Fucoidan Fractions Research Articles

Size-dependent pharmacological activities of differently degraded fucoidan fractions from Fucus vesiculosus

Fucose-containing sulfated glycans (syn. fucoidans) from brown algae exhibit a wide range of bioactivities and are therefore considered promising candidates for health-supporting and medical applications. In this study, we investigated the pharmacological activities of fucoidan from Fucus vesiculosus and 18 gradually depolymerized fractions, which were obtained by hydrothermal and H2O2 treatment, respectively. All the activities decreased with decreasing molecular mass (Mw) but to a different extent resulting in some modified pharmacological profiles in dependence on the Mw as well as on the degradation method. H2O2 treatment was not only more efficient, simpler and cheaper than hydrothermal degradation, but also led to superior activity profiles and additionally eliminated co-extracted contaminants. Compared to heparin, the prime example of biologically active sulfated glycans, evenly sized H2O2 fractions exhibited considerable effects being relevant for anti-inflammatory activity, however only negligible anticoagulant activity and FXII activating potency. Due to their improved biopharmaceutical characteristics and favorable activities, degraded fucoidan fractions are worth to be further investigated as anti-inflammatory and anticomplementary agents.

Structural characteristics and anticancer activity in vitro of fucoidan from brown alga Padina boryana

The sulfated and acetylated fucoidan fraction, containing fucose, galactose, mannose, glucose and uronic acid residues, was isolated from the brown alga Padina boryana. The structure of galactofucan part was studied after different modifications by NMR spectroscopy and mass spectrometry. It was shown that galactofucan contained the main chain of alternating 1,4-linked α-l-fucopyranose and 1,3-linked β-d-Galactopyranose. Single fucose residues were found as branches at C4 of galactose residues. Also, fucoidan contained 1,3- or 1,4-linked Fuc-Fuc and Gal-Gal fragments. The sulfate groups occupied positions C2, C3 and C4 of both fucose and galactose residues, which was shown by tandem mass spectrometry of fragments, labeled with heavy-oxygen. The anticancer effect of native and modified fucoidan fractions was studied in vitro on the colorectal carcinoma cells DLD-1 and HCT-116. All fucoidans had no cytotoxicity under 400 μg/mL and inhibited colony formation of cancer cells at concentration of 200 μg/mL.

Ultrasound-assisted extraction of polysaccharides from brown alga Fucus evanescens. Structure and biological activity of the new fucoidan fractions.

The application of an ultrasound-assisted extraction method, combined with ion-exchange chromatography, has allowed separation of the total fucoidan fraction (F1) from the brown alga Fucus evanescens into two fractions, F2 and F3, in the ratio 1:0.2. The traditionally extracted F1 differs from F3 only by the acetate groups at C3 being somewhat predominant. F2 is described as having acetate groups located chaotically, and contains galactose and xylose residues, in addition to fucose. F3 consists of fucose residues acetylated almost exclusively at C3. Therefore, with ultrasound-assisted extraction from the brown alga Fucus evanescens, a new regular 1 → 3;1 → 4-α-L-fucan was obtained. It is sulphated at C2 and acetylated at C3 of the fucose residue and showed anticancer activity in vitro towards human colon carcinoma cells comparable to the total fraction F1.

STUDIES ON FUCOIDAN AND ITS PRODUCTION FROM VIETNAMESE BROWN SEAWEEDS

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.

Comparative study of the effect of different fucoidans from Sargassum maclurei and Saccharina japonica on FGFs/FGFR signaling activation in BaF3 cells

Different sulfated polysaccharides have distinct abilities to activate specific fibroblast growth factor (FGF) signaling pathways in FGFR1c-expressing BaF3 cells. In the current study, we first isolated and characterized different fucoidan fractions from Sargassum maclurei and Saccharina japonica. All of the fucoidan fractions were incubated with BaF3 cells in the presence of FGF-1, -2, -7, -8, -9, and -10, respectively, to evaluate their FGFs/FGFR1c signal-activating ability. Our data showed that low molecular weight fucoidan fraction from S. japonica with highest sulfate content (LMWF-2M) had the most potent activity among all of the six tested FGFs. Low sulfated heteropolysacchairde fraction LMWF-0.5M, along with SMP-1, SMP-D-1, and SMP-A-1, only activated the FGF-2/FGFR1c pair (P<0.05). In contrast, SMP, SMP-A, and SMP-D stimulated BaF3 cell proliferation except for FGF-8. Both LMWF-1M and LMWF-2M facilitated FGF-1-, -2-, -8-, and -9-based signaling. The sulfate content was the major contributing factor to the observed activity followed by the molecular weight. The monosaccharide composition also affected the activity, in that SMP and its derivatives with varied monosaccharide composition could not induce BaF3 cell proliferation in the presence of FGF-8. The structure-activity relationships revealed in current study provided useful information for the potential application of fucoidans in FGF/FGFR signaling regulation.

The structure property and endothelial protective activity of fucoidan from Laminaria japonica

Four antithrombotic fucoidan fractions F1, F2, LF1, and LF2 with different monosaccharide composition, molecular weight, and degree of sulfation and sulfate position were prepared from Laminaria japonica by hot water extraction and radical degradation. Their endothelial protective activity and possible action mechanism were studied using both cell- and rat-based models systematically. By comparison, the low molecular weight (LMW) fucoidan LF1 and LF2 were more potent than the medium molecular weight (MMW) fucoidan F1 and F2 in endothelial protection, down-regulation of von Willebrand Factor, CD31 and CD51 expressing endothelial microparticles in adrenalin-induced arterial endothelial injury rats and human umbilical vein endothelial cell system. However, the highly sulfated fucoidan fractions F2 and LF2 were better at inducing FGFR1c-expressing BaF3 cell proliferation in the presence of FGF-1, -2, -7, -8, -9 or -10. These results indicated that the chemical property of fucoidan was correlated to its specific biological activity tested. Therefore, defying fucoidan’s monosaccharide composition, molecular weight, and degree of sulfation might be important in developing it into a medicine.

A fucoidan fraction purified from Chnoospora minima; a potential inhibitor of LPS-induced inflammatory responses

Fucoidans are an interesting group of bioactive sulfated polysaccharides abundant in brown seaweeds. The current study highlights the enrichment and extraction of fucoidan from Chnoospora minima by means of enzyme-assistant extraction using Celluclast and evaluation of its anti-inflammatory potential through in vitro and in vivo studies. The purified C. minima fucoidan (F2,4) inhibited the nitrous oxide (NO) production (IC50=27.82±0.88μg/ml) and expression of PGE2 through the subsequent downregulation of iNOS and COX-2 expression in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophages. F2,4 downregulated TNF-α, IL1-β, and IL-6 in RAW 264.7 macrophages in a dose-dependent manner and suppressed NO and ROS production in LPS stimulated zebrafish embryos while exerting a protective effect against the cell damage caused by LPS. Polysaccharide structural characterization was performed using FTIR, HPAE-PAD analysis of the monosaccharide content and NMR spectroscopy. Current findings confirm the potential anti-inflammatory activity of fucoidan purified from C. minima and elaborate its potential application as a functional ingredient in consumer products.

Structural Characteristics and Antitumor Activity of Fucoidans from the Brown Alga Sargassum muticum

Water-soluble polysaccharides from two specimens of brown alga Sargassum muticum (April 2014 and June 2015), which synthesized heterogeneous sulfated fucoidans, were isolated and studied. Both specimens produced insignificant amounts of laminarans. Two of three fucoidan fractions from alga collected in April contained mannogalactofucans; one, galactofucan (Fuc–Gal, 2:1). The alga specimen collected in June afforded two galactofucans of different structures (Fuc–Gal, 1:1 and 3:1). Studies of the antitumor activity of the obtained fucoidans and their modified derivatives showed a lack of cytotoxicity and the manifestation of activity against DLD-1 human colon carcinoma cells.

Polysaccharides of algae 68. Sulfated polysaccharides from the Kamchatka brown alga Laminaria bongardiana

Several fucoidan fractions were isolated from the biomass of the Kamchatka brown alga Laminaria bongardiana by hot water extraction followed by anion-exchange chromatography. Fucoidans were found to be composed of l-fucose, d-galactose, and sulfate as the major components, whereas d-xylose, d-mannose, d-glucuronic acid, and acetate were detected as the minor constituents. Highly sulfated fucoidan fractions F-2 and F-3 were solvolytically desulfated by heating in dimethyl sulfoxide in the presence of pyridine. The structures of native and desulfated polysaccharides were investigated by the methylation analysis and NMR spectroscopy. It was shown that F-2 contains fucan sulfate, the backbone of which is made of 1→3-linked α-l-fucopyranose residues with single α-l-Fucp branches at positions 2 and sulfate groups predominantly at positions 4. Sulfated fucoglucuronomannan, fucoglucuronan, and fucogalactan were detected in F-2 as concomitant polysaccharides. Fucan sulfate and sulfated fucogalactan were the major components of the fraction F-3. The anticoagulant properties of fucoidan fractions were assessed. It was demonstrated that the activity of the fraction F-3 is comparable with that of low-molecular-weight heparin (enoxaparin), whereas the activity of total fucoidan F and the fraction F-2 is ~2/3 and ~1/2, respectively, of the activity of F-3, which is in accordance with the lower sulfate content in these samples. Desulfated preparations F-2deS and F-3deS were completely devoid of anticoagulant activity.

Extraction, fractionation, and chemical characterisation of fucoidans from the brown seaweed Sargassum pallidum

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.

Identification of a Pro-Angiogenic Potential and Cellular Uptake Mechanism of a LMW Highly Sulfated Fraction of Fucoidan from Ascophyllum nodosum.

Herein we investigate the structure/function relationships of fucoidans from Ascophyllum nodosum to analyze their pro-angiogenic effect and cellular uptake in native and glycosaminoglycan-free (GAG-free) human endothelial cells (HUVECs). Fucoidans are marine sulfated polysaccharides, which act as glycosaminoglycans mimetics. We hypothesized that the size and sulfation rate of fucoidans influence their ability to induce pro-angiogenic processes independently of GAGs. We collected two fractions of fucoidans, Low and Medium Molecular Weight Fucoidan (LMWF and MMWF, respectively) by size exclusion chromatography and characterized their composition (sulfate, fucose and uronic acid) by colorimetric measurement and Raman and FT-IR spectroscopy. The high affinities of fractionated fucoidans to heparin binding proteins were confirmed by Surface Plasmon Resonance. We evidenced that LMWF has a higher pro-angiogenic (2D-angiogenesis on Matrigel) and pro-migratory (Boyden chamber) potential on HUVECs, compared to MMWF. Interestingly, in a GAG-free HUVECs model, LMWF kept a pro-angiogenic potential. Finally, to evaluate the association of LMWF-induced biological effects and its cellular uptake, we analyzed by confocal microscopy the GAGs involvement in the internalization of a fluorescent LMWF. The fluorescent LMWF was mainly internalized through HUVEC clathrin-dependent endocytosis in which GAGs were partially involved. In conclusion, a better characterization of the relationships between the fucoidan structure and its pro-angiogenic potential in GAG-free endothelial cells was required to identify an adapted fucoidan to enhance vascular repair in ischemia.

Mechanism study of endothelial protection and inhibits platelet activation of low molecular weight fucoidan from Laminaria japonica

Several studies have indicated that fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica could inhibit the activation of platelets directly by reducing the platelet aggregation. To explore the direct effect of LMW fucoidan on the platelet system furthermore and examine the possible mechanism, the endothelial protection and inhibits platelet activation effects of two LMW fucoidan were investigated. In the present study, Endothelial injury model of rats was made by injection of adrenaline (0.4 mg kg−1) and human umbilical vein endothelial cells were cultured. vWF level was be investigated in vivo and in vitro as an important index of endothelial injury. LMW fucoidan could significantly reduce vWF level in vascular endothelial injury rats and also significantly reduce vWF level in vitro. The number of EMPs was be detected as another important index of endothelial injury. The results showed that LMW fucoidan reduced EMPs stimulated by tumor necrosis factor. In this study, it was found that by inhibiting platelet adhesion, LMW fucoidan played a role in anti-thrombosis and the specific mechanism of action is to inhibit the flow of extracellular Ca2+. All in a word, LMW fucoidan could inhibit the activation of platelets indirectly by reducing the concentration of EMPs and vWF, at the same time; LMW fucoidan inhibited the activation of platelets directly by inhibiting the flow of extracellular Ca2+.

Fucoidans from Brown Alga Fucus evanescens: Structure and Biological Activity

Brown alga Fucus evanescens, widespread in the Far Eastern seas of Russia, is valuable source of sulfated polysaccharides – fucoidans with beneficial biological activities. The most homogenous fraction of fucoidan from F. evanescens was shown to be molecule containing linear main chain of alternating 2-sulfated 1,3- and 1,4-linked α-L-fucose residues. Few sulfate groups were found in position 4 of some 1,3-linked fucose residues. Acetyl groups occupied free C-3 of 1,4-linked residues and/or the C-4 of 1,3-linked fucose residues. Enzymatic hydrolysis, mild acid hydrolysis and autohydrolysis of native fucoidan were used for elucidation of the fine structural characteristics of fucoidan from F. evanescens. The aim of this review to summarize published data on biological activities of fucoidan from F. evanescens: antiviral, anticoagulant, thrombolytic, hepatoprotective, immunomodulatory, anticancer, and their practical application.

Fucoidans in Nanomedicine.

Fucoidans are widespread cost-effective sulfated marine polysaccharides which have raised interest in the scientific community over last decades for their wide spectrum of bioactivities. Unsurprisingly, nanomedicine has grasped these compounds to develop innovative therapeutic and diagnostic nanosystems. The applications of fucoidans in nanomedicine as imaging agents, drug carriers or for their intrinsic properties are reviewed here after a short presentation of the main structural data and biological properties of fucoidans. The origin and the physicochemical specifications of fucoidans are summarized in order to discuss the strategy of fucoidan-containing nanosystems in Human health. Currently, there is a need for reproducible, well characterized fucoidan fractions to ensure significant progress.

The comparison of structure and anticancer activity in vitro of polysaccharides from brown algae Alaria marginata and A. angusta

Laminaran and three fucoidan fractions were obtained from the brown alga Alaria marginata. Alaria angusta, studied earlier by us, has the same polysaccharide composition. Galactofucan AmF3 from A. marginata has a main chain of →3)-α-l-Fucp-(2,4-SO3−)-(1→residues, similar to galactofucan from A. angusta. However, the structure of the branches in fucoidan AmF3 can differ from those in the fucoidan from A. angusta. The following fragments were identified in AmF3: HexA-(1→2)-Fuc, HexA-(1→2)-Gal, Gal-(1→4)-HexA, Fuc-(1→2)-Gal-6-SO3−, Fuc-4-SO3−-(1→6)-Gal, Gal-(1→2)-Gal-2-SO3−, Gal-4-SO3−-(1 →6)-Gal, Gal-4-SO3−-(1→3)-Fuc-(1→3)-Fuc, Fuc-4-SO3−-(1→6)-Gal-(1→4)-Gal, Gal-(1→4)-Gal-(1→3)-Fuc, Gal-2-SO3−-(1→4)-Gal-(1→4)-Gal, Gal-(1→4)-Gal-6-SO3−-(1→2)-Gal. Chains of galactose residues (DP up to 9) were found in AmF3 fucoidan. The laminarans, galactofucans and their derivatives from both algae exhibited no cytotoxicity in vitro. Polysaccharides from A. angusta were more effective against colony formation of HT-29 cells, while those from A. marginata had a greater effect on T-47D cells. Sulfated and desulfated fucoidans possessed weak antitumor activity using SK-MEL-28 cells.

Antithrombotic activity of oral administered low molecular weight fucoidan from Laminaria Japonica

IntroductionFucoidans extracted from brown algae have been documented to have excellent antithrombotic activity when administered by either intravenous or subcutaneous route in animal models. However, it is unknown if the fucoidans also have antithrombotic activity when administered orally, a highly desirable feature of oral antithrombotic agents. In the present study, we compared the oral absorption, bioavailability and antithrombotic activity of two fucoidan fractions from Laminaria japonica with different molecular weight by oral administration in an electricity induced arterial thrombosis model and the underlying molecular mechanisms. Results and conclusionsAfter a single dose of oral administration, the fucoidan content in plasma and urine in rats was assessed using the reverse-phased HPLC analysis of 1-phenyl-3-methyl-5-pyrazolone (PMP)-labeled fucose. The fucose content in the low molecular weight (LMW) fucoidan-treated rats increased up to 2-fold and peaked at 15h, indicating that the LMW fucoidan had much better absorption and bioavailability than the MMW fucoidan in vivo. Oral administration of the LMW fucoidan at 400 and 800mg/kg for 30days inhibited the arterial thrombosis formation effectively induced by electrical shock in rats, accompanied by moderate anticoagulation activity, regulation on TXB2 and 6-keto-PGF1α, significant antiplatelet activity and effective fibrinolysis. The LMW fucoidan showed better oral absorption and antithrombotic activity in addition to different antithrombotic mechanisms compared to those of the medium molecular weight (MMW) fucoidan. Thus, the LMW fucoidan has a potential to become an oral antithrombotic agent.

In vitro anti-HIV-1 activity of fucoidan from Sargassum swartzii

Sargassum swartzii, a marine brown algae with wide range of biological properties belongs to the family Sargassaceae. Bioactive fucoidan fractions (CFF, FF1 and FF2) were isolated from S. swartzii and characterized by linear gradient anion-exchange chromatography and FT-IR. The characterized fucoidan fractions contained mainly sugars, sulfate and uronic acid. In the present study, anti-HIV-1 property of the fucoidan fractions was investigated. Fraction FF2 was found to exhibit significant anti-HIV-1 activity at concentrations of 1.56 and 6.25μg/ml as observed by >50% reduction in HIV-1 p24 antigen levels and reverse transcriptase activity. Fucoidan fractions have no cytotoxic effects on PBMCs at the concentration range of 1.56–1000μg/ml. These results suggest that fucoidan fractions could have inhibitory activity against HIV and has potential as an anti-HIV-1 agent.

Abstract 5508: Fucoidan from Turbinaria conoides attenuates pancreatic cancer progession by regulating p53 - NFκB crosstalk

Abstract Poor prognosis of pancreatic cancer (PC) has been attributed to its resistance to apoptosis and propensity for early systemic dissemination. Existing therapeutic strategies are often circumvented by the molecular crosstalk between cell signaling pathways. The fact that p53 is mutated in more than 50% of PC tissues and NFκB is constitutively activated in therapy resistant residual PC accounts for the evaded cell death and dissemination. In this study, we examined the benefit of fucoidan from a marine brown alga, Turbinaria conoides against PC progression. Five fractions of fucoidan isolated and fractionated using ion exchange chromatography were tested for their potential in this setting using two (MiaPaCa-2, Panc-1) genetically diverse human PC cell-lines. All fractions investigated exerted significant dose dependent and time dependent regulation of cell survival. Coherently, fucoidans induced apoptosis and activated caspase -3, -8 and -9 and cleaved PARP. Pathway-specific transcriptional analysis (QPCR profiling) recognized inhibition of 57 and 38 NFκB pathway molecules with fucoidan-F5 in MiaPaCa-2 and Panc-1 cells, respectively. In addition, fucoidan-F5 was also found to inhibit both the constitutive and TNFα mediated NFκB DNA-binding activity (EMSA) in PC cells. Upregulation of cytoplasmic IκB levels and significant reduction of NFκB dependent luciferase activity further substantiate inhibitory potential of seaweed fucoidans on NF-κB. Moreover, fucoidan(s) treatment increases cellular p53 in PC cells. Together, the results suggests that fucoidan regulates PC progression and further imply that fucoidans may selectively target p53-NFκB crosstalk and dictate apoptosis in PC cells. Citation Format: Caroline R. Delma, Guru Prasad Srinivasan, Nune Raviprakash, Sunil K. Manna, Somasundaram T. Somasundaram, Natarajan Aravindan. Fucoidan from Turbinaria conoides attenuates pancreatic cancer progession by regulating p53 - NFκB crosstalk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5508. doi:10.1158/1538-7445.AM2015-5508

Structure and anticancer activity in vitro of sulfated galactofucan from brown alga Alaria angusta

Laminaran and three fractions of fucoidan were isolated from brown alga Alaria angusta. The laminaran AaL was characterized as a typical 1,3;1,6-β-D-glucan (ratio of bonds 1,3:1,6=10:1). Fucoidans AaF1 and AaF2 are sulfated heteropolysaccharides, containing fucose, galactose, mannose and xylose. The fraction AaF3 is sulfated and acetylated galactofucan with the main chain represented by a repeating unit →3)-α-L-Fucp-(2,4-SO3−)-(1→. According the data of methylation analysis, AaF3 contains mainly 1,3-linked fucose, less 1,4-linked and 1,4,6-linked galactose residues. The autohydrolysis (37°C) of fucoidan AaF3 allowed to obtain selectively 2-desulfaled polysaccharide fraction, built up of fucose only, and low molecular weight (LMW) fraction. The negative-ion tandem mass spectrometry of LMW fraction, further hydrolyzed by acid hydrolysis identified the following fragments: Gal-2-SO3−-(1→4)-Gal, Gal-4-SO3−-(1→4)-Gal, Gal-(1→2)-Gal-4-SO3−, Fuc-2-SO3−-(1→4)-Gal, Gal-2-SO3−-(1→3)-Fuc-(1→3)-Fuc, Fuc-2-SO3−-(1→3)-Fuc-(1→4)-Gal. The laminaran AaL and the fucoidan AaF3 exhibited no cytotoxicity in vitro for HT 29, T-47D, and SK-MEL-28 cell lines. The AaF3 fraction suppressed colony formation of HT 29 and T-47D cells, AaL—only HT 29 cells.

Valorization of Sargassum muticum Biomass According to the Biorefinery Concept.

The biorefinery concept integrates processes and technologies for an efficient biomass conversion using all components of a feedstock. Sargassum muticum is an invasive brown algae which could be regarded as a renewable resource susceptible of individual valorization of the constituent fractions into high added-value compounds. Microwave drying technology can be proposed before conventional ethanol extraction of algal biomass, and supercritical fluid extraction with CO2 was useful to extract fucoxanthin and for the fractionation of crude ethanol extracts. Hydrothermal processing is proposed to fractionate the algal biomass and to solubilize the fucoidan and phlorotannin fractions. Membrane technology was proposed to concentrate these fractions and obtain salt- and arsenic-free saccharidic fractions. Based on these technologies, this study presents a multipurpose process to obtain six different products with potential applications for nutraceutical, cosmetic and pharmaceutical industries.