Fucose-containing Sulfated Polysaccharides Research Articles

Antioxidant Fucoidans Obtained from Tropical Seaweed Protect Pre-Osteoblastic Cells from Hydrogen Peroxide-Induced Damage.

Some antioxidant compounds decrease the amount of intracellular reactive oxygen species (ROS) and consequently reduce the deleterious effects of ROS in osteoblasts. Thus, these compounds fight against osteoporosis. Brown seaweeds are a rich source of antioxidant fucose-containing sulfated polysaccharides (fucans and fucoidans). We obtained six fucoidans (FRFs)—F0.3, F0.5, F0.7, F1.0, F1.5, and F2.1—from Dictyota mertensii by proteolytic digestion followed by sequential acetone precipitation. Except for F0.3, all FRFs showed antioxidant activity in different in vitro tests. In pre- osteoblast-like cells (MC3T3-L1) exposed to H2O2-oxidative stress, caspase-3 and caspase-9 were activated, resulting in apoptosis of the cells. We also observed a decrease in superoxide dismutase (SOD) and alkaline phosphatase (ALP) activity. The antioxidant FRFs protected the cells from the oxidative damage caused by H2O2, decreasing intracellular ROS and caspase activation, and increasing SOD activity. The most effective protection against damage was provided by F0.7, F1.5, and F2.1. At 0.5 mg/mL, these FRFs also suppressed the H2O2-mediated inhibition of ALP activity. The data indicated that FRFs F0.7, F1.5, and F2.1 from D. mertensii were antioxidants that protected bone tissue from oxidative stress and could represent possible adjuvants for the treatment of bone fragility through counteracting oxidative phenomena.

Unravelling property of polysaccharides from Sargassum sp. as an anti-wrinkle and skin whitening property

In recent years, the natural ingredients are in high demand in formulating the cosmetic products. Seaweed polysaccharides signify the attractive natural ingredient with a wide range of functional properties that are expected for cosmeceutical formulations. The present work aimed to study the skin protection ability of polysaccharides extracted from Sargassum vachellianum (SvP), Sargassum horneri (ShoP) and Sargassum hemiphyllum (SheP). The extracted crude polysaccharides were characterized by HPLC and FTIR, which revealed that the polysaccharides are fucose-containing sulfated polysaccharides. Skin whitening and anti-wrinkling activity were analyzed by the ability to inhibit tyrosinase and elastase. The results revealed that the ShoP showed maximum tyrosinase inhibition (64.72 ± 0.46%) and SvP exhibited considerable elastase inhibition (30.12 ± 0.33%). The maximum moisture absorption (79.7 ± 0.62%) and retention (68.99 ± 0.64%) ability were observed in ShoP. The antioxidant activity was estimated by DPPH, superoxide radical scavenging, reducing power and total antioxidant activity. All the tested polysaccharides showed antioxidant activity in a dose-dependent manner, among them ShoP exhibited maximum total antioxidant (80.93 ± 0.17%) and superoxide radical scavenging activity (67.4 ± 0.42%) whereas SheP showed maximum DPPH radical scavenging activity (74.56 ± 0.10%). Therefore, the present study indicates the potential of polysaccharides, ShoP, SvP and SheP as a promising cosmetic ingredient in cosmeceuticals.

Isolation and purification of fucoidan fraction in Turbinaria ornata from the Maldives; Inflammation inhibitory potential under LPS stimulated conditions in in-vitro and in-vivo models.

Fucoidan, referred to as fucose containing sulfated polysaccharides (FCSP), is a polymer from brown algae cell wall that is reported to exhibit potential anti-inflammatory activity. In the present study, the fucoidans are extracted from Turbinaria ornata (TO) from the Maldives. The method involves enzyme assisted extraction and is modified in order to improve the effectiveness and purity of final product. Purified fucoidan fraction was identified as F10, and its chemical properties were verified via FTIR, 1H NMR and monosaccharide analysis. Selected inflammatory mediators were studied to evaluate the anti-inflammatory potential using RAW 264.7 macrophages. F10 successfully inhibited NO production (IC50 = 30.83 ± 1.02 μg mL-1). F10 dose-dependently down-regulated iNOS, COX-2, and pro-inflammatory cytokines including PGE2 levels. The in vivo experiments were assisted by zebrafish embryo model. This exhibited reduction in ROS, NO expression levels. To our knowledge, this is the first report to illustrate potential anti-inflammatory activity of FCSPs' extracted from the brown algae T. ornata. Concisely, the results suggest that fucoidan purified from T. ornata increases the macrophage cellular and zebrafish embryo resistance against LPS-induced inflammation. Based on the observations, the fucoidans are promising candidates to be used in the pharmaceutical and cosmeceutical sectors.

Evolutionary Evidence of Algal Polysaccharide Degradation Acquisition by Pseudoalteromonas carrageenovora 9T to Adapt to Macroalgal Niches.

About half of seaweed biomass is composed of polysaccharides. Most of these complex polymers have a marked polyanionic character. For instance, the red algal cell wall is mainly composed of sulfated galactans, agars and carrageenans, while brown algae contain alginate and fucose-containing sulfated polysaccharides (FCSP) as cell wall polysaccharides. Some marine heterotrophic bacteria have developed abilities to grow on such macroalgal polysaccharides. This is the case of Pseudoalteromonas carrageenovora 9T (ATCC 43555T), a marine gammaproteobacterium isolated in 1955 and which was an early model organism for studying carrageenan catabolism. We present here the genomic analysis of P. carrageenovora. Its genome is composed of two chromosomes and of a large plasmid encompassing 109 protein-coding genes. P. carrageenovora possesses a diverse repertoire of carbohydrate-active enzymes (CAZymes), notably specific for the degradation of macroalgal polysaccharides (laminarin, alginate, FCSP, carrageenans). We confirm these predicted capacities by screening the growth of P. carrageenovora with a large collection of carbohydrates. Most of these CAZyme genes constitute clusters located either in the large chromosome or in the small one. Unexpectedly, all the carrageenan catabolism-related genes are found in the plasmid, suggesting that P. carrageenovora acquired its hallmark capacity for carrageenan degradation by horizontal gene transfer (HGT). Whereas P. carrageenovora is able to use lambda-carrageenan as a sole carbon source, genomic and physiological analyses demonstrate that its catabolic pathway for kappa- and iota-carrageenan is incomplete. This is due to the absence of the recently discovered 3,6-anhydro-D-galactosidase genes (GH127 and GH129 families). A genomic comparison with 52 Pseudoalteromonas strains confirms that carrageenan catabolism has been recently acquired only in a few species. Even though the loci for cellulose biosynthesis and alginate utilization are located on the chromosomes, they were also horizontally acquired. However, these HGTs occurred earlier in the evolution of the Pseudoalteromonas genus, the cellulose- and alginate-related loci being essentially present in one large, late-diverging clade (LDC). Altogether, the capacities to degrade cell wall polysaccharides from macroalgae are not ancestral in the Pseudoalteromonas genus. Such catabolism in P. carrageenovora resulted from a succession of HGTs, likely allowing an adaptation to the life on the macroalgal surface.

Gradual degradation of fucoidan from Fucus vesiculosus and its effect on structure, antioxidant and antiproliferative activities

The fucose-containing sulfated polysaccharides (syn. fucoidans) from brown algae exhibit a wide range of bioactivities and are therefore considered promising candidates for health-supporting and medical applications. During the past three decades, research on isolation, molecular characterization, and screening of in vitro and in vivo pharmacological activities has significantly increased. Until now, however, fucoidans are only used as ingredients in cosmetics and food supplements, especially due to the proclaimed antioxidant activities of fucoidan. One obstacle to medical applications is the usually high molecular mass of native fucoidans, as it is associated with unfavorable biopharmaceutical properties and possibly undesired effects. Therefore, it seems reasonable to develop fucoidan derivatives with reduced size. So far, in this study, fucoidan from Fucus vesiculosus was gradually degraded from Mw 38.2 down to 4.9 kDa without concomitant desulfation. Compared to hydrothermal treatment, the degradation with H2O2 showed to be more efficient and additionally eliminated the antioxidant and antiproliferative activities of the genuine fucoidan. This confirmed our previous hypothesis that rather co-extracted compounds like terpenoids and polyphenols than the fucoidan itself exhibit these effects.

Compositional Characteristics and In Vitro Evaluations of Antioxidant and Neuroprotective Properties of Crude Extracts of Fucoidan Prepared from Compressional Puffing-Pretreated Sargassum crassifolium.

Fucoidan, a fucose-containing sulfated polysaccharide with diverse biological functions, is mainly recovered from brown algae. In this study, we utilized a compressional-puffing process (CPP) to pretreat Sargassum crassifolium (SC) and extracted fucoidans from SC by warm water. Three fucoidan extracts (SC1: puffing at 0 kg/cm2; SC2: puffing at 1.7 kg/cm2; and SC3: puffing at 6.3 kg/cm2) were obtained, and their composition, and antioxidant and neuroprotective activities were examined. The results suggest that CPP decreased the bulk density of algal samples, expanded the algal cellular structures, and eliminated the unpleasant algal odor. The extraction yields of fucoidans were increased and impurities of fucoidans were decreased by increasing the pressures used in CPP. The SC1–SC3 extracts displayed various characteristics of fucoidan as illustrated by the analyses of composition, Fourier transform infrared (FTIR) spectroscopy, and molecular weight. All three extracts SC1–SC3 showed antioxidant activity dose-dependently. Although both SC1 and SC2 possessed high and similar neuronal protective properties, SC2 showed a higher extraction yield, higher efficacy in the reversion of H2O2-induced cytotoxicity in rat pheochromocytoma PC-12 cells, and lower impurities compared with SC1, and thus SC2 is suggested as a good candidate for a therapeutic agent in the preventive treatment of neurodegenerative diseases.

Insoluble (1\u2009\u2192\u20093), (1\u2009\u2192\u20094)-\u03b2-D-glucan is a component of cell walls in brown algae (Phaeophyceae) and is masked by alginates in tissues

Brown algae are photosynthetic multicellular marine organisms. They belong to the phylum of Stramenopiles, which are not closely related to land plants and green algae. Brown algae share common evolutionary features with other photosynthetic and multicellular organisms, including a carbohydrate-rich cell-wall. Brown algal cell walls are composed predominantly of the polyanionic polysaccharides alginates and fucose-containing sulfated polysaccharides. These polymers are prevalent over neutral and crystalline components, which are believed to be mostly, if not exclusively, cellulose. In an attempt to better understand brown algal cell walls, we performed an extensive glycan array analysis of a wide range of brown algal species. Here we provide the first demonstration that mixed-linkage (1 → 3), (1 → 4)-β-d-glucan (MLG) is common in brown algal cell walls. Ultra-Performance Liquid Chromatography analyses indicate that MLG in brown algae solely consists of trisaccharide units of contiguous (1 → 4)-β-linked glucose residues joined by (1 → 3)-β-linkages. This regular conformation may allow long stretches of the molecule to align and to form well-structured microfibrils. At the tissue level, immunofluorescence studies indicate that MLG epitopes in brown algae are unmasked by a pre-treatment with alginate lyases to remove alginates. These findings are further discussed in terms of the origin and evolution of MLG in the Stramenopile lineage.

Effects of fucoidans and heparin on reactions of neutrophils induced by IL-8 and C5a

Fucose-containing sulfated polysaccharides (fucoidans) from brown algae exhibit anti-inflammatory activity in vivo, however, there is only limited knowledge about their mode of action. Potential targets may be the chemokine interleukin 8 (IL-8) and the anaphylatoxin C5a, as they are closely linked to inflammatory processes. In this study, two fucoidans from Saccharina latissima and Fucus vesiculosus, and unfractionated heparin (UFH) were examined for their binding properties to IL-8 and C5a and their effects on IL-8- and C5a-induced reactions of polymorphonuclear neutrophils (PMN).As proved by a competitive sulfated polysaccharide-coating-ELISA, both fucoidans bind to IL-8 and C5a, whereby they showed higher affinity to IL-8. Whereas UFH displayed only moderate effects, the fucoidans concentration-dependently reduced the IL-8- and C5a-induced intracellular calcium release, Erk1/2 phosphorylation and chemotaxis of PMN. Their inhibitory potency is dependent on the target protein, but also other aspects than the binding turned out to play a role.

Seasonal variations in the fucoidan content of brown algae from Peter the Great Bay, Sea of Japan

The seasonal dynamics in the level of fucose-containing sulfated polysaccharides (fucoidans) have been studied in three brown alga species from Peter the Great Bay, Sea of Japan: Saccharina japonica, Sargassum pallidum, and Stephanocystis crassipes. In the latter two species, seasonal variations in the fucoidan content have been analyzed for the first time. During the year, the level of fucoidan in S. japonica varied from 0.98 to 4.19% dry weight; in S. crassipes, from 2.50 to 5.23%; in S. pallidum, from 1.86 to 6.31%. The maximum amount of this polysaccharide is accumulated in algae during reproduction: in August–October for S. japonica; in June and July for S. crassipes; and in July for S. pallidum. No significant correlation has been found between the level of fucoidan in algal tissues and the annual dynamics in sea water temperature, salinity, and concentration of biogenic elements. The obtained data can be helpful in determining the time to harvest algae for fucoidan extraction.

Antioxidant activity and growth inhibition of human colon cancer cells by crude and purified fucoidan preparations extracted from Sargassum cristaefolium

Fucose-containing sulfated polysaccharides, also termed “fucoidans”, which are known to possess antioxidant, anticoagulant, anticancer, antiviral, and immunomodulating properties, are normally isolated from brown algae via various extraction techniques. In the present study, two methods (SC1 and SC2) for isolation of fucoidan from Sargassum cristaefolium were compared, with regard to the extraction yields, antioxidant activity, and inhibition of growth of human colon cancer cells exhibited by the respective extracts. SC1 and SC2 differ in the number of extraction steps and concentration of ethanol used, as well as the obtained sulfated polysaccharide extracts, namely, crude fucoidan preparation (CFP) and purified fucoidan preparation (PFP), respectively. Thin layer chromatography, Fourier transform infrared analysis, and measurements of fucose and sulfate contents revealed that the extracts were fucoidan. There was a higher extraction yield for CFP, which contained less fucose and sulfate but more uronic acid, and had weaker antioxidant activity and inhibition of growth in human colon cancer cells. In contrast, there was a lower extraction yield for PFP, which contained more fucose and sulfate but less uronic acid, and had stronger antioxidant activity and inhibition of growth in human colon cancer cells. Thus, since the difference in bioactive activities between CFP and PFP was not remarkable, the high extraction yield of SC1 might be favored as a method in industrial usage for extracting fucoidan.

Fucoidans of brown algae: Biosynthesis, localization, and physiological role in thallus

The issues of the structure and biosynthesis of fucose-containing sulfated polysaccharides are considered in this review; the data on the localization of fucoidans in tissues and their significance for algae are provided. Fucoidans participate in the building of cell walls and the support of their structure, as well as in extrusion of spores and gametes from reproductive organs. Due to the sulfated groups, these polysaccharides can bind cations (mainly K+, Na+, Ca2+, Mg2+) and participate in ion exchange with the environment, which facilitates adaptation of algae to water salinity fluctuations and to the toxic effects of heavy metals. Fucoidans play a substantial role in morphogenesis of zygotes of fucoid algae, as they participate in establishing the cell polarity and fixing the cell-division axis, thus determining the direction for the development of the rhizoidal and apical poles of young thalli.

Interference with the CXCL12/CXCR4 axis as potential antitumor strategy: superiority of a sulfated galactofucan from the brown alga Saccharina latissima and fucoidan over heparins.

The present study demonstrates that fucose-containing sulfated polysaccharides (FCSP) from brown algae interfere with the CXCL12/CXCR4 axis in human Burkitt's lymphoma cells by binding CXCL12 and thereby blocking both CXCL12-induced CXCR4 receptor activation and downstream effects like migration and secretion of matrix metalloproteinase-9. This mode of action is currently considered as promising strategy for tumor therapy and may contribute to the known in vivo antitumor, antimetastatic and antiangiogenic activity of FCSP. In terms of the inhibition of the CXCR4 activation, FCSP from Saccharina latissima (S.l.-FCSP) proved to be more active than a commercial "Fucoidan" from Fucus vesiculosus, and both FCSP were superior to heparins by more than one order of magnitude. Fractionation of S.l.-FCSP revealed that its main fraction is composed of a homogeneous, higher sulfated galactofucan (S.l.-SGF) which consistently exhibited stronger activities and can therefore be considered as the active ingredient of S.l.-FCSP. By subjecting Fucoidan to the same fractionation procedure, the inhibitory activity of the obtained purified Fucoidan on the CXCL12/CXCR4 axis tended to be weaker and its antioxidant and antiproliferative effects were lost. This was probably due to the separation of contaminants including phenolic compounds, whose content additionally showed marked batch-to-batch variability. Regarding the need of standardized, well-characterized FCSP preparations for any potential medical application, our results indicate that S.l.-SGF is a promising candidate for further investigations and that S. latissima may be a more appropriate source of FCSP than F. vesiculosus or other algae species with high contents of co-extractable compounds.

Sulfated galactofucan from the brown alga Saccharina latissima--variability of yield, structural composition and bioactivity.

The fucose-containing sulfated polysaccharides (SP) from brown algae exhibit a wide range of bioactivities and are, therefore, considered promising candidates for health-supporting and medicinal applications. A critical issue is their availability in high, reproducible quality. The aim of the present study was to fractionate and characterize the SP extracted from Saccharina latissima (S.l.-SP) harvested from two marine habitats, the Baltic Sea and North Atlantic Ocean, in May, June and September. The fractionation of crude S.l.-SP by anion exchange chromatography including analytical investigations revealed that S.l.-SP is composed of a homogeneous fraction of sulfated galactofucan (SGF) and a mixture of low-sulfated, uronic acid and protein containing heteropolysaccharides. Furthermore, the results indicated that S.l. growing at an intertidal zone with high salinity harvested at the end of the growing period delivered the highest yield of S.l.-SP with SGF as the main fraction (67%). Its SGF had the highest degree of sulfation (0.81), fucose content (86.1%) and fucose/galactose ratio (7.8) and was most active (e.g., elastase inhibition: IC50 0.21 μg/mL). Thus, S.l. from the North Atlantic harvested in autumn proved to be more appropriate for the isolation of S.l.-SP than S.l. from the Baltic Sea and S.l. harvested in spring, respectively. In conclusion, this study demonstrated that habitat and harvest time of brown algae should be considered as factors influencing the yield as well as the composition and thus also the bioactivity of their SP.

Chemical and enzymatic fractionation of cell walls from Fucales: insights into the structure of the extracellular matrix of brown algae.

Brown algae are photosynthetic multicellular marine organisms evolutionarily distant from land plants, with a distinctive cell wall. They feature carbohydrates shared with plants (cellulose), animals (fucose-containing sulfated polysaccharides, FCSPs) or bacteria (alginates). How these components are organized into a three-dimensional extracellular matrix (ECM) still remains unclear. Recent molecular analysis of the corresponding biosynthetic routes points toward a complex evolutionary history that shaped the ECM structure in brown algae. Exhaustive sequential extractions and composition analyses of cell wall material from various brown algae of the order Fucales were performed. Dedicated enzymatic degradations were used to release and identify cell wall partners. This approach was complemented by systematic chromatographic analysis to study polymer interlinks further. An additional structural assessment of the sulfated fucan extracted from Himanthalia elongata was made. The data indicate that FCSPs are tightly associated with proteins and cellulose within the walls. Alginates are associated with most phenolic compounds. The sulfated fucans from H. elongata were shown to have a regular α-(1→3) backbone structure, while an alternating α-(1→3), (1→4) structure has been described in some brown algae from the order Fucales. The data provide a global snapshot of the cell wall architecture in brown algae, and contribute to the understanding of the structure-function relationships of the main cell wall components. Enzymatic cross-linking of alginates by phenols may regulate the strengthening of the wall, and sulfated polysaccharides may play a key role in the adaptation to osmotic stress. The emergence and evolution of ECM components is further discussed in relation to the evolution of multicellularity in brown algae.

Protective effect of polysaccharides from Sargassum horneri against oxidative stress in RAW264.7 cells

This study was designed to investigate chemical composition and the protective effects of polysaccharides isolated from Sargassum horneri against hydrogen peroxide (H2O2)-induced oxidative injury in RAW264.7 cells. Results showed that isolated polysaccharides (SHSc) and the major fractions (SHS1, SHS0.5) contained sulfate ester, and SHS1 was high fucose-containing sulfated polysaccharide. After preincubation with three isolated polysaccharides, RAW264.7 cells viability were significantly restored and decreased in cellular LDH release (P<0.05). SHS1 and SHS0.5 decreased intracellular ROS level, intracellular NO and malonic dialdehyde (MDA) level (P<0.05), restoring activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) (P<0.05), decreasing inducible nitric oxide synthase (iNOS) (P<0.05). Moreover, preincubation of SHS1 with RAW264.7 cells resulted in the increase of the gene expression level of endogenous antioxidant enzymes such as MnSOD and GSH-Px (P<0.05). These results clearly showed that SHSc and its fractions could attenuate H2O2-induced stress injury in RAW264.7 cells, and a similar efficiency in protecting RAW264.7 cells against H2O2-induced oxidative injury between SHS1 and Vitamin C. Taken together, our findings suggested that SHS1 can effectively protect RAW264.7 cells against oxidative stress by H2O2, which might be used as a potential natural antioxidant in the functional food and pharmaceutical industries.

Antioxidant activity of fucose-containing sulfated polysaccharides obtained from Fucus evanescens by different extraction methods

The fucose-containing sulfated polysaccharides (FCSPs) from Fucus evanescens were obtained via different procedures: by hot acidic extraction and with aqueous calcium chloride solution, followed by separation FCSPs using anion-exchanging chromatography. Chemical characteristics of these polysaccharide fractions were determined. It was shown that extraction with aqueous calcium chloride solution provides a purified preparation of the FCSPs. The crude polysaccharide and its chromatography purified fractions obtained by this method have significantly lower contents of laminaran, uronic acids, and polyphenols in comparison with FCSPs obtained by hot acid extraction. All polysaccharides exhibited total antioxidant capacity and 1,1-diphenyl-2-pycrilhydrazyl (DPPH) radical-scavenging activity and low 2,2′-azino-bis 3-ethyl benzothiazoline-6-sulfuric acid (ABTS) radical-scavenging activity. A strong positive correlation between polyphenol content in FCSPs and their antioxidant activity was found. This fact may indicate that phenols play a key role in the previously described antioxidant capacity of FCSPs.

Fucoidan as a Marine Anticancer Agent in Preclinical Development

Fucoidan is a fucose-containing sulfated polysaccharide derived from brown seaweeds, crude extracts of which are commercially available as nutritional supplements. Recent studies have demonstrated antiproliferative, antiangiogenic, and anticancer properties of fucoidan in vitro. Accordingly, the anticancer effects of fucoidan have been shown to vary depending on its structure, while it can target multiple receptors or signaling molecules in various cell types, including tumor cells and immune cells. Low toxicity and the in vitro effects of fucoidan mentioned above make it a suitable agent for cancer prevention or treatment. However, preclinical development of natural marine products requires in vivo examination of purified compounds in animal tumor models. This review discusses the effects of systemic and local administration of fucoidan on tumor growth, angiogenesis, and immune reaction and whether in vivo and in vitro results are likely applicable to the development of fucoidan as a marine anticancer drug.

Fucose-containing sulfated polysaccharides from brown macroalgae Lobophora variegata with antioxidant, anti-inflammatory, and antitumoral effects

This study analyzed sulfated polysaccharides, such as fucans, from the brown alga Lobophora variegata to verify their antioxidant activity in vitro, antitumoral effect on human colon adenocarcinoma cell line HT-29, and anti-inflammatory activity. Sulfated polysaccharide fractions containing fucans were obtained after fractionation with increasing volumes (v) of acetone (0.3–2.0 v). The polysaccharide was eluted with 1.5 v of acetone and named F1.5. The results showed that F1.5 contained a high yield. Chemical and structure analyses were performed by infrared spectroscopy, electrophoresis in agarose gel, and chemical dosages (sugar, protein, phenolic compounds, and sulfate). We observed that this sulfated polysaccharide had antioxidant activity and antitumoral effect. Anti-inflammatory activity in vivo of F1.5 was observed in the croton oil mouse-ear model at 75 mg kg-1. The results were correlated with histopathological analysis.

Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds Inhibit Proliferation of Melanoma Cells and Induce Apoptosis by Activation of Caspase-3 in Vitro

Fucose-containing sulfated polysaccharides (FCSPs) extracted from seaweeds, especially brown macro-algae, are known to possess essential bioactive properties, notably growth inhibitory effects on tumor cells. In this work, we conducted a series of in vitro studies to examine the influence of FCSPs products from Sargassum henslowianum C. Agardh (FSAR) and Fucus vesiculosus (FVES), respectively, on proliferation of melanoma B16 cells and to investigate the underlying apoptosis promoting mechanisms. Cell viability analysis showed that both FCSPs products, i.e., FSAR and FVES, decreased the proliferation of the melanoma cells in a dose-response fashion, with FSAR being more potent at lower dosages, and FVES being relatively more anti-proliferative than FSAR at higher dosages. Flow cytometric analysis by Annexin V staining of the melanoma cells exposed to the FCSPs products confirmed that both FSAR and FVES induced apoptosis. The FCSPs-induced apoptosis was evidenced by loss of plasma membrane asymmetry and translocation of the cell membrane phospholipids and was accompanied by the activation of caspase-3. The FCSPs bioactivity is proposed to be attributable to distinct structural features of the FCSPs, particularly the presence of sulfated galactofucans (notably in S. henslowianum) and sulfated fucans (notably in F. vesiculosus). This study thus indicates that unfractionated FCSPs may exert bioactive effects on skin cancer cells via induction of apoptosis through cascades of reactions that involve activation of caspase-3.

Important Determinants for Fucoidan Bioactivity: A Critical Review of Structure-Function Relations and Extraction Methods for Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds

Seaweeds—or marine macroalgae—notably brown seaweeds in the class Phaeophyceae, contain fucoidan. Fucoidan designates a group of certain fucose-containing sulfated polysaccharides (FCSPs) that have a backbone built of (1→3)-linked α-l-fucopyranosyl or of alternating (1→3)- and (1→4)-linked α-l-fucopyranosyl residues, but also include sulfated galactofucans with backbones built of (1→6)-β-d-galacto- and/or (1→2)-β-d-mannopyranosyl units with fucose or fuco-oligosaccharide branching, and/or glucuronic acid, xylose or glucose substitutions. These FCSPs offer several potentially beneficial bioactive functions for humans. The bioactive properties may vary depending on the source of seaweed, the compositional and structural traits, the content (charge density), distribution, and bonding of the sulfate substitutions, and the purity of the FCSP product. The preservation of the structural integrity of the FCSP molecules essentially depends on the extraction methodology which has a crucial, but partly overlooked, significance for obtaining the relevant structural features required for specific biological activities and for elucidating structure-function relations. The aim of this review is to provide information on the most recent developments in the chemistry of fucoidan/FCSPs emphasizing the significance of different extraction techniques for the structural composition and biological activity with particular focus on sulfate groups.