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1.
Physiol Plant ; 176(3): e14325, 2024.
Article in English | MEDLINE | ID: mdl-38715548

ABSTRACT

Boosting plant immunity by priming agents can lower agrochemical dependency in plant production. Levan and levan-derived oligosaccharides (LOS) act as priming agents against biotic stress in several crops. Additionally, beneficial microbes can promote plant growth and protect against fungal diseases. This study assessed possible synergistic effects caused by levan, LOS and five levan- and LOS-metabolizing Bacillaceae (Bacillus and Priestia) strains in tomato and wheat. Leaf and seed defense priming assays were conducted in non-soil (semi-sterile substrate) and soil-based systems, focusing on tomato-Botrytis cinerea and wheat-Magnaporthe oryzae Triticum (MoT) pathosystems. In the non-soil system, seed defense priming with levan, the strains (especially Bacillus velezensis GA1), or their combination significantly promoted tomato growth and protection against B. cinerea. While no growth stimulatory effects were observed for wheat, disease protective effects were also observed in the wheat-MoT pathosystem. When grown in soil and subjected to leaf defense priming, tomato plants co-applied with levan and the bacterial strains showed increased resistance to B. cinerea compared with plants treated with levan or single strains, and these effects were synergistic in some cases. For seed defense priming in soil, more synergistic effects on disease tolerance were observed in a non-fertilized soil as compared to a fertilized soil, suggesting that potential prebiotic effects of levan are more prominent in poor soils. The potential of using combinations of Bacilliaceae and levan in sustainable agriculture is discussed.


Subject(s)
Bacillus , Fructans , Plant Diseases , Solanum lycopersicum , Triticum , Fructans/metabolism , Triticum/microbiology , Triticum/metabolism , Triticum/immunology , Triticum/growth & development , Solanum lycopersicum/microbiology , Solanum lycopersicum/immunology , Solanum lycopersicum/metabolism , Solanum lycopersicum/growth & development , Plant Diseases/microbiology , Plant Diseases/immunology , Bacillus/physiology , Botrytis , Plant Immunity , Disease Resistance , Plant Leaves/metabolism , Plant Leaves/microbiology , Plant Leaves/immunology , Oligosaccharides/metabolism , Oligosaccharides/pharmacology , Seeds/growth & development , Seeds/metabolism , Seeds/microbiology , Seeds/immunology , Ascomycota
2.
Molecules ; 29(9)2024 May 02.
Article in English | MEDLINE | ID: mdl-38731604

ABSTRACT

Edible grey oyster mushroom, Pleurotus sajor-caju, ß (1,3), (1,6) glucan possesses a wide range of biological activities, including anti-inflammation, anti-microorganism and antioxidant. However, its biological activity is limited by low water solubility resulting from its high molecular weight. Our previous study demonstrated that enzymatic hydrolysis of grey oyster mushroom ß-glucan using Hevea ß-1,3-glucanase isozymes obtains a lower molecular weight and higher water solubility, Pleurotus sajor-caju glucanoligosaccharide (Ps-GOS). Additionally, Ps-GOS potentially reduces osteoporosis by enhancing osteoblast-bone formation, whereas its effect on osteoclast-bone resorption remains unknown. Therefore, our study investigated the modulatory activities and underlying mechanism of Ps-GOS on Receptor activator of nuclear factor kappa-Β ligand (RANKL) -induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells. Cell cytotoxicity of Ps-GOS on RAW 264.7 cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and its effect on osteoclast differentiation was determined by tartrate-resistant acid phosphatase (TRAP) staining. Additionally, its effect on osteoclast bone-resorptive ability was detected by pit formation assay. The osteoclastogenic-related factors were assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), Western blot and immunofluorescence. The results revealed that Ps-GOS was non-toxic and significantly suppressed the formation of mature osteoclast multinucleated cells and their resorption activity by reducing the number of TRAP-positive cells and pit formation areas in a dose-dependent manner. Additionally, Ps-GOS attenuated the nuclear factor kappa light chain-enhancer of activated B cells' P65 (NFκB-P65) expression and their subsequent master osteoclast modulators, including nuclear factor of activated T cell c1 (NFATc1) and Fos proto-oncogene (cFOS) via the NF-κB pathway. Furthermore, Ps-GOS markedly inhibited RANK expression, which serves as an initial transmitter of many osteoclastogenesis-related cascades and inhibited proteolytic enzymes, including TRAP, matrix metallopeptidase 9 (MMP-9) and cathepsin K (CTK). These findings indicate that Ps-GOS could potentially be beneficial as an effective natural agent for bone metabolic disease.


Subject(s)
Cell Differentiation , NF-kappa B , NFATC Transcription Factors , Osteoclasts , Pleurotus , RANK Ligand , Receptor Activator of Nuclear Factor-kappa B , Signal Transduction , Animals , Mice , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteoclasts/cytology , RAW 264.7 Cells , RANK Ligand/metabolism , Cell Differentiation/drug effects , Signal Transduction/drug effects , NF-kappa B/metabolism , Pleurotus/chemistry , Receptor Activator of Nuclear Factor-kappa B/metabolism , NFATC Transcription Factors/metabolism , Proto-Oncogene Proteins c-fos/metabolism , beta-Glucans/pharmacology , beta-Glucans/chemistry , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Osteogenesis/drug effects
3.
Sci Rep ; 14(1): 11127, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38750102

ABSTRACT

Nutraceutical interventions supporting microbiota and eliciting clinical improvements in metabolic diseases have grown significantly. Chronic stress, gut dysbiosis, and metainflammation have emerged as key factors intertwined with sleep disorders, consequently exacerbating the decline in quality of life. This study aimed to assess the effects of two nutraceutical formulations containing prebiotics (fructooligosaccharides (FOS), galactooligosaccharides (GOS), yeast ß-glucans), minerals (Mg, Se, Zn), and the herbal medicine Silybum marianum L. Gaertn., Asteraceae (Milk thistle or Silymarin). These formulations, namely NSupple (without silymarin) and NSupple_Silybum (with silymarin) were tested over 180 days in overweight/obese volunteers from Brazil's southeastern region. We accessed fecal gut microbiota by partial 16S rRNA sequences; cytokines expression by CBA; anthropometrics, quality of life and sleep, as well as metabolic and hormonal parameters, at baseline (T0) and 180 days (T180) post-supplementation. Results demonstrated gut microbiota reshaping at phyla, genera, and species level post-supplementation. The Bacteroidetes phylum, Bacteroides, and Prevotella genera were positively modulated especially in the NSupple_Silybum group. Gut microbiota modulation was associated with improved sleep patterns, quality-of-life perception, cytokines expression, and anthropometric parameters post-supplementation. Our findings suggest that the nutraceutical blends positively enhance cardiometabolic and inflammatory markers. Particularly, NSupple_Silybum modulated microbiota composition, underscoring its potential significance in ameliorating metabolic dysregulation. Clinical trial registry number: NCT04810572. 23/03/2021.


Subject(s)
Cytokines , Dietary Supplements , Gastrointestinal Microbiome , Quality of Life , Humans , Gastrointestinal Microbiome/drug effects , Male , Brazil , Female , Double-Blind Method , Adult , Cytokines/metabolism , Middle Aged , Prebiotics/administration & dosage , Feces/microbiology , Silymarin/pharmacology , Minerals/pharmacology , Obesity/microbiology , Oligosaccharides/pharmacology , Oligosaccharides/administration & dosage
4.
Mar Drugs ; 22(5)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38786584

ABSTRACT

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, and accumulating evidence suggests a link between dysbiosis of the gut microbiota and the onset and progression of PD. In our previous investigations, we discovered that intraperitoneal administration of glucuronomannan oligosaccharides (GMn) derived from Saccharina japonica exhibited neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. However, the complicated preparation process, difficulties in isolation, and remarkably low yield have constrained further exploration of GMn. In this study, we optimized the degradation conditions in the preparation process of GMn through orthogonal experiments. Subsequently, an MPTP-induced PD model was established, followed by oral administration of GMn. Through a stepwise optimization, we successfully increased the yield of GMn, separated from crude fucoidan, from 1~2/10,000 to 4~8/1000 and indicated the effects on the amelioration of MPTP-induced motor deficits, preservation of dopamine neurons, and elevation in striatal neurotransmitter levels. Importantly, GMn mitigated gut microbiota dysbiosis induced by MPTP in mice. In particular, GM2 significantly reduced the levels of Akkermansia, Verrucomicrobiota, and Lactobacillus, while promoting the abundance of Roseburia and Prevotella compared to the model group. These findings suggest that GM2 can potentially suppress PD by modulating the gut microbiota, providing a foundation for the development of a novel and effective anti-PD marine drug.


Subject(s)
Disease Models, Animal , Gastrointestinal Microbiome , Mice, Inbred C57BL , Oligosaccharides , Animals , Gastrointestinal Microbiome/drug effects , Mice , Oligosaccharides/pharmacology , Male , Neuroprotective Agents/pharmacology , Dysbiosis/drug therapy , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Dopaminergic Neurons/drug effects , Parkinson Disease/drug therapy , Mannose/pharmacology , Mannose/chemistry , Mannose/analogs & derivatives , Glucuronates/pharmacology
5.
Eur J Med Chem ; 272: 116455, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38728868

ABSTRACT

The selectin family consisting of E-, P- and L-selectin plays dominant roles in atherosclerosis, ischemia-reperfusion injury, inflammatory diseases, and metastatic spreading of some cancers. An early goal in selectin-targeted drug discovery campaigns was to identify ligands binding to all three selectins, so-called pan-selectin antagonists. The physiological epitope, tetrasaccharide sialyl Lewisx (sLex, 1) binds to all selectins, albeit with very different affinities. Whereas P- and L-selectin require additional interactions contributed by sulfate groups for high binding affinity, E-selectin can functionally bind sLex-modified glycolipids and glycoproteins. Rivipansel (3) marked the first pan-selectin antagonist, which simultaneously interacted with both the sLex and the sulfate binding site. The aim of this contribution was to improve the pan-selectin affinity of rivipansel (3) by leveraging a new class of sLex mimetics in combination with an optimized linker length to the sulfate bearing group. As a result, the pan-selectin antagonist 11b exhibits an approximatively 5-fold improved affinity for E-, as well as P-selectin.


Subject(s)
Selectins , Humans , Selectins/metabolism , Structure-Activity Relationship , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Oligosaccharides/chemical synthesis , Molecular Structure , Sialyl Lewis X Antigen , Dose-Response Relationship, Drug , E-Selectin/metabolism , E-Selectin/antagonists & inhibitors , Glycolipids
6.
Int J Biol Macromol ; 269(Pt 1): 132033, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38702000

ABSTRACT

The role of mannanases is diverse and they are used in many industrial applications, in animal feed, in the food industry and in healthcare. They are also applied in biomass processing, because they play an important role in the breakdown of hemicellulose. Among the mannanase inhibitors, heavy metal ions and general enzyme inhibitors are mainly mentioned. Unfortunately, almost no data are available on carbohydrate-based natural inhibitors of mannanases. According to the literature, carbohydrates do not play an important role in the inhibition of mannanases, so neither do oligosaccharides. This is in contrast to the action and inhibition of other O-glycosyl hydrolases. My hypothesis is that mannanases, like other polysaccharide-degrading enzymes, work in the same way and can be inhibited by oligosaccharides. Evidence from docking and modeling results supports and makes probable the hypothesis that oligosaccharides can inhibit the activity of mannanases, similar to the inhibition of other O-glycosyl hydrolases. Among natural carbohydrate oligomers, several potential mannanase inhibitors have been identified and characterized. In addition to expensive research, it is very important to use research based on cheaper modeling to explore the processes. The results obtained are novel and forward-looking, enabling in-depth and targeted research to be carried out.


Subject(s)
Enzyme Inhibitors , Mannosidases , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Mannosidases/antagonists & inhibitors , Mannosidases/metabolism , Mannosidases/chemistry , Molecular Docking Simulation , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Hydrolysis
7.
Int J Biol Macromol ; 269(Pt 1): 132072, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705339

ABSTRACT

Chitosan (CTS) and chitosan oligosaccharides (COS) have been widely applied in food industry due to their bioactivities and functions. However, CTS and COS with positive charges could interact with proteins, such as whey protein isolate (WPI), influencing their digestion. Interaction among CTS/COS, FUC, and WPI/enzymes was studied by spectroscopy, chromatography, and chemical methods in order to reveal the role of FUC in relieving the inhibition of protein digestibility by CTS/COS and demonstrate the action mechanisms. As shown by the results, the addition of FUC increased degree of hydrolysis (DH) and free protein in the mixture of CTS and WPI to 3.1-fold and 1.8-fold, respectively, while raise DH value and free protein in the mixture of COS and WPI to 6.7-fold and 1.2-fold, respectively. The interaction between amino, carboxyl, sulfate, and hydroxyl groups from carbohydrates and protein could be observed, and notably, FUC could interact with CTS/COS preferentially to prevent CTS/COS from combining with WPI. In addition, the addition of FUC could also relieve the combination of CTS to trypsin, increasing the fluorescence intensity and concentration of trypsin by 83.3 % and 4.8 %, respectively. Thus, the present study demonstrated that FUC could alleviate the inhibitory effect of CTS/COS on protein digestion.


Subject(s)
Chitosan , Oligosaccharides , Polysaccharides , Chitosan/chemistry , Chitosan/pharmacology , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/metabolism , Hydrolysis , Whey Proteins/chemistry , Whey Proteins/pharmacology , Whey Proteins/metabolism , Trypsin/metabolism , Trypsin/chemistry , Proteolysis/drug effects
8.
Int J Biol Macromol ; 269(Pt 2): 132068, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38719001

ABSTRACT

Pullulan was used as the wall material for microencapsulation of L. plantarum CRD7 by spray drying, while isomalto-oligosaccharides (IMO) was used as prebiotic. Also, the effect of different thermal protectants on survival rate during microencapsulation was evaluated. Taguchi orthogonal array design showed that pullulan at 14 % concentration, IMO at 30 % concentration and whey protein isolate at 20 % rate were the optimized wall material, prebiotic and thermal protectant, respectively for microencapsulation of L. plantarum. FESEM images revealed that the spray-dried encapsulates were fibrous similar to those produce by electrospinning, while fluorescence microscopy ascertained that most of the probiotic cells were alive and intact after microencapsulation. The adsorption-desorption isotherm was of Type II and the encapsulate had specific surface area of 1.92 m2/g and mean pore diameter of 15.12 nm. The typical amide II and III bands of the bacterial proteins were absent in the FTIR spectra, suggestive of adequate encapsulation. DSC thermogram showed shifting of melting peaks to wider temperature range due to interactions between the probiotic and wall materials. IMO at 30 % (w/w) along with WPI at 20 % concentration provided the highest storage stability and the lowest rate of cell death of L. plantarum after microencapsulation. Acid and bile salt tolerance results confirmed that microencapsulated L. plantarum could sustain the harsh GI conditions with >7.5 log CFU/g viability. After microencapsulation, L. plantarum also possessed the ability to ferment milk into curd with pH of 4.62.


Subject(s)
Glucans , Lactobacillus plantarum , Prebiotics , Glucans/chemistry , Glucans/pharmacology , Lactobacillus plantarum/chemistry , Spray Drying , Probiotics/chemistry , Microbial Viability/drug effects , Drug Compounding , Whey Proteins/chemistry , Oligosaccharides/chemistry , Oligosaccharides/pharmacology
9.
Int J Biol Macromol ; 269(Pt 2): 132131, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38719017

ABSTRACT

Chitosan oligosaccharide (COS) modification is a feasible way to develop novel green nematicides. This study involved the synthesis of various COS sulfonamide derivatives via hydroxylated protection and deprotection, which were then characterized using NMR, FTIR, MS, elemental analysis, XRD, and TG/DTG. In vitro experiments found that COS-alkyl sulfonamide derivatives (S6 and S11-S13) exhibited high mortality (>98 % at 1 mg/mL) against Meloidogyne incognita second-instar larvaes (J2s) among the derivatives. S6 can cause vacuole-like structures in the middle and tail regions of the nematode body and effectively inhibit egg hatching. In vivo tests have found that S6 has well control effects and low plant toxicity. Additionally, the structure-activity studies revealed that S6 with a high degree of substitution, a low molecular weight, and a sulfonyl bond on the amino group of the COS backbone exhibited increased nematicidal activity. The sulfonamide group is a potential active group for developing COS-based nematicides.


Subject(s)
Antinematodal Agents , Chitosan , Oligosaccharides , Sulfonamides , Tylenchoidea , Chitosan/chemistry , Chitosan/pharmacology , Animals , Tylenchoidea/drug effects , Antinematodal Agents/pharmacology , Antinematodal Agents/chemistry , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Sulfonamides/chemistry , Sulfonamides/pharmacology , Structure-Activity Relationship , Larva/drug effects
10.
Int Immunopharmacol ; 135: 112293, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38795596

ABSTRACT

Oligosaccharides, namely, chitosan oligosaccharides (COS), fructooligosaccharides (FOS), and 2'-fucosyllactose (2-FL) were used to prevent the dextran sulfate sodium (DSS)-induced colitis in vivo based on antioxidant properties and anti-inflammatory activities, further comparing their alleviating effects to investigate the optimal anti-inflammatory agent. The results showed COS demonstrated the highest antioxidant properties, with a DPPH scavenging rate of 37.4% and an ABTS scavenging rate of 46.4% in these oligosaccharides. Consequently, COS exhibited the best anti-inflammatory activities on inflamed RAW 264.7 cells. Furthermore, the COS intervention demonstrated the best attenuated effects on decrease in the body weight and increase in DAI score, as well as on the overexpressed inflammatory factors and underexpressed short-chain fatty acids (SCFAs) compare to FOS and 2-FL. Therefore, these beneficial changes help prevent the damage to the inflammatory lesions in colonic histopathology. Additionally, COS significantly increased the diversity of gut microbiota and the ratio of Firmicutes/Bacteroidetes at phylum level. It also up-regulated the abundance of Lactobacillaceae and down-regulated Helicobacteraceae and Desulfovibrionaceae more effectively at family level to maintain oral tolerance against DSS. In short, COS intervention could be a promising nutritional strategy for alleviating colitis.


Subject(s)
Anti-Inflammatory Agents , Colitis , Dextran Sulfate , Gastrointestinal Microbiome , Oligosaccharides , Animals , Oligosaccharides/pharmacology , Oligosaccharides/therapeutic use , Mice , Colitis/chemically induced , Colitis/drug therapy , RAW 264.7 Cells , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Gastrointestinal Microbiome/drug effects , Male , Colon/pathology , Colon/drug effects , Chitosan/pharmacology , Antioxidants/pharmacology , Antioxidants/therapeutic use , Trisaccharides/therapeutic use , Trisaccharides/pharmacology , Disease Models, Animal , Fatty Acids, Volatile/metabolism , Mice, Inbred C57BL
11.
Bioorg Chem ; 148: 107406, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38728907

ABSTRACT

Bacterial infections are the second leading cause of death worldwide, and the evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens exacerbate the threat crisis. Carbohydrates participate in bacterial infection, drug resistance and the process of host immune regulation. Numerous antimicrobials derived from carbohydrates or contained carbohydrate scaffolds that are conducive to an increase in pathogenic bacteria targeting, the physicochemical properties and druggability profiles. In the paper, according to the type and number of sugar residues contained in antimicrobial molecules collected from the literatures ranging from 2014 to 2024, the antimicrobial activities, action mechanisms and structure-activity relationships were delineated and summarized, for purpose to provide the guiding template to select the type and size of sugars in the design of oligosaccharide-based antimicrobials to fight the looming antibiotic resistance crisis.


Subject(s)
Anti-Bacterial Agents , Microbial Sensitivity Tests , Oligosaccharides , Structure-Activity Relationship , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Molecular Structure , Bacteria/drug effects , Humans , Monosaccharides/chemistry , Monosaccharides/pharmacology , Disaccharides/chemistry , Disaccharides/pharmacology
12.
Int J Biol Macromol ; 270(Pt 2): 132283, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38735605

ABSTRACT

A new conjugate, galloyl-oligochitosan nanoparticles (GOCNPs), was fabricated and used as nano-vehicle for effective and controlled delivery of propolis extract (PE) in the form of PE#GOCNPs, targeting improving its pharmaceutical potential. H-bonding interactions between the carboxyl, amino, and hydroxyl groups of the GOCNPs and PE resulted in successful encapsulation, with an entrapment efficacy of 97.3 %. The PE#GOCNPs formulation also exhibited excellent physicochemical stability and time-triggered drug release characteristics under physiological conditions. Furthermore, PE#GOCNPs showed significant activity against MCF-7 and HEPG2 carcinoma cells by scavenging free oxygen radicals and upregulating antioxidant enzymes. Additionally, PE#GOCNPs displayed anti-inflammatory properties by increasing IL10 and reducing pro-inflammatory cytokines more effectively than celecoxib. Furthermore, PE#GOCNPs reduced the expression of epidermal growth factor receptor (EGFR) and survivin genes. Furthermore, the encapsulated PE demonstrated significant activity in suppressing sonic hedgehog protein (SHH). The use of GOCNPs in combination with propolis presents a promising new strategy for chemotherapy with reduced toxicity and enhanced biocompatibility. This novel approach has the potential to revolutionize the field of chemotherapy. Future studies should focus on the application of the encapsulated PE in various cancer cell lines, distinct gene expression factors, and cell cycles.


Subject(s)
Antioxidants , Cell Proliferation , Chitin , Chitosan , Nanoparticles , Oligosaccharides , Propolis , Humans , Propolis/chemistry , Propolis/pharmacology , Chitosan/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Nanoparticles/chemistry , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Chitin/analogs & derivatives , Chitin/chemistry , Chitin/pharmacology , Cell Proliferation/drug effects , Hep G2 Cells , MCF-7 Cells , Drug Liberation , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Drug Carriers/chemistry , Drug Delivery Systems
13.
Food Funct ; 15(11): 5908-5920, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38738338

ABSTRACT

Non-digestible oligosaccharides have attracted attention due to their critical role in maintaining the balance of a host's gut microbiota. Lactiplantibacillus plantarum ZDY2013 was isolated from traditional fermented acid beans, which could metabolize many complex carbohydrates and had intestinal immunomodulatory effects. In our study, the ameliorative effect of a combination of non-digestible isomaltooligosaccharide (IMO) and L. plantarum ZDY2013 was investigated in dextran sulfate sodium (DSS)-induced colitis mice. The results showed that IMO could specifically promote L. plantarum ZDY2013 intestinal colonization after five days of gavage and ameliorate the symptoms of colitis (survival rate, DAI score, colon length, etc.) as well as colon tissue integrity. IMO combined with L. plantarum ZDY2013 increased the levels of intestinal tight junction proteins (ZO-1 and claudin) and mucin (MUC-2), followed by alleviation of inflammatory responses (decreased the expression of IL-1ß, TNF-α, and IL-6 and increased the expression of IL-10 and IL-22) and the level of oxidative stress (decreased the level of COX-2 and iNOS and increased the expression of T-AOC and SOD). Furthermore, the combination increased the diversity of the gut microbiota and modulated the microbial structural component (decreased the abundance of Escherichia and Helicobacter and increased the abundance of Lactobacillus and SCFA-producing related species). Taken together, our results suggested that the consumption of IMO and L. plantarum ZDY2013 could improve the symptoms of colitis in mice by improving the intestinal barrier along with regulating the composition and metabolites of the gut microbiota.


Subject(s)
Colitis , Dextran Sulfate , Gastrointestinal Microbiome , Oligosaccharides , Animals , Gastrointestinal Microbiome/drug effects , Mice , Colitis/chemically induced , Oligosaccharides/pharmacology , Oligosaccharides/administration & dosage , Male , Dietary Supplements , Lactobacillus plantarum , Probiotics/pharmacology , Probiotics/administration & dosage , Mice, Inbred C57BL , Intestinal Mucosa/metabolism , Disease Models, Animal
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 441-446, 2024 Mar 20.
Article in Chinese | MEDLINE | ID: mdl-38645870

ABSTRACT

Objective: To study the immunoadjuvant effects of chitosan oligosaccharide (COS), including the immune activation and the triggering of lysosomal escape, and to explore whether COS can be used as an adjuvant for attenuated live bacteria vector vaccines. Methods: 1) Mouse macrophages RAW264.7 cells were cultured with COS at 0 mg/mL (the control group) and 0.1-4 mg/mL for 24 h and the effect on cell viability was measured by CCK8 assay. Mouse macrophages RAW264.7 were treated with COS at 0 (the control group), 1, 2, and 4 mg/mL for 24 h. Then, the mRNA expression levels of the cytokines, including IFN-γ, IL-10, TGF-ß, and TLR4, were determined by RT-qPCR assay. 2) RAW264.7 cells were treated with 1 mL of PBS containing different components, including calcein at 50 µg/mL, COS at 2 mg/mL, and bafilomycin A1, an inhibitor, at 1 µmol/mL, for culturing. The cells were divided into the Calcein group, Calcein+COS group, and Calcein+COS+Bafilomycin A1 group accordingly. Laser scanning confocal microscopy was used to observe the phagocytosis and the intracellular fluorescence distribution of calcein, a fluorescent dye, in RAW264.7 cells in the presence or absence of COS intervention to determine whether COS was able to trigger lysosomal escape. 3) LM∆E6E7 and LI∆E6E7, the attenuated Listeria vector candidate therapeutic vaccines for cervical cancer, were encapsulated with COS at the mass concentrations of 0.5 mg/mL, 1 mg/mL, 2 mg/mL , 4 mg/mL, and 8 mg/mL. Then, the changes in zeta potential were measured to select the concentration of COS that successfully encapsulated the bacteria. Phagocytosis of the vaccine strains by RAW264.7 cells was measured before and after LM∆E6E7 and LI∆E6E7 were coated with COS at 2 mg/mL. Results: 1) CCK8 assays showed that, compared with the findings for the control group, the intervention of RAW264.7 cells with COS at different concentrations for 24 h was not toxic to the cells and promoted cell proliferation, with the difference being statistically significant (P<0.05). According to the RT-qPCR results, compared with those of the control group, the COS intervention up-regulated the mRNA levels of TLR4 and IFN-γ in RAW264.7 cells, while it inhibited the mRNA expression levels of TGF-ß and IL-10, with the most prominent effect being observed in the 4 mg/mL COS group (P<0.05). 2) Laser scanning confocal microscopy revealed that the amount of fluorescent dye released from lysosomes into the cells was greater in the Calcein+COS group than that in the Calcein group. In other words, a greater amount of fluorescent dye was released from lysosomes into the cells under COS intervention. Furthermore, this process could be blocked by bafilomycin A1. 3) The zeta potential results showed that COS could successfully encapsulate the surface of bacteria when its mass concentration reached 2 mg/mL. Before and after the vaccine strain was encapsulated by COS, the phagocytosis of LM∆E6E7 by RAW264.7 cells was 5.70% and 22.00%, respectively, showing statistically significant differences (P<0.05); the phagocytosis of LI∆E6E7 by RAW264.7 cells was 1.55% and 6.12%, respectively, showing statistically significant differences (P<0.05). Conclusion: COS has the effect of activating the immune response of macrophages and triggering lysosomal escape. The candidates strains of coated live attenuated bacterial vector vaccines can promote the phagocytosis of bacteria by macrophages. Further research is warranted to develop COS into an adjuvant for bacterial vector vaccine.


Subject(s)
Adjuvants, Immunologic , Bacterial Vaccines , Chitosan , Oligosaccharides , Animals , Mice , RAW 264.7 Cells , Oligosaccharides/pharmacology , Adjuvants, Immunologic/pharmacology , Bacterial Vaccines/immunology , Macrophages/metabolism , Macrophages/immunology , Macrophages/drug effects , Vaccines, Attenuated/immunology , Cytokines/metabolism , Cell Survival/drug effects
15.
Carbohydr Polym ; 336: 122129, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38670770

ABSTRACT

Hyaluronan, a linear glycosaminoglycan comprising D-N-acetylglucosamine and D-glucuronic acid, is the main component of the extracellular matrix. Its influence on cell proliferation, migration, inflammation, signalling, and other functions, depends heavily on its molecular weight and chemical modification. Unsaturated HA oligosaccharides are available in defined length and purity. Their potential therapeutic utility can be further improved by chemical modification, e. g., reduction. No synthesis of such modified oligosaccharides, either stepwise or by hyaluronan cleavage, has been reported yet. Here we show a three-step synthesis (esterification, depolymerization and reduction) of unsaturated even numbered hyaluronan oligosaccharides with carboxylates and the reducing terminus reduced to an alcohol. Particular oligosaccharides were synthesised. The modified oligosaccharides are not cleaved by mammalian or bacterial hyaluronidase and do not affect the growth of mouse and human fibroblasts. Further, MTT and NRU viability tests showed that they inhibit the growth of human colon carcinoma cells HT-29 by 20-50 % in concentrations 500-1000 µg/mL. Interestingly, this effect takes place regardless of CD44 receptor expression and was not observed with unmodified HA oligosaccharides. These compounds could serve as enzymatically stable building blocks for biologically active substances.


Subject(s)
Cell Proliferation , Cytostatic Agents , Hyaluronic Acid , Hyaluronoglucosaminidase , Oligosaccharides , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Humans , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Animals , Mice , Cell Proliferation/drug effects , Hyaluronoglucosaminidase/metabolism , Hyaluronoglucosaminidase/antagonists & inhibitors , Cytostatic Agents/pharmacology , Cytostatic Agents/chemistry , Cytostatic Agents/chemical synthesis , HT29 Cells , Hyaluronan Receptors/metabolism , Fibroblasts/drug effects
16.
Mol Nutr Food Res ; 68(9): e2300758, 2024 May.
Article in English | MEDLINE | ID: mdl-38639319

ABSTRACT

SCOPE: Obesity and metabolic diseases are closely associated, and individuals who become obese are also prone to type 2 diabetes and cardiovascular disorders. Gut microbiota is mediated by diet and can influence host metabolism and the incidence of metabolic disorders. Recent studies have suggested that improving gut microbiota through a fructooligosaccharide (FOS)-supplemented diet may ameliorate obesity and other metabolic disorders. Although accumulating evidence supports the notion of the developmental origins of health and disease, the underlying mechanisms remain obscure. METHODS AND RESULTS: ICR mice are fed AIN-93G formula-based cellulose -, FOS-, acetate-, or propionate-supplemented diets during pregnancy. Offspring are reared by conventional ICR foster mothers for 4 weeks; weaned mice are fed high fat diet for 12 weeks and housed individually. The FOS and propionate offspring contribute to suppressing obesity and improving glucose intolerance. Gut microbial compositions in FOS-fed mothers and their offspring are markedly changed. However, the beneficial effect of FOS diet on the offspring is abolished when antibiotics are administered to pregnant mice. CONCLUSION: The findings highlight the link between the maternal gut environment and the developmental origin of metabolic syndrome in offspring. These results open novel research avenues into preemptive therapies for metabolic disorders by targeting the maternal gut microbiota.


Subject(s)
Diet, High-Fat , Gastrointestinal Microbiome , Mice, Inbred ICR , Obesity , Oligosaccharides , Animals , Pregnancy , Oligosaccharides/pharmacology , Oligosaccharides/administration & dosage , Diet, High-Fat/adverse effects , Female , Gastrointestinal Microbiome/drug effects , Male , Mice, Obese , Mice , Prenatal Exposure Delayed Effects , Phenotype , Maternal Nutritional Physiological Phenomena , Dietary Supplements
17.
J Agric Food Chem ; 72(17): 9782-9794, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38597360

ABSTRACT

Uncontrolled inflammation contributes significantly to the mortality in acute respiratory infections. Our previous research has demonstrated that maize bran feruloylated oligosaccharides (FOs) possess notable anti-inflammatory properties linked to the NF-kB pathway regulation. In this study, we clarified that the oral administration of FOs moderately inhibited H1N1 virus infection and reduced lung inflammation in influenza-infected mice by decreasing a wide spectrum of cytokines (IFN-α, IFN-ß, IL-6, IL-10, and IL-23) in the lungs. The mechanism involves FOs suppressing the transduction of the RIG-I/MAVS/TRAF3 signaling pathway, subsequently lowering the expression of NF-κB. In silico analysis suggests that FOs have a greater binding affinity for the RIG-I/MAVS signaling complex. This indicates that FOs have potential as promising targets for immune modulation. Moreover, in MAVS knockout mice, we confirmed that the anti-inflammatory function of FOs against influenza depends on MAVS. Comprehensive analysis using 16S rRNA gene sequencing and metabolite profiling techniques showed that FOs have the potential to restore immunity by modulating the gut microbiota. In conclusion, our study demonstrates that FOs are effective anti-inflammatory phytochemicals in inhibiting lung inflammation caused by influenza. This suggests that FOs could serve as a potential nutritional strategy for preventing the H1N1 virus infection and associated lung inflammation.


Subject(s)
DEAD Box Protein 58 , Influenza A Virus, H1N1 Subtype , Influenza, Human , Mice, Knockout , Oligosaccharides , Orthomyxoviridae Infections , Signal Transduction , TNF Receptor-Associated Factor 3 , Animals , Mice , Oligosaccharides/administration & dosage , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/metabolism , Influenza A Virus, H1N1 Subtype/immunology , Humans , Signal Transduction/drug effects , Signal Transduction/immunology , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/metabolism , TNF Receptor-Associated Factor 3/genetics , TNF Receptor-Associated Factor 3/metabolism , TNF Receptor-Associated Factor 3/immunology , DEAD Box Protein 58/genetics , DEAD Box Protein 58/metabolism , DEAD Box Protein 58/immunology , Pneumonia/immunology , Pneumonia/prevention & control , Pneumonia/metabolism , Pneumonia/virology , Mice, Inbred C57BL , Lung/immunology , Lung/metabolism , Lung/drug effects , Lung/virology , Cytokines/metabolism , Cytokines/immunology , Cytokines/genetics , Female , NF-kappa B/immunology , NF-kappa B/genetics , NF-kappa B/metabolism , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology
18.
Fitoterapia ; 175: 105974, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663563

ABSTRACT

Alhagi honey is derived from the secretory granules of Alhagi pseudoalhagi Desv., a leguminous plant commonly known as camelthorn. Modern medical research has demonstrated that the extract of Alhagi honey possesses regulatory properties for the gastrointestinal tract and immune system, as well as exerts anti-tumor, anti-oxidative, anti-inflammatory, anti-bacterial, and hepatoprotective effects. The aim of this study was to isolate and purify oligosaccharide monomers (referred to as Mel) from camelthorn and elucidate their structural characteristics. Subsequently, the impact of Mel on liver injury induced by carbon tetrachloride (CCl4) in mice was investigated. The analysis identified the isolated oligosaccharide monomer (α-D-Glcp-(1 â†’ 3)-ß-D-Fruf-(2 â†’ 1)-α-D-Glcp), with the molecular formula C18H32O16. In a mouse model of CCl4-induced liver fibrosis, Mel demonstrated significant therapeutic effects by attenuating the development of fibrosis. Moreover, it enhanced anti-oxidant enzyme activity (glutathione peroxidase and superoxide dismutase) in liver tissues, thereby reducing oxidative stress markers (malondialdehyde and reactive oxygen species). Mel also improved serum albumin levels, lowered liver enzyme activities (aspartate aminotransferase and alanine aminotransferase), and decreased inflammatory factors (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6). Immunohistochemistry, immunofluorescence, and western blotting analyses confirmed the ability of Mel to downregulate hepatic stellate cell-specific markers (collagen type I alpha 1 chain, alpha-smooth muscle actin, transforming growth factor-beta 1. Non-targeted metabolomics analysis revealed the influence of Mel on metabolic pathways related to glutathione, niacin, pyrimidine, butyric acid, and amino acids. In conclusion, the results of our study highlight the promising potential of Mel, derived from Alhagi honey, as a viable candidate drug for treating liver fibrosis. This discovery offers a potentially advantageous option for individuals seeking natural and effective means to promote liver health.


Subject(s)
Honey , Liver Cirrhosis , Oligosaccharides , Animals , Mice , Liver Cirrhosis/drug therapy , Liver Cirrhosis/chemically induced , Oligosaccharides/pharmacology , Oligosaccharides/isolation & purification , Oligosaccharides/chemistry , Male , Fabaceae/chemistry , Carbon Tetrachloride , Liver/drug effects , Liver/pathology , Molecular Structure , Oxidative Stress/drug effects , Antioxidants/pharmacology , Superoxide Dismutase/metabolism , Glutathione Peroxidase/metabolism , Malondialdehyde/metabolism
19.
J Nutr Biochem ; 129: 109640, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38583497

ABSTRACT

Midlife overweight and obesity are risk factors of cognitive decline and Alzheimer' s disease (AD) in late life. In addition to increasing risk of obesity and cognitive dysfunction, diets rich in fats also contributes to an imbalance of gut microbiota. Xylo-oligosaccharides (XOS) are a kind of prebiotic with several biological advantages, and can selectively promote the growth of beneficial microorganisms in the gut. To explore whether XOS can alleviate cognitive decline induced by high-fat diet (HFD) through improving gut microbiota composition, mice were fed with normal control or 60% HFD for 9 weeks to induce obesity. After that, mice were supplemented with XOS (30 g or 60 g/kg-diet) or without, respectively, for 12 weeks. The results showed that XOS inhibited weight gain, decreased epidydimal fat weight, and improved fasting blood sugar and blood lipids in mice. Additionally, XOS elevated spatial learning and memory function, decreased amyloid plaques accumulation, increased brain-derived neurotrophic factor levels, and improved neuroinflammation status in hippocampus. Changes in glycerolipids metabolism-associated lipid compounds caused by HFD in hippocampus were reversed after XOS intervention. On the other hand, after XOS intervention, increase in immune-mediated bacteria, Faecalibacterium was observed. In conclusion, XOS improved gut dysbiosis and ameliorated spatial learning and memory dysfunction caused by HFD by decreasing cognitive decline-associated biomarkers and changing lipid composition in hippocampus.


Subject(s)
Diet, High-Fat , Gastrointestinal Microbiome , Mice, Inbred C57BL , Oligosaccharides , Prebiotics , Animals , Gastrointestinal Microbiome/drug effects , Diet, High-Fat/adverse effects , Oligosaccharides/pharmacology , Oligosaccharides/administration & dosage , Male , Mice , Hippocampus/metabolism , Hippocampus/drug effects , Obesity/metabolism , Obesity/microbiology , Glucuronates/pharmacology , Brain/metabolism , Brain/drug effects , Lipids/blood , Cognitive Dysfunction/prevention & control , Dysbiosis , Lipid Metabolism/drug effects
20.
J Ethnopharmacol ; 329: 118149, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38580188

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Calcium oxalate crystals play a key role in the development and recurrence of kidney stones (also known as urolithiasis); thus, inhibiting the formation of these crystals is a central focus of urolithiasis prevention and treatment. Previously, we reported the noteworthy in vitro inhibitory effects of Aspidopterys obcordata fructo oligosaccharide (AOFOS), an active polysaccharide of the traditional Dai medicine Aspidopterys obcordata Hemsl. (commonly known as Hei Gai Guan), on the growth of calcium oxalate crystals. AIM OF THE STUDY: To investigated the effectiveness and mechanism of AOFOS in treating kidney stones. MATERIALS AND METHODS: A kidney stones rats model was developed, followed by examining AOFOS transport dynamics and effectiveness in live rats. Additionally, a correlation between the polysaccharide and calcium oxalate crystals was studied by combining crystallization experiments with density functional theory calculations. RESULTS: The results showed that the polysaccharide was transported to the urinary system. Furthermore, their accumulation was inhibited by controlling their crystallization and modulating calcium ion and oxalate properties in the urine. Consequently, this approach helped effectively prevent kidney stone formation in the rats. CONCLUSIONS: The present study emphasized the role of the polysaccharide AOFOS in modulating crystal properties and controlling crystal growth, providing valuable insights into their potential therapeutic use in managing kidney stone formation.


Subject(s)
Calcium Oxalate , Crystallization , Kidney Calculi , Animals , Calcium Oxalate/chemistry , Calcium Oxalate/metabolism , Male , Rats , Kidney Calculi/prevention & control , Kidney Calculi/drug therapy , Rats, Sprague-Dawley , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Urolithiasis/drug therapy , Urolithiasis/prevention & control , Disease Models, Animal , Inulin/chemistry , Inulin/pharmacology
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