Special Issue "Fucoidans"

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: 28 August 2020.

Special Issue Editor

Prof. Dr. You-Jin Jeon
Website
Guest Editor
School of Marine Biomedical Science, Jeju National University, South Korea
Interests: Marine Biotechnology; Marine drugs; Algal biotechnology; Functionalities and bioactivities; Isolation of bioactive compounds; Functional Foods and Nutraceuticals; Cosmetics and Cosmeceuticals

Special Issue Information

Dear Colleagues,

Fucoidans are a group of fucose-containing sulfated polysaccharides found in many species of brown seaweed with numerous bioactive properties. As a highly bioactive seaweed substance with many promising physiological activities, fucoidan has attracted attention from many industries all over the world. Even though fucoidans are a rich source of bioactive properties, the structural properties and bioactive mechanisms of fucoidans are poorly understood. Therefore, novel studies that either characterize the physical properties or biological activities of fucoidans will fill the knowledge gap between industrial applications and the scientific background of those applications. 

Both purified and partially purified fucoidans isolated from brown seaweeds present high potential as preventative and therapeutic agents against number of chronic diseases due to their anti-inflammatory, antioxidant, anticancer, neuroprotective, antiviral, antimicrobial, and anticoagulative properties.

This Special Issue is aimed at presenting updated information on well-documented studies of the structural characterization and major biological actions relevant for medical, cosmeceutical, and pharmaceutical applications that fucoidans isolated from brown seaweed can offer.

As the guest Editor, I would like to invite scientists to submit their latest research findings in this area related to the biological activities, mechanisms of action in cells, tissues, and/or organs.

Prof. You-Jin Jeon
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • fucoidan
  • seaweeds
  • bioactivities
  • inflammation
  • antioxidant
  • anticancer
  • antimicrobial
  • immunomodulation

Published Papers (12 papers)

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Research

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Open AccessArticle
Degradation of Sargassum crassifolium Fucoidan by Ascorbic Acid and Hydrogen Peroxide, and Compositional, Structural, and In Vitro Anti-Lung Cancer Analyses of the Degradation Products
Mar. Drugs 2020, 18(6), 334; https://doi.org/10.3390/md18060334 - 26 Jun 2020
Abstract
Fucoidans possess multiple biological functions including anti-cancer activity. Moreover, low-molecular-weight fucoidans are reported to possess more bioactivities than native fucoidans. In the present study, a native fucoidan (SC) was extracted from Sargassum crassifolium pretreated by single-screw extrusion, and three degraded fucoidans, namely, SCA [...] Read more.
Fucoidans possess multiple biological functions including anti-cancer activity. Moreover, low-molecular-weight fucoidans are reported to possess more bioactivities than native fucoidans. In the present study, a native fucoidan (SC) was extracted from Sargassum crassifolium pretreated by single-screw extrusion, and three degraded fucoidans, namely, SCA (degradation of SC by ascorbic acid), SCH (degradation of SC by hydrogen peroxide), and SCAH (degradation of SC by ascorbic acid + hydrogen peroxide), were produced. The extrusion pretreatment can increase the extraction yield of fucoidan by approximately 4.2-fold as compared to the non-extruded sample. Among SC, SCA, SCH, and SCAH, the chemical compositions varied but structural features were similar. SC, SCA, SCH, and SCAH showed apoptotic effects on human lung carcinoma A-549 cells, as illustrated by loss of mitochondrial membrane potential (MMP), decreased B-cell leukemia-2 (Bcl-2) expression, increased cytochrome c release, increased active caspase-9 and -3, and increased late apoptosis of A-549 cells. In general, SCA was found to exhibit high cytotoxicity to A-549 cells and a strong ability to suppress Bcl-2 expression. SCA also showed high efficacy to induce cytochrome c release, activate caspase-9 and -3, and promote late apoptosis of A-549 cells. Therefore, our data suggest that SCA could have an adjuvant therapeutic potential in the treatment of lung cancer. Additionally, we explored that the Akt/mammalian target of rapamycin (mTOR) signaling pathway is involved in SC-, SCA-, SCH-, and SCAH-induced apoptosis of A-549 cells. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessArticle
Protective Effect of Fucoidan against MPP+-Induced SH-SY5Y Cells Apoptosis by Affecting the PI3K/Akt Pathway
Mar. Drugs 2020, 18(6), 333; https://doi.org/10.3390/md18060333 - 25 Jun 2020
Abstract
The main pathologic changes of the Parkinson’s disease (PD) is dopaminergic (DA) neurons lost. Apoptosis was one of the important reasons involved in the DA lost. Our previous study found a fucoidan fraction sulfated heterosaccharide (UF) had neuroprotective activity. The aim of this [...] Read more.
The main pathologic changes of the Parkinson’s disease (PD) is dopaminergic (DA) neurons lost. Apoptosis was one of the important reasons involved in the DA lost. Our previous study found a fucoidan fraction sulfated heterosaccharide (UF) had neuroprotective activity. The aim of this study was to clarify the mechanism of UF on DA neurons using human dopaminergic neuroblastoma (SH-SY5Y) cells a typical as a PD cellular model. Results showed that UF prevented MPP+-induced SH-SY5Y cells apoptosis and cell death. Additionally, UF pretreated cells increased phosphorylation of Akt, PI3K and NGF, which means UF-treated active PI3K–Akt pathway. Moreover, UF treated cells decreased the expression of apoptosis-associated protein, such as the ratio of Bax/Bcl-2, GSK3β, caspase-3 and p53 nuclear induced by MPP+. This effect was partially blocked by PI3K inhibitor LY294002. Our data suggested that protective effect of UF against MPP+-induced SH-SY5Y cells death by affecting the PI3K–Akt pathway. These findings contribute to a better understanding of the critical roles of UF in treating PD and may elucidate the molecular mechanisms of UF effects in PD. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessArticle
Protective Effect of a Fucose-Rich Fucoidan Isolated from Saccharina japonica against Ultraviolet B-Induced Photodamage In Vitro in Human Keratinocytes and In Vivo in Zebrafish
Mar. Drugs 2020, 18(6), 316; https://doi.org/10.3390/md18060316 - 15 Jun 2020
Abstract
A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT [...] Read more.
A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT cells were determined. The results indicate that the purified fucoidan significantly reduced the intracellular reactive oxygen species levels and improved the viability of UVB-irradiated HaCaT cells. Furthermore, the purified fucoidan remarkably decreased the apoptosis by regulating the expressions of Bax/Bcl-xL and cleaved caspase-3 in UVB-irradiated HaCaT cells in a dose-dependent manner. In addition, the in vivo UV protective effect of the purified fucoidan was investigated using a zebrafish model. It significantly reduced the intracellular reactive oxygen species level, the cell death, the NO production, and the lipid peroxidation in UVB-irradiated zebrafish in a dose-dependent manner. These results suggest that purified fucoidan has a great potential to be developed as a natural anti-UVB agent applied in the cosmetic industry. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessArticle
Effects of a Newly Developed Enzyme-Assisted Extraction Method on the Biological Activities of Fucoidans in Ocular Cells
Mar. Drugs 2020, 18(6), 282; https://doi.org/10.3390/md18060282 - 26 May 2020
Abstract
Fucoidans from brown seaweeds are promising substances as potential drugs against age-related macular degeneration (AMD). The heterogeneity of fucoidans requires intensive research in order to find suitable species and extraction methods. Ten different fucoidan samples extracted enzymatically from Laminaria digitata (LD), Saccharina latissima [...] Read more.
Fucoidans from brown seaweeds are promising substances as potential drugs against age-related macular degeneration (AMD). The heterogeneity of fucoidans requires intensive research in order to find suitable species and extraction methods. Ten different fucoidan samples extracted enzymatically from Laminaria digitata (LD), Saccharina latissima (SL) and Fucus distichus subsp. evanescens (FE) were tested for toxicity, oxidative stress protection and VEGF (vascular endothelial growth factor) inhibition. For this study crude fucoidans were extracted from seaweeds using different enzymes and SL fucoidans were further separated into three fractions (SL_F1-F3) by ion-exchange chromatography (IEX). Fucoidan composition was analyzed by high performance anion exchange chromatography (HPAEC) after acid hydrolysis. The crude extracts contained alginate, while two of the fractionated SL fucoidans SL_F2 and SL_F3 were highly pure. Cell viability was assessed with an 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay in OMM-1 and ARPE-19. Protective effects were investigated after 24 h of stress insult in OMM-1 and ARPE-19. Secreted VEGF was analyzed via ELISA (enzyme-linked immunosorbent assay) in ARPE-19 cells. Fucoidans showed no toxic effects. In OMM-1 SL_F2 and several FE fucoidans were protective. LD_SiAT2 (Cellic®CTec2 + Sigma-Aldrich alginate lyase), FE_SiAT3 (Cellic® CTec3 + Sigma-Aldrich alginate lyase), SL_F2 and SL_F3 inhibited VEGF with the latter two as the most effective. We could show that enzyme treated fucoidans in general and the fractionated SL fucoidans SL_F2 and SL_F3 are very promising for beneficial AMD relevant biological activities. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessArticle
Are Helicobacter pylori Infection and Fucoidan Consumption Associated with Fucoidan Absorption?
Mar. Drugs 2020, 18(5), 235; https://doi.org/10.3390/md18050235 - 30 Apr 2020
Abstract
We examined the associations of Helicobacter pylori and mozuku consumption with fucoidan absorption. Overall, 259 Japanese volunteers consumed 3 g fucoidan, and their urine samples were collected to measure fucoidan values and H. pylori titers before and 3, 6, and 9 h after [...] Read more.
We examined the associations of Helicobacter pylori and mozuku consumption with fucoidan absorption. Overall, 259 Japanese volunteers consumed 3 g fucoidan, and their urine samples were collected to measure fucoidan values and H. pylori titers before and 3, 6, and 9 h after fucoidan ingestion. Compared to the basal levels (3.7 ± 3.4 ng/mL), the urinary fucoidan values significantly increased 3, 6, and 9 h (15.3 ± 18.8, 24.4 ± 35.1, and 24.2 ± 35.2 ng/mL, respectively) after fucoidan ingestion. The basal fucoidan levels were significantly lower in H. pylori-negative subjects who rarely ate mozuku than in those who regularly consumed it. Regarding the ΔMax fucoidan value (highest value − basal value) in H. pylori-positive subjects who ate mozuku at least once a month, those aged ≥40 years exhibited significantly lower values than <40 years old. Among subjects ≥40 years old who regularly consumed mozuku, the ΔMax fucoidan value was significantly lower in H. pylori-positive subjects than in H. pylori-negative ones. In H. pylori-positive subjects who ate mozuku at least once monthly, basal fucoidan values displayed positive correlations with H. pylori titers and ΔMax fucoidan values in subjects <40 years old. No correlations were found in H. pylori-positive subjects who ate mozuku once every 2–3 months or less. Thus, fucoidan absorption is associated with H. pylori infection and frequency of mozuku consumption. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessArticle
Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway
Mar. Drugs 2020, 18(4), 220; https://doi.org/10.3390/md18040220 - 20 Apr 2020
Abstract
Fucoidan has a variety of pharmacological activities, but the understanding of the mechanism of fucoidan-induced apoptosis of colorectal cancer cells remains limited. The results of the present study demonstrated that the JNK signaling pathway is involved in the activation of apoptosis in colorectal [...] Read more.
Fucoidan has a variety of pharmacological activities, but the understanding of the mechanism of fucoidan-induced apoptosis of colorectal cancer cells remains limited. The results of the present study demonstrated that the JNK signaling pathway is involved in the activation of apoptosis in colorectal cancer-derived HT-29 cells, and fucoidan induces apoptosis by activation of the DR4 at the transcriptional and protein levels. The survival rate of HT-29 cells was approximately 40% in the presence of 800 μg/mL of fucoidan, but was increased to 70% after DR4 was silenced by siRNA. Additionally, fucoidan has been shown to reduce the mitochondrial membrane potential and destroy the integrity of mitochondrial membrane. In the presence of an inhibitor of cytochrome C inhibitor and DR4 siRNA or the presence of cytochrome C inhibitor only, the cell survival rate was significantly higher than when cells were treated with DR4 siRNA only. These data indicate that both the DR4 and the mitochondrial pathways contribute to fucoidan-induced apoptosis of HT-29 cells, and the extrinsic pathway is upstream of the intrinsic pathway. In conclusion, the current work identified the mechanism of fucoidan-induced apoptosis and provided a novel theoretical basis for the future development of clinical applications of fucoidan as a drug. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessArticle
Antioxidant Potential of Sulfated Polysaccharides from Padina boryana; Protective Effect against Oxidative Stress in In Vitro and In Vivo Zebrafish Model
Mar. Drugs 2020, 18(4), 212; https://doi.org/10.3390/md18040212 - 14 Apr 2020
Abstract
Elevated levels of reactive oxygen species (ROS) damage the internal cell components. Padina boryana, a brown alga from the Maldives, was subjected to polysaccharide extraction. The Celluclast enzyme assisted extract (PBE) and ethanol precipitation (PBP) of P. boryana were assessed against hydrogen [...] Read more.
Elevated levels of reactive oxygen species (ROS) damage the internal cell components. Padina boryana, a brown alga from the Maldives, was subjected to polysaccharide extraction. The Celluclast enzyme assisted extract (PBE) and ethanol precipitation (PBP) of P. boryana were assessed against hydrogen peroxide (H2O2) induced cell damage and zebra fish models. PBP which contains the majority of sulfated polysaccharides based on fucoidan, showed outstanding extracellular ROS scavenging potential against H2O2. PBP significantly declined the intracellular ROS levels, and exhibited protection against apoptosis. The study revealed PBPs’ ability to activate the Nrf2/Keap1 signaling pathway, consequently initiating downstream elements such that catalase (CAT) and superoxide dismutase (SOD). Further, ROS levels, lipid peroxidation values in zebrafish studies were declined with the pre-treatment of PBP. Collectively, the results obtained in the study suggest the polysaccharides from P. boryana might be a potent source of water soluble natural antioxidants that could be sustainably utilized in the industrial applications. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessArticle
Fucoidan Purified from Sargassum polycystum Induces Apoptosis through Mitochondria-Mediated Pathway in HL-60 and MCF-7 Cells
Mar. Drugs 2020, 18(4), 196; https://doi.org/10.3390/md18040196 - 08 Apr 2020
Cited by 1
Abstract
Fucoidans are biocompatible, heterogeneous, and fucose rich sulfated polysaccharides biosynthesized in brown algae, which are renowned for their broad-spectrum biofunctional properties. As a continuation of our preliminary screening studies, the present work was undertaken to extract polysaccharides from the edible brown algae Sargassum [...] Read more.
Fucoidans are biocompatible, heterogeneous, and fucose rich sulfated polysaccharides biosynthesized in brown algae, which are renowned for their broad-spectrum biofunctional properties. As a continuation of our preliminary screening studies, the present work was undertaken to extract polysaccharides from the edible brown algae Sargassum polycystum by a modified enzyme assisted extraction process using Celluclast, a food-grade cellulase, and to purify fucoidan by DEAE-cellulose anion exchange chromatography. The apoptotic and antiproliferative properties of the purified fucoidan (F5) were evaluated on HL-60 and MCF-7 cells. Structural features were characterized by FTIR and NMR analysis. F5 indicated profound antiproliferative effects on HL-60 leukemia and MCF-7 breast cancer cells with IC50 values of 84.63 ± 0.08 µg mL−1 and 93.62 ± 3.53 µg mL−1 respectively. Further, F5 treatment increased the apoptotic body formation, DNA damage, and accumulation of HL-60 and MCF-7 cells in the Sub-G1 phase of the cell cycle. The effects were found to proceed via the mitochondria-mediated apoptosis pathway. The Celluclast assisted extraction is a cost-efficient method of yielding fucoidan. With further studies in place, purified fucoidan of S. polycystum could be applied as functional ingredients in food and pharmaceuticals. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessArticle
Improvement of Psoriasis by Alteration of the Gut Environment by Oral Administration of Fucoidan from Cladosiphon Okamuranus
Mar. Drugs 2020, 18(3), 154; https://doi.org/10.3390/md18030154 - 10 Mar 2020
Abstract
Psoriasis is a chronic autoimmune inflammatory disease for which there is no cure; it results in skin lesions and has a strong negative impact on patients’ quality of life. Fucoidan from Cladosiphon okamuranus is a dietary seaweed fiber with immunostimulatory effects. The present [...] Read more.
Psoriasis is a chronic autoimmune inflammatory disease for which there is no cure; it results in skin lesions and has a strong negative impact on patients’ quality of life. Fucoidan from Cladosiphon okamuranus is a dietary seaweed fiber with immunostimulatory effects. The present study reports that the administration of fucoidan provided symptomatic relief of facial itching and altered the gut environment in the TNF receptor-associated factor 3-interacting protein 2 (Traf3ip2) mutant mice (m-Traf3ip2 mice); the Traf3ip2 mutation was responsible for psoriasis in the mouse model used in this study. A fucoidan diet ameliorated symptoms of psoriasis and decreased facial scratching. In fecal microbiota analysis, the fucoidan diet drastically altered the presence of major intestinal opportunistic microbiota. At the same time, the fucoidan diet increased mucin volume in ileum and feces, and IgA contents in cecum. These results suggest that dietary fucoidan may play a significant role in the prevention of dysfunctional immune diseases by improving the intestinal environment and increasing the production of substances that protect the immune system. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessArticle
Comparative Study of Fucoidan from Saccharina japonica and Its Depolymerized Fragment on Adriamycin-Induced Nephrotic Syndrome in Rats
Mar. Drugs 2020, 18(3), 137; https://doi.org/10.3390/md18030137 - 27 Feb 2020
Abstract
Nephrotic syndrome (NS) is a clinical syndrome with a variety of causes, mainly characterized by heavy proteinuria, hypoalbuminemia, and edema. At present, identification of effective and less toxic therapeutic interventions for nephrotic syndrome remains to be an important issue. In this study, we [...] Read more.
Nephrotic syndrome (NS) is a clinical syndrome with a variety of causes, mainly characterized by heavy proteinuria, hypoalbuminemia, and edema. At present, identification of effective and less toxic therapeutic interventions for nephrotic syndrome remains to be an important issue. In this study, we isolated fucoidan from Saccharina japonica and prepared its depolymerized fragment by oxidant degradation. Fucoidan and its depolymerized fragment had similar chemical constituents. Their average molecular weights were 136 and 9.5 kDa respectively. The effect of fucoidan and its depolymerized fragment on adriamycin-induced nephrotic syndrome were investigated in a rat model. The results showed that adriamycin-treated rats had heavy proteinuria and increased blood urea nitrogen (BUN), serum creatinine (SCr), total cholesterol (TC), and total triglyceride (TG) levels. Oral administration of fucoidan or low-molecular-weight fucoidan for 30 days could significantly inhibit proteinuria and decrease the elevated BUN, SCr, TG, and TC level in a dose-dependent manner. At the same dose (100 mg/kg), low-molecular-weight fucoidan had higher renoprotective activity than fucoidan. Their protective effect on nephrotic syndrome was partly related to their antioxidant activity. The results suggested that both fucoidan and its depolymerized fragment had excellent protective effect on adriamycin-induced nephrotic syndrome, and might have potential for the treatment of nephrotic syndrome. Full article
(This article belongs to the Special Issue Fucoidans)
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Review

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Open AccessReview
Brown Seaweed Fucoidan in Cancer: Implications in Metastasis and Drug Resistance
Mar. Drugs 2020, 18(5), 232; https://doi.org/10.3390/md18050232 - 28 Apr 2020
Cited by 1
Abstract
Fucoidans are sulphated polysaccharides that can be obtained from brown seaweed and marine invertebrates. They have anti-cancer properties, through their targeting of several signaling pathways and molecular mechanisms within malignant cells. This review describes the chemical structure diversity of fucoidans and their similarity [...] Read more.
Fucoidans are sulphated polysaccharides that can be obtained from brown seaweed and marine invertebrates. They have anti-cancer properties, through their targeting of several signaling pathways and molecular mechanisms within malignant cells. This review describes the chemical structure diversity of fucoidans and their similarity with other molecules such as glycosaminoglycan, which enable them to participation in diverse biological processes. Furthermore, this review summarizes their influence on the development of metastasis and drug resistance, which are the main obstacles to cure cancer. Finally, this article discusses how fucoidans have been used in clinical trials to evaluate their potential synergy with other anti-cancer therapies. Full article
(This article belongs to the Special Issue Fucoidans)
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Open AccessReview
Fucoidans: Downstream Processes and Recent Applications
Mar. Drugs 2020, 18(3), 170; https://doi.org/10.3390/md18030170 - 18 Mar 2020
Cited by 1
Abstract
Fucoidans are multifunctional marine macromolecules that are subjected to numerous and various downstream processes during their production. These processes were considered the most important abiotic factors affecting fucoidan chemical skeletons, quality, physicochemical properties, biological properties and industrial applications. Since a universal protocol for [...] Read more.
Fucoidans are multifunctional marine macromolecules that are subjected to numerous and various downstream processes during their production. These processes were considered the most important abiotic factors affecting fucoidan chemical skeletons, quality, physicochemical properties, biological properties and industrial applications. Since a universal protocol for fucoidans production has not been established yet, all the currently used processes were presented and justified. The current article complements our previous articles in the fucoidans field, provides an updated overview regarding the different downstream processes, including pre-treatment, extraction, purification and enzymatic modification processes, and shows the recent non-traditional applications of fucoidans in relation to their characters. Full article
(This article belongs to the Special Issue Fucoidans)
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