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Gupta, Dhanak, Melissa Silva, Karolina Radziun, Diana C. Martinez, Christopher J. Hill, Julie Marshall, Vanessa Hearnden, Miguel A. Puertas-Mejia y Gwendolen C. Reilly. "Fucoidan Inhibition of Osteosarcoma Cells is Species and Molecular Weight Dependent". Marine Drugs 18, n.º 2 (8 de febrero de 2020): 104. http://dx.doi.org/10.3390/md18020104.
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Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anti-cancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10–50 kDa), medium (MMW, 50–100 kDa) and high (HMW, >100 kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had the highest levels of sugars, acids and sulphation among molecular weight fractions. There was a dose-dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in the sub-G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress-induced apoptosis-like cell death for F. vesiculosus fucoidan and features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.
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Obeidi, Narges, Mohammad Javad Mousavi, Arghavan Hosseinpouri, Hamideh Malekhayati y Elham Ehsandoost. "nticoagulative Effect of Two Species of Brown Algae; Sargassum Angustifolium and Cystoseira Indica". Research in Molecular Medicine 8, n.º 3 (1 de julio de 2020): 125–32. http://dx.doi.org/10.32598/rmm.8.3.1099.3.
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Background: Fucoidans are a group of sulfated fucose-rich polysaccharides that are isolated from brown marine algae and echinoderms, and recently have been found in seagrasses. Fucoidans, as well as their derivatives, have several beneficial biological effects and therapeutic potentials. In the present study, we aimed to evaluate the anticoagulative effects of two species of brown algae, namely Sargassum angustifolium (S. angustifolium) and Cystoseira indica (C. indica). Methods: Fucoidan C and fucoidan S were extracted by an ethanol/water solvent system from S. angustifolium and C. indicia, respectively. The anticoagulative effects of fucoidan C and fucoidan S were tested on 10 normal serum samples by evaluating the rate of thrombin time (PT) and prothrombin time (PTT). Results: Both fucoidan C and fucoidan S significantly increased PTT. However, no significant difference was observed in PT. Fucoidan C had a greater effect on PTT prolongation compared with fucoidan S. Conclusion: Both fucoidans extracted from S. angustifolium and C. indicia can be used as anticoagulants in biotechnology and human disorders.
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Nguyen, Thuan Thi, Maria Dalgaard Mikkelsen, Vy Ha Nguyen Tran, Vo Thi Dieu Trang, Nanna Rhein-Knudsen, Jesper Holck, Anton B. Rasin, Hang Thi Thuy Cao, Tran Thi Thanh Van y Anne S. Meyer. "Enzyme-Assisted Fucoidan Extraction from Brown Macroalgae Fucus distichus subsp. evanescens and Saccharina latissima". Marine Drugs 18, n.º 6 (2 de junio de 2020): 296. http://dx.doi.org/10.3390/md18060296.
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Fucoidans from brown macroalgae (brown seaweeds) have different structures and many interesting bioactivities. Fucoidans are classically extracted from brown seaweeds by hot acidic extraction. Here, we report a new targeted enzyme-assisted methodology for fucoidan extraction from brown seaweeds. This enzyme-assisted extraction protocol involves a one-step combined use of a commercial cellulase preparation (Cellic®CTec2) and an alginate lyase from Sphingomonas sp. (SALy), reaction at pH 6.0, 40 °C, removal of non-fucoidan polysaccharides by Ca2+ precipitation, and ethanol-precipitation of crude fucoidan. The workability of this method is demonstrated for fucoidan extraction from Fucus distichus subsp. evanescens (basionym Fucus evanescens) and Saccharina latissima as compared with mild acidic extraction. The crude fucoidans resulting directly from the enzyme-assisted method contained considerable amounts of low molecular weight alginate, but this residual alginate was effectively removed by an additional ion-exchange chromatographic step to yield pure fucoidans (as confirmed by 1H NMR). The fucoidan yields that were obtained by the enzymatic method were comparable to the chemically extracted yields for both F. evanescens and S. latissima, but the molecular sizes of the fucoidans were significantly larger with enzyme-assisted extraction. The molecular weight distribution of the fucoidan fractions was 400 to 800 kDa for F. evanescens and 300 to 800 kDa for S. latissima, whereas the molecular weights of the corresponding chemically extracted fucoidans from these seaweeds were 10–100 kDa and 50–100 kDa, respectively. Enzyme-assisted extraction represents a new gentle strategy for fucoidan extraction and it provides new opportunities for obtaining high yields of native fucoidan structures from brown macroalgae.
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Dockal, Michael, Susanne Till, Zhenqing Zhang, Sabine Knappe, Sabrina Reutterer, Catherine Quinn, Christoph Redl, Hartmut J. Ehrlich, Friedrich Scheiflinger y Christina Szabo. "Structure-Activity Relationship of Pro- and Anticoagulant Effects of Fucus Vesiculosus Fucoidan". Blood 120, n.º 21 (16 de noviembre de 2012): 3353. http://dx.doi.org/10.1182/blood.v120.21.3353.3353.
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Abstract Abstract 3353 Fucoidans are sulfated polysaccharides extracted from brown algae. Fucoidans have a wide variety of biological activities including pro- and anticoagulant activities, which occur at different concentration ranges. Therefore, fucoidans have also been described as non-anticoagulant sulfated polysaccharides (NASPs, Liu et al. Thromb Haemost 2006; 95:68). Fucoidans have complex structures due to their large molecular weight (Mw), wide Mw distribution, variable degree and pattern of sulfation, diverse monosaccharide composition, branching of the sugar chain and different monomer linkages. This structural complexity challenges identification of the components responsible for fucoidan activities. The aim of the presented study was to fractionate Fucus vesiculosus (F.v.) fucoidan by size and to de- and oversulfate it to obtain compounds of varying Mw or degree of sulfation (DS), respectively. The fucoidans were then to be analyzed for their pro-and anticoagulant activities and structure, and the effect of modified fucoidan on the target protein Tissue Factor Pathway Inhibitor (TFPI) investigated. Two approaches were applied to generate F.v. fucoidan with different structural properties to the original. Firstly, fucoidan was fractionated by size using ultrafiltration. The Mw of the resulting fractions ranged from 8–180 kD. NMR, elemental analysis and HPAEC showed that other structural features, such as sulfate content and monosaccharide composition, were similar to those of the original fucoidan. Thrombin generation (CAT) assays showed an EC50 for procoagulant activity of 0.3–3 μg/mL; aPTT increased by 50% at 4–25 μg/mL. Generally, higher Mw increased procoagulant activity. Below 15 kD, this activity was markedly reduced. The minimum active length of F.v. fucoidan was 70 carbohydrate units. De- and oversulfated F.v. fucoidans were used to investigate the impact of charge on pro- and anticoagulant activities. In the CAT assay, oversulfated fucoidans showed improved procoagulant activity with an EC50 of 0.09–0.12 μg/mL, while desulfated fucoidans demonstrated reduced procoagulant activity compared to the original. A DS of 0.5 was estimated to be the limit for procoagulant activity. Inhibition of TFPI by fucoidan was assessed with a dilute prothrombin time assay (dPT) with added full-length TFPI. TFPI-blocking activity was mainly dependent on the DS and less on the fucoidans' Mw. Interestingly, oversulfation also stimulated an undesired activation of the contact pathway. The presented study determined the minimal structural requirements for procoagulant activity of fucoidan molecules and identified features causing undesired biological effects. Disclosures: No relevant conflicts of interest to declare.
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Fitton, Stringer, Park y Karpiniec. "Therapies from Fucoidan: New Developments". Marine Drugs 17, n.º 10 (9 de octubre de 2019): 571. http://dx.doi.org/10.3390/md17100571.
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Since our last review in 2015, the study and use of fucoidan has extended in several research areas. Clinical use of fucoidan for the treatment of renal disease has become available and human safety studies have been undertaken on radiolabeled fucoidan for the purpose of imaging thrombi. Fucoidan has been incorporated into an increasing number of commercially available supplements and topical treatments. In addition, new measuring techniques are now available to assess the biologically relevant uptake of fucoidans and to assist in production. Microbiome modulation and anti-pathogenic effects are increasingly promising applications for fucoidans, due to the need for alternative approaches to antibiotic use in the food chain. This review outlines promising new developments in fucoidan research, including potential future therapeutic use.
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Van Weelden, Geert, Marcin Bobiński, Karolina Okła, Willem Jan Van Weelden, Andrea Romano y Johanna M. A. Pijnenborg. "Fucoidan Structure and Activity in Relation to Anti-Cancer Mechanisms". Marine Drugs 17, n.º 1 (7 de enero de 2019): 32. http://dx.doi.org/10.3390/md17010032.
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Fucoidan is a natural derived compound found in different species of brown algae and in some animals, that has gained attention for its anticancer properties. However, the exact mechanism of action is currently unknown. Therefore, this review will address fucoidans structure, the bioavailability, and all known different pathways affected by fucoidan, in order to formulate fucoidans structure and activity in relation to its anti-cancer mechanisms. The general bioactivity of fucoidan is difficult to establish due to factors like species-related structural diversity, growth conditions, and the extraction method. The main pathways influenced by fucoidan are the PI3K/AKT, the MAPK pathway, and the caspase pathway. PTEN seems to be important in the fucoidan-mediated effect on the AKT pathway. Furthermore, the interaction with VEGF, BMP, TGF-β, and estrogen receptors are discussed. Also, fucoidan as an adjunct seems to have beneficial effects, for both the enhanced effectiveness of chemotherapy and reduced toxicity in healthy cells. In conclusion, the multipotent character of fucoidan is promising in future anti-cancer treatment. However, there is a need for more specified studies of the structure–activity relationship of fucoidan from the most promising seaweed species.
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Sinurat, Ellya, Endang Saepudin y Fildzah Alfita Qosthalani. "Effect of Hydrolyzed Fucoidan from The Brown Seaweed Sargassum Binderi Sonder Towards Human Breast Cancer T47d Cell Lines". Squalen Bulletin of Marine and Fisheries Postharvest and Biotechnology 12, n.º 2 (15 de agosto de 2017): 49. http://dx.doi.org/10.15578/squalen.v12i2.275.
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Fucoidan, a sulfated heteropolysaccharide, consists of L-fucose and sulfate ester groups as the main component. Over the past three decades, fucoidan structures and bioactivities have been widely studied. The chemical components (fucose, galactose, small monosaccharides and also the sulfate) and the molecular weights of fucoidans from different brown seaweed species produce different characteristics and structures of fucoidan. The activity of fucoidan against cancer cells has been reported to be affected strongly by their sulfate content and molecular weight. Low-molecular-weight fucoidans tend to have higher solubility and easily penetrate into cancer cells. The objective of this study was to investigate the effect of hydrolyzed of fucoidan on its anti cancer activity againts the breast cancer T47D cells. In this study, the fucoidan from the brown seaweed Sargassum binderi Sonder was extracted using 0.1 N HCl and was depolymerized by acid hydrolysis at various times and concentrations. Result showed that fucoidan hydrolyzed with 1 M trifluoroacetic acid (TFA) for 1.5 hours reached the maximum depolymerization process and resulted in the decrement of molecular weight from 785.12 kDa to 5.79 kDa as well as sulfate content from 18.63% to 8.69%. The IC50 values of fucoidan and low molecular weight fucoidan against the breast cancer T47D cells were 60.03 mg/mL and 182.34 mg/ respectively. This result indicated that the sulfate content of fucoidan probably affected its anticancer bioactivities.
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Dockal, Michael, Erwin Panholzer, Rudolf Hartmann, Hartmut J. Ehrlich y Friedrich Scheiflinger. "A New Procoagulant Mechanism Mediated by Fucoidans". Blood 116, n.º 21 (19 de noviembre de 2010): 4420. http://dx.doi.org/10.1182/blood.v116.21.4420.4420.
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Abstract Abstract 4420 Fucoidans are heterogeneous, polyanionic molecules with procoagulant activities in a wide concentration range. They have been described as non-anticoagulant sulfated polysaccharides (NASP) and shown to improve clotting in FVIII- and FIX-deficient plasma. In vitro characterization has suggested that fucoidans exert their procoagulant activity by inhibiting tissue factor pathway inhibitor (Liu et al. Thromb Haemost 2006; 95:68) and by accelerating thrombin-dependent FVa formation (Mutch et al. J Thromb Haemost 2007; 5 Suppl2). In our study we describe a new, previously unrecognized mechanism by which fucoidans act as procoagulant agents. The procoagulant activity of several fucoidans was characterized by calibrated automated thrombography in tissue factor (TF)-dependent experiments and by using coagulation factor-deficient plasmas. Spiking experiments with purified coagulation factors or inhibitory antibodies verified the mechanism. Stimulation of thrombin generation (TG) by fucoidans requires anionic lipid surfaces like synthetic phospholipid vesicles which contain phosphatidylserine and is TF-dependent (0-20pM). However, stimulatory activity was most pronounced in the absence of TF. Control experiments with corn trypsin inhibitor or FXII-deficient plasma excluded any involvement of the contact system. Plasmas from patients with congenital coagulation factor deficiencies were screened for TG to identify the target coagulation factor by which fucoidans exert their procoagulant activities. In the absence of TF, plasmas deficient in coagulation factors from the common pathway do not support fucoidan-mediated thrombin generation, whereas FVII-deficient plasma does. FXI was identified as the most upstream factor of the intrinsic pathway which is required for fucoidan-stimulated thrombin generation, suggesting it to be the target for the procoagulant activities of fucoidan. Spiking 30nM FXI to FXI-deficient plasma restored fucoidan-mediated TG and addition of polyclonal FXI inhibitory antibodies to normal plasma abrogated TG. Fucoidan-dependent TG did not improve when FXIa (60pM) was added to FXI-deficient plasma, suggesting activation of FXI by fucoidan. The relevance of this mechanism in hemophilia A plasma was studied by addition of low levels of FVIII (0.2-10%) resulting in a FVIII concentration-dependent increase in fucoidan-mediated TG. These results highlight the requirement of a functional intrinsic pathway for this new mechanism of fucoidans. Our findings present FXI activation at low TF concentrations as a possible mechanism for fucoidan. Disclosures: Dockal: Baxter Innovations GmbH: Employment. Panholzer:Baxter Innovations GmbH: Employment. Hartmann:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment.
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Dockal, Michael, Susanne Till, Sabine Knappe, Hartmut J. Ehrlich y Friedrich Scheiflinger. "Anticoagulant Activity and Mechanism of Non-Anticoagulant Sulfated Polysaccharides". Blood 118, n.º 21 (18 de noviembre de 2011): 1208. http://dx.doi.org/10.1182/blood.v118.21.1208.1208.
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Abstract Abstract 1208 Fucoidans are sulfated polysaccharides which are extracted from brown seaweeds and echinoderms and have a wide variety of biological activities. Described as non-anticoagulant polysaccharides (NASPs), they have been demonstrated to improve clotting in FVIII- and FIX-deficient plasma (Liu et al., 2006), making them good candidates for hemophilia treatment. However, fucoidans have also been extensively studied for their anticoagulant effects (Pereira et al., 1999), which usually occur at much higher concentrations than the procoagulant activity. This opens a large procoagulant window where procoagulant activities exceed anticoagulant effects. When analyzed by a global hemostatic thrombin generation assay in hemophilia plasma the onset of procoagulant activity is observed at concentrations as low as 0.01 μg/mL with optimal activity at about 1 μg/mL. Reversal of procoagulant activity is seen at concentrations higher than 10 μg/mL. Fucoidans and other sulfated polysaccharides activate different anticoagulant mechanisms depending on their structural properties. Branched fucoidans extracted from brown algae have been shown to directly inhibit thrombin, while linear fucoidan from echinoderms activates antithrombin III (ATIII) or heparin cofactor II (HCII)-mediated thrombin inhibition (Pereira et al., 1999). Sulfated galactans also have serpin-dependent and -independent anticoagulant activities (Glauser et al., 2009). In this study we analyzed fucoidans from several brown algae species for their anticoagulant properties and mode of action to identify the candidate with the best procoagulant and lowest anticoagulant activity. NASPs from several brown algae species including L. japonica (L.j.), F. vesiculosus (F.v.), and U. pinnatifida (U.p.) showed different anticoagulant activities in an activated partial thromboplastin time (aPTT) assay. U.p. fucoidan was about twice as anticoagulant as the other fucoidan preparations, increasing clotting time by 50% at a concentration of 4 μg/mL. In addition, NASPs were analyzed in ATIII- and HCII-thrombin model assays. L.j. fucoidan activated ATIII-mediated thrombin inhibition, whereas the other fucoidans showed no effect on ATIII. Fucoidans from L.j. and F.v. had a direct effect on thrombin, starting at about 10 μg/mL. By contrast, U.p. fucoidan did not directly affect thrombin. However, all preparations increased HCII-mediated thrombin inhibition at concentrations below 1 μg/mL. This suggests that HCII is the main target for the anticoagulant activity of fucoidans. Nevertheless, we observed substantial differences between the fucoidan candidates which will be correlated to structural properties. Our work describes the assessment of anticoagulant activities of a variety of fucoidan species to better understand their intertwined pro- and anticoagulant effects. This provides important mechanistic insights for the development of hemophilia therapies. Disclosures: Dockal: Baxter Innovations GmbH: Employment. Till:Baxter Innovations GmbH: Employment. Knappe:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter BioScience: Employment.
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Silchenko, Artem S., Anton B. Rasin, Anastasiya O. Zueva, Mikhail I. Kusaykin, Tatiana N. Zvyagintseva, Anatoly I. Kalinovsky, Valeriya V. Kurilenko y Svetlana P. Ermakova. "Fucoidan Sulfatases from Marine Bacterium Wenyingzhuangia fucanilytica CZ1127T". Biomolecules 8, n.º 4 (21 de septiembre de 2018): 98. http://dx.doi.org/10.3390/biom8040098.
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Fucoidans belong to a structurally heterogeneous class of sulfated polysaccharides isolated from brown algae. They have a wide spectrum of biological activities. The complex structures of these polysaccharides hinder structure-activity relationships determination. Fucoidan sulfatases can make useful tools for the determination of the fine chemical structure of fucoidans. In this study, identification and preparation of two recombinant sulfatases able to catalyze the cleavage of sulfate groups from fragments of fucoidan molecules is described for the first time. Two genes of sulfatases swf1 and swf4 of the marine bacterium Wenyingzhuangia fucanilytica CZ1127T were cloned and the proteins were produced in Escherichia coli cells. Sulfatases SWF1 and SWF4 are assigned to S1_17 and S1_25 subfamilies of formylglycine-dependent enzymes of S1 family (SulfAtlas). Some molecular and biochemical characteristics of recombinant fucoidan sulfatases have been studied. Detailed specificity and catalytic features of sulfatases were determined using various sulfated fucooligosaccharides. Structures of products produced by SWF1 and SWF4 were established by nuclear magnetic resonance (NMR) spectroscopy. Based on the obtained data, the enzymes are classified as fucoidan exo-2O-sulfatase (SWF1) and fucoidan exo-3O-sulfatase (SWF4). In addition, we demonstrated the sequential action of sulfatases on 2,3-di-O-sulfated fucooligosacchrides, which indicates an exolitic degradation pathway of fucoidan by a marine bacterium W. fucanilytica CZ1127T.
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Kuznetsova, Tatyana A., Tatyana P. Smolina, Ilona D. Makarenkova, Lydmila A. Ivanushko, Elena V. Persiyanova, Svetlana P. Ermakova, Artem S. Silchenko et al. "Immunoadjuvant Activity of Fucoidans from the Brown Alga Fucus evanescens". Marine Drugs 18, n.º 3 (11 de marzo de 2020): 155. http://dx.doi.org/10.3390/md18030155.
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The study presents the results of a comparative evaluation of the effect of structural modifications of fucoidans from the brown alga Fucus evanescens (native, highly purified product of fucoidan enzymatic hydrolysis, a new regular 1→3;1→4-α-L-fucan, sulphated mainly at C2 and acetylated at C4 of the fucose residue) on the effector functions of innate and adaptive immunity cells in vitro and in vivo. Using flow cytometry, we found that all examined fucoidans induce the maturation of dendritic cells, enhance the ability of neutrophils to migrate and adhere, activate monocytes and enhance their antigen-presenting functions, and increase the cytotoxic potential of natural killers. Fucoidans increase the production of hepatitis B virus (HBs) specific IgG and cytokine Th1 (IFN-γ, TNF-α) and Th2 (IL-4) profiles in vivo. The data obtained suggest that in vitro and in vivo adjuvant effects of the products of fucoidan enzymatic hydrolysis with regular structural characteristics are comparable to those of the native fucoidan. Based on these data, the products of fucoidan enzymatic hydrolysis can be considered as an effective and safe candidate adjuvant to improve the efficacy of prophylactic and therapeutic vaccines.
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Khil'chenko, S. R., T. S. Zaporozhets, T. N. Zvyagintseva, N. M. Shevchenko y N. N. Besednov. "The Role of Sulfates in Fucoidan Extracted from Fucus evanescens in Proinflammatory Cytokines Production by Human Peripheral Blood Cells in vitro". Antibiotics and Chemotherapy 65, n.º 5-6 (26 de agosto de 2020): 3–10. http://dx.doi.org/10.37489/0235-2990-2020-65-5-6-3-10.
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Fucoidans, sulfated polysaccharides extracted from brown algae (Phaeophyceae), have a wide spectrum of bioactivity. Studies of molecular structures of fucoidans and deciphering of molecular elements' impact on their biological activities are at their active stage. The article shows the role of sulfates and acetyl groups in fucoidan isolated from Fucus evanescens in proinflammatory cytokines production by human heparinized unfractionated peripheral blood cells. Material and Methods. The cells were incubated with native fucoidan (N) and its deacetylated (deA), partially desulfated (deS), and both deacetylated and partially desulfated (deAdeS) derivatives (100 μg/mL). Cytokine concentrations were determined in cell supernatants by ELISA in a 'sandwich' modification with commercial kits. Results. Incubation with N fucoidan led to an increase of IL-6, TNF-α, IL-8 levels in supernatants. Partial removal of sulfate groups cancelled or decreased stimulating effect for IL-6, TNF-α, cytokines, but not for IL-8. deAc fucoidan action was comparable with N polysaccharide. Native polysaccharide and its chemically modified derivatives did not change IFN-γ и IL-10 cytokine production. Conclusion. The obtained results suggest that sulfates have a significant role in cytokine-producing properties of fucoidan extracted from brown algae F.evanescens.
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Zhao, Xue, Jing Feng Wang y Chang Hu Xue. "The Inhibitory Effects of Fucoidans from Laminaria japonica on Oxidation of Human Low-Density Lipoproteins". Advanced Materials Research 236-238 (mayo de 2011): 2067–71. http://dx.doi.org/10.4028/www.scientific.net/amr.236-238.2067.
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Five Fucoidan fractions from Laminaria japonica with different sulfate content and molecular weight were obtained by anion-exchange chromatography and mild acid hydrolysis. Their antioxidant effects on azo radicals AAPH- and AMVN -induced oxidation of human low-density lipoprotein (LDL) were evaluated by monitoring cholesteryl ester hydroperoxides (CHE-OOH) formation kinetics by HPLC analysis. Two antioxidants probucol and Vc were used as comparison. Fucoidan F-C with low molecular weight 2,000-8,000 and sulfate content 24.3% had much stronger protective antioxidant effects than other four Fucoidan fractions on both hydrophilic radical AAPH and lipophilic radical AMVN induced LDL oxidation. In AMVN induced LDL oxidation system, the other four Fucoidan fractions with molecular weight of 200,000 and 20,000 were able to modify the kinetics of LDL oxidation with the similar efficiency. However, the highly sulfated Fucoidan fraction L-B with molecular weight 20,000 was completely ineffective in protecting LDL from AAPH induced oxidation, whilst it effectively suppressed the oxidation of LDL induced by AMVN. The different protective antioxidant effects of Fucoidans on AAPH and AMVN induced LDL oxidation were due to their various structures and properties, and their capacities to interact with the different sites Fucoidans reacted on LDL.
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Lin, Peichun, Suhua Chen, Min Liao y Weimin Wang. "Physicochemical Characterization of Fucoidans from Sargassum henslowianum C.Agardh and Their Antithrombotic Activity In Vitro". Marine Drugs 20, n.º 5 (28 de abril de 2022): 300. http://dx.doi.org/10.3390/md20050300.
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Sargassum fucoidan is a kind of sulfated heteropolysaccharide with a variety of biological activities. The aim of this study was to investigate the extraction, purification, physicochemical characterization and in vitro antithrombotic activity of fucoidan from Sargassum henslowianum C.Agardh. Hot-water-assisted ultrasound was used to extract fucoidan (F). Fucoidan was purified by DEAE cellulose 52 (F1), Vc-H2O2 (FD1) and Superdex 75 gel (FDS1). The physical and chemical properties of fucoidans were analyzed by chemical composition, monosaccharide composition, average molecular weight (Mw) and FTIR. The sulfate contents of F, F1, FD1 and FDS1 were 11.45%, 16.35% and 17.52%, 9.66%, respectively; the Mw was 5.677 × 105, 4.393 × 105, 2.176 × 104 and 6.166 × 103, respectively. The results of monosaccharide composition showed that the four fucoidans contained l-fucose, d-galactose, l-mannose, d-xylose, l-rhamnose and d-glucose, but the mass fraction ratio was different. The results of FTIR showed that fucoidan contained characteristic peaks of sugar and sulfate. In vitro, F1, FD1 and FDS1 could alleviate HUVEC damage induced by adrenaline (Adr). F1, FD1 and FDS1 decreased vWF and TF and increased the ratio of t-PA/PAI-1 in Adr-induced HUVEC.
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Zayed, Ahmed, Mona El-Aasr, Abdel-Rahim S. Ibrahim y Roland Ulber. "Fucoidan Characterization: Determination of Purity and Physicochemical and Chemical Properties". Marine Drugs 18, n.º 11 (19 de noviembre de 2020): 571. http://dx.doi.org/10.3390/md18110571.
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Fucoidans are marine sulfated biopolysaccharides that have heterogenous and complicated chemical structures. Various sugar monomers, glycosidic linkages, molecular masses, branching sites, and sulfate ester pattern and content are involved within their backbones. Additionally, sources, downstream processes, and geographical and seasonal factors show potential effects on fucoidan structural characteristics. These characteristics are documented to be highly related to fucoidan potential activities. Therefore, numerous chemical qualitative and quantitative determinations and structural elucidation methods are conducted to characterize fucoidans regarding their physicochemical and chemical features. Characterization of fucoidan polymers is considered a bottleneck for further biological and industrial applications. Consequently, the obtained results may be related to different activities, which could be improved afterward by further functional modifications. The current article highlights the different spectrometric and nonspectrometric methods applied for the characterization of native fucoidans, including degree of purity, sugar monomeric composition, sulfation pattern and content, molecular mass, and glycosidic linkages.
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Chua, Eng-Guan, Phebe Verbrugghe, Timothy T. Perkins y Chin-Yen Tay. "Fucoidans Disrupt Adherence ofHelicobacter pylorito AGS CellsIn Vitro". Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/120981.
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Fucoidans are complex sulphated polysaccharides derived from abundant and edible marine algae.Helicobacter pyloriis a stomach pathogen that persists in the hostile milieu of the human stomach unless treated with antibiotics. This study aims to provide preliminary data to determine,in vitro, if fucoidans can inhibit the growth ofH. pyloriand its ability to adhere to gastric epithelial cells (AGS). We analysed the activity of three different fucoidan preparations (FucusA,FucusB, andUndariaextracts). Bacterial growth was not arrested or inhibited by the fucoidan preparations supplemented into culture media. All fucoidans, when supplemented into tissue culture media at 1000 µg mL−1, were toxic to AGS cells and reduced the viable cell count significantly. Fucoidan preparations at 100µg mL−1were shown to significantly reduce the number of adherentH. pylori. Thesein vitrofindings provide the basis for further studies on the clinical use of sulphated polysaccharides as complementary therapeutic agents.
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Cao, Hang, Maria Mikkelsen, Mateusz Lezyk, Ly Bui, Van Tran, Artem Silchenko, Mikhail Kusaykin et al. "Novel Enzyme Actions for Sulphated Galactofucan Depolymerisation and a New Engineering Strategy for Molecular Stabilisation of Fucoidan Degrading Enzymes". Marine Drugs 16, n.º 11 (1 de noviembre de 2018): 422. http://dx.doi.org/10.3390/md16110422.
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Fucoidans from brown macroalgae have beneficial biomedical properties but their use as pharma products requires homogenous oligomeric products. In this study, the action of five recombinant microbial fucoidan degrading enzymes were evaluated on fucoidans from brown macroalgae: Sargassum mcclurei, Fucus evanescens, Fucus vesiculosus, Turbinaria ornata, Saccharina cichorioides, and Undaria pinnatifida. The enzymes included three endo-fucoidanases (EC 3.2.1.-GH 107), FcnA2, Fda1, and Fda2, and two unclassified endo-fucoglucuronomannan lyases, FdlA and FdlB. The oligosaccharide product profiles were assessed by carbohydrate-polyacrylamide gel electrophoresis and size exclusion chromatography. The recombinant enzymes FcnA2, Fda1, and Fda2 were unstable but were stabilised by truncation of the C-terminal end (removing up to 40% of the enzyme sequence). All five enzymes catalysed degradation of fucoidans containing α(1→4)-linked l-fucosyls. Fda2 also degraded S. cichorioides and U. pinnatifida fucoidans that have α(1→3)-linked l-fucosyls in their backbone. In the stabilised form, Fda1 also cleaved α(1→3) bonds. For the first time, we also show that several enzymes catalyse degradation of S. mcclurei galactofucan-fucoidan, known to contain α(1→4) and α(1→3) linked l-fucosyls and galactosyl-β(1→3) bonds in the backbone. These data enhance our understanding of fucoidan degrading enzymes and their substrate preferences and may assist development of enzyme-assisted production of defined fuco-oligosaccharides from fucoidan substrates.
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Takahashi, Hidenori, Mitsuhiko Kawaguchi, Kunihiro Kitamura, Seiji Narumiya, Munenori Kawamura, Isamu Tengan, Shinji Nishimoto et al. "An Exploratory Study on the Anti-inflammatory Effects of Fucoidan in Relation to Quality of Life in Advanced Cancer Patients". Integrative Cancer Therapies 17, n.º 2 (12 de febrero de 2017): 282–91. http://dx.doi.org/10.1177/1534735417692097.
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Background. Conventional anticancer therapies still cause difficulties with selective eradication and accompanying side effects that reduce patients’ quality of life (QOL). Fucoidan is extracted from seaweeds and has already exhibited broad bioactivities, including anticancer and anti-inflammatory properties, in basic studies. It is expected to enhance therapeutic efficacy and minimize side effects in cancer patients; however, despite its potential benefits, there are very few clinical trials using fucoidans. Therefore, we performed an exploratory clinical study for advanced cancer patients to examine the efficacy of fucoidans, especially focusing on inflammation in relation to QOL scores. Methods. We conducted a prospective, open-label clinical study for advanced cancer patients using fucoidans via oral administration; 20 advanced cancer patients with metastases were recruited and were given 400 mL/d fucoidan (10 mg/mL) for at least 4 weeks. Inflammatory biomarkers, including high-sensitivity C-reactive protein and various cytokines, and QOL scores were monitored before treatment, after 2 weeks, and after 4 weeks of fucoidan ingestion. Results. The main proinflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were significantly reduced after 2 weeks of fucoidan ingestion. QOL scores, including fatigue, stayed almost stable without significant changes during the study period. The univariate and multivariate analyses revealed that the responsiveness of IL-1β was a significant independent prognostic factor. Conclusion. This is the first study providing evidence of the anti-inflammatory effects of fucoidans for advanced cancer patients. In future studies, larger blinded, controlled trials are required to establish the efficacy of fucoidan as supportive care for cancer patients, especially those undergoing chemotherapy.
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Kuznetsova, T. A., L. A. Ivanushko, E. V. Persiyanova, A. L. Shutikova, S. P. Ermakova, M. Yu Khotimchenko y N. N. Besednova. "Evaluation of adjuvant effects of fucoidane from brown seaweed Fucus evanescens and its structural analogues for the strengthening vaccines effectiveness". Biomeditsinskaya Khimiya 63, n.º 6 (2017): 553–58. http://dx.doi.org/10.18097/pbmc20176306553.
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The use of sulfated polysaccharides from brown seaweed Fucus evanescens as adjuvants (native fucoidan in combination with polyphenols, fucoidan without polyphenols, a product of enzymatic hydrolysis of fucoidan) stimulated the formation of specific antibodies to the surface antigen of the hepatitis B virus (HBs-AG). Immunization of mice with vaccine compositions containing HBs-AG and fucoidan samples resulted in increasing the serum level of the pro-inflammatory (TNF-a, IFN-g, IL-2) cytokines. Increased production of these cytokines was detected in the culture of splenocytes additionally stimulated in vitro by fucoidans or phytohemagglutinin. The adjuvant effect of fucoidan and its structural modifications was comparable to that of the traditional licensed adjuvant aluminum hydroxide. The obtained results indicate a promising use of sulfated polysaccharides from F. evanescens as vaccine adjuvants.
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Miyazaki, Yoshiyuki, Juneha Bak, Hayato Nakano, Shugo Takeuchi, Hideaki Takeuchi y Daisuke Tachikawa. "Regulatory mechanism of fucoidan-mix AG in intestinal mucosal immune cells". Journal of Immunology 206, n.º 1_Supplement (1 de mayo de 2021): 17.08. http://dx.doi.org/10.4049/jimmunol.206.supp.17.08.
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Abstract Fucoidan is a series of natural sulfated polysaccharides contained in brown sea algae, and their beneficial physiological activities such as anti-tumor, anti-virus and immune regulatory effects have been reported. In previous studies, we proved that fucoidans derived from Cladosiphon okamuranus (C. okamuranus) and Undaria pinnatifida effectively improved anti-tumor immunity and tumor vaccine efficiency in combination with an Agaricus blazei mycelium extract. It is thought that the fucoidan-agaricus mix (named fucoidan-mix AG) stimulate innate immune cells to activate intestinal and mucosal immune reaction, but actual target immune tissues and cells by fucoidan have not been evidenced yet. In this study, we investigated action mechanisms of fucoidan in regulation of mucosal immune activities. At first, immune cells were isolated from Payer’s patches, mesenteric lymph node (MLN) and intestinal epithelia of Balb/c mice, then stained with fluorophore-labeled fucoidan. As the results, it was revealed that fucoidan directly interact with lymphocytes besides dendritic cells and macrophages existing in these intestinal immune tissues. Furthermore, immune cells from Payer’s patches and MLN stimulated with fucoidan from C. okamuranus and fucoidan-mix AG produced more TNF-α, IL-12 and Th1 cytokine IFN-γ. The production of an immunosuppressive cytokine IL-10 also was augmented in the fucoidan-treated immune cells, which suggesting that fucoidan balanced immune system to prevent occurrence of excessive reaction. In addition, it was newly proved that fucoidan directly stimulated T lymphocytes to induce enhanced IFN-γ production.
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Jiang, Cong, Sabine Knappe, Sabrina Reutterer, Christina Szabo, Michael Dockal, Zhenqing Zhang, Susanne Till y Friedrich Scheiflinger. "Structure-activity relationship of the pro- and anticoagulant effects of Fucus vesiculosus fucoidan". Thrombosis and Haemostasis 111, n.º 03 (2014): 429–37. http://dx.doi.org/10.1160/th13-08-0635.
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SummaryFucoidan is a highly complex sulfated polysaccharide commonly extracted from brown seaweed. In addition to their many biological activities, fucoidans have recently been demonstrated to inhibit or increase coagulation at different concentration ranges. Their structural features, i.e. molecular weight (Mw), Mw distribution, degree of sulfation, monosaccharide composition, and different linkages, are known to affect these activities. Therefore, structure-activity relationship (SAR) analysis of fucoidan is crucial for its potential use as a procoagulant. In this study, Fucus vesiculosus (F.v.) fucoidan was fractionated by charge and size as well as over- and desulfated to different degrees to yield preparations with various structural properties. The fractions’ pro- and anticoagulant activities were assessed by calibrated automated thrombography (CAT) and activated partial thromboplastin time (aPTT) assays. Binding to and inhibition of the anticoagulant protein tissue factor pathway inhibitor (TFPI) and the ability to activate coagulation via the contact pathway were also investigated. This paper discusses the impact of charge density, size, and sugar composition on fucoidan’s pro- and anticoagulant activities. Fucoidan requires a minimal charge density of 0.5 sulfates per sugar unit and a size of 70 sugar units to demonstrate desired procoagulant activities for improvement of haemostasis in factor VIII/factor IX-deficient plasma.
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Ahmad, Tauseef, Mathew Suji Eapen, Muhammad Ishaq, Ah Young Park, Samuel S. Karpiniec, Damien N. Stringer, Sukhwinder Singh Sohal et al. "Anti-Inflammatory Activity of Fucoidan Extracts In Vitro". Marine Drugs 19, n.º 12 (11 de diciembre de 2021): 702. http://dx.doi.org/10.3390/md19120702.
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Fucoidans are sulfated, complex, fucose-rich polymers found in brown seaweeds. Fucoidans have been shown to have multiple bioactivities, including anti-inflammatory effects, and are known to inhibit inflammatory processes via a number of pathways such as selectin blockade and enzyme inhibition, and have demonstrated inhibition of inflammatory pathologies in vivo. In this current investigation, fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for modulation of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) by human peripheral blood mononuclear cells (PBMCs) and in a human macrophage line (THP-1). Fucoidan extracts exhibited no signs of cytotoxicity in THP-1 cells after incubation of 48 h. Additionally, all fucoidan extracts reduced cytokine production in LPS stimulated PBMCs and human THP-1 cells in a dose-dependent fashion. Notably, the 5–30 kDa subfraction from Macrocystis pyrifera was a highly effective inhibitor at lower concentrations. Fucoidan extracts from all species had significant anti-inflammatory effects, but the lowest molecular weight subfractions had maximal effects at low concentrations. These observations on various fucoidan extracts offer insight into strategies that improve their efficacy against inflammation-related pathology. Further studies should be conducted to elucidate the mechanism of action of these extracts.
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Vu Duy, Hien, Duong Nguyen Binh y Trang Quan Thi Thu. "Study on Preparation and Characterization of Chitosan-Fucoidan-Curcumin Nanoparticles System". Vietnam Journal of Catalysis and Adsorption 10, n.º 1S (15 de octubre de 2021): 81–86. http://dx.doi.org/10.51316/jca.2021.095.
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The chitosan-fucoidan-curcumin nanosystems was synthesized by a simple polyelectrolyte self-assembly method together with the inclusions of complex system. The process was carried out with ultrasonic assistant and heating stirring. This nanosystem was not degraded when passing through the stomach, it was effectively released in the intestine, increasing absorption and bioavailability. The parameters of chitosan, fucoindan, curcumin, cyclodextrin were investigated to achieve a concentration higher nano curcumin. The total amount of chitosan and fucoidan was 10%, 13%, 15%, 17%, and 20% of the total agents. The corresponding amounts of curcumin were such that chitosan, fucoindan, and curcumin remained constant at 30%. Cyclodextrin was added as 70%. The characteristics of the nanosystems have been determined by SEM, TEM, FTIR, and HPLC methods. As a result, the chitosan-fucoidan-curcumin nanosystems has been successfully synthesized, the nanoparticles have uniform sizes and are in the range of 30-100 nm. The maximum nano curcumin content is 15%. The suitable conditions of the reaction at 80oC, the content of chitosan 7.5%, fucoidan 7.5%, curcumin 15%, and cyclodextrin 70%.
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Fernando, Ilekuttige Priyan Shanura, Mawalle Kankanamge Hasitha Madhawa Dias, Dissanayaka Mudiyanselage Dinesh Madusanka, Eui Jeong Han, Min Ju Kim, Soo-Jin Heo y Ginnae Ahn. "Fucoidan Fractionated from Sargassum coreanum via Step-Gradient Ethanol Precipitation Indicate Promising UVB-Protective Effects in Human Keratinocytes". Antioxidants 10, n.º 3 (26 de febrero de 2021): 347. http://dx.doi.org/10.3390/antiox10030347.
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Fucoidans exhibit a wide range of bioactivities and receive significant attention in functional food and cosmetic research. Industrial applications of fucoidan are limited partially due to high extraction and purification costs. The present study implements an enzyme-assisted extraction and step-gradient ethanol precipitation for fractionating fucoidan from Sargassum coreanum based on its charge and molecular weight and evaluation of ultraviolet B (UVB) protective effects in human keratinocytes (HaCaT). The fucoidan fraction SCOC4 indicated higher fucose and sulfate contents with Fourier-transform infrared and 1H NMR spectral patterns resembling fucoidans. SCOC4 dose-dependently abated UVB-induced keratinocyte damage via suppressing intracellular reactive oxygen species, apoptotic body formation, DNA damage via suppressing mitochondria-mediated apoptosis. UVB-protective effects of SCOC4 were further attributable to the augmentation of nuclear factor erythroid 2-related factor 2 mediated cellular antioxidant defense enzymes. Step-gradient ethanol precipitation was a convenient approach of fractionating fucoidans based on molecular weight and charge (depend on the degree of sulfation). Further evaluation of seasonal variations, biocompatibility parameters, efficacy, and shelf life may widen the use of S. coreanum fucoidans in developing UVB-protective cosmetics and functional foods.
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Hsiao, Hui-Hua, Tien-Chiu Wu, Yung-Hsiang Tsai, Chia-Hung Kuo, Ren-Han Huang, Yong-Han Hong y Chun-Yung Huang. "Effect of Oversulfation on the Composition, Structure, and In Vitro Anti-Lung Cancer Activity of Fucoidans Extracted from Sargassum aquifolium". Marine Drugs 19, n.º 4 (12 de abril de 2021): 215. http://dx.doi.org/10.3390/md19040215.
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Intensive efforts have been undertaken in the fields of prevention, diagnosis, and therapy of lung cancer. Fucoidans exhibit a wide range of biological activities, which are dependent on the degree of sulfation, sulfation pattern, glycosidic branches, and molecular weight of fucoidan. The determination of oversulfation of fucoidan and its effect on anti-lung cancer activity and related signaling cascades is challenging. In this investigation, we used a previously developed fucoidan (SCA), which served as a native fucoidan, to generate two oversulfated fucoidan derivatives (SCA-S1 and SCA-S2). SCA, SCA-S1, and SCA-S2 showed differences in compositions and had the characteristic structural features of fucoidan by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) analyses. The anticancer properties of SCA, SCA-S1, and SCA-S2 against human lung carcinoma A-549 cells were analyzed in terms of cytotoxicity, cell cycle, Bcl-2 expression, mitochondrial membrane potential (MMP), expression of caspase-3, cytochrome c release, Annexin V/propidium iodide (PI) staining, DNA fragmentation, and the underlying signaling cascades. Our findings indicate that the oversulfation of fucoidan promotes apoptosis of lung cancer cells and the mechanism may involve the Akt/mTOR/S6 pathway. Further in vivo research is needed to establish the precise mechanism whereby oversulfated fucoidan mitigates the progression of lung cancer.
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Park, Ah Young, Maureen Bourtembourg, Aline Chrétien, Roland Hubaux, Céline Lancelot, Michel Salmon y J. Helen Fitton. "Modulation of Gene Expression in a Sterile Atopic Dermatitis Model and Inhibition of Staphylococcus aureus Adhesion by Fucoidan". Dermatopathology 8, n.º 2 (25 de marzo de 2021): 69–83. http://dx.doi.org/10.3390/dermatopathology8020012.
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Atopic dermatitis is a multifactorial pathology that includes perturbations of gene expression and increased adhesion of Staphylococcus aureus. Fucoidans are seaweed-derived sulfated fucose-rich polysaccharides that are known to be anti-inflammatory and may inhibit adhesion of pathogens. Fucoidan was assessed for effects on gene expression of an in vitro 3D model of atopic dermatitis. It was also assessed for inhibitory effects on the adhesion of bacteria onto 3D reconstructed skin. Fucoidan significantly altered gene expression in the atopic dermatitis model, and there was a trend to reduce periostin levels. Fucoidan significantly inhibited the adhesion of Staphylococcus aureus and Cutibacterium acnes but did not affect the adhesion of Staphylococcus epidermidis. Fucoidan may be a useful topical agent to assist in the management of atopic dermatitis.
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Miyazaki, Yoshiyuki, Juneha Bak, Hayato Nakano, Shugo Takeuchi, Hideaki Takeuchi y Daisuke Tachikawa. "Suppressive effects of fucoidan-agaricus mix (CUA-fucoidan) on angiogenesis and tumor growth in B16 melanoma-bearing mice". Journal of Immunology 204, n.º 1_Supplement (1 de mayo de 2020): 241.15. http://dx.doi.org/10.4049/jimmunol.204.supp.241.15.
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Abstract Fucoidan is a series of natural sulfated polysaccharides contained in brown sea algae. In previous studies, we proved that fucoidans derived from Cladosiphon okamuranus and Undaria pinnatifida effectively augmented anti-tumor immunity in combination with an Agaricus blazei mycelium extract. In this study, we evaluated dietary effects of the mixture consist of the two high-molecular weights fucoidan and the agaricus extract (named CUA-fucoidan) on tumor angiogenesis. For that purpose, C57BL/6 mice were subcutaneously injected basement membrane matrix (Geltrex) enclosing 5×104 mitomycin C-treated B16 melanoma cells or 500 ng/mL vascular endothelial growth factor (VEGF), and fed 2% CUA-fucoidan containing diet for 7 days before and after the matrix inoculation. The accumulation of hemoglobin and CD31-positive cells in the B16-enclosed Geltrex was lower in the CUA-fucoidan-fed mice than in the control mice, whereas the hemoglobin contents in the VEGF-enclosed Geltrex were not affected by the CUA-fucoidan feeding. These results suggested that CUA-fucoidan was effective in suppressing tumor angiogenesis, but did not inhibit the physiological action of VEGF. Rather, it was guessed that CUA-fucoidan suppressed VEGF production because the expression of VEGF mRNA was reduced in the matrix resected from CUA-fucoidan-fed mice. In this context, the infiltration of CD206-positive macrophages, which known to produce VEGF, were declined by the CUA-fucoidan feeding. Furthermore, CUA-fucoidan decreased accumulation of Treg in the B16-included Geltrex, and delayed B16 tumor growth. In conclusion, CUA-fucoidan was expected to be effective in inhibition of tumor angiogenesis by improving immunosuppressive tumor microenvironments.
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Zhang, Lei, Brian Hughes, Gregory Tombline, Luise Angelini, Matt Yousefzadeh, Vera Gorbunova, Laura Niedernhofer y Paul Robbins. "FUCOIDANS ARE NOVEL SENOTHERAPEUTICS THAT ENHANCE SIRT6 AND DNA REPAIR ACTIVITY". Innovation in Aging 6, Supplement_1 (1 de noviembre de 2022): 130. http://dx.doi.org/10.1093/geroni/igac059.522.
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Abstract With age, senescent cells accumulate in various tissues where they contribute to loss of tissue homeostasis, aging, and age-related diseases through their inflammatory senescence-associated secretory phenotypes (SASPs). Senotherapeutics able to selectively eliminate senescent cells, termed senolytics, or suppress the detrimental SASPs, termed senomorphics, have been demonstrated to improve age-associated comorbidities and aging phenotypes. To discover novel senotherapeutics translatable to promote healthy longevity, we conducted a drug screening of diverse natural products based on the characteristic senescence-associated β-galactosidase activity. Several fucoidans from different brown seaweed were found to exhibit potent senotherapeutic activity. Fucoidans are long-chain sulfated polysaccharides found in various species of brown algae including seaweed. The best senomorphic fucoidan was able to suppress senescence in cultured senescent fibroblasts, in ex vivo human tissue explants, and in vivo in mouse models of natural and accelerated aging. Specifically, fucoidan reduced markers of cellular senescence and SASP in senescent mouse and human cells. Acute treatment of the fucoidan in naturally aged mice reduced tissue senescence, especially in the kidney and lung. Chronic treatment of the fucoidan in Ercc1-/Δ progeria mice attenuated composite aging symptoms and extended healthspan. Interestingly, preliminary mechanistic studies demonstrated that fucoidan can improve non-homologous end-joining-directed DNA damage repair and increase the mono-ADP-ribosylation activity of SIRT6, suggesting a relationship between cellular senescence, DNA repair, and SIRT6 signaling pathways. Collectively, fucoidans were identified as novel senotherapeutics with translational potential for reducing cellular senescence, ameliorating age-associated phenotypes, and extending healthspan as well as able improve DNA repair pathways through modulation of SIRT6 activity.
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Zhang, Lei, Brian Hughes, Gregory Tombline, Luise Angelini, Matt Yousefzadeh, Vera Gorbunova, Laura Niedernhofer y Paul Robbins. "FUCOIDANS ARE NOVEL SENOTHERAPEUTICS THAT ENHANCE SIRT6 AND DNA REPAIR ACTIVITY". Innovation in Aging 6, Supplement_1 (1 de noviembre de 2022): 732. http://dx.doi.org/10.1093/geroni/igac059.2666.
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Abstract With age, senescent cells accumulate in various tissues where they contribute to loss of tissue homeostasis, aging, and age-related diseases through their inflammatory senescence-associated secretory phenotypes (SASPs). Senotherapeutics able to selectively eliminate senescent cells, termed senolytics, or suppress the detrimental SASPs, termed senomorphics, have been demonstrated to improve age-associated comorbidities and aging phenotypes. To discover novel senotherapeutics translatable to promote healthy longevity, we conducted a drug screening of diverse natural products based on the characteristic senescence-associated β-galactosidase activity. Several fucoidans from different brown seaweed were found to exhibit potent senotherapeutic activity. Fucoidans are long-chain sulfated polysaccharides found in various species of brown algae including seaweed. The best senomorphic fucoidan was able to suppress senescence in cultured senescent fibroblasts, in ex vivo human tissue explants, and in vivo in mouse models of natural and accelerated aging. Specifically, fucoidan reduced markers of cellular senescence and SASP in senescent mouse and human cells. Acute treatment of the fucoidan in naturally aged mice reduced tissue senescence, especially in the kidney and lung. Chronic treatment of the fucoidan in Ercc1-/Δ progeria mice attenuated composite aging symptoms and extended healthspan. Interestingly, preliminary mechanistic studies demonstrated that fucoidan can improve non-homologous end-joining-directed DNA damage repair and increase the mono-ADP-ribosylation activity of SIRT6, suggesting a relationship between cellular senescence, DNA repair, and SIRT6 signaling pathways. Collectively, fucoidans were identified as novel senotherapeutics with translational potential for reducing cellular senescence, ameliorating age-associated phenotypes, and extending healthspan as well as able improve DNA repair pathways through modulation of SIRT6 activity.
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Lakshmanan, Archana, Balamuralikrishnan Balasubramanian, Viji Maluventhen, Arunkumar Malaisamy, Rathinasamy Baskaran, Wen-Chao Liu y Maruthupandian Arumugam. "Extraction and Characterization of Fucoidan Derived from Sargassum ilicifolium and Its Biomedical Potential with In Silico Molecular Docking". Applied Sciences 12, n.º 24 (18 de diciembre de 2022): 13010. http://dx.doi.org/10.3390/app122413010.
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Fucoidan, a polymer derived from seaweed, poses a broad range of biological applications, and its potential medicinal benefits have been widely studied over the past decade. In this study, fucoidan was extracted from marine macroalga Sargassum ilicifolium and its bioactive potential for in silico molecular docking was investigated. Additionally, the computational in silico docking studies were applied on the fucoidan against anticancer and antioxidant target proteins by using Glide ligand docking, Schrodinger software. The FT-IR analysis revealed that fucoidan mainly consisted of the fucose residues (59.1%) and a few monosaccharides, such as uronic acid (11.7%) and sulphate (18.3%). The in vitro tests revealed that fucoidan possessed various antioxidative properties and anticoagulant activities. Fucoidans played an inhibitory role in the colony formation of HepG2 cells. The NADPH oxidase (−7.169 Kcal/mol) and cellular tumor antigen p53 protein (−6.205 Kcal/mol) exhibited the highest antioxidant and anticancer proteins, respectively. Overall, the present study results provide a theoretical foundation for broadening the application of fucoidan from S. ilicifolium as a pharmaceutical ingredient.
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Wang, Juanjuan, Zebin Liu, Xiaowei Pan, Ning Wang, Legong Li, Yuguang Du, Jianjun Li y Mei Li. "Structural and Biochemical Analysis Reveals Catalytic Mechanism of Fucoidan Lyase from Flavobacterium sp. SA-0082". Marine Drugs 20, n.º 8 (20 de agosto de 2022): 533. http://dx.doi.org/10.3390/md20080533.
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Fucoidans represent a type of polyanionic fucose-containing sulfated polysaccharides (FCSPs) that are cleaved by fucoidan-degrading enzymes, producing low-molecular-weight fucoidans with multiple biological activities suitable for pharmacological use. Most of the reported fucoidan-degrading enzymes are glycoside hydrolases, which have been well studied for their structures and catalytic mechanisms. Little is known, however, about the rarer fucoidan lyases, primarily due to the lack of structural information. FdlA from Flavobacterium sp. SA-0082 is an endo-type fucoidan-degrading enzyme that cleaves the sulfated fuco-glucuronomannan (SFGM) through a lytic mechanism. Here, we report nine crystal structures of the catalytic N-terminal domain of FdlA (FdlA-NTD), in both its wild type (WT) and mutant forms, at resolutions ranging from 1.30 to 2.25 Å. We show that the FdlA-NTD adopts a right-handed parallel β-helix fold, and possesses a substrate binding site composed of a long groove and a unique alkaline pocket. Our structural, biochemical, and enzymological analyses strongly suggest that FdlA-NTD utilizes catalytic residues different from other β-helix polysaccharide lyases, potentially representing a novel polysaccharide lyase family.
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Hees, Bettina. "Fucoidan aus Braunalgen". Deutsche Zeitschrift für Onkologie 53, n.º 04 (diciembre de 2021): 148–56. http://dx.doi.org/10.1055/a-1615-0382.
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ZusammenfassungFucoidan ist ein Polysaccharid, das in Meeresbraunalgen, vor allem der Wakame-Alge, vorkommt. Es ist in vielen Ländern Asiens Bestandteil der täglichen Ernährung mit Algen, darüber hinaus wird es in der traditionellen asiatischen Medizin zur komplementären Behandlung von Tumorerkrankungen eingesetzt. Seit Kurzem ist Fucoidan auch in der EU als „Novel Food“-Lebensmittel bzw. Nahrungsergänzung zugelassen. Fucoidane besitzen eine Vielzahl an antikanzerogenen Wirkungen, was in vitro, in vivo und in klinischen Pilotstudien nachgewiesen werden konnte: Sie reduzieren proinflammatorische Prozesse, können die Proliferation von Krebszellen unterdrücken, aktivieren die Apoptose-Signale von Krebszellen und hemmen die Bildung von vaskulären Wachstumsfaktoren (VEGF), wodurch Angiogenese und Metastasierung unterdrückt werden können. Fucoidan besitzt sowohl systemische Wirkungen – erstmalig nachgewiesen mit Hilfe der microRNA Biomarker-Diagnostik – als auch lokale Wirkungen. Als Biological Response Modifier aktiviert und verbessert Fucoidan die Immunantwort im Darm als First-Line-Abwehr von Tumorzellen und Schlüsselfaktor der Tumorbekämpfung, es wirkt zusätzlich als Booster der natürlichen Killerzellaktivität. Fucoidan kann die Nebenwirkungen von Chemo- und Strahlentherapien reduzieren und es kann die therapeutischen Effekte konventioneller Tumortherapien verbessern. Der Beitrag stellt klinische Ergebnisse zu Fucoidan beim metastasierten Kolonkarzinom sowie bei Brustkrebs vor.
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Ohmes, Julia, Yuejun Xiao, Fanlu Wang, Maria Dalgaard Mikkelsen, Thuan Thi Nguyen, Harald Schmidt, Andreas Seekamp, Anne S. Meyer y Sabine Fuchs. "Effect of Enzymatically Extracted Fucoidans on Angiogenesis and Osteogenesis in Primary Cell Culture Systems Mimicking Bone Tissue Environment". Marine Drugs 18, n.º 9 (21 de septiembre de 2020): 481. http://dx.doi.org/10.3390/md18090481.
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Angiogenesis, the formation of new blood vessels from existing ones, is an essential process for successful bone regeneration. Further, angiogenesis is a key factor for the development of bone-related disorders like osteosarcoma or arthritis. Fucoidans, sulfated polysaccharides from brown algae, have been shown to affect angiogenesis as well as a series of other physiological processes including inflammation or infection. However, the chemical properties of fucoidan which define the biological activity vary tremendously, making a prediction of the bioactivity or the corresponding therapeutic effect difficult. In this study, we compare the effect of four chemically characterized high molecular weight fucoidan extracts from Fucus distichus subsp. evanescens (FE_crude and fractions F1, F2, F3) on angiogenic and osteogenic processes in bone-related primary mono- and co-culture cell systems. By determining the gene expression and protein levels of the regulatory molecules vascular endothelial growth factor (VEGF), angiopoietin-1 (ANG-1), ANG-2 and stromal-derived factor 1 (SDF-1), we show that the extracted fucoidans negatively influence angiogenic and osteogenic processes in both the mono- and co-culture systems. We demonstrate that purer fucoidan extracts with a high fucose and sulfate content show stronger effects on these processes. Immunocytochemistry of the co-culture system revealed that treatment with FE_F3, containing the highest fucose and sulfate content, impaired the formation of angiogenic tube-like structures, indicating the anti-angiogenic properties of the tested fucoidans. This study highlights how chemical properties of fucoidan influence its bioactivity in a bone-related context and discusses how the observed phenotypes can be explained on a molecular level—knowledge that is indispensable for future therapies based on fucoidans.
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Hwang, Pai-An, Hong-Ting Lin, Hsin-Yuan Lin y Szu-Kuan Lo. "Dietary Supplementation with Low-Molecular-Weight Fucoidan Enhances Innate and Adaptive Immune Responses and Protects against Mycoplasma pneumoniae Antigen Stimulation". Marine Drugs 17, n.º 3 (18 de marzo de 2019): 175. http://dx.doi.org/10.3390/md17030175.
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In this study, the low-molecular-weight (LMW) fucoidan, rich in fucose and sulfate, was extracted and purified from the edible brown seaweed, Laminaria japonica. In this study, we orally administered LMW fucoidan to mice for 6 weeks. We then examined fucoidan’s effects on innate immunity, adaptive immunity, and Mycoplasma pneumoniae (MP)-antigen-stimulated immune responses. Our data showed that LMW fucoidan stimulated the innate immune system by increasing splenocyte proliferation, natural killer (NK) cell activity, and phagocytic activity. LMW fucoidan also increased interleukin (IL)-2, IL-4, and interferon (IFN)-γ secretion by splenocytes and immunoglobulin (Ig)-G and IgA content in serum, which help regulate adaptive immune cell functions, and decreased allergen-specific IgE. In MP-antigen-stimulated immune responses, the IgM and IgG content in the serum were significantly higher in the LMW fucoidan group after MP-antigen stimulation. Our study provides further information about the immunomodulatory effects of LMW fucoidan and highlights a potential role in preventing M. pneumoniae infection.
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Stefaniak–Vidarsson, Magdalena M., María Gudjónsdóttir, Gudrun Marteinsdottir, Olafur E. Sigurjonsson y Kristberg Kristbergsson. "Evaluation of bioactivity of fucoidan from laminaria with in vitro human cell cultures (THP-1)". Functional Foods in Health and Disease 7, n.º 9 (30 de septiembre de 2017): 688. http://dx.doi.org/10.31989/ffhd.v7i9.373.
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Background: Seaweeds represent one of the few remaining food sources available globally which are not being fully utilized or even over utilized. Kelps (Laminaria spp.) are one of the numerous species of brown seaweeds, a popular marine vegetable, which has been used as a source of iodine and minerals for centuries. Kelps contain anionic polysaccharides called fucoidans heteroglycans with L – fucose units. Their monosaccharide composition, physicochemical and bioactive properties vary between seaweed species. The objective of this work was to evaluate the bioactive properties of laminaria fucoidan (L. digitata and L. hyperborea) toward THP–1 macrophages, a human macrophage like cell line, and investigate its potential antioxidant and immunomodulatory characteristics.Methods: THP-1 macrophages were incubated with five fucoidan concentrations. The Oxygen Radical Absorbance Capacity (ORAC) assay was determined for cell lysates and for the fucoidan extract, in addition to Total Polyphenol Content (TPC). Cytotoxicity of fucoidan was assessed by light microscopy, followed by XTT proliferation assay. Enzyme–linked immunosorbant assays (ELISA) were performed to determine concentrations of the secreted tumor necrosis factor α (TNF-α), interleukin 6 (IL–6), and interleukin 10 (IL–10). Results: Fucoidan did not affect macrophage ability to scavenge oxygen radicals (ORAC) confirming its antioxidant properties toward activated macrophages. The laminaria fucoidan extract at 100 µg/ml concentration lowered macrophage viability. Lower concentrations of laminaria fucoidan did not have impact on cell viability. Very low concentration of fucoidan at 0.1 µg/ml triggered secretion of TNF-α. However, IL–6 and interleukin IL–10 were expressed when concentration of applied fucoidan was 10 µg/ml indicating bioactivity of laminaria fucoidan through immunomodulatory actions.Conclusions: The study demonstrated how laminaria fucoidan may have bioactive properties towards THP–1 macrophages. Changes in cytokine secretion between pro–inflammatory (TNF–α, and IL–6) and anti–inflammatory (IL–10) cytokines confirmed bioactivity of the laminaria fucoidan extracts.Keywords: Seaweeds, Kelps, Laminaria, fucoidan, bioactivity, macrophages
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Vuillemin, Marlene, Artem S. Silchenko, Hang Thi Thuy Cao, Maxim S. Kokoulin, Vo Thi Dieu Trang, Jesper Holck, Svetlana P. Ermakova, Anne S. Meyer y Maria Dalgaard Mikkelsen. "Functional Characterization of a New GH107 Endo-α-(1,4)-Fucoidanase from the Marine Bacterium Formosa haliotis". Marine Drugs 18, n.º 11 (17 de noviembre de 2020): 562. http://dx.doi.org/10.3390/md18110562.
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Fucoidans from brown macroalgae are sulfated fucose-rich polysaccharides, that have several beneficial biological activities, including anti-inflammatory and anti-tumor effects. Controlled enzymatic depolymerization of the fucoidan backbone can help produce homogeneous, defined fucoidan products for structure-function research and pharmaceutical uses. However, only a few endo-fucoidanases have been described. This article reports the genome-based discovery, recombinant expression in Escherichia coli, stabilization, and functional characterization of a new bacterial endo-α-(1,4)-fucoidanase, Fhf1, from Formosa haliotis. Fhf1 catalyzes the cleavage of α-(1,4)-glycosidic linkages in fucoidans built of alternating α-(1,3)-/α-(1,4)-linked l-fucopyranosyl sulfated at C2. The native Fhf1 is 1120 amino acids long and belongs to glycoside hydrolase (GH) family 107. Deletion of the signal peptide and a 470 amino acid long C-terminal stretch led to the recombinant expression of a robust, minimized enzyme, Fhf1Δ470 (71 kDa). Fhf1Δ470 has optimal activity at pH 8, 37–40 °C, can tolerate up to 500 mM NaCl, and requires the presence of divalent cations, either Ca2+, Mn2+, Zn2+ or Ni2+, for maximal activity. This new enzyme has the potential to serve the need for controlled enzymatic fucoidan depolymerization to produce bioactive sulfated fucoidan oligomers.
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Lu, Jun, Keyu Shi, Shuping Chen, Junqiao Wang, Amira Hassouna, Loretta White, Fabrice Merien et al. "Fucoidan Extracted from the New Zealand Undaria pinnatifida—Physicochemical Comparison against Five Other Fucoidans: Unique Low Molecular Weight Fraction Bioactivity in Breast Cancer Cell Lines". Marine Drugs 16, n.º 12 (22 de noviembre de 2018): 461. http://dx.doi.org/10.3390/md16120461.
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Fucoidan, the complex fucose-containing sulphated polysaccharide varies considerably in structure, composition, and bioactivity, depending on the source, species, seasonality, and extraction method. In this study, we examined five fucoidans extracted from the same seaweed species Undaria pinnatifida but from different geological locations, and compared them to the laboratory-grade fucoidan from Sigma (S). The five products differed in molecular composition. The amount of over 2 kDa low molecular weight fraction (LMWF) of the New Zealand crude fucoidan (S1) was larger than that of S, and this fraction was unique, compared to the other four fucoidans. The difference of molecular compositions between S and S1 explained our previous observation that S1 exhibited different anticancer profile in some cancer cell lines, compared with S. Since we observed this unique LMWF, we compared the cytotoxic effects of a LMWF and a high molecular weight fucoidan (HMWF) in two breast cancer cell lines—MCF-7 and MDA-MB-231. Results indicated that the molecular weight is a critical factor in determining the anti-cancer potential of fucoidan, from the New Zealand U. pinnatifida, as the LMWF exhibited a dose-dependent inhibition on the proliferation of breast cancer cells, significantly better than the HMWF, in both cell lines. A time-dependent inhibition was only observed in the MCF-7. Induction of caspase-dependent apoptosis was observed in the MDA-MB-231 cells, through the intrinsic apoptosis pathway alone, or with the extrinsic pathway. LMWF stimulated a dose-dependent NOS activation in the MDA-MB-231 cells. In conclusion, the fucoidan extracted from the New Zealand U. pinnatifida contains a unique LMWF, which could effectively inhibit the growth of breast cancer cell lines. Therefore, the LMWF from New Zealand U. pinnatifida could be used as a supplement cancer treatment.
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Lin, Peichun, Suhua Chen y Siyan Zhong. "Nutritional and Chemical Composition of Sargassum zhangii and the Physical and Chemical Characterization, Binding Bile Acid, and Cholesterol-Lowering Activity in HepG2 Cells of Its Fucoidans". Foods 11, n.º 12 (15 de junio de 2022): 1771. http://dx.doi.org/10.3390/foods11121771.
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Fucoidan is a marine sulfated polysaccharide that is rich in Sargassum and has a wide range of biological activities. In this study, the chemical composition and bile acid binding ability of six crude fucoidans were compared, the nutrition and chemical composition of Sargassum zhangii were analyzed, and fucoidan from Sargassum zhangii was extracted and purified. The purified fractions (ZF1, ZF2, and ZF3) were analyzed by physicochemical characterization, and the ability of binding bile acid and cholesterol lowering in HepG2 cells were evaluated. The results showed that the contents of sulfate in crude fucoidan from Sargassum Zhangii (ZF) was as high as13.63%. Its ability of binding bile acid was better than other five crude fucoidans. Sargassum zhangii was a kind of brown seaweed with high carbohydrate, and low fat and rich in minerals. The sulfate content of ZF1, ZF2, and ZF3 was 3.29%, 19.39%, and 18.89% respectively, and the molecular weight (Mw) was 4.026 × 105, 2.893 × 105, and 3.368 × 105, respectively. Three fucoidans all contained the characteristic absorption bands of polysaccharides and sulfate groups and were rich in fucose. Three fucoidans can bind to bile acid, and ZF2 showed the best binding capability. In vitro experiments showed that ZF1, ZF2, and ZF3 could reduce intracellular total cholesterol (TC) content in HepG2 cells without affecting their viability. ZF2 showed the best ability to reduce TC.
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Kim, Hyojin, Chae Yeon Lim, Dan Bi Lee, Jong Hyeon Seok, Kyung Hyun Kim y Mi Sook Chung. "Inhibitory Effects of Laminaria japonica Fucoidans Against Noroviruses". Viruses 12, n.º 9 (7 de septiembre de 2020): 997. http://dx.doi.org/10.3390/v12090997.
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Norovirus is the leading cause of nonbacterial foodborne disease outbreaks. Human noroviruses (HuNoVs) bind to histo-blood group antigens as the host receptor for infection. In this study, the inhibitory effects of fucoidans from brown algae, Laminaria japonica (LJ), Undaria pinnatifida and Undaria pinnatifida sporophyll, were evaluated against murine norovirus (MNoV), feline calicivirus (FCV) and HuNoV. Pretreatment of MNoV or FCV with the fucoidans at 1 mg/mL showed high antiviral activities, with 1.1 average log reductions of viral titers in plaque assays. They also showed significant inhibition on the binding of the P domains of HuNoV GII.4 and GII.17 to A- or O-type saliva and the LJ fucoidan was the most effective, reaching 54–72% inhibition at 1 mg/mL. In STAT1−/− mice infected with MNoV, oral administration of the LJ fucoidan, composed of mainly sulfated fucose and minor amounts of glucose and galactose, improved the survival rates of mice and significantly reduced the viral titers in their feces. Overall, these results provide the LJ fucoidan can be used to reduce NoV outbreaks.
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Minh Ly, Bui, Ngo Quoc Buu, Nguyen Duy Nhut, Pham Duc Thinh y Tran Thi Thanh Van. "STUDIES ON FUCOIDAN AND ITS PRODUCTION FROM VIETNAMESE BROWN SEAWEEDS". ASEAN Journal on Science and Technology for Development 22, n.º 4 (11 de noviembre de 2017): 371. http://dx.doi.org/10.29037/ajstd.173.
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Sulfated fucans are among the most widely studied of all the sulfated polysaccharides of plant origin that exhibit biological activities in mammalian systems. In this report fucoidans from some Vietnamese Sargassumspecies such as S.polycystum, S.oligocystum, S.mcclurei, S. Swartzii and denticaprum were extracted and fractionated on a DEAE-Sephadex A-25 column. On the basis of chemical and spectral analyses, the fucoidan fractions obtained were found to be the sulfated fucogalactans containing sulfate ester groups and uronic acid, and composed essentially of fucose and galactose, as well as a minor amount of other sugars. The polysaccharide fractions were tested for anticancer activity. The primarily obtained results showed that all fucoidan fractions isolated from S. swartziidemonstrate bioactivity effects against cancer cells, while fraction F5 with a highest sulfate content exhibits the strongest anti-invasion activity. This indicates that sulfate content plays an important role in the anticancer activity of the brown algal fucoidans. A laboratory scale pilot for fuco idan production from Vietnamese brown seaweeds has been set with a capacity of 500 g of crude fucoidan per day.
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Xin, Liu, Liu Bin, Wei Xiao-Lei, Sun Zhen-Liang y Wang Chang-Yun. "Extraction, Fractionation, and Chemical Characterisation of Fucoidans from the Brown Seaweed Sargassum pallidum". Czech Journal of Food Sciences 34, No. 5 (1 de noviembre de 2016): 406–13. http://dx.doi.org/10.17221/322/2015-cjfs.
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The fucoidans were obtained by extraction with water and gradient precipitation with different concentrations of ethanol. The main structural characterisations and bioactivities were achieved. Four fractions of water-soluble crude fucoidans with different molecular weights – SPC60, SPC70, SPH60, SPH70 – were extracted from S. pallidum collected from the Yellow Sea, China, using cold water and hot water extraction, and fractional precipitation with gradient concentrations of ethanol. Chemical analysis demonstrated that all of these fucoidan fractions consisted of fucose, rhamnose, xylose, mannose, glucose, and galactose with different monosaccharide mole ratios. Fractions SPC60, SPC70, and SPH70 showed moderate cytotoxic activity against P388 murine leukaemia cells. Fucoidan is a kind of bioactive polysaccharide from the brown algae. This study provides a fast and feasible method to obtain fucoidans from S. pallidum, which can be used as pharmaceutical material and functional food.
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Al Monla, Reem, Zeina Dassouki, Nouha Sari-Chmayssem, Hiba Mawlawi y Hala Gali-Muhtasib. "Fucoidan and Alginate from the Brown Algae Colpomenia sinuosa and Their Combination with Vitamin C Trigger Apoptosis in Colon Cancer". Molecules 27, n.º 2 (6 de enero de 2022): 358. http://dx.doi.org/10.3390/molecules27020358.
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Brown seaweeds are producers of bioactive molecules which are known to inhibit oncogenic growth. Here, we investigated the antioxidant, cytotoxic, and apoptotic effects of two polysaccharides from the brown algae Colpomenia sinuosa, namely fucoidan and alginate, in a panel of cancer cell lines and evaluated their effects when combined with vitamin C. Fucoidan and alginate were isolated from brown algae and characterized by HPLC, FTIR, and NMR spectroscopy. The results indicated that highly sulfated fucoidans had higher antioxidant and cytotoxic effects than alginate. Human colon cancer cells were the most sensitive to the algal treatments, with fucoidan having an IC50 value (618.9 µg/mL−1) lower than that of alginate (690 µg/mL−1). The production of reactive oxygen species was increased upon treatment of HCT-116 cells with fucoidan and alginate, which suggest that these compounds may trigger cell death via oxidative damage. The combination of fucoidan with vitamin C showed enhanced effects compared to treatment with fucoidan alone, as evidenced by the significant inhibitory effects on HCT-116 colon cancer cell viability. The combination of the algal polysaccharides with vitamin C caused enhanced degeneration in the nuclei of cells, as evidenced by DAPI staining and increased the subG1 population, suggesting the induction of cell death. Together, these results suggest that fucoidan and alginate from the brown algae C. sinuosa are promising anticancer compounds, particularly when used in combination with vitamin C.
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Mabate, Blessing, Chantal Désirée Daub, Samkelo Malgas, Adrienne Lesley Edkins y Brett Ivan Pletschke. "Fucoidan Structure and Its Impact on Glucose Metabolism: Implications for Diabetes and Cancer Therapy". Marine Drugs 19, n.º 1 (11 de enero de 2021): 30. http://dx.doi.org/10.3390/md19010030.
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Fucoidans are complex polysaccharides derived from brown seaweeds which consist of considerable proportions of L-fucose and other monosaccharides, and sulphated ester residues. The search for novel and natural bioproduct drugs (due to toxicity issues associated with chemotherapeutics) has led to the extensive study of fucoidan due to reports of it having several bioactive characteristics. Among other fucoidan bioactivities, antidiabetic and anticancer properties have received the most research attention in the past decade. However, the elucidation of the fucoidan structure and its biological activity is still vague. In addition, research has suggested that there is a link between diabetes and cancer; however, limited data exist where dual chemotherapeutic efforts are elucidated. This review provides an overview of glucose metabolism, which is the central process involved in the progression of both diseases. We also highlight potential therapeutic targets and show the relevance of fucoidan and its derivatives as a candidate for both cancer and diabetes therapy.
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Mabate, Blessing, Chantal Désirée Daub, Samkelo Malgas, Adrienne Lesley Edkins y Brett Ivan Pletschke. "Fucoidan Structure and Its Impact on Glucose Metabolism: Implications for Diabetes and Cancer Therapy". Marine Drugs 19, n.º 1 (11 de enero de 2021): 30. http://dx.doi.org/10.3390/md19010030.
Texto completoResumen
Fucoidans are complex polysaccharides derived from brown seaweeds which consist of considerable proportions of L-fucose and other monosaccharides, and sulphated ester residues. The search for novel and natural bioproduct drugs (due to toxicity issues associated with chemotherapeutics) has led to the extensive study of fucoidan due to reports of it having several bioactive characteristics. Among other fucoidan bioactivities, antidiabetic and anticancer properties have received the most research attention in the past decade. However, the elucidation of the fucoidan structure and its biological activity is still vague. In addition, research has suggested that there is a link between diabetes and cancer; however, limited data exist where dual chemotherapeutic efforts are elucidated. This review provides an overview of glucose metabolism, which is the central process involved in the progression of both diseases. We also highlight potential therapeutic targets and show the relevance of fucoidan and its derivatives as a candidate for both cancer and diabetes therapy.
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Dockal, Michael, Werner Hoellriegl, Zhenqing Zhang, Susanne Till, Sabine Knappe, Michael Palige, Alexandra Schiviz et al. "Structural and Functional Characterization of Fucoidan and Its Procoagulant Effect in An Ex Vivo Model of Factor VIII-Inhibited Guinea Pigs". Blood 118, n.º 21 (18 de noviembre de 2011): 2262. http://dx.doi.org/10.1182/blood.v118.21.2262.2262.
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Abstract Abstract 2262 Fucoidans are sulfated polysaccharides extracted and purified from brown seaweeds. Described as non-anticoagulant polysaccharides (NASPs), they have been shown to improve clotting in FVIII- and FIX-deficient plasma (Liu et al. Thromb Haemost 2006;95:68), making them good candidates for hemophilia treatment. NASP orally administered to hemophilia A dogs over several weeks resulted in correction to normal ranges in thromboelastography (TEG) parameters and improvement of the cuticle bleeding time (Prasad et al. Blood 2008;111:672). We screened extracts of eleven brown algae species to select the most active, high-quality, homogeneous fucoidan. In-depth structural analysis and assessment of the pro-/anticoagulant and TFPI-inhibiting activities of a selected set of fucoidan preparations was performed. The effect of the best fucoidan candidate was studied in a novel guinea pig model by whole blood TEG monitoring supported by calibrated automated thrombographic (CAT) analysis. Comparative structural studies of fucoidans included monosaccharide composition and elemental analysis, molecular weight and overall structural determination by NMR. 13C-NMR spectroscopy gave a comprehensive picture of fucoidan structure including fucose and alginate content and the relative heterogeneity of the preparation distinguishing between fucoidans of different algae species. Heterogeneity of the materials was highest in U. pinnatifida and L. japonica and lowest in F. vesiculosus (F.v.) samples. Procoagualant activity was shown by CAT and rotation thromboelastometry. Clotting parameters of FVIII-inhibited human blood or plasma were corrected to normal levels at 1 and 3 μg/mL depending on the fucoidan. In addition, the fucoidans were analyzed by BiaCore and a modified dilute prothrombin time assay to show binding to TFPI and inhibition of full-length TFPI activity. The screening process supported the identification and optimization of new fucoidan-specific analytical methods. Furthermore, a CAT protocol optimized for guinea pig plasma was used to show the procoagulant effect of the overall best fucoidan candidate. We spiked F.v. fucoidan into FVIII-inhibited guinea pig plasma between 1 and 100μg/mL and triggered thrombin generation with low amounts of tissue factor. The FVIII-inhibited guinea pig plasma was corrected to normal CAT parameters at ∼30μg/mL NASP. Based on our findings in the CAT assay, we designed a dosage pattern for studying the procoagulant effect using TEG in FVIII-inhibited Dunkin Hartley guinea pigs (n=10) after intravenous administration of 0.1 to 1.6mg/kg NASP. The primary endpoint assessed was R-time (time to clotting). FVIII-inhibited guinea pigs showed a median R-time of ≥120min (no clotting), while R-time was reduced in a non-linear dose-dependent manner after administration of NASP down to 69min (0.4mg/kg NASP). Thus, the results generated in in vitro tests, were confirmed in vivo. This new animal model of induced hemophilia will support the development of alternative hemophilia therapeutics. Disclosures: Dockal: Baxter Innovations GmbH: Employment. Hoellriegl:Baxter Innovations GmbH: Employment. Zhang:Baxter Healthcare Corporation: Employment. Till:Baxter Innovations GmbH: Employment. Knappe:Baxter Innovations GmbH: Employment. Palige:Baxter Innovations GmbH: Employment. Schiviz:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Szabo:Baxter Healthcare Corporation: Employment. Muchitsch:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment.
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Kuznetsova, T. A., T. P. Smolina, E. V. Persiyanova, L. A. Ivanushko, A. S. Silchenko, S. P. Ermakova y N. N. Besednova. "Effects of enzymatically depolymerised fucoidan on effector functions of innate and adaptive immunity cells". Biological Products. Prevention, Diagnosis, Treatment 22, n.º 3 (10 de octubre de 2022): 308–17. http://dx.doi.org/10.30895/2221-996x-2022-22-3-308-317.
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The use of sulfated polysaccharides (fucoidans) as active pharmaceutical ingredients or adjuvants poses the challenge of obtaining structurally characterised and homogeneous samples or their oligomeric fractions maintaining high biological activity. The authors obtained a highly purified enzymatic hydrolysate of fucoidan from the brown alga Fucus evanescens and compared its biological activity with that of a native sample. The aim of the study was to compare, in vitro and in vivo, the effects of depolymerised fucoidan from the brown alga F. evanescens and native fucoidan on the effector functions of innate and adaptive immunity cells loaded with ovalbumin (OVA). Materials and methods: the effects of the fucoidan samples (depolymerised and native) on the expression of the main immunophenotypic markers by innate and adaptive immunity cells (neutrophils, monocytes, natural killers, and lymphocytes) were studied in vitro using flow cytometry. The levels of serum OVA-specific antibodies (IgG, IgG1, IgG2а) and cytokines (IFN-γ, IL-2, IL-10, IL-12) were studied in vivo using BALB/c mice immunised with OVA. The statistical analysis of the data obtained was performed using the Statistica 10 software package. Results: in vitro, both fucoidan samples altered the expression of the main immunophenotypic markers by innate and adaptive immunity cells, indicating their activation. In vivo, mice treated with the fucoidan samples demonstrated an increase in the levels of OVA-specific antibodies (IgG, IgG1 and IgG2a) and in the production of cytokines (IFN-γ, IL-2, IL-10). Conclusions: the effects of enzymatically depolymerised fucoidan on functional activity of innate and adaptive immunity cells are comparable to those of native fucoidan. The findings indicate the possibility of using enzymatic hydrolysis products of fucoidan as adjuvants for a wide range of prophylactic and therapeutic vaccines.
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Zayed, Ahmed, Doris Finkelmeier, Thomas Hahn, Lisa Rebers, Anusriha Shanmugam, Anke Burger-Kentischer y Roland Ulber. "Characterization and Cytotoxic Activity of Microwave-Assisted Extracted Crude Fucoidans from Different Brown Seaweeds". Marine Drugs 21, n.º 1 (11 de enero de 2023): 48. http://dx.doi.org/10.3390/md21010048.
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Microwave-assisted extraction (MAE) is recognized as a green method for extraction of natural products. The current research aimed to explore the MAE for fucoidans extraction from different brown seaweeds, including Fucus vesiculosus, F. spiralis, and Laminaria saccharina. Following several solvent-extraction pre-treatment steps and MAE optimization, the algal biomasses were extracted in a ratio of 1:25 in 0.1 M HCl containing 2 M CaCl2 for 1.0 min. The results showed that L. saccharina’s extract was different from the others, regarding the highest sugar content reached 0.47 mg glucose equivalent/mg extract being confirmed by monosaccharide composition analysis and the lowest fucoidan content and sulfation degree at 0.09 mg/mg extract and 0.13, respectively. Moreover, these findings were confirmed by tentative structural elucidation based on Fourier-transform infrared spectrometry which also showed a different spectrum. However, the MAE enhanced melanoidins formation in products, which was confirmed by the intense band at 1420 cm−1. Interestingly, the results of monomeric composition showed that fucoidan extract by MAE from F. vesiculosus belonged to sulfated galactofucans which are known for their potential bioactivities. Furthermore, the cytotoxic activity of the four fucoidans in concentrations ranging from 4.9 µg/mL to 2500 µg/mL was investigated and correlated with the chemical characterization showing that F. vesiculosus_MAE fucoidan was the most potent and safest. The current research revealed the chemical heterogeneity of fucoidans regarding taxonomical class and used greener extraction method of fucoidans toward the achievement of the UN sustainability goals.
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Ohmes, Julia, Lena Marie Saure, Fabian Schütt, Marie Trenkel, Andreas Seekamp, Regina Scherließ, Rainer Adelung y Sabine Fuchs. "Injectable Thermosensitive Chitosan-Collagen Hydrogel as A Delivery System for Marine Polysaccharide Fucoidan". Marine Drugs 20, n.º 6 (18 de junio de 2022): 402. http://dx.doi.org/10.3390/md20060402.
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Fucoidans, sulfated polysaccharides from brown algae, possess multiple bioactivities in regard to osteogenesis, angiogenesis, and inflammation, all representing key molecular processes for successful bone regeneration. To utilize fucoidans in regenerative medicine, a delivery system is needed which temporarily immobilizes the polysaccharide at the injured site. Hydrogels have become increasingly interesting biomaterials for the support of bone regeneration. Their structural resemblance with the extracellular matrix, their flexible shape, and capacity to deliver bioactive compounds or stem cells into the affected tissue make them promising materials for the support of healing processes. Especially injectable hydrogels stand out due to their minimal invasive application. In the current study, we developed an injectable thermosensitive hydrogel for the delivery of fucoidan based on chitosan, collagen, and β-glycerophosphate (β-GP). Physicochemical parameters such as gelation time, gelation temperature, swelling capacity, pH, and internal microstructure were studied. Further, human bone-derived mesenchymal stem cells (MSC) and human outgrowth endothelial cells (OEC) were cultured on top (2D) or inside the hydrogels (3D) to assess the biocompatibility. We found that the sol-gel transition occurred after approximately 1 min at 37 °C. Fucoidan integration into the hydrogel had no or only a minor impact on the mentioned physicochemical parameters compared to hydrogels which did not contain fucoidan. Release assays showed that 60% and 80% of the fucoidan was released from the hydrogel after two and six days, respectively. The hydrogel was biocompatible with MSC and OEC with a limitation for OEC encapsulation. This study demonstrates the potential of thermosensitive chitosan-collagen hydrogels as a delivery system for fucoidan and MSC for the use in regenerative medicine.
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Gueven, Nuri, Kevin J. Spring, Sandra Holmes, Kiran Ahuja, Raj Eri, Ah Young Park y J. Helen Fitton. "Micro RNA Expression after Ingestion of Fucoidan; A Clinical Study". Marine Drugs 18, n.º 3 (28 de febrero de 2020): 143. http://dx.doi.org/10.3390/md18030143.
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Fucoidans are a class of fucose-rich sulfated polysaccharides derived from brown macroalgae that exert a range of biological activities in vitro and in vivo. To generate an unbiased assessment of pathways and processes affected by fucoidan, a placebo-controlled double-blind pilot study was performed in healthy volunteers. Blood samples were taken immediately before and 24 h after ingestion of a single dose of 1 g of Undaria pinnatifida fucoidan (UPF) or placebo. Levels of isolated miRNAs were analyzed using Taqman Open Array Human MicroRNA panels. Out of 754 miRNAs screened, UPF affected a total of 53 miRNAs. Pathway analysis using the TALOS data analysis tool predicted 29 different pathways and processes that were largely grouped into cell surface receptor signaling, cancer-related pathways, the majority of which were previously associated with fucoidans. However, this analysis also identified nine pathways and processes that have not been associated with fucoidans before. Overall, this study illustrates that even a single dose of fucoidans has the potential to affect the expression of genes related to fundamental cellular processes. Moreover, it confirms previous data that fucoidans influence immunity, cancer cells, inflammation, and neurological function.
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Li, Yani, Eileen McGowan, Size Chen, Jerran Santos, Haibin Yin y Yiguang Lin. "Immunopotentiating Activity of Fucoidans and Relevance to Cancer Immunotherapy". Marine Drugs 21, n.º 2 (15 de febrero de 2023): 128. http://dx.doi.org/10.3390/md21020128.
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Fucoidans, discovered in 1913, are fucose-rich sulfated polysaccharides extracted mainly from brown seaweed. These versatile and nontoxic marine-origin heteropolysaccharides have a wide range of favorable biological activities, including antitumor, immunomodulatory, antiviral, antithrombotic, anticoagulant, antithrombotic, antioxidant, and lipid-lowering activities. In the early 1980s, fucoidans were first recognized for their role in supporting the immune response and later, in the 1990s, their effects on immune potentiation began to emerge. In recent years, the understanding of the immunomodulatory effects of fucoidan has expanded significantly. The ability of fucoidan(s) to activate CTL-mediated cytotoxicity against cancer cells, strong antitumor property, and robust safety profile make fucoidans desirable for effective cancer immunotherapy. This review focusses on current progress and understanding of the immunopotentiation activity of various fucoidans, emphasizing their relevance to cancer immunotherapy. Here, we will discuss the action of fucoidans in different immune cells and review how fucoidans can be used as adjuvants in conjunction with immunotherapeutic products to improve cancer treatment and clinical outcome. Some key rationales for the possible combination of fucoidans with immunotherapy will be discussed. An update is provided on human clinical studies and available registered cancer clinical trials using fucoidans while highlighting future prospects and challenges.