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1.
Int J Biol Macromol ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31751735

RESUMO

The structural elucidation of polysaccharides is essential for understanding their structure-bioactivity relationship and related drug development. In this study, fucoidan (Fuchp) was extracted and purified from sea cucumber Holothuria polii. Its sulfate content was 39.5 ± 1.4%, and the "weight-average" molecular mass was 103.1 ± 2.8 kDa. The primary structure of Fuchp was clarified using a combination of acid degradation, tandem mass spectrometry, and nuclear magnetic resonance spectroscopy analysis. As a result, Fuchp was found to be composed of a tetrafucose repeating unit [→3-α-l-Fucp-1→3-α-l-Fucp2(OSO3-)-1→3-α-l-Fucp2(OSO3-) -1→3-α-l-Fucp2,4(OSO3-)-1→]. The stimulating hematopoiesis was further evaluated in a mouse model induced by cyclophosphamide. Based on these findings, intraperitoneally administered Fuchp may accelerate the recovery of white blood cells and neutrophils, in which its activity exceeded that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Meanwhile, in the background of cyclophosphamide-induced immunosuppression, treatment with Fuchp reduces platelet aggregation caused by CTX, so it might have the effect of reducing the risk of thrombosis. Therefore, Fuchp can be expolited as potentially promising stimulator of hematopoiesis in the future.

2.
Int J Biol Macromol ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715242

RESUMO

A preliminary relationship was illustrated between the structural characteristics and corresponding immunomodulatory activities of G. lucidum polysaccharides. Two polysaccharides (GLP-1 and GLP-2) were purified from Ganoderma lucidum extracts by gradient ethanol precipitation and a Q-Sepharose Fast Flow (QFF) strong anion-exchange column. The monosaccharide composition, high-performance gel permeation chromatography-multi-angle laser light scattering-refractive index (HPGPC-MALLS-RI), Fourier-transform infrared spectroscopy (FT-IR), atomic force microscopy (AFM), methylation analysis, and nuclear magnetic resonance (NMR) were used to characterize these polysaccharides. The GLP-1 polysaccharide was elucidated as D-galactoglucan with a flexible random linear conformation that mainly composed of →6)-ß-D-Glcp-(1→, →6)-α-D-Galp-(1→, and →3)-ß-D-Glcp-(1→ residues. GLP-2 was found to be a relatively homogeneous ß-D-glucan that possessing →6)-ß-D-Glcp-(1→ and →3)-ß-D-Glcp-(1→ residues packaged into a spherical conformation. Immunomodulatory activities in vivo demonstrated that GLP-1 produced better protection of the spleen and thymus and was more effective for promoting hematopoiesis and improving IgA levels in serum. Our results suggest that the immunomodulatory activities of G. lucidum polysaccharides are highly corresponded to their structural characteristics such as carbohydrate composition, molecular weight and advanced conformation. This study provides a preliminary basis for studying the relationship between polysaccharide structure characterization and pharmacological activities.

3.
Molecules ; 24(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547311

RESUMO

Recent studies have reported that dietary fiber improved metabolic syndrome (MetS). However, the effects of fucoidans on MetS were still not clear. In this study, we evaluated the activity of fucoidan from Fucus vesiculosus (FvF) on attenuating MetS and first elucidated the underlying mechanism. In vitro, FvF treatment remarkably lowered the level of reactive oxygen species (ROS) compared with the sodium palmitate (PA)-induced insulin resistance (IR) group. The phosphorylation level of c-Jun N-terminal kinase (JNK) was significantly decreased, while phosphorylation of protein kinase B (pAkt) level increased, compared with that of the HepG2 cells treated with PA. Thus, FvF increased glucose consumption and relieved IR via ROS-mediated JNK and Akt signaling pathways. In addition, these changes were accompanied by the activation of adenosine 5'-monophosphate-ativated protein kinase (AMPK) and its downstream targets (e.g., HMG-CoA reductase (HMGCR), acetyl-CoA carboxylase (ACC), and sterol-regulatory element-binding protein-1c (SREBP-1C)), which improved lipid metabolism in IR HepG2 cells. In vivo, FvF improved hyperglycemia and decreased serum insulin level in mice with MetS. Furthermore, we evaluated the inhibition of glucose transport by in vitro (Caco-2 monolayer model), semi-in vivo (everted gut sac model) and oral glucose tolerance test (OGTT), which indicated that FvF could significantly reduce the absorption of glucose into the blood stream, thus it could improve blood-glucose levels and IR in mice with MetS. Moreover, FvF decreased serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels and liver lipid accumulation, while increased the serum high density lipoprotein cholesterol (HDL-C) level in mice with MetS. Therefore, FvF could be considered as a potential candidate for the treatment of MetS by alleviating IR, inhibiting glucose transportation, and regulating lipid metabolism.

4.
Glycoconj J ; 36(5): 419-428, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31297734

RESUMO

Gangliosides altered during the pathological conditions and particularly in cancers. Here, we aimed to profile the gangliosides in breast cancer serum and propose potential biomarkers. LC-FTMS method was first used to identify all the ganglioside species in serum, then LC-MS/MS-MRM method was employed to quantitate the levels of gangliosides in serum from healthy volunteers and patients with benign breast tumor or breast cancer. 49 ganglioside species were determined, including GM1, GM2, GM3, GD1, GD3 and GT1 species. Compared to healthy volunteers, the levels of GM1, GM2, GM3, GD1 and GD3 displayed a rising trend in breast cancer patients. In particular, as the major glycosphingolipid component, GM3 showed excellent diagnostic accuracy in cancer serum (AUC > 0.9). PCA profile of the GM3 species showed clear distinction between normal and cancer serum. What's more, ROC curve proved great diagnostic accuracy of GM3 between cancer and benign serum. In addition, GM3 was discovered as a diagnostic marker to differentiate luminal B subtype from other subtypes. Furthermore, a positive correlation between GM3 and Ki-67 status of patients was identified. In conclusion, our results introduced the alteration patterns of serum gangliosides in breast cancer and suggested serum GM3 as a potential diagnostic biomarker in breast cancer diagnosis and luminal B subtype distinction.

5.
Carbohydr Polym ; 222: 114993, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320068

RESUMO

ß-glucans trigger the proinflammatory responses of innate immune cells to enhance the host defense. A variety of ß-glucans were identified as strong immune stimulator and exerted antitumor activities. Our previous work indicates that a ß-1,3/1,6-glucan (BG136) derived from marina alga Durvillaea antarctica promotes the proinflammatory responses in macrophage cell line RAW264.7. In the present study, we further explored its antitumor effects in vivo as an immune stimulator. The data shows that BG136 alone decreases the tumor burdens in DLD1 xenograft and AOM-DSS induced tumor models. BG136 also augments the antitumor effects of PD-1 antibody in B16 syngeneic tumor model. BG136 increases macrophage phagocytosis, enhances cytokine/chemokine secretion and modulates the systemic and intratumoral immune cell composition. Collectively, these data suggest that BG136 might act as an immune stimulator to exert antitumor effects in vivo.


Assuntos
Adjuvantes Imunológicos/farmacologia , Glucanos/farmacologia , Neoplasias/imunologia , Animais , Linhagem Celular Tumoral , Citocinas/imunologia , Humanos , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Feófitas/metabolismo , Fagocitose/efeitos dos fármacos , Receptor de Morte Celular Programada 1/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
6.
Biomacromolecules ; 20(10): 3798-3808, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31361469

RESUMO

Fucosylated chondroitin sulfate (fCS), a representative marine polysaccharide isolated from sea cucumber, possesses diverse biological functions especially as a promising anticoagulant. However, its supply suffers from the challenges of high-cost materials, different species, and batch-to-batch variability. In the present study, we designed a concise route for the synthesis of functional glycomimetics by natural fCS as a template. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride-mediated amidation was applied on chondroitin sulfates for site-selective alkynylation with controllable ratios between 0.15 and 0.78. A small library of 12 fCS glycomimetics with specific sulfation patterns and fucose branches was prepared through copper-catalyzed azide-alkyne cycloaddition, which was fully characterized by nuclear magnetic resonance spectroscopy and size-exclusion chromatography with multiangle light scattering and refractive index. Through screening of their biological activities, CSE-F1 and CSE-SF1 exhibited anticoagulant activities through intrinsic pathway and inhibition of factor Xa by antithrombin III. The concise approach developed herein supplies novel glycopolymers to mimic the distinct functions of natural polysaccharides and promote the development of marine carbohydrate-based drugs.

7.
Curr Pharm Des ; 25(11): 1290-1311, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237200

RESUMO

Marine plants, animals and microorganisms display steady growth in the ocean and are abundant carbohydrate resources. Specifically, natural polysaccharides obtained from brown algae have been drawing increasing attention owing to their great potential in pharmaceutical applications. This review describes the structural and biological features of brown algal polysaccharides, including alginates, fucoidans, and laminarins, and it highlights recently developed approaches used to obtain the oligo- and polysaccharides with defined structures. Functional modification of these polysaccharides promotes their advanced applications in biomedical materials for controlled release and targeted drug delivery, etc. Moreover, brown algal polysaccharides and their derivatives possess numerous biological activities with anticancer, anticoagulant, wound healing, and antiviral properties. In addition, we also discuss carbohydrate- based substrates from brown algae, which are currently in clinical and preclinical studies, as well as the marine drugs that are already on the market. The present review summarizes the recent development in carbohydratebased products from brown algae, with promising findings that could rapidly facilitate the future discovery of novel marine drugs.

8.
Mikrochim Acta ; 186(7): 451, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201523

RESUMO

The first example of metallic bismuth encapsulated into a mesoporous metal-organic framework of the type MIL-101(Cr) matrix is presented. Bi(III)-impregnated MIL-101(Cr) (Bi(III)/MIL-101(Cr)) was dropped onto a conductive carbon cloth electrode (CCE). Then, bismuth was generated by electrochemical reduction of the Bi(III)/MIL-101(Cr) supported on CCE (Bi/MIL-101(Cr)/CCE). The resulting Bi/MIL-101(Cr)/CCE display impressive performance in terms of peak currents for the ions Cd(II) and Pb(II) when compared to the single-component counterparts. Differential pulse anodic stripping voltammetry (DPASV) enabled sensing of the two ions over linear working range of 0.1 to 30 µg L-1 and 30 to 90 µg L-1. The parameters are refined before the detection of two metal ions, including the amount of bismuth in MIL-101(Cr), optimum pH (5.0), deposition potential (-1.2 V) and deposition time (600 s). The respective detection limits are 60 and 70 ng L-1 (at S/N = 3). This is strikingly lower than the guideline values of domestic water given by the WHO which are 3 µg L-1 for Cd(II) and 10 µg L-1 for Pb(II). The Bi/MIL-101(Cr) onto CCE is fairly specific for Cd(II) (at around -0.76 V) and Pb(II) (at around -0.54 V), well reproducible and has excellent recovery in real water analysis. Graphical abstract Schematic illustration of the preparation of a Bi(III)/MIL-101(Cr) metal-organic framework, its deposition on a carbon cloth electrode (CCE), and its application for detection of Cd(II) and Pb(II) by differential pulse adsorptive stripping voltammetry (DPASV).

9.
Chem Commun (Camb) ; 55(49): 7101-7104, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31157332

RESUMO

Here, we report the fabrication of mixed-matrix membranes based on CAU-21 as the filler and PIM-1 as the matrix. The filler of the CAU-21 MOF with a crystallite size in the nanoscale and high uniformity was synthesized by a microwave-assisted approach. This small-pore CAU-21 was blended with a highly porous PIM-1 matrix to yield mixed-matrix membranes. The prepared membranes were applied for separating hydrogen from nitrogen and the results revealed very high selectivity of 127 for H2 over N2 and memorable H2 permeability of 7199 Barrer.

10.
Carbohydr Polym ; 217: 232-239, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31079681

RESUMO

Heparan sulfate (HS) and heparin, representative members of the glycosaminoglycans, possess distinct biological functions in terms of their specific interactions with hundreds of binding proteins. However, the structural properties of HS and heparin are complex due to their variable repeating motifs, different chain lengths and sulfation patterns. A concise chemoenzymatic approach has been developed to obtain well-defined low molecular weight (LMW) HS analogues. Pasteurella multocida heparosan synthase-2 (PmHS2) was utilized to fabricate the HS backbones with controllable chain lengths ranging from 14mer to 26mer. Moreover, regioselective and overall sulfation were conducted by chemical approach. The persulfated HS analogues exhibited more potent beta-site amyloid precursor protein (APP)-cleaving enzyme-1 (BACE-1) inhibitory activity than heparin and enoxaparin, and enhanced BACE-1 inhibitions were also found with the increasing molecular size of the HS analogues. This approach supplies the promising LMW HS analogues for the potential development of novel anti-Alzheimer's drugs.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Heparitina Sulfato/análogos & derivados , Inibidores de Proteases/química , Sequência de Carboidratos , Glicosiltransferases/química , Heparitina Sulfato/síntese química , Humanos , Peso Molecular , Pasteurella multocida/enzimologia , Inibidores de Proteases/síntese química
11.
Molecules ; 24(7)2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-30959980

RESUMO

Intestinal mucins constitute the major component of the mucus covering the epithelium of the gastrointestinal tract, thereby forming a barrier against microbial colonization. Rabbits are bred in large numbers worldwide, with little known about intestinal O-glycosylation despite this insight being crucial to the understanding of host-pathogen interactions. In the present study, a major mucin-type glycopeptide (RIF6) of hyla rabbit intestine was isolated and the O-glycans were extensively characterized based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with bioinformatics approaches. Thirty-three O-glycans were identified, and most of them were sulfated or sialylated glycans. It was worth noting that Neu5Gc-containing structures within sialylated O-glycans accounted for 91%, which were extremely different from that of other species including humans, mice, chickens, etc. Sulfated glycans accounted for 58%, unique disufated and sulfated-sialylated glycans were also detected in rabbit intestinal mucin. These structural characterization reflected species diversity and may provide deeper insights into explaining the adaptability of hyla rabbit to the environment.


Assuntos
Metaboloma , Metabolômica , Mucinas/química , Ácidos Neuramínicos/química , Polissacarídeos/química , Sulfatos/química , Animais , Cromatografia Líquida , Fucose/química , Trato Gastrointestinal/metabolismo , Metabolômica/métodos , Mucinas/isolamento & purificação , Mucinas/metabolismo , Ácidos Neuramínicos/metabolismo , Polissacarídeos/metabolismo , Coelhos , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem
12.
Molecules ; 24(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022848

RESUMO

The purpose of this study is to develop a robust approach to obtain ß glucans from Lentinus edodes and to characterize their structural and biological properties for sustainable utilization. The alkali extraction was optimized with an orthogonal experimental design, and a concise process for obtaining specific targeting polysaccharides from Lentinus edodes was developed in this study. After purification with a Q-Sepharose Fast Flow strong anion-exchange column, the monosaccharide composition, a methylation analysis, and NMR spectroscopy were employed for their structural characterizations. LeP-N2 was found to be composed of (1→6)-ß-d-glucans with minor ß-(1→3) glucosidic side chains. Atomic force microscopy (AFM) and high-performance gel permeation chromatography-refractive index-multi-angle laser light scattering (HPGPC-RI-MALLS) also revealed LeP-N2 exhibiting a compact unit in aqueous solution. This (1→6)-ß-d-glucan was tested for antioxidant activities with IC50 at 157 µg/mL. Moreover, RAW 264.7 macrophage activation indicated that the release of nitric oxide (NO) and reactive oxygen species (ROS) was markedly increased with no cytotoxicity at a dose of 100 µg/mL. These findings suggest that the (1→6)-ß-d-glucans obtained from Lentinus edodes could serve as potential agents in the fields of functional foods or medicine.


Assuntos
Antioxidantes/química , Polissacarídeos/química , Cogumelos Shiitake/química , beta-Glucanas/química , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Cromatografia em Gel , Espectroscopia de Ressonância Magnética , Camundongos , Microscopia de Força Atômica , Estrutura Molecular , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Espécies Reativas de Oxigênio/química , Água/química , beta-Glucanas/isolamento & purificação , beta-Glucanas/farmacologia
13.
Rev Med Virol ; 29(3): e2043, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30942528

RESUMO

The constant outbreak of diseases caused by viral infections has caused serious harm to human health all over the world. Although many antiviral drugs have been approved for clinical use during the past decade, important issues, such as unsatisfactory efficacy, toxicity, and high cost of drugs, remain unresolved. Glycans are major components of the surfaces of both host cells and most viruses and play critical roles in the steps of viral infection. Marine glycans have more structural diversities than those found in humans. Most importantly, low toxicity and low-cost marine glycans have demonstrated potent antiviral activities through multiple molecular mechanisms. As a result, a series of marine glycan-derived agents are undergoing preclinical and clinical trials. This review discusses the recent progress in research on the marine glycan-based antiviral agents in clinical trials, relating to their structural features and clinical applications. In addition, molecular mechanisms of marine glycans involved in viral infection and novel strategies used in glycan-based drug development are critically reviewed and discussed.


Assuntos
Antivirais/isolamento & purificação , Antivirais/uso terapêutico , Organismos Aquáticos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos
14.
Int J Biol Macromol ; 132: 864-870, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30914369

RESUMO

A water soluble polysaccharide CP-III was extracted and purified from Cyclocarya paliurus. CP-III is identified as a novel pectin-like polysaccharide with molecular weight (Mw) of 72.7 kDa. The structural features of CP-III were characterized by methylation and nuclear magnetic resonance (NMR) spectroscopy. Its depolymerized fragments were analyzed by hydrophilic interaction chromatography-Fourier transform mass spectrometry (HILIC-FTMS). The main chain of CP-III is composed of →4)GalAp(α1 → and →2)Rhap(α1 → 4)GalAp(α1→, repeatedly. The residue of →4)Galp(ß1 → and →5)Araf(α1 → alternately exists on the O-4 of partial →2)Rhap(α1 → residues as side chains. On the O-3 of sectional →5)Araf(α1 → residues is a secondary branch assembled by →3)Araf(α1→. Moreover, on the non-reducing terminus of →4)Galp(ß1 → occasionally have an →5)Araf(α1 → chain. Surprisingly, a sub-branch constructed by →6)Hexp(ß1 → with a galacturonate or methyl galacturonate exists on the O-3 of certain →4)Galp(ß1 → residues in the non-reducing terminus. In addition, a terminal Xyl is located on the O-3 of fractional →4)GalAp(ß1 → residue. The highly branched polysaccharide CP-III with high water solubility can be used as food supplement and medicinal carrier in the future.


Assuntos
Fagales/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Sequência de Carboidratos , Metilação , Monossacarídeos/análise
15.
J Proteome Res ; 18(6): 2559-2570, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-30889355

RESUMO

Aberrant protein glycosylation is observed in the progression of many types of diseases, including different cancers. In this study, we assess differential N-glycan patterns of human breast cancer cells and tissues by PGC-ESI-MS/MS. Compared with mammary epithelial cells, high-mannose glycans were significantly elevated in breast cancer cells. However, the alteration of N-glycans in tissues was more obvious than that in cells. Sixty-three kinds of different N-glycans were stably identified, and 38 types of them exhibited significant differences between para-carcinoma and breast cancer tissues. High-mannose glycans and core-fucosylated glycans were increased in the breast cancer tissues, while bisected glycans and sialylated glycans were decreased. Moreover, a total of 27 types of N-glycans displayed evident differences between benign breast tumor and breast cancer tissues, and most of them including bisected and sialylated glycans exhibited decreased relative abundances in cancer tissues. Overall, three high-mannose N-glycans (F0H6N2S0, F0H7N2S0, F0H8N2S0) exhibited significant diagnostic accuracy in both breast cancer cells and tissues, suggesting their potential role in biomarkers. Furthermore, a negative correlation between sialylated glycans and age of patients was identified. In conclusion, our results may be beneficial to understand the role that N-glycan plays on the progression of breast cancer and propose potential diagnostic biomarkers.

16.
Adv Mater ; 31(15): e1806853, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803076

RESUMO

Most metal-organic-framework- (MOF-) based hybrid membranes face the challenge of low gas permeability in CO2 separation. This study presents a new strategy of interweaving UiO-66 and PIM-1 to build freeways in UiO-66-CN@sPIM-1 membranes for fast CO2 transport. In this strategy, sPIM-1 is rigidified via thermal treatment to make polymer voids permanent, and concurrently polymer chains are mutually linked onto UiO-66-CN crystals to minimize interfacial defects. The pore chemistry of UiO-66-CN is kept intact in hybrid membranes, allowing full utilization of MOF pores and selective adsorption for CO2 . Separation results show that UiO-66-CN@sPIM-1 membranes possess exceptionally high CO2 permeability (15433.4-22665 Barrer), approaching to that of UiO-66-NH2 crystal (65-75% of crystal-derived permeability). Additionally, the CO2 /N2 permeation selectivity for a representative membrane (23.9-28.6) moves toward that of single crystal (24.6-29.6). The unique structure and superior CO2 /N2 separation performance make UiO-66-CN@sPIM-1 membranes promising in practical CO2 separations.

17.
Molecules ; 23(10)2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30332830

RESUMO

This review discusses different forms of nanomaterials generated from chitosan and its derivatives for controlled drug delivery. Nanomaterials are drug carriers with multiple features, including target delivery triggered by environmental, pH, thermal responses, enhanced biocompatibility, and the ability to cross the blood-brain barrier. Chitosan (CS), a natural polysaccharide largely obtained from marine crustaceans, is a promising drug delivery vector for therapeutics and diagnostics, owing to its biocompatibility, biodegradability, low toxicity, and structural variability. This review describes various approaches to obtain novel CS derivatives, including their distinct advantages, as well as different forms of nanomaterials recently developed from CS. The advanced applications of CS-based nanomaterials are presented here in terms of their specific functions. Recent studies have proven that nanotechnology combined with CS and its derivatives could potentially circumvent obstacles in the transport of drugs thereby improving the drug efficacy. CS-based nanomaterials have been shown to be highly effective in targeted drug therapy.

18.
Int J Biol Macromol ; 120(Pt B): 1817-1822, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30223052

RESUMO

The sulfated polysaccharide NP2 was isolated and purified from Nemacystus decipiens, the structure and antithrombotic activity of NP2 was further studied. NP2 was composed of fucose, glucuronic acid, galactose and xylose at molar ratios of 76.3:20.5:1.5:1.7. ES-CID-MS/MS results showed that NP2 had a backbone of α (1 → 3)-linked fucose and a branch was composed of Fuc-(2 → 1)-GlcA, which was agree with the results of NMR and methylation analysis. The results also show that the sulfate groups were substituted at the C2 or C4 positions of the fucose residues. In addition, analysis of the antithrombotic activity results indicated that NP2 can increase the percentage of t-PA/PAI-1, thereby suggesting that NP2 has high fibrinolytic activity and should be explored as a novel antithrombotic agent.

19.
Mar Drugs ; 16(5)2018 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-29772753

RESUMO

Recently, accumulating evidence has suggested that Enteromorpha clathrata polysaccharide (ECP) could contribute to the treatment of diseases. However, as a promising candidate for marine drug development, although ECP has been extensively studied, less consideration has been given to exploring its effect on gut microbiota. In this light, given the critical role of gut microbiota in health and disease, we investigated here the effect of ECP on gut microbiota using 16S rRNA high-throughput sequencing. As revealed by bioinformatic analyses, ECP considerably changed the structure of the gut microbiota and significantly promoted the growth of probiotic bacteria in C57BL/6J mice. However, interestingly, ECP exerted different effects on male and female microbiota. In females, ECP increased the abundances of Bifidobacterium spp. and Akkermansia muciniphila, a next-generation probiotic bacterium, whereas in males, ECP increased the population of Lactobacillus spp. Moreover, by shaping a more balanced structure of the microbiota, ECP remarkably reduced the antigen load from the gut in females. Altogether, our study demonstrates for the first time a prebiotic effect of ECP on gut microbiota and forms the basis for the development of ECP as a novel gut microbiota modulator for health promotion and disease management.


Assuntos
Organismos Aquáticos/metabolismo , Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Ulva/metabolismo , Proteínas da Fase Aguda/imunologia , Administração Oral , Animais , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/isolamento & purificação , Proteínas de Transporte/sangue , Proteínas de Transporte/imunologia , Biologia Computacional , Suplementos Nutricionais , Modelos Animais de Doenças , Disbiose/sangue , Disbiose/imunologia , Feminino , Humanos , Lactobacillus/efeitos dos fármacos , Lactobacillus/isolamento & purificação , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Organismos Livres de Patógenos Específicos , Verrucomicrobia/efeitos dos fármacos , Verrucomicrobia/isolamento & purificação
20.
Carbohydr Polym ; 195: 601-612, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29805017

RESUMO

Marine polysaccharides (MPs), including plant, animal, and microbial-derived polysaccharides, can alleviate metabolic syndrome (MetS) by different regulation mechanisms. MPs and their derivatives can attenuate MetS by vary cellular signal pathways, such as peroxisome proliferator-activated receptor, 5' adenosine monophosphate-activated protein kinase, and CCAAT/enhancer binding protein-α. Also, most of MPs cannot be degraded by human innate enzymes, but they can be degraded and fermented by human gut microbiota. The final metabolic products of these polysaccharides are usually short-chain fatty acids (SCFAs), which can change the gut microbiota ecology by altering the existing percentage of special microorganisms. In addition, the SCFAs and changed gut microbiota can regulate enteroendocrine hormone secretion, blood glucose, lipid metabolism levels, and other MetS symptoms. Here, we summarize the up-to-date findings on the effects of MPs, particularly marine microbial-derived polysaccharides, and their metabolites on attenuating MetS.


Assuntos
Organismos Aquáticos/química , Microbioma Gastrointestinal/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Polissacarídeos/farmacologia , Animais , Fermentação , Humanos , Síndrome Metabólica/microbiologia , Polissacarídeos/metabolismo , Polissacarídeos/uso terapêutico
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