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Diabetic foot ulcer (DFU) is a chronic and non-healing wound in all age categories with a high prevalence and mortality in the world. An ideal wound dressing for DFU should possess the ability of adsorbing high contents of exudate and actively promote wound healing. Here, we introduced the calcium alginate sulfate as a new biomaterial appropriate for use in wound dressing to promote the healing of full-thickness ulcers in a diabetic mouse model. In this regard, alginate sulfate (Alg-S) solutions with different degrees of substitution (DS) of 0.2, 0.5, and 0.9 were synthesized, freeze-dried, crosslinked by calcium cations, purified by washing and refreeze-dried. Primary analyses including swelling ratio, porosity content and mechanical properties revealed that all Alg-S scaffolds possess necessities for use as a wound dressing. After confirming the cytocompatibility of both alginate and alginate sulfate-based scaffolds by MTT assay, they were used as wound dressing for healing of full-thickness ulcers in diabetic mice. The results of wound healing process confirmed that calcium alginate sulfate scaffolds can heal the wounds faster than both alginate-treated and non-treated wounds. Furthermore, the histological analyses of healed tissues reveled normal regeneration of the skin tissue layers and collagen deposition similar to the healthy tissue. [ABSTRACT FROM AUTHOR]

In this work, by using molecular dynamics simulations, we elucidate the effect of sulfation substitution on the stability of the curdlan triple helix structure. The simulation results indicate that the stability of the triple helix structure is significantly influenced by the sites of sulfation substitution. The substitution at the O 2 site directly disrupts the hydrogen bonding network between the triple helix chains, significantly destroying the triple helix conformation. When substitutions occur at both the O 4 and O 6 sites simultaneously (O 4,6), the electrostatic repulsion between numerous sulfate groups introduces considerable energy perturbation to the triple helix, leading to alterations in the glucan chain conformation and consequent destabilization of the triple helix structure. Meanwhile, we find that even if the sulfation substitution is performed at the same substitution sites, the difference in the degree of substitution also has an impact on the triple helix stability. The resistance of the triple helix to sulfation substitution at O 2 is weak, and low degree of substitution can lead to the unwinding of the triple helix. However, it demonstrates higher resistance to substitution at O 4,6 where only higher degree of substitution results in triple helix destabilization. • The stability of Curdlan triple helix is significantly influenced by the sites and degrees of sulfation substitution. • Curdlan triple helix has low resistance to sulfation substitution at O 2 due to the damaged hydrogen bonding network. • Energy perturbation caused by sulfation at O 4 /O 6 can hardly disrupt the triple helix except high degree of substitution. [ABSTRACT FROM AUTHOR]

Anemarrhena asphodeloides Bge. (AA), a traditional Chinese medicine, is used clinically to treat inflammation, diabetes, osteoporosis, and tumors. Polysaccharides are the most abundant components in AA, and have antioxidant, immunomodulatory, anti-inflammatory, hypoglycemic, anti-osteoporosis, and laxative effects. It is necessary to conduct a comprehensive analysis on the structure and pharmacological activity of the polysaccharides from AA (PAAs). This review systematically summarizes the structural characteristics of PAAs, including the monosaccharide compositions, molecular weights, and backbone structures. We discuss the relationship between the structure and pharmacological activities of PAAs. The chemical modification methods of PAAs, including zinc chelation, carboxymethylation, and sulfation, are then reviewed. This review may offer new insights for research on the PAAs and polysaccharides with similar structures. [ABSTRACT FROM AUTHOR]

Many polysaccharides produced by Paenibacillus spp. have attractive properties, such as rheological modification and immunomodulation. However, properties of P. edaphicus polysaccharides are not understood sufficiently. Here, the polysaccharide (PUM) was obtained from P. edaphicus strain UJ1 by batch fermentation, and the chemical characteristics, rheological and anti-inflammatory properties of PUM and its sulfate derivative (PUM-S) were investigated. The results indicated that PUM was a typical shear-thinning biopolymer with an estimated weight average molecular weight of 2.45 × 107 Da. PUM molecule consisted of D-Man, D-GlcA, D-Glc, D-Gal, and L-Fuc with the molar ratio of 3.00:1.07:3.21:0.81:0.76. It had the backbone → 3)-β-D-Man-(1 → 3)-β-D-Glc-(1 → 3)-β-D-Man-(1 → 3)β-D-Glc-(1 → 4)-β-D-GlcA-(1 → 3)-β-D-Man-(1 → and two side chains, namely, pyruvoyl-Glc-(1→ and β-L-Fuc-(1 → 3)-β-D-Gal-(1→. Moreover, PUM-S was prepared by SO 3 -pyridine method and had the weight average molecular weight of 1.42 × 105 Da. The bioactivity of PUM and PUM-S was analyzed in vitro in RAW 264.7 cells. The results indicated that both PUM and PUM-S facilitated cell proliferation at 50–500 μg/mL. Besides, PUM-S showed potential anti-inflammatory effect in the LPS-induced cells. According to transcription and molecular dynamics analyses, PUM-S expressed its activity probably by interacting with the Toll-like receptor 4. In general, P. edaphicus produced a polysaccharide with new chemical structure and promising rheological and bioactive properties. • A polysaccharide PUM was obtained from Paenibacillus edaphicus strain UJ1. • PUM was a 2.45 × 107 Da macromolecular polysaccharide with good rheological properties. • Chemical characteristics of PUM and the sulfated PUM (PUM-S) was determined. • PUM and PUM-S facilitated proliferation of RAW 264.6 cells in vitro. • PUM-S showed potential anti-inflammatory activity by binding to TLR4. [ABSTRACT FROM AUTHOR]

Polysaccharides from sea cucumbers are known for their biological activities, but little is known about those from sea cucumber viscera. The present study isolated a sulfated polysaccharide (SCVP-2) from the viscera of Apostichopus japonicas , which had a molecular weight of 209.1 kDa. SCVP-2 comprised 66.3 % total sugars, 2.1 % uronic acid, 4.5 % proteins, and 25.5 % sulfate groups, containing glucosamine, galactosamine, glucose, galactose, and fucose. FT-IR and NMR analyses identified SCVP-2 as a fucoidan sulfate with sulfation patterns of the fucose branches as Fuc2S, Fuc4S, and Fuc0S. SEM and AFM analyses showed irregular clusters and linear conformations. SCVP-2 demonstrated strong anti-inflammatory properties both in vitro and in vivo. In lipopolysaccharide (LPS)-induced inflammation in macrophage RAW264.7 cells, SCVP-2 significantly reduced nitric oxide (NO) and cytokine secretion (IL-1β, IL-6, TNF-α). Additionally, it downregulated the expression of these cytokine genes. Furthermore, the anti-inflammatory mechanism of SCVP-2 was related to the inhibition of the MAPKs and NF-κB pathways. SCVP-2's anti-inflammatory capacity was confirmed in acute inflammation models, including xylene-induced ear swelling and acetic acid-induced peritoneal capillary permeability, and in high-fat diet-induced systemic low-grade chronic inflammation. In conclusion, SCVP-2 exhibits significant anti-inflammatory activity, suggesting its potential for development as a functional food ingredient or therapeutic agent for inflammation-related diseases. [ABSTRACT FROM AUTHOR]

Sulfated polysaccharides (SPSs) have excellent physicochemical properties, attracting research interest in the pharmaceutical industry. A previous study extracted SPS (named Suc40) from the edible fungus, Poria cocos and demonstrated that it exhibited anti-inflammatory and anticancer activities. In this study, three fractions of Suc40, Suc40 F1, Suc40 F2, and Suc40 F3, with different molecular weights and sulfate contents were prepared through gel-filtration column chromatography. The molecular weights of F1, F2, and F3 were approximately 616.23, 82.57, and 6.21 kDa, respectively, and their sulfate content were 0.23, 1.65, and 1.90 mmol/g, respectively. The fractions' anti-inflammatory activities were determined by assessing their ability to suppress inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Suc40 F2 and Suc40 F3 suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production by 60 % and 35 %, respectively. Suc40 F2 and Suc40 F3 suppressed protein kinase B (AKT)/p38 and p38 signaling, which resulted in anti-inflammatory effects. The fractions' anti–lung cancer activity was evaluated by assessing their H1975 cell proliferation inhibition. Suc40 F3 at a concentration of 800 μg/ml exhibited maximal cell proliferation inhibition. The low molecular weight and high sulfate content of Suc40 F3 were associated with its enhanced anti-inflammatory and anti–lung cancer activities. [Display omitted] • Suc40 (F1- F3) with different molecular weights and sulfation degrees were prepared • Low molecular weight and high sulfation degree of Suc40 F3 • Suc40 F2 and Suc40 F3 showed maximal anti-inflammatory potentialSuppression of AKT/p38 resulting in anti-inflammatory effects of Suc40 F2 and Suc40 F3 • Suc40 F3 showed better anti-inflammatory and anti-lung cancer activities [ABSTRACT FROM AUTHOR]

Sulfation of polysaccharides can affect their biological activity by introducing sulfate groups. Skin burns occur regularly and have a great impact on normal survival. In this study, sulfated arabinogalactan (SAG) was prepared by sulfation, and polyvinyl alcohol (PVA) was used to prepare hydrogels for the treatment of scalded skin in mouse. The results show that the main chain of SAG consists of →3-β-D-Galactose (Gal)-(1, →3, 6)-β-D-Gal-(1 and →4)-β- d -Glucose (Glc)-(1. The chain is a neutral polysaccharide composed of T-β-L-Arabinose (Araf)-(1→, with a molecular weight of 17.9 kDa. At the same time, PVA + SAG hydrogel can promote the scald repair of mouse skin by promoting collagen deposition and angiogenesis, and regulating the TLR4/MyD88/NF-κB signaling pathway. Interestingly, the effect of SAG on promoting the repair of scald wounds is enhanced after AG is derivatized by sulfation. Therefore, the preparation of SAG by sulfation can promote scald repair, and has great application potential in the field of food and medicine. [ABSTRACT FROM AUTHOR]

Alginate is a linear polysaccharide with a modifiable structure and abundant functional groups, offers immense potential for tailoring diverse alginate-based materials to meet the demands of biomedical applications. Given the advancements in modification techniques, it is significant to analyze and summarize the modification of alginate by physical, chemical and biological methods. These approaches provide plentiful information on the preparation, characterization and application of alginate-based materials. Physical modification generally involves blending and physical crosslinking, while chemical modification relies on chemical reactions, mainly including acylation, sulfation, phosphorylation, carbodiimide coupling, nucleophilic substitution, graft copolymerization, terminal modification, and degradation. Chemical modified alginate contains chemically crosslinked alginate, grafted alginate and oligo-alginate. Biological modification associated with various enzymes to realize the hydrolysis or grafting. These diverse modifications hold great promise in fully harnessing the potential of alginate for its burgeoning biomedical applications in the future. In summary, this review provides a comprehensive discussion and summary of different modification methods applied to improve the properties of alginate while expanding its biomedical potentials. [ABSTRACT FROM AUTHOR]

Chitooligosaccharides (COS) has attracted increasing attention due to the various promising bioactivities, tremendous potential in agricultural, environmental nutritional and functional food fields. COS as the major degradation product from chitosan or chitin is prepared via enzymatic, chemical and physical methods. Further obtained COS generally possesses different structural characteristics, such as molecular weight, degree of acetylation and degree of polymerization. Innovations into COS modification has also broadened application of COS in nutrition as well as in agricultural safety. Due to the affinity between structure and bioactivity, diversity of structural characteristics endows COS with various bioactivities like antitumor, antioxidant and anti-inflammatory effects, especially hepatoprotective activity. Therefore, the present review narrates the recent developments in COS physicochemical properties, while paying considerable attention to preparation strategies of COS and their advantages and disadvantages. Moreover, the modification of COS is also discussed including alkylation, quaternization and sulfation, herein the structure-activity relationship of COS was highlighted. Additionally, we summarize the latest research on hepatoprotective activity and mechanisms of COS. Eventually, the future directions of research on COS were discussed, which would provide a new appreciation for the future use of COS. [ABSTRACT FROM AUTHOR]

Two novel sulfated polysaccharides (SPs), N10 and K5 were isolated from ammonium sulfate or potassium sulfate at concentrations of 10 mM and 5 mM in liquid cultures of Antrodia cinnamomea, respectively. N10 and K5 were galactoglucans with a galactose:glucose molar ratio of approximately 1:3. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, N10 and K5 exhibited strong anti-inflammatory potential, of 56 % and 23 % maximal inhibition of IL-6 and TNF-α production, respectively. Mechanical analysis revealed differences between N10 and K5, with N10 inhibiting the LPS-stimulated phosphorylation of ERK and p38 in RAW264.7 cells. K5 inhibited the LPS-stimulated phosphorylation of AKT and TGFβR-II. N10 and K5 were fragmented into F1, F2, and F3, the molecular weights of which were 455, 24, 0.9, and 327, 36, 1.9 kDa, respectively. K5 F2 and K5 F3 exhibited high degrees of sulfation of 1:3 and 1:8, resulting in strong anti-inflammation, of 83 % and 37 % highest inhibition of IL-6 and TNF-α production, respectively. Therefore, low-molecular-weight and high-sulfation-degree SPs exhibited strong anti-inflammatory activity. Specifically, K5 F2 inhibited the phosphorylation of p38, and K5 F3 suppressed the signaling pathway of p38/JNK. Overall, the sulfation degree of SPs is concluded to affect the anti-inflammatory responses. • Two novel SPs of N10 and K5 showed anti-inflammatory activities. • K5 showed a higher sulfation degree and anti-inflammatory activity. • Fragmenting N10 and K5 increases their anti-inflammatory potential. • K5 (F2 and F3) have the highest anti-inflammatory activity, inhibiting IL-6 and TNF-α. • Low molecular weight SPs is more effective than high molecular weight SPs. [ABSTRACT FROM AUTHOR]

The chemokine receptor CXCR4 and its cognate ligand CXCL12 mediate pathways that lead to cell migration and chemotaxis. Although the structural details of related receptor-ligand complexes have been resolved, the roles of the N-terminal domain of the receptor and post-translational sulfation that are determinants of ligand selectivity and affinity remain unclear. Here, we analyze the structural dynamics induced by receptor sulfation by combining molecular dynamics, docking and network analysis. The sulfotyrosine residues, 7YsN-term, 12YsN-term and 21YsN-term allow the N-terminal domain of the apo -sulfated receptor to adopt an "open" conformation that appears to facilitate ligand binding. The overall topology of the CXCR4-CXCL12 complex is independent of the sulfation state, but an extensive network of protein-protein interactions characterizes the sulfated receptor, in line with its increased ligand affinity. The altered interactions of sulfotyrosine residues, such as 21YsN-term-47RCXCL12 replacing the 21YN-term-13FCXCL12 interaction, propagate via allosteric pathways towards the receptor lumen. In particular, our results suggest that the experimentally-reported receptor-ligand interactions 262D6.58-8RCXCL12 and 277E7.28-12RCXCL12 could be dependent on the sulfation state of the receptor and need to be carefully analyzed. Our work is an important step in understanding chemokine-receptor interactions and how post-translational modifications could modulate receptor-ligand complexes. [ABSTRACT FROM AUTHOR]

The Cyclocarya paliurus polysaccharide (CP) was chemically modified to produce sulfated derivatives (S-CP) and carboxymethylated derivatives (CM-CP). Subsequently, the antioxidant activity, cytoprotective effect and antitumor activity of these derivatives were investigated to establish the relationship between their structure and functional activity. The results found that chemical modifications resulted in remarkable variations in the chemical compositions and apparent structures of CP. S-CP with the highest amount of glucose had the strongest antioxidant capacity to scavenge DPPH• and HO•, but CM-CP was lower than CP in terms of HO• scavenging. More importantly, S-CP and CM-CP more effectively protected RAW264.7 from H 2 O 2 -induced damage compared to CP by reducing the secretion of lactate dehydrogenase (LDH), intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), enhancing phagocytosis and superoxide dismutase (SOD) levels, and suppressing abnormal apoptosis. Further experiments showed that the anti-apoptotic effect of S-CP and CM-CP was in intimate association with down-regulation of Caspase-9/3 activities and alleviation of cell cycle arrest in the S phase. In addition, S-CP and CM-CP decreased the cell viability of tumor cells. These findings suggest that the type of functional group plays important roles in the biological function of the derivatives and provide a theoretical basis for the development of novel natural anti-oxidants or low-toxicity anti-tumor drugs. • Sulfated and carboxymethylated derivatives of polysaccharide were prepared. • The composition and surface morphology were changed after chemical modification. • Their antioxidant, cytoprotective effect and antitumor effects were compared. • The bioactivities are affected by the type of substituent and the molar ratio. [ABSTRACT FROM AUTHOR]

Fucan sulfates from echinoderm possess characteristic structures and various biological activities. Herein, comprehensive methods including enzymolysis, ion-exchange chromatography and size exclusion chromatography lead to the purification of five fucan sulfates (FSI, FSII, FSIII, FSIV, FSV) from the sea cucumber Pattalus mollis. Chemical composition analysis showed that they were all composed of l -fucose. Their sulfate content was determined by a conductimetric method. The molecular weight (Mw) of FSI, FSII, FSIII, FSIV and FSV were measured as 238.3 kDa, 81.0 kDa, 82.0 kDa, 23.2 kDa and 6.12 kDa, respectively. Detailed NMR spectroscopic analysis revealed that the structural sequence of FSI and FSII was →3)- l -Fuc S -α(1→, where Fuc S were Fuc 2S4S (10%), Fuc 2S (44%), Fuc 0S (10%), Fuc 4S (36%), that of FSIII was →4)- l -Fuc 2S -(α1 → 4)- l -Fuc 2S -(α1 → 4)- l -Fuc 0S/3S -(α1→, where Fuc 0S and Fuc 3S were in equal molar, and that FSIV was →4)- l -Fuc 2S3S -(α1 → 4)- l -Fuc 2S3S -(α1 → 4)- l -Fuc 2S -(α1→4)- l -Fuc 2S -(α1 → 4)- l -Fuc 2S -(α1 → 4)- l -Fuc 2S -(α1 →. This is the first report that such a diversity of fucan sulfates were obtained from the same sea cucumber species. Biological activity showed that FSI, FSII, FSIII and FSIV exhibited potent anticoagulant by prolonging the APTT. Among them, FSII, FSIII and FSIV showed the similar potency, while FSI owned the strongest. Structure-activity relationships analysis showed that molecular weight and sulfation degree should be the crucial factors for the activity. • Five fucan sulfates were purified from sea cucumber Pattalus mollis. • The physicochemical properties of four fucan sulfates were characterized. • Structural unit of FSI and FSIII was →3)- l -Fuc S -α(1→ and →4)- l -Fuc 2S -(α1→4)- l -Fuc 2S -(α1→4)- l -Fuc 0S/3S -(α1→, respectively. • FSIV was composed of an α1,4-linked hexafucose repeating unit. • FSI exhibit strong inhibition of the intrinsic coagulation pathway. [ABSTRACT FROM AUTHOR]

A sulfated Chinese yam polysaccharide (S-CYP) was obtained from non-starch Chinese yam polysaccharide (CYP) by chlorosulfonic acid-pyridine (CSA-Pyr) method. The physicochemical characteristics and immunological activity of S-CYP were evaluated in this study. Results showed that sulfated modification changed the physicochemical properties of Chinese yam polysaccharide. Body weights and thymus index of the mice in polysaccharides group were increased compared with the cyclophosphamide (Cy)-induced immunosuppressed mice in model group, and could restore the splenomegaly that caused by Cy. It also showed that S-CYP could enhance the immunomodulatory activity on splenic lymphocytes since it could increase the proliferation of splenic lymphocytes and effectively cooperate with ConA to induce splenic lymphocytes differentiation into T lymphocytes. Meanwhile, the number of CD3+CD4+ and CD3+CD8+ T lymphocytes was elevated, the CD4+/CD8+ ratio was restored in polysaccharides group. The levels of splenic lymphocytes cytokines (interleukin (IL)-1β, tumor necrosis (TNF)-α), and the levels of immunoglobulin (IgG and IgM) secretion in serum were also increased by S-CYP significantly. These findings demonstrate that CYP and S-CYP can serve as a promising immunomodulator with potential application in functional food and nutraceutical industry. Preparation of sulfated yam polysaccharide and its immunological effects on immunosuppressed mice. Unlabelled Image • The sulfated derivative (S-CYP) was obtained from yam polysaccharide (CYP). • Physicochemical characteristics of CYP changed after sulfated. • S-CYP showed more obvious immunomodulatory activity in vivo. [ABSTRACT FROM AUTHOR]

Polysaccharide modification exerts important significance for enhancing biological activity. In the present study, a fructan (AAP70-1) extracted from Anemarrhena asphodeloides Bunge was modified by carboxymethylation and sulfation modifications to obtain carboxymethylated derivatives (CM-AAP70-1s) and a sulfated derivative (S-AAP70-1), which were prepared by the chloroacetic acid-isopropanol and the chlorosulfonic acid-pyridine methods, respectively. Physicochemical characteristics and antioxidant activities in vitro of modified derivatives were determined. The results of degree of substitution (DS) and FT-IR analysis indicated that the carboxymethylated and sulfated groups were introduced successfully. After modifications, the DS of CM-AAP70-1s varied from 0.18 to 0.52 and the molecular weights (Mw) were between 4.50 × 103 and 8.65 × 103 g/mol. The DS and Mw of S-AAP70-1 were calculated to be 0.61 and 9.76 × 103 g/mol, respectively. The assays of the antioxidant properties demonstrated that the modified derivatives exhibited stronger scavenging effects toward DPPH and hydroxyl radicals compared with AAP70-1. These results revealed that the chemical modifications could effectively improve the potential of polysaccharides as oxidation inhibitor. Unlabelled Image • CM-AAP70-1s with different DS were prepared successfully for the first time. • S-AAP70-1 was produced triumphantly for the first time. • CM-AAP70-1s and DS had some relationships on antioxidant activities. • CM-AAP70-1s and S-AAP70-1 performed higher antioxidant activities than AAP70-1. [ABSTRACT FROM AUTHOR]

Genomic analysis of the marine bacterium Wenyingzhuangia fucanilytica CZ1127T revealed the presence of four fucoidanase genes fwf1 , fwf2 , fwf3 , fwf4 that belonged to the glycoside hydrolase family 107 (GH107, CAZy), which is located in one gene cluster putatively involved in fucoidan catabolism. Genes encoding two fucoidanases fwf1 and fwf2 were cloned, and the proteins FWf1 and FWf2 were produced in Escherichia coli cells. The recombinant fucoidanases were purified and the biochemical properties of these enzymes were studied. The amino acid sequences of FWf1 and FWf2 showed 41 and 51% identity respectively with a fucoidanase FcnA from the marine bacterium Mariniflexile fucanivorans , with the established 3D structure. Structures of the oligosaccharides produced during enzymatic hydrolysis of fucoidan by FWf1 and FWf2 have been determined by NMR spectroscopy. Detailed substrate specificities of FWf1 and FWf2 were studied using fucoidans and sulfated fucooligosaccharides with different structures. Both fucoidanases catalyzed hydrolysis of 1→4-glycosidic bonds between sulfated α- l -fucose residues but had different specificities regarding sulfation patterns of the fucose residues in fucoidan molecules. Specific cleavage sites recognizable by the fucoidanases in fucoidan molecules were determined. The obtained results provide new knowledge about differences between specificities of the fucoidanases belonging to the GH107 family. • Detailed substrate specificities of two fucoidanases from W. fucanilytica were studied • The enzymes catalyze hydrolysis of 1 → 4-glycosidic bonds between sulfated fucose residues • Both enzymes recognize the different sulfation patterns and substrate lengths • Specific sites recognizable by the fucoidanases in fucoidan molecules were determined [ABSTRACT FROM AUTHOR]

Bleomycin is a clinically used anticancer drug, but it induces lung fibrosis in certain cancer patients with unknown mechanism. Glycosaminoglycans (GAGs) are required for lung morphogenesis during animal development. In current study, GAG disaccharides including heparan sulfate (HS) and chondroitin sulfate (CS) from bleomycin-induced and control lung tissues in lung fibrosis mouse model were tagged with 1-phenyl-3-methyl-5-pyrazolone (PMP) and deuterated PMP, respectively. The differentially isotope-tagged disaccharides were quantitatively compared by LC-MS. At day 10, the amount of CS disaccharides (U0a0, U0a6, and U0a4) and non-sulfated HS disaccharide (U0A0) were increased by 1.3-, 1.6-, 11.7-, and 2.2-fold, respectively, whereas the amount of CS disaccharide (U0a2), hyaluranan disaccharide (UβA0), and six HS disaccharides (U0A6, U2A0, U0H6, U0S0, U2S0, and U2S6) were decreased from1.1- to 14.3-fold compared to that of the controls. At day 15, under-sulfation of both HS and CS disaccharides was persisted. At day 30, the CS disaccharide compositions were recovered to that of the control levels whereas the HS were still remarkably under-sulfated. In conclusion, GAGs, especially HS, from fibrotic lungs induced by a single injection of bleomycin were significantly under-sulfated up to 30 days, suggesting GAGs might be another class of defective signaling molecules involved in bleomycin-induced lung fibrosis. [ABSTRACT FROM AUTHOR]

In this study, a crude and purified polysaccharide from Cyclocarya paliurus (CPP, CPP 0.05) were performed with chlorosulfonic acid–pyridine (CSA–Pyr) method to obtain sulfated derivatives (S-CPP, S-CPP 0.05). After comparatively investigating, characterization results showed that the modifications were successful. Polysaccharides were used to culture mouse bone marrow-derived dendritic cells (BM-DCs) to evaluate their immunomodulatory activity and explore mechanism. The functional activity of CPP was significantly stronger than that of the purified polysaccharide CPP 0.05. Meanwhile, S-CPP showed stronger immunomodulatory activity than CPP through determination of cytokine expression levels. We found that p-JNK, p-p38MAPK and NF-κB p65 proteins were significantly increased by stimulus of CPP and S-CPP, blocking TLR2/4 could significantly decreased proteins above which proved that immune regulation effect of CPP and S-CPP on DCs was performed via MAPK and NF-κB signaling pathways by triggering TLR2/4. S-CPP could serve as potential immunomodulatory agents used as complementary medicine or functional foods. [ABSTRACT FROM AUTHOR]

In the present study, regioselective sulfation of β-glucan (GLP) from Ganoderma lucidum were firstly established by using 4,4′-dimethoxytrityl chloride and hexamethyldisilazane as protecting precursor. 2,4,6-O-sulfated, 6-O-sulfated and 2,4-O-sulfated GLP derivatives were prepared and the molecular weights (M w) of derivatives were determined to range from 0.94 × 104 to 6.27 × 104 g/mol, while the degrees of sulfation (DS) were calculated to vary from 0.83 to 1.74. The regioselective sulfation of GLP was confirmed by FT-IR, 13C NMR spectroscopy and methylation analysis. Results indicated that the sulfated substitution sites were predominantly at C-6 in 6-O-sulfated GLP (S 6-O GLP) and C-4 in 2,4-O-sulfated GLP (S 2,4-O GLP), respectively. Clotting assays (APTT, PT and TT) in vitro showed that sulfate groups were essential for anticoagulant activity and S 6-O GLP exhibited much higher than others. Meanwhile, sulfated GLP with higher DS and M w showed stronger anticoagulant activity in the case of the same condition. • Regioselective sulfation of β-glucan from Ganoderma lucidum was established. • 2,4,6-O-sulfated, 6-O-sulfated and 2,4-O-sulfated β-glucans were prepared. • The structure-anticoagulant activity relationship of sulfated glucan was evaluated. • 6-O-sulfated β-glucan showed strongest anticoagulant activity. • The anticoagulant activity was mainly dependent on position of sulfate groups. [ABSTRACT FROM AUTHOR]

Interest in galactomannans and its derivatives as a functional health supplement is growing based on physicochemical properties. In this work, the optimized conditions of sulfated tara gum (STG) with a maximum DS of 0.66 by box-behnken design (BBD) were obtained as following: ratio of chlorosulfonic acid/pyridine 3:1, reaction time 4 h and reaction temperature 40 °C. The structure features of STG such as the degree of substitution (DS), substitution position, weight average molar mass (M W), monosaccharide components and chain conformation were investigated. Decreasing of M W , the increasing of Z -average radius of gyration (〈 S 2〉 Z 1/2) and specific volume for gyration (SV g) were obtained by SEC-MALLS. In addition, the structural properties of four sulfated galactomannans were comparatively investigated and analyzed based on our earlier reports of sulfated fenugreek gum, guar gum and locust bean gum. A conclusion was drown that higher galactose branch could enhance steric hindrance, which was inferred as one of the significant factors for the derivatization efficiency, thus affecting the DS, M W and conformational transition of sulfated galactomannans. This study will provide valuable information for further research on the comparison of bioactivities and medical application of galactomannans family. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein-2 (BMP-2) is a critical growth factor of bone extracellular matrix (ECM), pivotal for osteogenesis. Glycosaminoglycans (GAGs), another vital ECM biomolecules, interact with growth factors, affecting signal transduction. Our study primarily focused on hyaluronic acid (HA), a prevalent GAG, and its sulfated derivative (SHA). We explored their impact on BMP-2's conformation, aggregation, and mechanistic pathways of aggregation using diverse optical and rheological methods. In the presence of HA and SHA, the secondary structure of BMP-2 underwent a structured transformation, characterized by a substantial increase in beta sheet content, and a detrimental alteration, manifesting as a shift towards unstructured content, respectively. Although both HA and SHA induced BMP-2 aggregation, their mechanisms differed. SHA led to rapid amorphous aggregates, while HA promoted amyloid fibrils with a lag phase and sigmoidal kinetics. Aggregate size and shape varied; HA produced larger structures, SHA smaller. Each aggregation type followed distinct pathways influenced by viscosity and excluded volume. Higher viscosity, low diffusivity of protein and higher excluded volume In the presence of HA promotes fibrillation having size in micrometer range. Low viscosity, high diffusivity of protein and lesser excluded volume leads to amorphous aggregate of size in nanometer range. Bone Morphogenetic Protein-2 aggregates as amyloid aggregate upon interaction with the Hyaluronic acid (HA) and forms amorphous aggregate interaction with Sulfated Hyaluronic acid (SHA). Both the aggregation processes follow different pathways due to differential viscosity and excluded volume. [Display omitted] [ABSTRACT FROM AUTHOR]

Diabolican is an exopolysaccharide (EPS) produced by Vibrio diabolicus HE800, a mesophilic bacterium firstly isolated from a deep-sea hydrothermal field. Its glycosaminoglycan (GAG)-like structure, consisting of a tetrasaccharide repeating unit composed of two aminosugars (N -acetyl-glucosamine and N -acetyl-galactosamine) and two glucuronic acid units, suggested to subject it to regioselective sulfation processes, in order to obtain some sulfated derivatives potentially acting as GAG mimics. To this aim, a multi-step semi-synthetic approach, relying upon tailored sequence of regioselective protection, sulfation and deprotection steps, was employed in this work. The chemical structure of the obtained sulfated diabolican derivatives was characterized by a multi-technique analytic approach, in order to define both degree of sulfation (DS) and sulfation pattern within the polysaccharide repeating unit, above all. Finally, binding affinity for some growth factors relevant for biomedical applications was measured for both starting diabolican and sulfated derivatives thereof. Collected data suggested that sulfation pattern could be a key structural element for the selective interaction with signaling proteins not only in the case of native GAGs, as already known, but also for GAG-like structures obtained by regioselective sulfation of naturally unsulfated polysaccharides. [ABSTRACT FROM AUTHOR]

This study focuses on the production of sulfated cellulose microfibers and nanocellulose hydrogels from native cellulose microfibers (CMF). The process involves using a combination of H 2 SO 4 and urea, resulting in highly sulfated cellulose microfiber hydrogel (SC) with notable properties such as a sulfur content of 7.5 %, a degree of sulfation of 0.49, a surface charge content of 2.2 mmol. g−1, and a high yield of 81 %. The SC hydrogel can be easily fibrillated into sulfated nanocellulose hydrogel (S-NC) with elongated nanocellulose structures having an average diameter of 6.85 ± 3.11 nm, as determined using atomic force microscopy (AFM). X-ray photoelectron spectroscopy (XPS) analysis confirms the presence of sulfate groups on the surface of the nanocellulose material. Transparent films with good mechanical properties can be produced from both cellulose microfiber and nanocellulose hydrogels. The sulfate functionality gives the hydrogel attractive rheological properties and makes S-NC re-dispersible in water, which can be beneficial for various applications. This study demonstrates the potential of this process to address previous challenges related to nanocellulose materials production. [Display omitted] [ABSTRACT FROM AUTHOR]

Fucoidans are natural polysaccharides with pronounced antitumoral activities. Their modes of action include the antagonization of the chemokine CXCL12, which plays a central role in tumor development and metastasis. However, the usually high molecular mass (M w) of fucoidans represents an obstacle to their medical application. We therefore investigated two series of degraded fucoidan fractions with regard to their CXCL12 binding and inhibition of CXCL12-induced effects in Raji cells. In addition, semisynthetic β-1,3-glucan sulfates were examined to get more information about the impact of M w and degree of sulfation (DS). Degradation of the fucoidans from Saccharina latissima (S.l. -SP; 481–77.0 kDa) and Fucus vesiculosus (F.v. -SP; 38.2–20.6 kDa) did not affect the respective binding capacity to CXCL12. Both the M w independence and the DS dependence were confirmed by the β-1,3-glucan sulfates having significantly higher affinity to CXCL12. The chemokine binding resulted in reduced CXCL12-induced Erk1/2 signaling and chemotaxis of Raji cells which was also independent of the M w. Solely the oxidatively degraded fucoidan fraction displayed a significantly reduced chemotaxis inhibition. In conclusion, degradation of fucoidans to obtain biopharmaceutically more favorable M w is possible without impairing their activities targeting CXCL12. Moreover, the β-1,3-glucan sulfates should also be considered as promising candidates for further development. [ABSTRACT FROM AUTHOR]

For a more insightful investigation into the specificity of bacterial heparinase I, a series of structurally well-defined heparin oligosaccharides was synthesized using a highly efficient chemoenzymatic strategy. Apart from the primary cleavage site, five glycosidic linkages of oligosaccharides with varying modifications to obtain secondary cleavage sites were degraded by a high concentration of heparinase I. The reactivity of linkages toward heparinase I was not entirely dependent on the 2- O -sulfated iduronic acid being cleaved or the neighboring 6- O -sulfated glucosamine residues, but it was dependent on higher degrees of sulfation of oligosaccharides and indispensable N -substituted glucosamine adjacent to the cleavable linkage. Moreover, the enzyme demonstrated less preferential cleavage toward glycosidic linkages containing glucuronic acid than those containing iduronic acid of the counterpart oligosaccharides. Biolayer interferometry revealed differences in reactivity that are not completely consistent with different affinities of substrates to enzyme. Our study presented accurate information on the cleavage promiscuity of heparinase I that is crucial for heparin depolymerization. • Heparin oligosaccharides were chemoenzymatically synthesized as substrates of heparinase I. • Five secondary cleavage sites of oligosaccharides were degraded to less extents by heparinase I. • The enzymatic reactivity was dependent on different modification of uronic acid or GlcN. • Heparinase I had less preferential cleavage towards GlcA-formed linkages than IdoA. • BLI proved differences in reactivity are partially consistent with substrate affinity to enzyme. [ABSTRACT FROM AUTHOR]

Echinacea purpurea polysaccharide (EPP) was obtained by modern separation technology and sulfated EPP (sEPP) was prepared by sulfation modification. The immunological effects of EPP and sEPP were compared on chicken bone marrow-derived dendritic cells (chBM-DCs). The results showed that the surface marker expression of CD11c and CD80 was increased after chBM-DCs were cultured with three dosage of sEPP, especially in sEPP M group. Three dosage of sEPP, EPP L and LPS could significantly enhance the effects of chBM-DCs on the proliferation of allogenic mixed lymphocytes. After chBM-DCs treatment with EPP or sEPP in vitro, the levels of IL-2 of sEPP H and EPP M groups were significantly higher than those of LPS group (P < 0.05). All sEPP and EPP groups could enhance the level of IFN-γ and down-regulated the level of IL-4 and IL-10. Results indicated that both sEPP and EPP had immunoregulatory effects on chBM-DCs, sEPP possessed better immunoregulatory effects as compared with EPP. [ABSTRACT FROM AUTHOR]

Polysaccharides with different structures have been reported to regulate iron uptake in opposite direction. The present study investigated the interaction between a sulfated polysaccharide (AGSP) from marine shellfishes and Fe(III)/Fe(II) in order to reveal the mechanism for the effect of AGSP on iron bioavailability. The Fe(III) chelating activity and resulting Fe(III)-chelates of AGSP and its desulfated derivative (dS-AGSP) were studied, their ferric reducing activity and Fe(II) chelating activity were compared, and their inhibition effects on the Fe absorption were evaluated by using Caco-2 cell models treated with Fe(III) and Fe(II). As indicated by the results, polysaccharides could chelate Fe(III) with the sulfate and carboxyl groups via Fe O bond along with conformation change, resulting in unstable particles. Both AGSP and dS-AGSP inhibited the iron uptake in a dose-dependent manner. Notably, the chelating property of polysaccharides showed a negative correlation with the iron bioavailability while their reducing capability demonstrated a positive correlation. Moreover, sulfate substitution enhanced the chelating and reducing capabilities so to regulate the effects of AGSP on Fe absorption in contradictory ways. Thus, the present study elucidated the mechanism of the influence of AGSP on bioavailability of non-heme iron. Unlabelled Image • A polysaccharide (AGSP) and its desulfated derivative (dS-AGSP) inhibit Fe absorption. • AGSP has a higher capability to chelate Fe(III) and Fe(II) than dS-AGSP. • Interaction between Fe(III) and sulfate and carboxyl groups of polysaccharides were confirmed. • AGSP has a stronger ferric reducing activity than dS-AGSP. • Chelating and reducing activities have opposite effects on the iron uptake. [ABSTRACT FROM AUTHOR]

The provisioning of compound libraries with a high degree of diversity and attractive pharmacological properties is a limiting step in drug development. This study reports the production of highly bioactive sulfated polysaccharides, originally present in a nonsulfated, dormant state in natural sources, and demonstrates their antiviral activity (human cytomegalovirus EC 50 values of 2.34–7.77 μg/mL) at a low degree of cytotoxicity. Furthermore, data strongly suggested the inhibition of virus entry as the main mode of antiviral action. Remarkably, the utilized oleum-DMF reagent was able to generate a range of sulfated polysaccharides from various natural sources, possessing varying saccharide compositions, degrees of sulfation (0.4–1.7) and molecular masses (38–94,000 g/mol). Typically, in a matter of minutes, this reagent not only solubilized polysaccharides but also chemically converted their hydroxyl functionality into sulfates. The most active sulfated polysaccharide (EC 50 of 2.62 μg/mL) proved to be a 94,000 g/mol branched glucan with sulfates at C-6/C-3,6/C-2,3,6 positions. In conclusion, the important determinants of such compounds' antiviral activity are: (i) degree of sulfation, (ii) molecular mass and (iii) structural features. Thus, our approach offers a huge prospect for the improvement of natural source-derived libraries based on biologically active polysaccharides with diversified chemical profiles. • Polysaccharides with varied structures were produced and activated from natural sources. • Concurrent extraction and sulfation of polysaccharides was achieved by one-pot strategy. • Produced compounds exhibited strong antiviral activity and low degree of cytotoxicity. • Huge prospect for the generation of bioactive polysaccharides from other natural sources [ABSTRACT FROM AUTHOR]

Abstract Sulfated derivatives of the galactomannan family have multiple biological activities. In the present study, sulfated galactomannan from fenugreek gum (SFG) were prepared by chlorosulfuric acid/pyridine (CSA/Py) method. In order to acquire the derivatives with the highest degree of substitution (DS), the experiment optimum conditions of the sulfation were determined by Box-Behnken design (BBD). The quadratic regression model analysis confirmed that reaction time was the most significant parameter for the impact of DS. Under the selected conditions, maximum DS was obtained as 0.490. Results of FT-IR and X-ray photoelectron spectroscopy (XPS) indicated the present of SO 3 − group. In 13C NMR spectroscopy, the original C-6 peaks did not disappear completely and the newly peaks appeared at δ 63.2 and 64.0 illustrating the incomplete substitution were predominantly on C-6 position. After sulfation, size exclusion chromatography combined with multi-angle laser light scattering (SEC-MALLS) detected all the weight average molecular mass (M W) of sulfated derivatives decrease rapidly. The introduction of the electrostatic interaction of negatively charged SO 3 − groups and the decrease in M W could have a significant effect on its biological activity. Highlights • Sulfated galactomannan of fenugreek gum is synthesized and characterized in the present work. • Sulfation conditions are optimized by response surface methodology with a maximum degree of substitution 0.490. • Structure characterization illustrated the introduction of SO 3 − and the substitution at C-6. • All sulfated fenugreek gum derivatives showed a rapidly decrease in weight average molar mass. [ABSTRACT FROM AUTHOR]

In this study, furcellaran (FUR) obtained from Furcellaria lumbricalis was firstly employed for sulfation via various methods, including SO 3 -pyridine (SO 3 ∙Py) complex in different aprotic solvents, chlorosulfonic acid and sulfuric acid with a "coupling" reagent N,N′-Dicyclohexylcarbodiimide. Structural characterization through FT-IR, GPC, XPS and elemental analyses confirmed the successful synthesis of 6- O -sulfated FUR derivates characterized by varying degrees of sulfation (DS) ranging from 0.15 to 0.91 and molecular weight (M w) spanning from12.5 kDa to 2.7 kDa. In vitro clotting assays, partial thromboplastin time (aPTT), thrombin time (TT), and prothrombin time (PT) underscored the essential role of sulfate esters in conferring anticoagulant activity whereas FUR prepared via chlorosulfonic acid with DS of 0.91 reached 311.4 s in aPPT showing almost 4-fold higher anticoagulant activity than native FUR at the concentration 2 mg/mL. MTT test showed all tested samples decreased cell viability in a dose dependent manner while all of them are non-cytotoxic up to the concentration of 0.1 mg/mL. Furthermore, sulfated derivates deposited onto polyethylene terephthalate surface presented substantial decrease in platelet adhesion, as well as absence of the most activated platelet stages. These findings support the pivotal role of O -6 FUR sulfates in enhancing hemocompatibility and provide valuable insights for a comparative assessment of effective sulfating approaches. • Furcellaran from Furcellaria lumbricalis was chemically modified via various sulfating methods. • Sulfated derivatives with different degrees of sulfation (DS) and molecular weights (Mw) were successfully obtained. • Anticoagulant activities and platelet adhesion in vitro of sulfated derivatives were investigated. • Relationship between molecular properties and bioactivity were discussed. [ABSTRACT FROM AUTHOR]

Herpes simplex viruses (HSVs) have an affinity for heparan sulfate proteoglycans on cell surfaces, which is a determinant for virus entry. Herein, several sulfated galactans that mimic the active domain of the entry receptor were employed to prevent HSV infection. They were produced from Grateloupia indica using chlorosulfonic acid-pyridine (ClSO 3 H.Py)/ N , N -dimethylformamide reagent (fraction G-402), SO 3.Py/DMF reagent (G-403), or by aqueous extraction (G-401). These galactans contained varied molecular masses (33–55 kDa), and sulfate contents (12–20 %), and have different antiviral activities. Especially, the galactan (G-402) generated by using ClSO 3 H.Py/DMF, a novel reagent, exhibited the highest level of antiviral activity (EC 50 = 0.36 μg/mL) compared to G-403 (EC 50 = 15.6 μg/mL) and G-401 (EC 50 = 17.9 μg/mL). This most active sulfated galactan possessed a linear chain containing β-(1 → 3)- and α-(1 → 4)-linked Gal p units with sulfate group at the O -2/4/6 and O -2/3/6 positions, respectively. The HSV-1 and HSV-2 strains were specifically inhibited by this novel 33 ± 15 kDa galactan, which also blocked the virus from entering the host cell. These results highlight the significant potential of this sulfated galactan for antiviral research and drug development. Additionally, the reagent used for the effective conversion of galactan hydroxy groups to sulfate during extraction may also be useful for the chemical transformation of other natural products. • Synchronized extraction and chemical sulfation of polysaccharides from Grateloupia indica was done. • Two sulfated galactan with different structures were synthesized using ClSO 3 H.Py/DMF and SO 3.Py/DMF reagents. • The ClSO 3 H.Py/DMF-generated sulfated galactan was the most potent and selective inhibitor of HSV-1. • This 33 kDa galactan having 20 % sulfate contained (1,3)- & (1,4)-linked galactan backbone. • Inhibition of viral entry, possibly linked to additional later effects is the main mode of action. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease. NSAIDS, cyclophosphamide and glucocorticoid were commonly used to treat RA in clinical application, which long-term administration of these drugs caused serious adverse reactions. Therefore, sulfated hyaluronic acid (sHA) gel (SG) was prepared to firstly treat the RA and avoid the problem of toxic side effect caused by long-term application. In vitro evaluation showed that sHA inhibited the level of reactive oxygen species and TNF-α, IL-1β, and IL-6, and decreased the ratio of macrophage M1/M2 type, which exerted better anti-inflammatory capacity. In vivo studies showed that the injection of SG into the joint cavity of collagen-induced rheumatoid arthritis (CIA) rats could effectively treat joint swelling and reduce the level of inflammatory factors in the serum. Immunofluorescence showed that SG exerted its anti-inflammatory activity by decreasing the ratio of M1/M2 type macrophages in synovial tissue. Cartilage tissue sections showed that SG reduced bone erosion and elevated chondrocyte expression. These results confirmed that sHA is expected to be developed as a drug to treat or relieve RA, which could effectively regulate the level of macrophages in rat RA, alleviate the physiological state of inflammatory over-excitation, and improve its anti-inflammatory and antioxidant capacity. [Display omitted] • mHA was modified by sulfation to synthesize sHA. • SG reduced ratio of MI/M2 type macrophages in inflammatory cells and rats. • SG decreased synovial tissue proliferation and increased Col II and chondrocytes. [ABSTRACT FROM AUTHOR]

Sea cucumbers contain a wide range of biomolecules, including sulfated polysaccharides (SPs), with immense therapeutic and nutraceutical potential. SPs in sea cucumbers are mainly fucosylated chondroitin sulfate (FCS) and fucan sulfate (FS) which exhibit a series of pharmacological effects, including anticoagulant activity, in several biological systems. FCS is a structurally distinct glycosaminoglycan in the sea cucumber body wall, and its biological properties mainly depend on the degree of sulfation, position of sulfate group, molecular weight, and distribution of branches along the backbone. So far, FCS and FS have been recognized for their antithrombotic, anti-inflammatory, anticancer, antidiabetic, anti-hyperlipidemic, anti-obesity, and antioxidant potential. However, the functions of these SPs are mainly dependent on the species, origins, harvesting season, and extraction methods applied. This review focuses on the SPs of sea cucumbers and how their structural diversities affect various biological activities. In addition, the mechanism of actions of SPs, chemical structures, factors affecting their bioactivities, and their extraction methods are also discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

Glycosaminoglycans (GAGs) are naturally existing extracellular components with a variety important biological functions. However, their heterogeneous chemical compositions and the challenges in purification have become the main disadvantages for clinical applications. Thus, various synthetic glycopolymers have been designed to mimic the structures and functions of natural GAGs. In the current study, glycopolymers from structurally simple glucose or N -acetylglucosamine monomers were synthesized, which were further subjected to sulfation of different degrees and grafting onto silica nanoparticles, leading to spherical-shaped nano-structures of uniform diameters. With the successively strengthened multivalent effect, the obtained glycopolymer nanoparticles not only showed excellent effects on promotion of cell proliferation by stabilizing growth factors, but also significantly inhibited tumor metastasis by weakening the adhesion between tumor cells and activated platelets. Among the prepared nanoparticles, S 3 -PGNAc@Si with N -acetylglucosamine segment and the highest sulfation degree exhibited the strongest bioactivities, which were even close to those of heparin. This work presents a novel approach for structural and functional mimicking of natural GAGs from simple and low-cost monosaccharides, holding great potential for a range of biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract The aqueous polysaccharide from Polygonatum sibiricum was extracted and fractionated using anion-exchange chromatography to obtain F 1 fraction. The F 1 was chemically sulfated and partially acid-hydrolyzed for the production of its over-sulfated (OS 1,2,3) and hydrolyzed (HP 1,2,3) derivatives, in which the sulfate content of OS 1,2,3 was 7.5–17.1%, and the M w of HP 1,2,3 ranged from 18.2 × 103 to 57.3 × 103 g/mol. Considerable RAW264.7 cell activation was observed by HP 1,2,3 with NO production of 34.9, 44.3 and 42.7 μM, respectively, as well as the mRNA expression of cytokines (IL-1β, IL-6, IL-10 and IL-12). NK cell cytotoxicity against HT-29 cell was facilitated by OS 1,2,3 treatment with the increased gene expressions of INF-γ, Granzyme-B, perforin, NKG2D, and FasL. RAW264.7 cells appeared to be activated via MR and TLR4 mediated signaling pathway, but CR3 and TRL2 might play a main role in stimulating NK cells. Overall, the present study suggests the potential application of polysaccharides from P. sibiricum in functional foods and pharmacological industries. Highlights • Polysaccharide was extracted and purified from Polygonatum sibiricum. • Fraction 1 (F 1) was over-sulfated and acid hydrolyzed. • The M w of F 1 appeared to influence the RAW264.7 cell activation. • The sulfation was beneficial for improving its NK cell cytotoxicity. [ABSTRACT FROM AUTHOR]

Abstract In order to develop new and low cost anticoagulants as potential heparin alternatives, sulfation of a pectin-like polysaccharide from Opuntia ficus indica cladodes using SO 3 -DMF complex was performed with a significant sulfate content (7%). FTIR and NMR assays indicated that the sulfation reaction had occurred. In addition, GC–MS analyses demonstrated that sulfation was carried out on the arabinose units of native polysaccharide. Moreover, Physico-chemical characterization indicated an evident decrease of the average molecular weight (M w) and sugar rates after sulfation. Finally, anticoagulant assays demonstrated that the anticoagulant activity was significantly enhanced by the addition of sulfate groups. Thus, sulfated polysaccharides exhibited the most potent anticoagulant activity by prolonging activated partial thromboplastin time (APTT) and thrombin time (TT). Highlights • Pectin was isolated from Opuntia ficus indica (OFI) cladodes with yield of 24.50% from dry matter. • Chemical sulfation of extracted pectin was performed using SO 3 -DMF complex. • FTIR, NMR and GC–MS indicated that the sulfation reaction had occurred with a highest sulfate content of 7.04%. • Sulfated polysaccharides showed significant anticoagulant potential depending on the sulfate content. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the chemical characterization of a sulfated polysaccharide isolated from Codium fragile alga (CFSP), using various assays such as FTIR, XRD, GC-MS and NMR spectroscopy including 1 H, 13 C, COSY, HSQC, HMBC and NOESY experiments as well as its inhibitory effects on α-amylase activity, liver-kidney toxicities and lipid profile disorders in alloxan-induced diabetic rats. Combined results showed that the CFSP is composed mainly by a galactopyranose and d -glucose, with these various bonds and these various functional groups. The antihyperglycaemic effect of this polysaccharide resulted in a significant decrease in blood glucose and intestinal amylase levels. It had the effect of significantly restoring the hepatic, pancreatic and renal antioxidant enzymes with a significant reduction in TBARS levels. The CFSP also acted at the tissue by moderating the appearance of lipid vacuoles at the hepatocytes and restoring the general histological organization of the kidneys and pancreas. [ABSTRACT FROM AUTHOR]

In the present study, three sulfated polysaccharides, two fractions of fucosylated chondroitin sulfates, and one sulfated fucan were isolated from the body wall of the Vietnamese sea cucumber Stichopus variegatus . The structure of the sulfated fucan fraction SvF3 from S. variegatus was investigated for the first time. According to NMR spectroscopy data, the sulfated fucan SvF3 contained 1,2- and 1,3-linked α- l -fucopyranose residues. Sulfate groups were found at the 2 and/or 4 positions. The structural analysis of fucoidan was assisted by tandem mass spectrometry; the recently-developed technique of autohydrolysis in heavy‑oxygen water for the obtaining of selectively labeled fucoidan fragments was applied. The labeling (+2 Da mass shift at the reducing end) allowed us to assign MS/MS data unambiguously, and thus to confirm the NMR data and revealed minor sulfation at position 3. It was shown that the sulfated fucan SvF3 was not cytotoxic to human breast cancer T-47D and MDA-MB-231 cell lines, and it inhibited colony formation of those cells in vitro . SvF3 also possessed slight activity against migration of MDA-MB-231 cells in vitro . [ABSTRACT FROM AUTHOR]

Polysaccharide is a kind of natural macromolecule polymer, which is widely existed in animals, plants and microorganisms, has a variety of biological activities, such as anti-tumor, anti-virus, anti-oxidation and immune regulation. Polysaccharides can affect macrophages, cells and other immune cells to improve the body's immune function, and have no toxic and side effects on normal cells, which make the polysaccharides receive widespread attention. In recent years, studies have shown that structural modification of polysaccharides can improve the immunological activity of polysaccharides. The common chemical modifications are sulfation, carboxymethylation, acetylation, phosphorylation, and so on. The chemical modification of polysaccharides and the immunomodulation of polysaccharides and polysaccharide derivatives were analyzed and discussed. [ABSTRACT FROM AUTHOR]

In this work, a purified Laminaria japonica polysaccharide (LJP61A) was chemically modified to obtain three sulfated polysaccharides (SLJP1, SLJP2 and SLJP3) with different degrees of sulfation using the method of chlorosulfonic acid/pyridine. The effects and underlying mechanism of SLJP1, SLJP2 and SLJP3 on the suppression of macrophage foam cell formation were further investigated using the model of oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation. Results exhibited that the macrophage foam cell formation induced by ox-LDL could be significantly alleviated by these sulfated polysaccharides in a dose-dependent manner. Meanwhile, the enhancement of PPAR- γ mRNA expression in ox-LDL induced macrophages was remarkably inhibited by these sulfated polysaccharides. Moreover, the cellular inflammation induced by ox-LDL could also be remarkably mitigated by these sulfated polysaccharides. These results indicated that the sulfated L. japonica polysaccharides could inhibit the conversion of macrophage into foam cell via obstructing PPAR- γ activation and alleviating cellular inflammation. [ABSTRACT FROM AUTHOR]

The current study assesses the potential of functionalised chitosan nanoparticles (CNPs) for proficient macrophage delivery of amphotericin B (AmpB) for the management of Candida glabrata fungemia. Chitosan was functionalised by the method of sulfation by using chlorosulfonic acid and the developed compound was confirmed by FTIR, 1 H NMR and degree of sulfation and CHNS analysis. Amphotericin B encapsulated sulfated chitosan (AmpB-SCNPs), when characterized showed a hydrodynamic diameter of 310 ± 14 nm and zeta potential of 41.5 ± 2 mV. The safety of AmpB-SCNPs was established by the alamar cytotoxicity assay in nanoparticle treated macrophages following 24 h incubation. The AmpB-SCNPs showed a significant increase in the reduction of C. glabrata in comparison with the bare AmpB and AmpB-CNPs (55.2 and 42.7 vs 11.12 cfu/ml) indicating that AmpB-SCNPs could be a promising carrier for specific delivery of AmpB to macrophages for effective treatment of Candida glabrata fungemia. [ABSTRACT FROM AUTHOR]

Sulfated modification was conducted to modify a homogenous polysaccharide from blackcurrant (BCP). The sulfated polysaccharides (SBCPs) with different degree of substitution (DS) were synthesized using the aminosulfonic acid (ASA)/4-dimethylaminopyridine method by varying reaction conditions such as the mass ratio of ASA to BCP, temperature, and time. Three sulfated derivatives were chosen for high-performance gel-permeation chromatography, gas chromatography, fourier-transform infrared (FT-IR) spectroscopy, and nuclear magnetic resonance (NMR), and activity studies, designated as SBCP-1, SBCP-2, and SBCP-3 with DS of 1.28, 0.95, and 0.53, respectively. Results showed that the sulfated modification was successful, and SBCPs had an increase in molecular weight compared to BCP. Both SBCPs and BCP were composed of rhamnose, arabinose, xylose, mannose, galactose, and glucose, with different molar ratios. Sulfate substitution was further confirmed by FT-IR and 13 C NMR analysis. SBCPs exhibited excellent antioxidant capacities (DPPH, hydroxyl, and superoxide radical scavenging, reducing power, and ferrous metal-chelating capacities) and α-amylase inhibitory activity in vitro , and the activities of SBCPs were significantly improved in positive correlation with the DS value. This study suggested that SBCPs could serve as potential antioxidant agents to be used as alternative supplements or functional foods. [ABSTRACT FROM AUTHOR]

Sulfated polysaccharides exhibit various biological properties, including anti-coagulant, anti-oxidant, anti-viral, anti-cancer, anti-inflammatory and immune regulatory activities. In the present study, the anti-inflammatory properties of GLPss58, a sulfated polysaccharide from Ganoderma lucidum formed by chemical sulfation, were investigated. We found that GLPss58 inhibited L-selectin/sTyr-sLeX binding significantly, blocked the binding of anti- l -selectin antibodies to L-selectin on the surface of human peripheral blood lymphocytes, and inhibited the secondary lymphoid tissue chemokine-induced chemotactic invasion of HPBLs. In vivo studies in mice showed that lymphocyte homing from peripheral blood to spleen and lymph nodes was significantly inhibited by GLPss58. Furthermore, GLPss58 also inhibited the activation of complement systems and blocked the binding of TNF-α and IFN-γ to their antibodies. These results indicate that GLPss58 is able to inhibit not only the L-selectin-mediated inflammation, but also the complement system- and cytokines mediated-inflammation. Our results suggest that GLPss58 is a favorable potential anti-inflammatory agent. [ABSTRACT FROM AUTHOR]