doi.org/10.1038/ncb1500
26. Ewaschuk JB, Backer JL, Churchill TA, et al. (2007) Surface expression of Toll-like receptor 9 is upregulated on intestinal epithelial cells in response to pathogenic bacterial DNA. Infect Immun 75: 2572–2579. https://doi.org/10.1128/IAI.01662-06
27. Eaton-Bassiri A, Dillon SB, Cunningham M, et al. (2004) Toll-like receptor 9 can be expressed at the cell surface of distinct populations of tonsils and human peripheral blood mononuclear cells. Infect Immun 72: 7202–7211. https://doi.org/10.1128/IAI.72.12.7202-7211.2004
28. Agier J, Żelechowska P, Kozłowska E, et al. (2016) Expression of surface and intracellular Tolllike receptors by mature mast cells. Cent Eur J Immunol 41: 333–338. https://doi.org/10.5114/ceji.2016.65131
29. Onji M, Kanno A, Saitoh SI, et al. (2013) An essential role for the N-terminal fragment of Tolllike receptor 9 in DNA sensing. Nat Com 4: 1949. https://doi.org/10.1038/ncomms2949
30. Jin JO, Park HY, Xu Q, et al. (2009) Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-α. Blood 113: 5839–5847. https://doi.org/10.1182/blood-2008-10-184796
31. Lin Z, Tan X, Zhang Y, et al. (2020) Molecular targets and related biologic activities of fucoidan: A review. Mar Drugs 18: 376. https://doi.org/10.3390/md18080376
32. Choi S, Jeon SA, Heo BY, et al. (2022) Gene set enrichment analysis reveals that fucoidan induces type I IFN pathways in BMDC. Nutrients 14: 2242. https://doi.org/10.3390/nu14112242
33. Yamazaki Y, Nakamura Y, Nakamura T (2016) A fluorometric assay for quantification of fucoidan, a sulfated polysaccharide from brown algae. Plant Biotechnol J 33: 117–121. https://doi.org/10.5511/plantbiotechnology.16.0217c
34. Makarenkovaa ID, Logunov DY, Tukhvatulin AI, et al. (2012) Sulfated polysaccharides of brown seaweeds are ligands of Toll-like receptors. Bio Chem 6: 75–80. https://doi.org/10.1134/S1990750812010118
35. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55–63. https://doi.org/10.1016/0022-1759(83)90303-4
36. Ghadimi D, de Vrese M, Heller KJ, et al. (2010) Effect of natural commensal-origin DNA on Toll-like receptor 9 (TLR9) signaling cascade, chemokine IL-8 expression, and barrier integrity of polarized intestinal epithelial cells. Inflamm Bowel Dis 16: 410–427. https://doi.org/10.1002/ibd.21057
37. Zhang X, Wei Z, Xue C (2021) Physicochemical properties of fucoidan and its applications as building blocks of nutraceutical delivery systems. Crit Rev Food Sci Nutr 2021: 1–19.
38. Ricós-Muñoz N, Maicas S, Pina-Pérez MC (2021) Probiotic Lactobacillus reuteri growth improved under fucoidan exposure. Proceedings 70: 106. https://doi.org/10.3390/foods_2020- 07724
39. Shang Q, Shan X, Cai C, et al. (2016) Dietary fucoidan modulates the gut microbiota in mice by increasing the abundance of Lactobacillus and Ruminococcaceae. Food Funct 7: 3224–3232. https://doi.org/10.1039/C6FO00309E
40. Hemmi H, Takeuchi O, Kawai T, et al. (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408: 740–745. https://doi.org/10.1038/35047123
41. Schneberger D, Caldwell S, Kanthan R, et al. (2013) Expression of Toll-like receptor 9 in mouse and human lungs. J Anat 222: 495–503. https://doi.org/10.1111/joa.12039
42. Leifer CA, Kennedy MN, Mazzoni A, et al. (2004) TLR9 is localized in the endoplasmic reticulum prior to stimulation. J Immunol 173: 1179–1183. https://doi.org/10.4049/jimmunol.173.2.1179
43. Latz E, Schoenemeyer A, Visintin A, et al. (2004) TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol 5: 190–198. https://doi.org/10.1038/ni1028
44. Varga MG, Lin HC (2020) The role of toll-like receptor 9 in maintaining gut homeostasis. Ann Syst Biol 3: 10–14. https://doi.org/10.17352/asb.000005
45. Mielcarska MB, Bossowska-Nowicka M, Toka FN (2021) Cell surface expression of endosomal toll-like receptors—A necessity or a superfluous duplication? Front Immunol 11: 620972. https://doi.org/10.3389/fimmu.2020.620972