RESUMEN
Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.
Asunto(s)
Antiinflamatorios , Enfermedades Inflamatorias del Intestino , Polifenoles , Polisacáridos , Polifenoles/química , Polifenoles/farmacología , Polifenoles/administración & dosificación , Humanos , Polisacáridos/química , Polisacáridos/farmacología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Antioxidantes/química , Antioxidantes/farmacologíaRESUMEN
In this study, we investigated how different proportions blends of Rhamnogalacturonan-I pectic polysaccharides and hesperidin impact the gut microbiota and metabolites using an in vitro simulated digestion and fermentation model. The results indicated that both of them could modulate the gut microbiota and produce beneficial metabolites. However, their blends in particular proportions (such as 1:1) exhibited remarkable synergistic effects on modulating the intestinal microenvironment, surpassing the effects observed with individual components. Specifically, these blends could benefit the host by increasing short-chain fatty acids production (such as acetate), improving hesperidin bioavailability, producing more metabolites (such as hesperetin, phenolic acids), and promoting the growth of beneficial bacteria. This synergistic and additive effect was inseparable from the role of gut microbiota. Certain beneficial bacteria, such as Blautia, Faecalibacterium, and Prevotella, exhibited strong preferences for those blends, thereby contributing to host health through participating in carbohydrate and flavonoid metabolism.
Asunto(s)
Bacterias , Microbioma Gastrointestinal , Hesperidina , Pectinas , Hesperidina/farmacología , Hesperidina/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Bacterias/metabolismo , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/aislamiento & purificación , Humanos , Pectinas/metabolismo , Pectinas/química , Pectinas/farmacología , Fermentación , Polisacáridos/farmacología , Polisacáridos/metabolismo , Polisacáridos/química , Ácidos Grasos Volátiles/metabolismo , Digestión , Modelos BiológicosRESUMEN
With the aim of expanding the potential application scope of mulberries, eleven pH-switchable deep eutectic solvents were screened for the ultrasonic-assisted extraction of mulberry polysaccharides, and a salt/salt aqueous two-phase system was constructed for the efficient separation of mulberry polysaccharides by regulating the system pH. DES-9 (tetraethylammonium chloride: octanoic acid molar ratio = 1: 2) with a critical response pH value of approximately 6.1 was concluded to be the best extraction solvent for extracting mulberry polysaccharides. A maximum polysaccharide extraction yield of 270.71 mg/g was obtained under the optimal conditions. The maximum polysaccharide extraction efficiency was 78.09 % for the pH-driven tetraethylammonium chloride/K2HPO4 aqueous two-phase system. An acidic ß-pyran mulberry polysaccharide with a low-molecular weight of 9.26 kDa and a confirmed monosaccharide composition were obtained. This efficient and environmentally friendly polysaccharide separation method offers a new approach for the efficient extraction and utilization of other plant polysaccharides.
Asunto(s)
Disolventes Eutécticos Profundos , Morus , Extractos Vegetales , Polisacáridos , Morus/química , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Concentración de Iones de Hidrógeno , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Disolventes Eutécticos Profundos/química , Fraccionamiento Químico/métodos , Peso Molecular , Frutas/química , Cloruro de Sodio/químicaRESUMEN
Tumor vaccines have become a promising approach for cancer treatment by triggering antigen-specific responses against tumors. However, autophagy and immunosuppressive tumor microenvironment (TME) reduce antigen exposure and immunogenicity, which limit the effect of tumor vaccines. Here, we develop fucoidan (Fuc) based chlorin e6 (Ce6)-chloroquine (CQ) self-assembly hydrogels (CCFG) as in situ vaccines. Ce6 triggers immune response in situ by photodynamic therapy (PDT) induced immunogenic cell death (ICD) effect, which is further enhanced by macrophage polarization of Fuc and autophagy inhibition of CQ. In vivo studies show that CCFG effectively enhances antigen presentation under laser irradiation, which induces a powerful in situ vaccine effect and significantly inhibits tumor metastasis and recurrence. Our study provides a novel approach for enhancing tumor immunotherapy and inhibiting tumor recurrence and metastasis.
Asunto(s)
Autofagia , Vacunas contra el Cáncer , Clorofilidas , Cloroquina , Hidrogeles , Inmunoterapia , Macrófagos , Fotoquimioterapia , Polisacáridos , Porfirinas , Animales , Polisacáridos/farmacología , Polisacáridos/química , Ratones , Vacunas contra el Cáncer/farmacología , Vacunas contra el Cáncer/inmunología , Porfirinas/química , Porfirinas/farmacología , Porfirinas/uso terapéutico , Autofagia/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Inmunoterapia/métodos , Fotoquimioterapia/métodos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Cloroquina/farmacología , Ratones Endogámicos C57BL , Microambiente Tumoral/efectos de los fármacos , Células RAW 264.7 , Línea Celular Tumoral , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Ratones Endogámicos BALB C , FemeninoRESUMEN
Licorice is not only a widely used food, but also a classic tonic Chinese medicine, which mainly contains glycyrrhiza polysaccharides (GP) and flavonoids with excellent anti-inflammatory and antioxidant pharmacological activities. In this study, a neutral homogeneous polysaccharide (GP1-2) was isolated from Glycyrrhiza uralensis Fisch. However, its gelation behavior and properties have yet to be comprehensively studied. In this study, a Ca2+ cross-linked physical hydrogel based on neutral GP1-2 (GP1-2-Ca2+) is fabricated. The ability of metal ions to cross-linked gelation with GP1-2 is explored with respect to the polysaccharide concentrations, ion species, and pH environments. The pH range of Ca2+ cross-linked with GP1-2 to form hydrogel is 8 to 10, and the gelation concentration ranges from 20.0 % to 50.0 % w/v. Subsequently, the properties of the GP1-2-Ca2+ hydrogels are investigated using rheological measurements, scanning electron microscopy, free radical scavenging, MTT assays, healing capability, and enzyme-linked immunosorbent assays. The results reveal that the structure of GP1-2 presents an irregular porous structure, however, the physical gel formed after cross-linking with Ca2+ microscopically showed a globular porous structure with uniform distribution, suggesting that this structure characteristic may be used as a carrier material for drug delivery. Meanwhile, the GP1-2-Ca2+ hydrogel also possessed extraordinary viscoelasticity, cytocompatibility, antioxidant properties, anti-inflammatory activity, and ability to promote wound healing. Furthermore, the potential of GP1-2-Ca2+ hydrogels as drug delivery materials was validated by using rhein as a model drug for encapsulation, it is demonstrated that its cumulative release behavior of GP1-2-Ca2+ is pH-dependent. All in all, this study reveals the potential application of natural polysaccharides in drug delivery, highlighting its dual roles as carrier materials and bioactive ingredients.
Asunto(s)
Glycyrrhiza , Hidrogeles , Polisacáridos , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Glycyrrhiza/química , Hidrogeles/química , Calcio , Antioxidantes/química , Antioxidantes/farmacología , Animales , Concentración de Iones de Hidrógeno , Ratones , Antiinflamatorios/química , Antiinflamatorios/farmacología , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/químicaRESUMEN
Gelation is a critical property of citrus pectin. However, the roles played by neutral sugar side-chains on acid-induced pectin gelation remain poorly understood. Herein, galactan- or/and arabinan-eliminated pectins (P-G, P-A, and P-AG) were used to investigate the effects of side-chains on gelation. The gel hardness values of citrus pectin, P-G, P-A, and P-AG were 42.6, 39.9, 5.3, and 2.1 g, respectively, suggesting that arabinan contributed more to gelation than galactan. We next found that arabinan branches promoted pectin chain entanglement more effectively than arabinan backbones. Destabilizer addition experiments showed that hydrogen bonding, electrostatic interaction, and hydrophobic interaction were the main forces affecting pectin gel networks and strength, which was further validated by molecular dynamic simulations. The total number of hydrogen bonds between the arabinan branches and galactan/HG (65.7) was significantly higher than that between the arabinan backbones and galactan/HG (39.1), indicating that arabinan branches predominated in terms of such interactions. This study thus elucidated the roles played by neutral-sugar side-chains, especially the arabinan branches of acid-induced pectin gels, in term of enhancing high-methoxyl pectin gelation, and offers novel insights into the structure-gelling relationships of citrus pectin.
Asunto(s)
Geles , Enlace de Hidrógeno , Pectinas , Pectinas/química , Geles/química , Polisacáridos/química , Simulación de Dinámica Molecular , Citrus/química , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
Bone defects caused by trauma, infection and congenital diseases still face great challenges. Dihydromyricetin (DHM) is a kind of flavone extracted from Ampelopsis grossedentata, a traditional Chinese medicine. DHM can enhance the osteogenic differentiation of human bone marrow mesenchymal stem cells with the potential to promote bone regeneration. Hydrogel can be used as a carrier of DHM to promote bone regeneration due to its unique biochemical characteristics and three-dimensional structure. In this study, oxidized phellinus igniarius polysaccharides (OP) and L-arginine chitosan (CA) are used to develop hydrogel. The pore size and gel strength of the hydrogel can be changed by adjusting the oxidation degree of oxidized phellinus igniarius polysaccharides. The addition of DHM further reduce the pore size of the hydrogel (213 µm), increase the mechanical properties of the hydrogel, and increase the antioxidant and antibacterial activities of the hydrogel. The scavenging rate of DPPH are 72.30 ± 0.33 %, and the inhibition rate of E.coli and S.aureus are 93.12 ± 0.38 % and 94.49 ± 1.57 %, respectively. In addition, PCAD has good adhesion and biocompatibility, and its extract can effectively promote the osteogenic differentiation of MC3T3-E1 cells. Network pharmacology and molecular docking show that the promoting effect of DHM on osteogenesis may be achieved by activating the PI3K/AKT and MAPK signaling pathways. This is confirmed through in vitro cell experiments and in vivo animal experiments.
Asunto(s)
Regeneración Ósea , Quitosano , Flavonoles , Hidrogeles , Sistema de Señalización de MAP Quinasas , Osteogénesis , Fosfatidilinositol 3-Quinasas , Polisacáridos , Proteínas Proto-Oncogénicas c-akt , Quitosano/química , Quitosano/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Flavonoles/farmacología , Flavonoles/química , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Polisacáridos/química , Polisacáridos/farmacología , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Arginina/química , Arginina/farmacología , Oxidación-Reducción/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Adhesivos/química , Adhesivos/farmacologíaRESUMEN
Potassium citrate (KC) and potassium lactate (KL) are considered as salt replacers due to their saltiness, processing advantages, and health benefits. However, the obvious bitter taste associated with these compounds has limited their use in salt substitutes. Despite this challenge, little attention has been paid to improving their sensory properties. This study provided evidence that dietary polysaccharide carrageenan can effectively mask the bitterness of KC and KL by specifically binding K+ and forming double helix chains. A highly accurate prediction model was then established for the saltiness and bitterness of low-sodium salts using mixture design principles. Three low-sodium salt formulas containing different potassium salts (KC, KL, KCl), NaCl, and carrageenan were created based on the prediction model. These formulas exhibited favorable saltiness potencies (>0.85) without any noticeable odor, preserving the sensory characteristics of high-sodium food products like seasoning powder while significantly reducing their sodium content. This research provides a promising approach for the food industry to formulate alternative low-sodium products with substantially reduced sodium content, potentially contributing to decreased salt intake.
Asunto(s)
Gusto , Humanos , Cloruro de Sodio Dietético , Citrato de Potasio/química , Carragenina/química , Masculino , Femenino , Polisacáridos/química , Adulto , Compuestos de Potasio/química , Lactatos/química , Dieta HiposódicaRESUMEN
Given the limited specificity and accuracy observed in the current official colorimetric quantification of polysaccharide in Lycium barbarum, our study aims to establish a novel, specific, accurate, and economic pre-column derivatization ultra-high-performance liquid chromatography (UHPLC) method for determining the monosaccharide and polysaccharide content in L. barbarum. The optimization of extraction, hydrolysis, and derivatization (using 1-phenyl-3-methyl-5-pyrazolone) processes for polysaccharide from L. barbarum was conducted initially, followed by separation of nine monosaccharides within 20 min using UHPLC with a C18 column. Subsequently, a novel method known as quantitative analysis of multiple components by single marker was developed, utilizing either additive 2-deoxy-D-ribose or any monosaccharide present in the sample as a single reference standard to simultaneously detect the contents of polysaccharide and nine monosaccharides in L. barbarum. To validate the accuracy of the established method, the quantitative results of our approach were compared to both external and internal standard method methods. The minimal relative errors in the quantitative determination of monosaccharides among the three methods confirmed the dependability of the method. By analyzing 20 batches of L. barbarum samples, D-galacturonic acid exhibited the highest content and the polysaccharide levels ranged from 3.02 to 13.04 mg/g. All data implied the specificity and accuracy of the method.
Asunto(s)
Lycium , Monosacáridos , Polisacáridos , Cromatografía Líquida de Alta Presión/métodos , Lycium/química , Monosacáridos/análisis , Monosacáridos/química , Polisacáridos/análisis , Polisacáridos/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisisRESUMEN
Osteoporosis, a prevalent skeletal disorder characterized by diminished bone density, compromised microstructure, and heightened fracture susceptibility, poses a growing public health concern exacerbated by aging demographics. Polysaccharides-based materials, derived from a diverse range of sources, exhibit exceptional biocompatibility. They possess a structure similar to the extracellular matrix, which can enhance cell adhesion in vivo, and demonstrate superior biological activity compared to artificial materials. This study delved into an in-depth examination of the various biomaterials and polysaccharide families associated with the treatment of osteoporosis. This article elucidates the benefits and attributes of polysaccharide-based materials in contrast to current clinical treatment modalities, delineating how these materials address prevalent challenges in the clinical management of osteoporosis. An overview of the prospective applications of polysaccharide-based materials in the future is also provided, as well as outlines the challenges that should be addressed prior to the clinical implementation of such materials.
Asunto(s)
Materiales Biocompatibles , Osteoporosis , Polisacáridos , Osteoporosis/tratamiento farmacológico , Polisacáridos/química , Polisacáridos/uso terapéutico , Polisacáridos/farmacología , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Animales , Densidad Ósea/efectos de los fármacosRESUMEN
Probiotics and polyphenols have multiple bioactivities, and developing co-encapsulated microcapsules (CM) is a novel strategy to enhance their nutritional diversity. However, the development of CMs is challenged by complicated processing, single types, and unclear in vivo effects and applications. In this study, the co-microencapsulations of polyphenol and probiotic were constructed using pectin, alginate (WGCA@LK), and Fu brick tea polysaccharides (WGCF@LK), respectively, with chitosan-whey isolate proteins by layer-by-layer coacervation reaction, and their protective effects, in vivo effectiveness, and application potential were evaluated. WGCA@LK improved the encapsulation rate of polyphenols (42.41 %), and remained high viability of probiotics after passing through gastric acidic environment (8.79 ± 0.04 log CFU/g) and storage for 4 weeks (4.59 ± 0.06 log CFU/g). WGCF@LK exhibited the highest total antioxidant activity (19.40 ± 0.25 µmol/mL) and its prebiotic activity removed the restriction on probiotic growth. WGCA@LK showed strong in vitro colonic adhesion, but WGCF@LK promoted in vivo retention of probiotics at 48 h. WGCF@LK showed excellent anti-inflammatory effects and alleviated symptoms of acute colitis in mice. These findings provide unique insights into the fortification of probiotic-polyphenol CMs by different polysaccharides and the development of novel health foods with rich functional hierarchies and superior therapeutic effects.
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Cápsulas , Colitis , Polifenoles , Polisacáridos , Probióticos , Probióticos/administración & dosificación , Probióticos/química , Animales , Polifenoles/química , Polifenoles/farmacología , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Ratones , Polisacáridos/química , Polisacáridos/farmacología , Alimentos Fortificados , Alginatos/química , Alginatos/farmacología , Masculino , Pectinas/química , Pectinas/farmacología , Té/química , Antioxidantes/química , Antioxidantes/farmacología , Quitosano/química , Sulfato de Dextran/química , Composición de Medicamentos/métodosRESUMEN
The healing of chronic diabetic wounds remains a formidable challenge in modern times. In this study, a novel traditional Chinese medicine microneedle patch was designed based on the physiological characteristics of wounds, with properties including hemostasis, anti-inflammatory, antioxidant, antimicrobial, and induction of angiogenesis. Initially, white peony polysaccharide (BSP) with hemostatic properties and carboxymethyl chitosan (CMCS) with antimicrobial capabilities were used as materials for microneedle fabrication. To endow it with antimicrobial, procoagulant, and adhesive properties. Among them, loaded with ROS-sensitive nanoparticles of Astragalus polysaccharides (APS) based on effective components baicalein (Bai) and berberine (Ber) from Scutellaria baicalensis (SB) and Coptis chinensis (CC) drugs (APB@Ber). Together, they are constructed into multifunctional traditional Chinese medicine composite microneedles (C/B@APB@Ber). Bai and Ber synergistically exert anti-inflammatory and antimicrobial effects. Microneedle patches loaded with BSP and APS exhibited significant effects on cell proliferation and angiogenesis induction. The combination of composite polysaccharides enabled the microneedles to adhere stably to wounds and provide sufficient strength to penetrate the biofilm and induce dispersion. The combination of composite polysaccharides enabled the microneedles to adhere stably to wounds and provide sufficient strength to penetrate the biofilm and induce dispersion. Therefore, traditional Chinese medicine multifunctional microneedle patches offer potential medical value in promoting the healing of diabetic wounds.
Asunto(s)
Astragalus propinquus , FN-kappa B , Nanopartículas , Polisacáridos , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/administración & dosificación , Astragalus propinquus/química , Ratones , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo , Células RAW 264.7 , Agujas , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/administración & dosificación , Quitosano/química , Quitosano/farmacología , Proliferación Celular/efectos de los fármacosRESUMEN
Chemical crosslinking is a method widely used to enhance the mechanical strength of biopolymer-based scaffolds. Polysaccharides are natural and biodegradable carbohydrate polymers that can act as crosslinking agents to promote the formation of scaffolds. Compared to synthetic crosslinking agents, Polysaccharide-based crosslinking agents have better biocompatibility for cell adhesion and growth. Traditional Chinese medicine has special therapeutic effects on various diseases and is rich in various bioactive ingredients. Among them, polysaccharides have immune regulatory, antioxidant, and anti-inflammation effects, which allow them to not only act as crosslinking agents but endow the scaffold with greater bioactivity. This article focuses on the latest developments of polysaccharide-based crosslinking agents for biomedical scaffolds, including hyaluronic acid, chondroitin sulfate, dextran, alginate, cellulose, gum polysaccharides, and traditional Chinese medicine polysaccharides. Also, we provide a summary and prospects on the research of polysaccharide-based crosslinking agents.
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Materiales Biocompatibles , Reactivos de Enlaces Cruzados , Polisacáridos , Bases de Schiff , Andamios del Tejido , Polisacáridos/química , Polisacáridos/farmacología , Reactivos de Enlaces Cruzados/química , Andamios del Tejido/química , Bases de Schiff/química , Bases de Schiff/farmacología , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos/métodos , Animales , Ácido Hialurónico/química , Ácido Hialurónico/farmacologíaRESUMEN
Yeast cell wall (YCW) polysaccharides, including ß-glucans, mannans, chitins, and glycogens, can be extracted from the waste of beer industry. They are environmentally friendly, abundant, inexpensive raw materials, and have shown broad biological activities and application potentials. The exploitation of yeast polysaccharides is of great importance for environmental protection and resource utilization. This paper reviews the structural features and preparation of YCW polysaccharides. The solubility and emulsification of yeast polysaccharides and the properties of binding metal ions are presented. In addition, biological activities such as blood glucose and lipid lowering, immune regulation, antioxidant, promotion of intestinal health, and promotion of wound healing are proposed, highlighting the beneficial effects of yeast polysaccharides on human health. Through modification, the physical and chemical properties of yeast polysaccharides are changed, which emphasizes the promotion of their biological activities and properties. In addition, the food applications of yeast polysaccharides, including the food packaging film, emulsifier, thickening agent, and fat alternatives, are focused and discussed.
Asunto(s)
Polisacáridos , Polisacáridos/química , Polisacáridos/farmacología , Saccharomyces cerevisiae/química , Levaduras/química , Humanos , Embalaje de Alimentos/métodos , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/farmacología , Emulsionantes/química , Pared Celular/químicaRESUMEN
Precision mapping of site-specific glycans using mass spectrometry is vital in glycoproteomics. However, the diversity of glycan compositions across species often exceeds database capacity, hindering the identification of rare glycans. Here, we introduce pGlycoNovo, a software within the pGlyco3 software environment, which employs a glycan first-based full-range Y-ion dynamic searching strategy. pGlycoNovo enables de novo identification of intact glycopeptides with rare glycans by considering all possible monosaccharide combinations, expanding the glycan search space to 16~1000 times compared to non-open search methods, while maintaining accuracy, sensitivity and speed. Reanalysis of SARS Covid-2 spike protein glycosylation data revealed 230 additional site-specific N-glycans and 30 previously unreported O-glycans. pGlycoNovo demonstrated high complementarity to six other tools and superior search speed. It enables characterization of site-specific N-glycosylation across five evolutionarily distant species, contributing to a dataset of 32,549 site-specific glycans on 4602 proteins, including 2409 site-specific rare glycans, and uncovering unexpected glycan fragments.
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Glicopéptidos , Polisacáridos , Programas Informáticos , Glicoproteína de la Espiga del Coronavirus , Glicosilación , Polisacáridos/metabolismo , Polisacáridos/química , Humanos , Glicopéptidos/química , Glicopéptidos/metabolismo , Glicopéptidos/análisis , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , SARS-CoV-2/metabolismo , SARS-CoV-2/química , Animales , Proteómica/métodos , COVID-19/virologíaRESUMEN
Polysaccharide fractions from the mycelium of the lion's mane medicinal mushroom Hericium erinaceus BP 16, cultivated on sterile grain substrates (barley, oats, wheat, rice, rye), were isolated and characterized. One percent solutions were prepared from the resulting fractions, mixed with blood, which was then subjected to cold stress at a temperature of 6°C for 3, 5 and 7 d. It has been shown that the fraction of H. erinaceus grown on rye is characterized by a high content of the protein fraction and arabinose monosaccharide and contributes to the preservation of higher phagocytic, bactericidal and antioxidant activity cells throughout the entire period of stress. Polysaccharide fractions of the fungus H. erinaceus, grown on various grain substrates, can serve as an immunomodulatory and antioxidant food additive and provide significant benefits in the daily life of people with stress and reduced immunity.
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Antioxidantes , Hericium , Neutrófilos , Antioxidantes/farmacología , Hericium/química , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Factores Inmunológicos/farmacología , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Micelio/química , Humanos , Estrés Fisiológico/efectos de los fármacos , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Polisacáridos Fúngicos/farmacología , Polisacáridos Fúngicos/químicaRESUMEN
Glycan-mediated interactions play a crucial role in biology and medicine, influencing signalling, immune responses, and disease pathogenesis. However, the use of glycans in biosensing and diagnostics is limited by cross-reactivity, as certain glycan motifs can be recognised by multiple biologically distinct protein receptors. To address this specificity challenge, we report the enzymatic synthesis of a 150-member library of site-specifically fluorinated Lewisx analogues ('glycofluoroforms') using naturally occurring enzymes and fluorinated monosaccharides. Subsequent incorporation of a subset of these glycans into nanoparticles or a microarray revealed a striking spectrum of distinct binding intensities across different proteins that recognise Lewisx. Notably, we show that for two proteins with unique binding sites for Lewisx, glycofluoroforms exhibited enhanced binding to one protein, whilst reduced binding to the other, with selectivity governed by fluorination patterns. We finally showcase the potential diagnostic utility of this approach in glycofluoroform-mediated bacterial toxin detection by lateral flow.
Asunto(s)
Polisacáridos , Polisacáridos/metabolismo , Polisacáridos/química , Unión Proteica , Sitios de Unión , Humanos , Halogenación , Antígeno Lewis X/metabolismo , Antígeno Lewis X/química , Nanopartículas/químicaRESUMEN
Glycan profile comparisons are one of the most tedious analytical exercises for establishing compliance with recombinant therapeutic protein batches. Based on its intensive research, the FDA has confirmed that lectin array binding with fluorescent monitoring is the fastest and most reliable method for profile comparisons. Using a database of over 150 biological products expressed in nine diverse mammalian cell systems, the FDA immobilized 74 lectins to study their binding using fluorescently labeled glycoproteins. The FDA identified nine distinct lectins from a custom-designed lectin microarray: rPhoSL, rOTH3, RCA120, rMan2, MAL_I, rPSL1a, PHAE, rMOA, and PHALs, which detect core fucose, terminal GlcNAc, terminal ß-galactose, high mannose, α-2,3-linked sialic acids, α-2,6-linked sialic acids, bisecting GlcNAc, terminal α-galactose, and triantennary structures, respectively. This method can be used for screening and routine testing and to monitor batch-to-batch variability of therapeutic proteins, including establishing analytical similarity as a crucial part of biosimilar development.
Asunto(s)
Biosimilares Farmacéuticos , Lectinas , Polisacáridos , Lectinas/metabolismo , Lectinas/química , Polisacáridos/química , Polisacáridos/análisis , Biosimilares Farmacéuticos/análisis , Biosimilares Farmacéuticos/química , Humanos , Estados Unidos , United States Food and Drug Administration , Glicoproteínas/química , Glicoproteínas/análisis , Aprobación de Drogas , Fluorescencia , AnimalesRESUMEN
Highly purified human menopausal gonadotropin (HP-hMG [Menopur®, Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur® and two of Menogon® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid®) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.
Asunto(s)
Gonadotropina Coriónica , Hormona Luteinizante , Espectrometría de Masas en Tándem , Humanos , Gonadotropina Coriónica/orina , Gonadotropina Coriónica/análisis , Hormona Luteinizante/orina , Hormona Luteinizante/análisis , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , Polisacáridos/análisis , Polisacáridos/química , Polisacáridos/orina , Glicosilación , Femenino , Menotropinas/orina , Menotropinas/análisis , Hormona Folículo Estimulante/orina , Hormona Folículo Estimulante/análisis , Oxidación-Reducción , Glicopéptidos/análisis , Glicopéptidos/química , Glicopéptidos/orinaRESUMEN
The global obesity epidemic, exacerbated by the sedentary lifestyle fostered by the COVID-19 pandemic, presents a growing socioeconomic burden due to decreased physical activity and increased morbidity. Current obesity treatments show promise, but they often come with expensive medications, frequent injections, and potential side effects, with limited success in improving obesity through increased energy expenditure. This study explores the potential of a refined sulfated polysaccharide (SPSL), derived from the brown seaweed Scytosiphon lomentaria (SL), as a safe and effective anti-obesity treatment by promoting energy expenditure. Chemical characterization revealed that SPSL, rich in sulfate and L-fucose content, comprises nine distinct sulfated glycan structures. In vitro analysis demonstrated potent anti-lipogenic properties in adipocytes, mediated by the downregulation of key adipogenic modulators, including 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Inhibiting AMPK attenuated the anti-adipogenic effects of SPSL, confirming its involvement in the mechanism of action. Furthermore, in vivo studies using zebrafish models showed that SPSL increased energy expenditure and reduced lipid accumulation. These findings collectively highlight the therapeutic potential of SPSL as a functional food ingredient for mitigating obesity-related metabolic dysregulation by promoting energy expenditure. Further mechanistic and preclinical investigations are warranted to fully elucidate its mode of action and evaluate its efficacy in obesity management, potentially offering a novel, natural therapeutic avenue for this global health concern.