Fucoidan alleviates high sucrose-induced metabolic disorders and enhances intestinal homeostasis through modulation of Notch signaling.

INTRODUCTION: The therapeutic potential of fucoidan (FUC), a natural polysaccharide, in metabolic disorders is recognized, yet its underlying mechanisms remain unclear. METHODS: We conducted investigations into the therapeutic mechanisms of FUC sourced from Sargassum fulvellum concerning metabolic disorders induced by a high-sucrose diet (HSD), employing Drosophila melanogaster and mice models. Drosophila larvae were subjected to HSD exposure to monitor growth inhibition, reduced pupation, and developmental delays. Additionally, we examined the impact of FUC on growth- and development-related hormones in Drosophila. Furthermore, we assessed the modulation of larval intestinal homeostasis by FUC, focusing on the regulation of Notch signaling. In mice, we evaluated the effects of FUC on HSD-induced impairments in intestinal epithelial barrier integrity and gut hormone secretion. RESULTS: FUC supplementation significantly enhanced pupal weight in Drosophila larvae and effectively countered HSD-induced elevation of glucose and triglyceride levels. It notably influenced the expression of growth- and development-related hormones, particularly augmenting insulin-like peptides production while mitigating larval growth retardation. FUC also modulated larval intestinal homeostasis by negatively regulating Notch signaling, thereby protecting against HSD-induced metabolic stress. In mice, FUC ameliorated HSD-induced impairments in ileum epithelial barrier integrity and gut hormone secretion. CONCLUSIONS: Our findings demonstrate the multifaceted therapeutic effects of FUC in mitigating metabolic disorders and maintaining intestinal health. FUC holds promise as a therapeutic agent, with its effects attributed partly to the sulfate group and its ability to regulate Notch signaling, emphasizing its potential for addressing metabolic disorders.

Sulfate groups position determines the ionic selectivity and syneresis properties of carrageenan systems.

The salt sensitivity and selectivity feature of α-carrageenan (α-Car) were investigated and compared with κ-carrageenan (κ-Car) and iota-carrageenan (ι-Car). These carrageenans are identified by one sulfate group on the 3,6-anhydro-D-galactose (DA) for α-Car, D-galactose (G) for κ-Car and on both carrabiose moieties (G and DA) for ι-Car. The viscosity and temperature, where order-disorder transition have been observed, were greater in presence of CaCl2 for α-Car and ι-Car compared with KCl and NaCl. Conversely, the reactivity of κ-Car systems were greater in presence of KCl than CaCl2. Unlike κ-Car systems, the gelation of α-Car in presence of KCl was observed without syneresis. Thus, the position of sulfate group on the carrabiose determines the importance of counterion valency too. The α-Car could be a good alternative to κ-Car to reduce the syneresis effects.

Keeping Superprotonic Conductivity over a Wide Temperature Region via Sulfate Hopping Sites-Decorated Zirconium-Oxo Clusters.

Metal-oxo clusters have emerged as advanced proton conductors with well-defined and tunable structures. Nevertheless, the exploitation of metal-oxo clusters with high and stable proton conductivity over a relatively wide temperature range still remains a great challenge. Herein, three sulfate groups decorated zirconium-oxo clusters (Zr6 , Zr18 , and Zr70 ) as proton conductors are reported, which exhibit ultrahigh bulk proton conductivities of 1.71 × 10-1 , 2.01 × 10-2 , and 3.73 × 10-2  S cm-1 under 70 °C and 98% relative humidity (RH), respectively. Remarkably, Zr6 and Zr70 with multiple sulfate groups as proton hopping sites show ultralow activation energies of 0.22 and 0.18 eV, respectively, and stable bulk conductivities of >10-2  S cm-1 between 30 and 70 °C at 98% RH. Moreover, a time-dependent proton conductivity test reveals that the best performing Zr6 can maintain high proton conductivity up to 15 h with negligible loss at 70 °C and 98% RH, representing one of the best crystalline cluster-based proton conducting materials.

ι-Carrageenan nanocomposites for enhanced stability and oral bioavailability of curcumin.

BACKGROUND: Carrageenan (CRN), a polygalactan consisting of 15 to 40% ester sulfate, is used in oral controlled-release technology due to its viscosity and large molecular weight. Curcumin (Cur) is a highly potent antioxidant and anti-inflammatory agent against various diseases, such as tumors, liver disease, rheumatism, and Alzheimer's disease. Although Cur shows excellent effects in the body, it has major problems, such as poor solubility and low bioavailability in water. METHOD: Nanocomposites containing Cur were developed by emulsion technique. Cur@CRN was characterized through the viscosity measurement, size analysis, stability test, and loading efficiency. Antioxidant effects was analyzed with DPPH reagent, and anti-inflammatory effects was analyzed by NFkB/IkBr signaling pathway with wester blot. Cellular interaction was confirmed by flow cytometry and confocal images. Especially, permeability test was demonstrated in MDCK and Caco-2 monolayer cells. RESULTS: Cur@CRN enhanced stability, antioxidant, and anti-inflammatory effects in vitro, compared with other polymer nanocomposites. Sulfate groups (SO42-) in CRN are transported across cell membranes by anion exchangers of the SLC26 gene families. We confirmed Caco-2 cells expressed SLC26A2 receptors interacted with CRN, expect for Tween 80 and hydroxypropyl cellulose. In contrary, other cells did not interact with CRN due to non-expression of SLC26A2 receptors. Based on this, Cur@CRN showed 44-fold better permeability than free Cur in MDCK cell assay. CONCLUSION: Enhanced intestinal permeability of Cur can be applied in various health care facilities with significant antioxidant and anti-inflammatory effects compared with nonformulated Cur. Since the CRN composed of nanocomposites has a high molecular weight, high viscosity, and sulfate groups, it will be a platform that can increase the bioavailability of various insoluble drugs as well as Cur.

Sea Cucumber Sterol Alleviates the Lipid Accumulation in High-Fat-Fructose Diet Fed Mice.

The effect of marine-derived sea cucumber sterol (SS) with a special sulfate group on lipid accumulation remains unknown, although phytosterol has been proved to have many biological activities, including lowering blood cholesterol. The purpose of the present study is to investigate the alleviation of SS on lipid accumulation and the possible underlying mechanism using high-fat-fructose diet fed mice. Dietary administration with SS for 8 weeks reduced significantly the body weight gain and lipid levels in serum and liver. Especially, SS was superior to phytosterol in lowering lipid accumulation due to the great promotion of fatty acid ß-oxidation, the inhibition of cholesterol synthesis, and the acceleration of cholesterol efflux. The findings found that sea cucumber sterol exhibited a more significant effect than phytosterol on alleviating HFF-diet-induced lipid accumulation through regulating lipid and cholesterol metabolism, which might be attributed to the difference in the branch chain and sulfate group.

[Production and application of 3-phosphoadenosine-5- phosphosulfate].

Sulfated compounds are widely present in cytoplasm, on cell surface, and in extracellular matrix. These compounds play important roles in cell development, differentiation, immune response, detoxication, and cell signal transduction. 3-Phosphoadenosine-5-phosphosulfate (PAPS) is the universal sulfate group donor for the biosynthesis of sulfated compounds. Up to now, the synthesis of PAPS is still too expensive for industrial applications. This review focuses on the recent progress of PAPS production and summaries the application of PAPS, particularly in the production of glucosinolate, heparin, condroitin sulfate, and oxamniquine production.

Bioactivities of Nizamuddinia zanardinii sulfated polysaccharides extracted by enzyme, ultrasound and enzyme-ultrasound methods.

Sulfated polysaccharide (fucoidan) was isolated from Nizamuddinia zanardinii by enzyme (alcalase), ultrasonic and enzyme-ultrasonic methods. The extracted fucoidans were assessed for their chemical compositions, molecular characteristics, anticancer and immunomodulatory activities. Enzyme-ultrasonic isolated fucoidan showed the maximum extraction yield (7.87%) while that obtained by ultrasonic had the minimum value (3.6%). fucoidans were composed of different levels of carbohydrates (52.78-58.65%), proteins (6.98-8.91%), sulfates (21.78-29.6%) and uronic acids (0.42-1.08%). The weight mean average molecular weight of fucoidans varied between 443.7 and 1020.85 kDa. The polysaccharide chains were consisted of fucose, galactose, glucose, mannose and xylose. All the recovered fucoidans showed strong growth inhibition against HeLa and Hep-G2 cancer cells. The isolated fucoidans were non-toxic and considerably stimulated the macrophage cells to release nitric oxide. Enzyme extraction produced fucoidan with the most macrophage stimulation capacity (> 42 µmol). These results suggested that enzyme treatment preserved more sulfate groups in fucoidan structure influencing its anticancer and immunostimulatory activities.

Production and application of 3-phosphoadenosine-5- phosphosulfate / 生物工程学报

Sulfated compounds are widely present in cytoplasm, on cell surface, and in extracellular matrix. These compounds play important roles in cell development, differentiation, immune response, detoxication, and cell signal transduction. 3-Phosphoadenosine-5-phosphosulfate (PAPS) is the universal sulfate group donor for the biosynthesis of sulfated compounds. Up to now, the synthesis of PAPS is still too expensive for industrial applications. This review focuses on the recent progress of PAPS production and summaries the application of PAPS, particularly in the production of glucosinolate, heparin, condroitin sulfate, and oxamniquine production.

Characterization of a water-soluble chitosan derivative and its potential for submucosal injection in endoscopic techniques.

To examine the potential of chitosan-based agents for submucosal injection in endoscopic techniques, a chitosan derivative was prepared with lactose moieties linked to the amino groups of its glucosamine units (CH-LA). After dissolving CH-LA in neutral pH solutions, including physiological saline (CH-LA-S), its response to different concentrations of anionic glycosaminoglycans and proteins in the surrounding environment was examined. The CH-LA-S form changed in the presence of sulfated glycosaminoglycans (heparin, chondroitin sulfate, and mucin) and protein (fibrinogen). High concentrations of sulfated substrates in the solution caused the formation of larger structures. In contrast, in the presence of hyaluronan, 30mg/mL CH-LA-S did not form any large structures. Submucosal injection of 30mg/mL CH-LA-S into extracted swine stomachs showed a strong lifting effect of the gastric mucosa. These results indicate the potential utility of CH-LA-S as a submucosal injection for endoscopic techniques such as endoscopic submucosal dissection and mucosal resection of tumors.

Structural requirements of glycosaminoglycans for facilitating amyloid fibril formation of human serum amyloid A.

Serum amyloid A (SAA) is a precursor protein of amyloid fibrils. Given that heparan sulfate (HS), a glycosaminoglycan (GAG), is detected in amyloid deposits, it has been suggested that GAG is a key component of amyloid fibril formation. We previously reported that heparin (an analog of HS) facilitates the fibril formation of SAA, but the structural requirements remain unknown. In the present study, we investigated the structural requirements of GAGs for facilitating the amyloid fibril formation of SAA. Spectroscopic analyses using structurally diverse GAG analogs suggested that the fibril formation of SAA was facilitated irrespective of the backbone structure of GAGs; however, the facilitating effect was strongly correlated with the degree of sulfation. Microscopic analyses revealed that the morphologies of SAA aggregates were modulated by the GAGs. The HS molecule, which is less sulfated than heparin but contains highly sulfated domains, exhibited a relatively high potential to facilitate fibril formation compared to other GAGs. The length dependence of fragmented heparins on the facilitating effect suggested that a high density of sulfate groups is also required. These results indicate that not only the degree of sulfation but also the lengths of sulfated domains in GAG play important roles in fibril formation of SAA.

Key factors for optimum performance in phosphate removal from contaminated water by a Fe-Mg-La tri-metal composite sorbent.

Eutrophication is typically due to excessive discharge of phosphate-containing wastewater into natural waters. In this study, a novel Fe-Mg-La trimetal composite sorbent with a Fe:Mg:La molar ratio of 2:1:1 was developed through a cost-effective co-precipitation approach for phosphate removal in contaminated water. It was found that the adsorption was greatly affected by solution pH. The experimental data was better described by Langmuir isotherm model, and the maximum adsorption capacity of 415.2 mg-P/g was achieved under pH 6.0, much higher than most of sorbents previously reported. Nitrate, sulfate, bicarbonate, fluoride and humic acid widely exist in natural water, and their presences would slightly retard the adsorption of phosphate. The adsorption kinetics experiment showed that most of adsorption occurred in the first 1h and the adsorption equilibrium was achieved in 10h; the adsorption history was well described by the intraparticle diffusion model. The performance of sorbent was further confirmed by treating phosphate contaminated lake water. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis indicated that hydroxyl group on the sorbent surface (M-OH) played the most key role in the phosphate adsorption. The presence of sulfate group was important in the uptake as well.

Preparation of low molecular weight fucoidan by gamma-irradiation and its anticancer activity.

Fucoidan is a marine sulfated polysaccharide with a wide variety of biological activities. Recently, it has been reported that low molecular weight fucoidan has the enhanced antioxidant and anticoagulative activities. However, degradation techniques such as enzymolysis and acid hydrolysis for obtaining low molecular weight fucoidan, have the disadvantages such as narrow substrate specificity and unfavorable hydrolysis of side groups, respectively. In this study, low molecular weight fucoidan was prepared by gamma-irradiation. When fucoidan was gamma-irradiated, the molecular weight rapidly dropped to 38 kDa when the sample was irradiated at 10 kGy, then gradually dropped to 7 kDa without the significant elimination of the sulfate groups. Low molecular weight fucoidan had higher cytotoxicity than native fucoidan in cancer cells, such as AGS, MCF-7, and HepG-2. In addition, low molecular weight fucoidan showed higher inhibitory activity of cell transformation, which resulted in higher anticarcinogenicity. This result suggests that low molecular weight fucoidan with enhanced biological activities can be produced by a simple irradiation method without changing the functional groups.

THE RELATIONSHIP BETWEEN FUCOIDANS STRUCTURE AND THEIR ACTIVITIES OF INHIBITING HYDROXYL RADICAL IN VITRO / 营养学报

Objective To study the relationship between fucoidans structure and their antioxidant activities. Method Fucoidans (HF) were extracted from Laminaria japonica and was separated by anion exchange chromatography on DEAE-Cellulose 52 column (2.5?40 cm), and two fractions HF1 and HF2 were obtained. Fucoidans of low molecular weight (LF) was made after hydrolysis of HF by hydrochloric acid and purification by ultrafiltration. Chemical methods and gas chromatography were used to analyse the sugar composition of these polysaccharides; and infrared spectrum was utilized to determine their structure. The activity of inhibiting hydroxyl radical (?O H ) was evaluated by means of Fenton reaction. Results In HF1, 18.834% uronic acid, 44.197% L-fucose, 31.193% D-galactose and 24.612% D-mannose were detected. As to HF2, 5.878% uronic acid, 81.119% L-fucose and 18.881% D-mannose were found. L-fucose content in LF was 13.033%, equal to 32.084% of that in HF 40.621%. Both in HF1 and LF, sulfate groups were at the C-2 and C-4 positions of L-fucose, while in HF2, sulfate groups only at C-4 position. The concentration of fucoidans inhibiting 50% ?O H (IC50) was 7.6, 5.2 and 8.9 mg/ml for HF, HF1 and HF2 respectively. Nevertheless, LF approximately lost this activity. Conclusion The molecular weight, content and composition of sugar and the combining sites of sulfate groups were found to be related with the activity of inhibiting ?O H radical in fucoidans.