Fucoidan Fractions Research Articles

CTNI-83. PROPOSAL FOR A PILOT PHASE 1B CLINICAL TRIAL WITH ADDITION OF NATURAL MARINE PRODUCT FUCOIDAN TO ANTI-NEOPLASTIC THERAPY FOR PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM) TO IMPROVE FATIGUE AND OTHER HEALTH-RELATED QUALITY OF LIFE (HRQOL) SYMPTOMS

Abstract BACKGROUND Recurrent Glioblastoma (rGBM) has poor outcome with limited treatment options. rGBM causes significant fatigue and other health-related quality of life (HRQOL) symptoms secondary to tumor progression and anti-neoplastic therapies. More than 80% of brain tumor patients were found to experience fatigue during anti-neoplastic therapy and the incidence of cancer related fatigue may reach 89-94% among patients with rGBM. Therefore, improvement of fatigue and HRQOL in rGBM patients are crucial. Marine natural product, fucoidan, available as health supplement in the US, was found to play important roles in oncological management as supportive therapy against cancer and chemoradiation-related adverse effects and as a potential anti-neoplastic therapy. Fucoidan is a seaweed-derived sulfated polysaccharide. Data resulted from randomized clinical trials for colon, head and neck, and lung cancer patients suggest that fucoidan can improve cancer and chemotherapy or chemoradiation therapy related negative symptoms. In addition, Tachikawa et al. reported >50% tumor regression and increased natural killer (NK) cell activity in sarcoma-transplanted mice treated with Fucoidan. In Vitro anticancer investigation found that Fucoidan fractions clearly suppressed the growth of GBM U-251MG cancer cells. Multiple studies have also shown that fucoidan is tolerable with a good safety profile. METHOD 18 rGBM patients will be enrolled. Fucoidan based product will be administered orally at established dose for cancer patients daily with anti-neoplastic therapy over 6 months. Patients will be evaluated monthly for AEs and HRQOL score; laboratory and brain MRI monitoring will be performed per SOC guidelines. NK cell activity will be measured. POTENTIAL OUTCOME Fucoidan is safe and has good tolerability in combination with anti-neoplastic therapy for rGBM and improves fatigue and other HRQOL symptoms by ameliorating tumor progression and treatment related negative impact. Fucoidan may also improve survival in rGBM patients by improving the tolerability of anti-tumor therapy, augmenting cytotoxic effects, and inhibiting angiogenesis.

Brown algae of the White Sea as a promising source of fucoidan for increasing resistance in laying hens

The purpose of this study was to evaluate the effect of a feed additive from fucus algae on resistance indicators of laying hens in industrial poultry farming conditions. In the algae F. vesiculosus and A. Nodosum, it was revealed that the mass fraction of fucoidan in terms of a.d.w. is 3.92±0.12%.When assessing the effect of using a feed additive from fucus algae on resistance indicators of laying hens, it was revealed that it has an effect on white and red blood parameters, leukogram and phagocyte activity. In chickens of the experimental group, there was a tendency towards an increase in the number of erythrocytes, an increase in the color index, a tendency towards a decrease in the number of leukocytes relative to the increase in the control group, while the indicators were within the reference values, after 30 days of using the additive – in the experimental group the proportion of pseudoeosinovils increased by 50% and the proportion of lymphocytes decreased by 6% compared to the control group. After 60 days of using the supplement, this trend continues: the proportion of pseudoeosinophils increased by 22% and the proportion of lymphocytes decreased by 4% in the experimental group relative to the control group. In our opinion, this indicates a normalization of the ratio of leukocyte forms in the experimental group, and, consequently, the immune status. In addition, in the experimental group relative to the control group, there was a significant decrease in the number of eosinophils by 67%, which may indicate a lower allergic reaction of the body’s immune system. Indicators of blood phagocytosis significantly changed after 60 days of use: in the experimental group, phagocytic activity increased by 23%, which indicates a higher ability of leukocytes in the experimental group to absorb foreign bacteria, and, consequently, stronger cellular immunity compared to the control group. Thus, the use of a feed additive from fucus algae for laying hens containing fucoidan in an amount of 3.92±0.12% helps to normalize the ratio of leukocyte forms and increase blood phagocytosis rates, which significantly increases resistance in laying hens.

Physiochemical changes, metabolite discrepancies of brown seaweed-derived sulphated polysaccharides in the upper gastrointestinal tract and their effects on bioactive expression

Brown seaweed-derived polysaccharides, notably fucoidan and laminarin, are known for their extensive array of bioactivities and physicochemical properties. However, the effects of upper digestive tract modification on the bioactive performance of fucoidan and laminarin fractions (FLFs) sourced from Australian native species are largely unknown. Here, the digestibility and bioaccessibility of FLFs were evaluated by tracking the dynamic changes in reducing sugar content (CR), profiling the free monosaccharide composition using LC-MS, and comparing high-performance gel permeation chromatography profile variation via LC-SEC-RI. The effects of digestive progression on bioactive performance were assessed by comparing the antioxidant and antidiabetic potential of FLFs and FLF digesta. We observed that molecular weight (Mw) decreased during gastric digestion indicating that FLF aggregates were disrupted in the stomach. During intestinal digestion, Mw gradually decreased and CR increased indicating cleavage of glycosidic bonds releasing free sugars. Although the antioxidant and antidiabetic capacities were not eliminated by the digestion progression, the bioactive performance of FLFs under a digestive environment was reduced contrasting with the same concentration level of the undigested FLFs. These data provide comprehensive information on the digestibility and bioaccessibility of FLFs, and shed light on the effects of digestive progression on bioactive expression.

Anti-inflammatory activity and structural analysis of fucoidan extracted from Sargassum fusiforme via ESI-TOF MS spectrometry

This study used Celluclast-assisted hydrolysis and DEAE-cellulose anion-exchange chromatography to extract, purify, and assess the anti-inflammatory activity of fucoidan derived from Sargassum fusiforme. The Celluclast-assisted hydrolysate was used for obtaining ethanol-precipitated S. fusiforme fucoidans (SFF) which were rich in polysaccharides and sulfates. Five fractions obtained through DEAE-cellulose chromatography, notably SFF-F5, displayed high sulfate content (29.16 ± 0.15%). The anti-inflammatory potential of these fractions was tested in lipopolysaccharide-induced RAW 264.7 macrophages. SFF-F5 was found to significantly reduce NO production at non-toxic concentrations of 12.5, 25, and 50 μg/mL. Structural analysis using Matrix assisted laser desorption/ionization time-of flight mass spectrometry (MALDI-TOF MS) revealed repetitive patterns in the fucoidan fractions. And Electrospray ionization mass spectrometry (ESI-TOF MS) spectrum of SFF fractions identified various structures of glycans bound with fucose and sulfate (Fuc1(SO3)1, Fuc2(SO3)1, Hex5Fuc1(SO3)1). In-silico evaluation based on the detected glycan structures indicated that fucoidan fractions could inhibit the dimerization of the TLR4-MD2 complex, demonstrating their potential as anti-inflammatory agents. This result confirm that the anti-inflammatory activity varies depending on the glycan composition of fucoidan. This study provides a foundation for further exploration into the relationship between the structure and anti-inflammatory activity of S. fusiforme-derived fucoidan, facilitating its effective industrial application.

Fucoidans from Laminaria hyperborea demonstrate bactericidal activity against diverse bacteria

Fucoidans are a heterogenous class of fucose-rich sulfated carbohydrates which have attracted increasing attention in cancer and inflammation research due to their bioactive properties. There are reports that fucoidans may have direct antibacterial effects and synergy with antibiotics. However, the literature is conflicting, potentially due to the limited reporting of origin, characteristics, and extraction methods of the fucoidans tested. Here we report the results of 18 defined fucoidans screened for direct, indirect, and synergistic antibacterial effects. 15 distinct fucoidan fractions, isolated from Laminaria hyperborea using a solvent-free extraction process, were characterised for molecular weight, pH, viscosity, and sulfur content. These, together with three commercially available crude fractions, were assessed at concentrations from 0.03125-24 mg mL-1 for minimum inhibitory concentration against Staphylococcus aureus, Streptococcus mutans and Streptococcus sanguinis. Furthermore, we tested a selection of fucoidans for antibacterial synergy with vancomycin and indirect antibacterial effects in whole blood survival assays. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was performed to assess the stress response in fucoidan-treated S. aureus cultures. We have identified one fucoidan fraction with bactericidal activity against diverse bacteria. This effect is dose-, fucoidan fraction- and bacteria-specific, and furthermore, not related to osmotic stress. No synergistic effects were observed with fucoidan in combination vancomycin. Fucoidans have exciting potential as antimicrobial agents. Further analysis is required to establish the precise molecular characteristics responsible for their potent bactericidal activity.

Anti-obesity effects of fucoidan from Sargassum thunbergii in adipocytes and high fat diet induced obese mice through inhibiting adipogenic specific transcription factor

The prevalence of obesity has increased and is a health concern worldwide. Due to the concerns regarding synthetic anti-obesity treatments, nowadays natural products become a trend. Previous studies proved that there is a potential to use marine algae as anti-obesity agents. Therefore, in this study, the lipid inhibitory effect of crude polysaccharide of amyloglucosidase-assisted hydrolysate from Sargassum thunbergii (STAC) and its fucoidan fractions (STAFs) on 3T3-L1 cells and high-fat diet (HFD)-induced obese mice were investigated. According to the results, the STAF3, showed the highest xylose content and exhibited significant inhibitory effects on lipid accumulation by downregulating adipogenic and lipogenic proteins in 3T3-L1 cells. Furthermore, oral supplementation with STAC significantly declined gain in body weight and fat weight, and serum lipid contents in an HFD-induced obesity mouse model. Structural and chemical characterizations demonstrated that purified STAF3 has consistent surface morphology and small particle size, with similar structural characteristics as commercial fucoidan. Together, these results indicate that STAC and purified STAF3 from Sargassum thunbergia is a potent source to develop as ananti-obesity agents or functional food products to counter obesity.

In vitro and in vivo anti-inflammatory properties of an active fucoidan fraction from Sargassum fusiforme and a fraction-based hydrogel

In a previous study, we separated an active fucoidan (JHCF4) from acid-processed Sargassum fusiforme, then analyzed and confirmed its structure. In the present study, we investigated the potential anti-inflammatory properties of JHCF4 and a JHCF4-based hydrogel in vitro and in vivo. JHCF4 reliably inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages, with an IC50 of 22.35 μg/ml. Furthermore, JHCF4 attenuated the secretion of prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, indicating that JHCF4 regulates inflammatory reactions. In addition, JHCF4 downregulated iNOS and COX-2 and inhibited the activation of the MAPK pathway. According to further in vivo analyses, JHCF4 significantly reduced the generation of reactive oxygen species (ROS), NO production, and cell death in an LPS-induced zebrafish model, suggesting that JHCF4 exhibits anti-inflammatory effects. Additionally, a JHCF4-based hydrogel was developed, and its properties were evaluated. The hydrogel significantly decreased inflammatory and nociceptive responses in carrageenan (carr)-induced mouse paws by reducing the increase in paw thickness and decreasing neutrophil infiltration in the basal and subcutaneous layers of the toe epidermis. These results indicate that JHCF4 exhibits potential anti-inflammatory activity in vitro and in vivo and that JHCF4-based hydrogels have application prospects in the cosmetic and pharmaceutical fields.

Investigation of Physical Characteristics and In Vitro Anti-Inflammatory Effects of Fucoidan from Padina arborescens: A Comprehensive Assessment against Lipopolysaccharide-Induced Inflammation.

A biocompatible, heterogeneous, fucose-rich, sulfated polysaccharide (fucoidan) is biosynthesized in brown seaweed. In this study, fucoidan was isolated from Padina arborescens (PAC) using celluclast-assisted extraction, purified, and evaluated for its anti-inflammatory potential in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Structural analyses were performed using Fourier transform infrared (FTIR) and scanning electron microscopy. Among the purified fucoidans, fucoidan fraction 5 (F5) exhibited strong inhibitory activity against LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine generation through the regulation of iNOS/COX-2, MAPK, and NF-κB signaling in LPS-induced RAW 264.7 cells. Determination of the structural characteristics indicated that purified F5 exhibited characteristics similar to those of commercial fucoidan. In addition, further analyses suggested that F5 inhibits LPS-induced toxicity, cell death, and NO generation in zebrafish models. Taken together, these findings imply that P. arborescens fucoidans have exceptional anti-inflammatory action, both in vitro and in vivo, and that they may have prospective uses in the functional food sector.

Sequential and enzyme-assisted extraction of algal bioproducts from Ecklonia maxima

Brown algae are gaining recognition as sources of bio-compounds with diverse properties and potential applications in the food, nutraceutical, and pharmaceutical industries. Compounds such as polyphenols, alginates and fucoidan possess multiple bioactivities, including antidiabetic, antioxidant, anticancer, anti-inflammatory, and antibacterial properties. Conventional extraction methods provide low yields, posing challenges for the industrial applications of biocompounds. However, innovations are rapidly emerging to address these challenges, and one such approach is enzyme-assisted extraction. Furthermore, extracting single compounds undervalues algal biomass as valuable compounds may remain in the waste. Therefore, the aim of our study was to develop a framework for the sequential and enzyme-assisted extraction of various bio-compounds using the same biomass in a biorefinery process. The Ecklonia maxima algal biomass was defatted, and polyphenols were extracted using solid-liquid extraction with aqueous ethanol. The remaining residue was treated with an enzyme combination (Cellic® Ctec 2 and Viscozyme L) to liberate carbohydrates into solution, where an alginate and fucoidan fraction were isolated. A second alginate fraction was harvested from the residue. The phenolic fraction yielded about 11% (dry weight of extract/dry weight of seaweed biomass), the alginate fraction 35% and the fucoidan fraction 18%. These were analysed using a variety of biochemical methods. Structural analyses, including FTIR, NMR and TGA, were performed to confirm the integrity of these compounds. This study demonstrated that a sequential extraction method for various algal bioproducts is possible, which can pave the way for a biorefinery approach. Furthermore, our study primarily employed environmentally and eco-friendly extraction technologies promoting an environmentally sustainable industrial approach. This approach enhances the feasibility and flexibility of biorefinery operations, contributing to the development of a circular bio-economy.

Anti-Hyperlipidemic Effect of Fucoidan Fractions Prepared from Iceland Brown Algae Ascophyllum nodosum in an Hyperlipidemic Mice Model.

Ascophyllum nodosum, a brown algae abundantly found along the North Atlantic coast, is recognized for its high polysaccharide content. In this study, we investigated the anti-hyperlipidemic effect of fucoidans derived from A. nodosum, aiming to provide information for their potential application in anti-hyperlipidemic therapies and to explore comprehensive utilization of this Iceland brown seaweed. The crude fucoidan prepared from A. nodosum was separated using a diethylethanolamine column, resulting in two fucoidan fractions, AFC-1 and AFC-2. Both fractions were predominantly composed of fucose and xylose. AFC-1 exhibited a higher sulfate content of 27.8% compared to AFC-2 with 17.0%. AFC-2 was primarily sulfated at the hydroxy group of C2, whereas AFC-1 was sulfated at both the hydroxy groups of C2 and C4. To evaluate the anti-hyperlipidemic effect, a hyperlipidemia mouse model was established by feeding mice a high-fat diet. The effects of AFC-1, AFC-2, and the crude extract were investigated, with the drug atorvastatin used as a positive comparison. Among the different fucoidan fractions and doses, the high dose of AFC-2 administration demonstrated the most significant anti-hyperlipidemic effect across various aspects, including physiological parameters, blood glucose levels, lipid profile, histological analysis, and the activities of oxidative stress-related enzymes and lipoprotein-metabolism-related enzymes (p < 0.05 for the final body weight and p < 0.01 for the rest indicators, compared with the model group), and its effect is comparable to the atorvastatin administration. Furthermore, fucoidan administration resulted in a lower degree of loss in gut flora diversity compared to atorvastatin administration. These findings highlight the significant biomedical potential of fucoidans derived from A. nodosum as a promising therapeutic solution for hypolipidemia.

In Vitro Plant Growth Promoting Effect of Fucoidan Fractions of Turbinaria decurrens for Seed Germination, Organogenesis, and Adventitious Root Formation in Finger Millet and Eggplant

Bioactive ingredients derived from brown algae have been extensively used in the food, medicine, and cosmetic industries. In this study, fucoidans of low and high molecular fractions (LMF and HMF) extracted and isolated from brown alga Turbinaria decurrens were analyzed for their efficacy on seed germination, seedling growth, callus induction, direct organogenesis, and adventitious root formation in eggplant and finger millet. The yield and sugar content of LMF were higher than HMF. FTIR confirmed that the isolated fractions containing fucoidan has more sulfate groups in HMF than in LMF. The results showed an enhanced seed germination and seedling growth in both crops. In eggplant, 1 mg/L LMF treatment showed the maximum germination (91.6%), whereas, in finger millet, 0.1 and 0.5 mg/L LMF recorded a substantial increase in germination percentage (41.6 and 46%). Maximum fresh weight (FW) was noted with 1.0 mg/L LMF, and 1.0 mg/L LMF and 0.5 mg/L HMF showed maximum dry weight (DW) in eggplant. In finger millet, maximum DW was observed in 0.5 mg/L LMF and 1.0 mg/L HMF. Maximum biomass was noted in the 0.1 mg/L LMF treated group in the case of callus growth in eggplant. Similarly, the shoot tip initiation, proliferation, and plantlet regeneration were significantly improved with fucoidan LMF (0.1 mg/L). In conclusion, fucoidan extracted from T. decurrens exhibiting natural growth promoter property is reported for the first time in this study. These fucoidan fractions, LMF and HMF, can be utilized as cost-effective supplements in plant tissue culture media replacing the commercial PGRs for micropropagation.

Fucoidan from Sargassum autumnale Inhibits Potential Inflammatory Responses via NF-κB and MAPK Pathway Suppression in Lipopolysaccharide-Induced RAW 264.7 Macrophages.

Fucoidans are sulfate-rich polysaccharides with a wide variety of beneficial biological activities. The present study aimed to highlight the anti-inflammatory activity of fucoidan from the brown seaweed Sargassum autumnale (SA) against lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. Among the isolated fucoidan fractions, the third fraction (SAF3) showed a superior protective effect on LPS-stimulated RAW 264.7 cells. SAF3 inhibits nitric oxide (NO) production and expression of prostaglandin E-2 (PGE2) via downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) expression in LPS-induced RAW 26.7 cells. SAF3 treatment decreased pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 expression in LPS-induced cells. LPS stimulation activated NF-κB and MAPK signaling cascades in RAW 264.7 cells, while treatment with SAF3 suppressed them in a concentration-dependent manner. Existing outcomes confirm that SAF3 from S. autumnale possesses potent anti-inflammatory activity and exhibits good potential for application as a functional food ingredient or for the treatment of inflammation-related disorders.

Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion

The endothelial cell lining creates an interface between circulating blood and adjoining tissue and forms one of the most critical barriers and targets for therapeutical intervention. Recent studies suggest that fucoidans, sulfated and fucose-rich polysaccharides from brown seaweed, show multiple promising biological effects, including anti-inflammatory properties. However, their biological activity is determined by chemical characteristics such as molecular weight, sulfation degree, and molecular structure, which vary depending on the source, species, and harvesting and isolation method. In this study, we investigated the impact of high molecular weight (HMW) fucoidan extract on endothelial cell activation and interaction with primary monocytes (MNCs) in lipopolysaccharide (LPS)-induced inflammation. Gentle enzyme-assisted extraction combined with fractionation by ion exchange chromatography resulted in well-defined and pure fucoidan fractions. FE_F3, with a molecular weight ranging from 110 to 800 kDa and a sulfate content of 39%, was chosen for further investigation of its anti-inflammatory potential. We observed that along with higher purity of fucoidan fractions, the inflammatory response in endothelial mono- and co-cultures with MNCs was reduced in a dose-dependent manner when testing two different concentrations. This was demonstrated by a decrease in IL-6 and ICAM-1 on gene and protein levels and a reduced gene expression of TLR-4, GSK3β and NF-kB. Expression of selectins and, consequently, the adhesion of monocytes to the endothelial monolayer was reduced after fucoidan treatment. These data indicate that the anti-inflammatory effect of fucoidans increases with their purity and suggest that fucoidans might be useful in limiting the inflammatory response of endothelial cells in cases of LPS-induced bacterial infection.

Structural characterization and anti-inflammatory potential of sulfated polysaccharides from Scytosiphon lomentaria; attenuate inflammatory signaling pathways

The brown seaweed, Scytosiphon lomentaria, is widely distributed worldwide but has received less research attention. Several studies have reported sulfated polysaccharides to be potential candidates for the development of nutraceuticals and functional foods. However, their anti-inflammatory properties and underlying mechanisms are yet to be elucidated. Our findings revealed that S. lomentaria fucoidan fraction 5 (SLCF5) has the potential to inhibit the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages. The structural characterization of SLCF5 was confirmed using Fourier-transform infrared spectroscopy and scanning electron microscopy. LPS stimulation induced Prostaglandin E2, pro-inflammatory cytokines, and phosphorylation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK)-related proteins, while SLCF5 treatment significantly downregulated their expression. In vivo results demonstrated that SLCF5 decreased heart rate, NO production, and cell death while increasing the survival percentage. Hence, this study will serve as a platform for future research while providing insight into the mediation of inflammatory disorders.

Structure and chemopreventive activity of fucoidans from the brown alga Alaria angusta

Six fucoidan fractions were isolated from the brown alga Alaria angusta. Structures of enzymatic hydrolysis products of the fraction 1AaF2 (Fuc:Gal ~ 1:1; 33 % of sulfates) by fucanase from Wenyingzhuangia fucanilytica were studied by chemical and instrumental (NMR spectroscopy and mass-spectrometry) methods. It was shown that 1AaF2 consisted of two structurally different fucoidans: a sulfated 1,3;1,4-α-L-fucan and an enzyme-resistant sulfated and acetylated complex fucogalactan (Fuc:Gal ~ 1:2; 19 % of sulfates) 1AaF2_HMP containing extended 1,3-linked fucose and 1,3/1,4-linked galactose fragments (up to 5 residues). The fractions 1AaF2 and 1AaF2_HMP were a non-cytotoxic, possessed dose-dependent chemopreventive effect on EGF-induced neoplastic cell transformation of mouse normal epidermal JB6 Cl41 cells and inhibited the colony formation of human melanoma SK-MEL-28 cells.

Characterization and therapeutic effect of Sargassum coreanum fucoidan that inhibits lipopolysaccharide-induced inflammation in RAW 264.7 macrophages by blocking NF-κB signaling

Inflammation is a complex host-protective response against harmful stimuli involving macrophage activation that results in secretion of inflammatory mediators, like nitric oxide (NO), pro-inflammatory cytokines, and prostaglandin E2 (PGE2). In this study, we evaluated fucoidan isolated using Viscozyme-assisted enzymatic extraction of Sargassum coreanum extract against lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 macrophages and zebrafish model. Among the fucoidan fractions isolated using ion exchange chromatography, SCVF5 showed the highest sulfate and fucose contents based on chemical composition and monosaccharide analysis. Fourier-transform infrared (FT-IR) spectroscopy confirmed the presence of sulfate esters by the stretching vibrations of the SO peak at 1240 cm−1. SCVF5 showed anti-inflammatory effects by inhibiting NO and PGE2 generation in LPS-stimulated RAW 264.7 macrophages by downregulating inducible NO synthase and cyclooxygenase-2 expression. Treatment with SCVF5 suppressed pro-inflammatory cytokine production, such as TNF-α, (IL)-1β, and IL-6 by modulating the nuclear factor-kappa B signaling cascade in LPS-induced RAW 264.7 cells. Furthermore, in vivo results showed that SCVF5 can potentially downregulate LPS-induced toxicity, cell death, and NO production in LPS-induced zebrafish model. Collectively, these results suggest that S. coreanum fucoidan has remarkable anti-inflammatory activity in vitro and in vivo and may have potential applications in the functional food, cosmetic, and pharmaceutical industries.

Co-activating the AMPK signaling axis by low molecular weight fucoidan LF2 and fucoxanthin improves the HFD-induced metabolic syndrome in mice

• FX&LF2 reduced hyperglycemia and alleviated insulin resistance significantly. • FX&LF2 alleviated the liver oxidative stress and inflammation in HFD mice. • FX&LF2 synergistically weakened the adipocyte differentiation in BATs and WATs. • FX&LF2 regulated the glycolipid metabolism through activation of AMPK signaling axis. Metabolic syndrome (MetS) is a pathological condition characterized by multiple metabolic abnormalities. With the global epidemic of obesity and diabetes, MetS needs more urgent treatments and interventions. Fucoxanthin (FX) and fucoidan are two important active components derived from brown algae, which have been recommended as adjunctive therapy for MetS. In this study, we found that FX and low molecular weight fucoidan fraction LF2 improved insulin resistance (IR) and enhanced insulin sensitivity in high fat diet (HFD)-induced MetS mice synergistically. LF2 and FX could ameliorate HFD-induced liver injury by reducing liver fat deposition, inflammatory response and oxidative stress. Adenosine 5‘-monophosphate -activated protein kinase (AMPK) signaling axis is a key target for LF2 and FX to improve MetS. FX and LF2 reduced adipogenesis and conversion through co-activation of AMPK and reduction of the expression of adipogenic differentiation factors. In addition, FX up-regulated the expression of uncoupling protein (UCP-1) and promoted the body's energy expenditure. However, LF2 did not significantly increase the anti-hyperlipidemic effect of FX. Collectively, this study elucidated the synergistic improvement of MetS by FX and LF2 from a molecular perspective. It also demonstrated the potential of fucoxanthin combined with fucoidan as an anti-MetS functional food.

Anti-Fine Dust Effect of Fucoidan Extracted from Ecklonia maxima Laves in Macrophages via Inhibiting Inflammatory Signaling Pathways.

Brown seaweeds contain fucoidan, which has numerous biological activities. Here, the anti-fine-dust activity of fucoidan extracted from Ecklonia maxima, an abundant brown seaweed from South Africa, was explored. Fourier transmittance infrared spectroscopy, high-performance anion-exchange chromatography with pulsed amperometric detection analysis of the monosaccharide content, and nuclear magnetic resonance were used for the structural characterization of the polysaccharides. The toll-like receptor (TLR)-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were evaluated. The results revealed that E. maxima purified leaf fucoidan fraction 7 (EMLF7), which contained the highest sulfate content, showed the best anti-inflammatory activity by attenuating the TLR-mediated NF-κB/MAPK protein expressions in the particulate matter-stimulated cells. This was solidified by the successful reduction of Prostaglandin E2, NO, and pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β. The current findings confirm the anti-inflammatory activity of EMLF7, as well as the potential use of E. maxima as a low-cost fucoidan source due to its abundance. This suggests its further application as a functional ingredient in consumer products.

Structural characterization and antagonistic effect against P-selectin-mediated function of SFF-32, a fucoidan fraction from Sargassum fusiforme

Ethnopharmacological relevanceSargassum fusiforme (Harvey) Setchell, or Haizao, has been used in traditional Chinese medicine (TCM) since at least the eighth century a.d. S. fusiforme is an essential component of several Chinese formulas, including Haizao Yuhu Decoction, used to treat goiter, and Neixiao Lei Li Wan used to treat scrofuloderma. The pharmacological efficacy of S. fusiforme may be related to its anti-inflammatory effect. Aim of the studyTo determine the structural characteristics of SFF-32, a fucoidan fraction from S. fusiforme, and its antagonistic effect against P-selectin mediated function. Materials and methodsThe primary structure of SFF-32 was determined using methylation/GC–MS and NMR analysis. Surface morphology and solution conformation of SFF-32 were determined by scanning electron microscopy (SEM), Congo red test, and circular dichroic (CD) chromatography, respectively. The inhibitory effects of SFF-32 against the binding of P-selectin to HL-60 cells were evaluated using flow cytometry, static adhesion assay, and parallel-plate flow chamber assay. Furthermore, the blocking effect of SFF-32 on the interaction between P-selectin and PSGL-1 was evaluated using an in vitro protein binding assay. ResultsThe main linkage types of SFF-32 were proven to →[3)-α-l-Fucp-(1→3,4)-α-l-Fucp-(1]2→[4)-β-d-Manp-(1→3)-d-GlcAp-(1]2→4)-β-d-Manp-(1→3)-β-d-Glcp-(1→4)-β-d-Manp-(1→2,3)-β-d-Galp-(1→4)-β-d-Manp-(1→[4)-α-l-Rhap-(1]3→. The sulfated unit or terminal xylose residues were attached to the backbone through the C-3 of some fucose residues and terminal xylose residues were attached to C-3 of galactose residues. Moreover, SFF-32 disrupted P-selectin-mediated cell adhesion and rolling as well as blocked the interaction between P-selectin and its physiological ligand PSGL-1 in a dose-dependent manner. ConclusionsBlocking the binding between P-selectin and PSGL-1 is the possible underlying mechanism by which SFF-32 inhibits P-selectin-mediated function, which demonstrated that SFF-32 may be a potential anti-inflammatory lead compound.

Hair growth-promoting effects of Sargassum glaucescens oligosaccharides extracts

Background: Brown algae have been used as food and traditional Chinese medicine for thousands of years and it is known to contain a bioactive component - fucoidan. However, little is known about the effect of fucoidan on cell differentiation and proliferation, particularly in topical application. Given that, this study focused on investigating the effect of different extraction methods of fucoidans on the promotion of human hair growth ability.Methods: Fucoidans from Sargassum glaucescens were extracted by a combination of microwave-assisted high-pressure water or subcritical water. Different molecular weight fractions of fucoidan were separated. The effect of these fractions on the proliferation and hair growth-related genes expression on hair follicle dermal papilla cells (HFDPC) was investigated. Mice models and ex vivo hair follicle culture assays were used to determine the efficacy.Significant Findings: Sargassum glaucescens fucoidan extracts higher than 1 KDa molecular weight demonstrated hair growth-promoting ability. The oligo-fucoidan was more effective in enhancing hair follicle cell proliferation. The effects of fucoidans on the proliferation of HFPDC correlated with IGF-1 and LEF-1 gene expressions. Hair growth-promoting activity was observed in mice models after being treated with Sargassum glaucescens fucoidan extracts. Thus, fucoidan could be a potential topical medicine in alopecia treatment.