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1.
Carbohydr Res ; 542: 109204, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38981322

ABSTRACT

The hexasaccharide arabinan domain of Mycobacterial Arabinogalactan was provided with the versatile methodology toward ß-selective arabinofuranosylation directed by B(C6F5)3, demonstrating the effectiveness of the ß-arabinofuranosylation strategy. Derivatization of the amino moiety at the reducing end are essential prerequisites for elucidating the biosynthetic pathway and conjugating of this compound to a protein carrier for vaccine generation.


Subject(s)
Galactans , Galactans/chemistry , Galactans/chemical synthesis , Oligosaccharides/chemical synthesis , Oligosaccharides/chemistry , Carbohydrate Sequence , Mycobacterium/chemistry , Polysaccharides
2.
Carbohydr Res ; 542: 109205, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38981321

ABSTRACT

There has been a sudden increase in viral diseases, such as coronavirus disease 2019 (COVID-19), causing significant harm to human and animal well-being, as well as economic development. Medicinal herbs, with a history of thousands of years in clinical use, contain versatile polysaccharides as one of their primary compounds. This review offers an overview of the antiviral effects of polysaccharides from medicinal herbs on viruses in humans, poultry, swine and aquaculture in recent years. The mechanism of these antiviral polysaccharides, involved in hindering various stages of the viral life cycle thereby blocking virus infection, is summarized. The review also explores other underlying mechanisms of antiviral effects, such as enhancing the immune response, regulating inflammatory reactions, balancing gut flora, reducing oxidative stress, and suppressing apoptosis through various corresponding signaling pathways. The structure-function relationships discussed in this article also aid in understanding the antiviral mechanism of natural polysaccharides, indicating the need for more in-depth research and analysis. Natural polysaccharides from medicinal herbs have emerged as valuable resources in the fight against viral infections, exhibiting high effectiveness. This review emphasizes the promising role of polysaccharides from medicinal herbs as potential candidates for blocking viral infections in humans and animals.


Subject(s)
Antiviral Agents , Plants, Medicinal , Polysaccharides , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Humans , Plants, Medicinal/chemistry , Animals , SARS-CoV-2/drug effects , COVID-19 Drug Treatment
3.
Hepatol Commun ; 8(8)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39023282

ABSTRACT

BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased in recent decades. Approximately 25% of patients with MASLD progress to metabolic dysfunction-associated steatohepatitis, which is characterized by hepatic steatosis plus hepatocyte damage, inflammation, and fibrosis. We previously reported that Neurotropin (NTP), a drug used for relieving pain in Japan and China, inhibits lipid accumulation in hepatocytes by preventing mitochondrial dysfunction. We hypothesized that inhibiting hepatic steatosis and inflammation by NTP can be an effective strategy for treating MASLD and tested this hypothesis in a MASLD mouse model. METHODS: Six-week-old C57BL/6NJ male mice were fed a normal diet and normal drinking water or a high-fat diet with high fructose/glucose water for 12 weeks. During the last 6 weeks, the mice were also given high-dose NTP, low-dose NTP, or control treatment. Histologic, biochemical, and functional tests were conducted. MitoPlex, a new proteomic platform, was used to measure mitochondrial proteins, as mitochondrial dysfunction was previously reported to be associated with MASLD progression. RESULTS: NTP inhibited the development of hepatic steatosis, injury, inflammation, and fibrosis induced by feeding a high-fat diet plus high fructose/glucose in drinking water. NTP also inhibited HSC activation. MitoPlex analysis revealed that NTP upregulated the expression of mitochondrial proteins related to oxidative phosphorylation, the tricarboxylic acid cycle, mitochondrial dynamics, and fatty acid transport. CONCLUSIONS: Our results indicate that NTP prevents the development of hepatic steatosis, injury, and inflammation by preserving mitochondrial function in the liver and inhibits liver fibrosis by suppressing HSC activation. Thus, repurposing NTP may be a beneficial option for treating MASLD/metabolic dysfunction-associated steatohepatitis.


Subject(s)
Diet, High-Fat , Disease Models, Animal , Drug Repositioning , Mice, Inbred C57BL , Animals , Mice , Male , Diet, High-Fat/adverse effects , Fatty Liver/drug therapy , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Analgesics/therapeutic use , Analgesics/pharmacology
5.
Plant Mol Biol ; 114(4): 84, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995453

ABSTRACT

Expansins are proteins without catalytic activity, but able to break hydrogen bonds between cell wall polysaccharides hemicellulose and cellulose. This proteins were reported for the first time in 1992, describing cell wall extension in cucumber hypocotyls caused particularly by alpha-expansins. Although these proteins have GH45 and CBM63 domains, characteristic of enzymes related with the cleavage of cell wall polysaccharides, demonstrating in vitro that they extend plant cell wall. Its participation has been associated to molecular processes such as development and growing, fruit ripening and softening, tolerance and resistance to biotic and abiotic stress and seed germination. Structural insights, facilitated by bioinformatics approaches, are highlighted, shedding light on the intricate interactions between alpha-expansins and cell wall polysaccharides. After more than thirty years of its discovery, we want to celebrate the knowledge of alpha-expansins and emphasize their importance to understand the phenomena of disassembly and loosening of the cell wall, specifically in the fruit ripening phenomena, with this state-of-the-art dedicated to them.


Subject(s)
Cell Wall , Fruit , Plant Proteins , Cell Wall/metabolism , Fruit/metabolism , Fruit/growth & development , Fruit/genetics , Plant Proteins/metabolism , Plant Proteins/genetics , Polysaccharides/metabolism
6.
Methods Mol Biol ; 2836: 97-109, 2024.
Article in English | MEDLINE | ID: mdl-38995538

ABSTRACT

Glycosylation is the most abundant and diverse post-translational modification occurring on proteins. Glycans play important roles in modulating cell adhesion, growth, development, and differentiation. Changes in glycosylation affect protein structure and function and contribute to disease processes. Therefore, understanding glycosylation patterns is key for the identification of targets for the diagnosis of diseases, cellular states, and therapy. Glycosylation is a non template-driven process governed by the action of numerous enzymes and substrate availability that varies among cell types and species. Therefore, qualitative and quantitative assessment of global glycosylation and individual glycans remains challenging because it requires integration of multiple complex data types. Glycan structure and quantity data are often integrated with assessments of gene expression to aid contextualization of observed glycosylation changes within biological processes. However, correlating glycogene expression to the glycan structure is challenging because transcriptional changes may not always concur with the final gene product; there is often a lack of information on nucleotide sugar pools, and the final glycan structure is the result of many different glycogenes acting in concert. To overcome these challenges, interactive online tools are emerging as key resources for facilitating the analysis and integration of glycomics and glycogene expression data. Importantly, these tools work in concurrence with glycan biosynthetic schemes and therefore provide a clear indication of the molecular pathways where the glycan and glycogene are involved. In this chapter, we describe the applications of four freely available online tools that can be used for integrated visualization, interpretation, and presentation of RNAseq and glycomics results.


Subject(s)
Glycomics , Polysaccharides , Software , Glycomics/methods , Polysaccharides/metabolism , Polysaccharides/analysis , Glycosylation , Humans , Protein Processing, Post-Translational , Computational Biology/methods , Internet , Glycoproteins/metabolism , Glycoproteins/genetics
7.
Methods Mol Biol ; 2836: 77-96, 2024.
Article in English | MEDLINE | ID: mdl-38995537

ABSTRACT

Glycosylation is a unique posttranslational modification that dynamically shapes the surface of cells. Glycans attached to proteins or lipids in a cell or tissue are studied as a whole and collectively designated as a glycome. UniCarb-DB is a glycomic spectral library of tandem mass spectrometry (MS/MS) fragment data. The current version of the database consists of over 1500 entries and over 1000 unique structures. Each entry contains parent ion information with associated MS/MS spectra, metadata about the original publication, experimental conditions, and biological origin. Each structure is also associated with the GlyTouCan glycan structure repository allowing easy access to other glycomic resources. The database can be directly utilized by mass spectrometry (MS) experimentalists through the conversion of data generated by MS into structural information. Flexible online search tools along with a downloadable version of the database are easily incorporated in either commercial or open-access MS software. This chapter highlights UniCarb-DB online search tool to browse differences of isomeric structures between spectra, a peak matching search between user-generated MS/MS spectra and spectra stored in UniCarb-DB and more advanced MS tools for combined quantitative and qualitative glycomics.


Subject(s)
Glycomics , Polysaccharides , Software , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Glycomics/methods , Polysaccharides/chemistry , Polysaccharides/analysis , Databases, Factual , Glycosylation , Humans
8.
Sci Rep ; 14(1): 15779, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982270

ABSTRACT

Ascomycetes, basidiomycetes and deuteromycetes can degrade wood, but less attention has been paid to basidiomycetes involved in Esca, a major Grapevine Trunk Disease. Using a wood sawdust microcosm system, we compared the wood degradation of three grapevine cultivars inoculated with Fomitiporia mediterranea M. Fisch, a basidiomycete responsible for white-rot development and involved in Esca disease. The grapevine cultivar Ugni blanc was more susceptible to wood degradation caused by F. mediterranea than the cultivars Cabernet Sauvignon and Merlot. Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy showed that F. mediterranea preferentially degrades lignin and hemicellulose over cellulose (preferential, successive or sequential white-rot). In addition, co-inoculation of sawdust with two cellulolytic and xylanolytic bacterial strains of Paenibacillus (Nakamura) Ash (Paenibacillus sp. (S231-2) and P. amylolyticus (S293)), enhanced F. mediterranea ability to degrade Ugni blanc. The NMR data further showed that the increase in Ugni blanc sawdust degradation products was greater when bacteria and fungi were inoculated together. We also demonstrated that these two bacterial strains could degrade the wood components of Ugni blanc sawdust. Genome analysis of these bacterial strains revealed numerous genes predicted to be involved in cellulose, hemicellulose, and lignin degradation, as well as several other genes related to bacteria-fungi interactions and endophytism inside the plant. The occurrence of this type of bacteria-fungus interaction could explain, at least in part, why necrosis develops extensively in certain grapevine varieties such as Ugni blanc.


Subject(s)
Lignin , Paenibacillus , Vitis , Wood , Wood/microbiology , Vitis/microbiology , Lignin/metabolism , Paenibacillus/genetics , Paenibacillus/metabolism , Plant Diseases/microbiology , Basidiomycota/genetics , Basidiomycota/metabolism , Polysaccharides/metabolism , Cellulose/metabolism , Genome, Bacterial
9.
Front Immunol ; 15: 1352018, 2024.
Article in English | MEDLINE | ID: mdl-38989282

ABSTRACT

In this study, we investigated how Radix pseudostellariae polysaccharide (RPP) enhances the immune response of the inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine through interactions with the microbiome and metabolome. We pretreated sows with 10 mg/kg body weight of RPP via drinking water for 7 days prior to intramuscular injection of the PRRSV vaccine. This significantly increased the concentrations of PRRSV GP5 protein antibody, interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-γ. Oral administration of RPP also significantly improved the abundance of beneficial bacteria in the stool, such as Parabacteroides distasonis, Prevotella_copri, Eubacterium_sp., and Clostridium_sp._CAG:226, and decreased the levels of potentially pathogenic bacteria, such as Paraeggerthella and [Clostridium] innocuum, compared to the vaccine alone. These bacterial changes were confirmed using quantitative real-time polymerase chain reaction (Q-PCR). Moreover, RPP treatment significantly increased the blood concentrations of L-theanine, taurodeoxycholic acid (TDCA), and N-arachidonoyl proline, and decreased the levels of L-glutamine, oclacitinib, lipoxin C4, and leukotriene C5 in sows after immunization (p< 0.05). The concentrations of various blood metabolites were validated using sandwich enzyme-linked immunosorbent assay (ELISA), confirming the accuracy of the metabolomics data. Intriguingly, the integration of microbiome and metabolome analyses highlighted the significance of Prevotella_copri and TDCA. We consequently developed a mouse immunity model using GP5 protein and discovered that oral administration of RPP significantly enhanced the levels of GP5 protein antibodies, IL-2, IL-4, IL-10, and IFN-γ in mouse serum. It also increased the number of CD3+ and CD3+CD4+ cells in the spleen. Additionally, Prevotella_copri was administered into the large intestine via the anus for 7 days prior to the intramuscular injection of the PRRSV GP5 protein. The results demonstrated a significant increase in TDCA and GP5 antibody concentration in the mouse serum, indicating that RPP modulates Prevotella_copri to elevate its metabolite TDCA, thereby enhancing the GP5 antibody level. In conclusion, oral administration of 10 mg/kg RPP optimizes gut flora diversity and blood metabolites, particularly Prevotella_copri and TDCA, thereby improving the immune response to the inactivated PRRSV vaccine.


Subject(s)
Metabolome , Polysaccharides , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Vaccines, Inactivated , Viral Vaccines , Animals , Swine , Porcine respiratory and reproductive syndrome virus/immunology , Porcine Reproductive and Respiratory Syndrome/immunology , Porcine Reproductive and Respiratory Syndrome/prevention & control , Viral Vaccines/immunology , Female , Vaccines, Inactivated/immunology , Antibodies, Viral/blood , Cytokines/metabolism , Microbiota/drug effects , Microbiota/immunology , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/immunology , Adjuvants, Immunologic
10.
Nat Methods ; 21(7): 1206-1215, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38951670

ABSTRACT

Glycans constitute the most complicated post-translational modification, modulating protein activity in health and disease. However, structural annotation from tandem mass spectrometry (MS/MS) data is a bottleneck in glycomics, preventing high-throughput endeavors and relegating glycomics to a few experts. Trained on a newly curated set of 500,000 annotated MS/MS spectra, here we present CandyCrunch, a dilated residual neural network predicting glycan structure from raw liquid chromatography-MS/MS data in seconds (top-1 accuracy: 90.3%). We developed an open-access Python-based workflow of raw data conversion and prediction, followed by automated curation and fragment annotation, with predictions recapitulating and extending expert annotation. We demonstrate that this can be used for de novo annotation, diagnostic fragment identification and high-throughput glycomics. For maximum impact, this entire pipeline is tightly interlaced with our glycowork platform and can be easily tested at https://colab.research.google.com/github/BojarLab/CandyCrunch/blob/main/CandyCrunch.ipynb . We envision CandyCrunch to democratize structural glycomics and the elucidation of biological roles of glycans.


Subject(s)
Deep Learning , Polysaccharides , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Polysaccharides/chemistry , Polysaccharides/analysis , Glycomics/methods , Humans , Chromatography, Liquid/methods , Software , Workflow , Neural Networks, Computer
11.
Nat Commun ; 15(1): 5841, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992036

ABSTRACT

The swimming device of archaea-the archaellum-presents asparagine (N)-linked glycans. While N-glycosylation serves numerous roles in archaea, including enabling their survival in extreme environments, how this post-translational modification contributes to cell motility remains under-explored. Here, we report the cryo-EM structure of archaellum filaments from the haloarchaeon Halobacterium salinarum, where archaellins, the building blocks of the archaellum, are N-glycosylated, and the N-glycosylation pathway is well-resolved. We further determined structures of archaellum filaments from two N-glycosylation mutant strains that generate truncated glycans and analyzed their motility. While cells from the parent strain exhibited unidirectional motility, the N-glycosylation mutant strain cells swam in ever-changing directions within a limited area. Although these mutant strain cells presented archaellum filaments that were highly similar in architecture to those of the parent strain, N-linked glycan truncation greatly affected interactions between archaellum filaments, leading to dramatic clustering of both isolated and cell-attached filaments. We propose that the N-linked tetrasaccharides decorating archaellins act as physical spacers that minimize the archaellum filament aggregation that limits cell motility.


Subject(s)
Archaeal Proteins , Halobacterium salinarum , Glycosylation , Halobacterium salinarum/metabolism , Halobacterium salinarum/genetics , Archaeal Proteins/metabolism , Archaeal Proteins/genetics , Archaeal Proteins/chemistry , Polysaccharides/metabolism , Cryoelectron Microscopy , Mutation , Cytoskeleton/metabolism , Protein Processing, Post-Translational , Cell Movement
12.
Commun Biol ; 7(1): 848, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992164

ABSTRACT

Filamentous fungi produce polysaccharide-degrading enzymes, which is controlled by poorly understood transcriptional circuits. Here we show that a circuit comprising RsrC-RsrA-RsrB (Rsr: production of raw-starch-degrading enzyme regulator) that positively regulates production of raw starch-degrading enzymes in Penicillium oxalicum. Transcription factor (TF) RsrA is essential for biosynthesis of raw starch-degrading enzymes. RsrB and RsrC containing Zn2Cys6- and C2H2-zinc finger domains, act downstream and upstream of RsrA, respectively. RsrA activates rsrB transcription, and three nucleotides (G-286, G-287 and G-292) of rsrB promoter region are required for RsrA, in terms of TF, for binding. RsrB165-271 binds to DNA sequence 5'-TCGATCAGGCACGCC-3' in the promoter region of the gene encoding key raw-starch-degrading enzyme PoxGA15A. RsrC specifically binds rsrA promoter, but not amylase genes, to positively regulate the expression of rsrA and the production of raw starch-degrading enzymes. These findings expand complex regulatory network of fungal raw starch-degrading enzyme biosynthesis.


Subject(s)
Fungal Proteins , Gene Expression Regulation, Fungal , Penicillium , Transcription Factors , Penicillium/genetics , Penicillium/metabolism , Penicillium/enzymology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Promoter Regions, Genetic , Polysaccharides/metabolism , Polysaccharides/biosynthesis , Gene Regulatory Networks
13.
Theranostics ; 14(10): 3810-3826, 2024.
Article in English | MEDLINE | ID: mdl-38994034

ABSTRACT

Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn2+), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn2+-pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn2+-pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro: promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn2+-embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.


Subject(s)
Dendrobium , Hydrogels , Manganese , Mice, Inbred C57BL , Microspheres , Polysaccharides , Animals , Mice , Hydrogels/chemistry , Manganese/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Dendrobium/chemistry , Macrophages/immunology , Macrophages/drug effects , Melanoma/immunology , Melanoma/drug therapy , Melanoma/therapy , Immunotherapy/methods , Dendritic Cells/immunology , Dendritic Cells/drug effects , Cell Line, Tumor , Female , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Reactive Oxygen Species/metabolism , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacology , Melanoma, Experimental/immunology , Melanoma, Experimental/therapy , Melanoma, Experimental/drug therapy
14.
Int J Mol Sci ; 25(13)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39000302

ABSTRACT

Dupuytren's disease (DD) is a prevalent fibroproliferative disorder of the hand, shaped by genetic, epigenetic, and environmental influences. The extracellular matrix (ECM) is a complex assembly of diverse macromolecules. Alterations in the ECM's content, structure and organization can impact both normal physiological functions and pathological conditions. This study explored the content and organization of glycosaminoglycans, proteoglycans, and collagen in the ECM of patients at various stages of DD, assessing their potential as prognostic indicators. This research reveals, for the first time, relevant changes in the complexity of chondroitin/dermatan sulfate structures, specifically an increase of disaccharides containing iduronic acid residues covalently linked to either N-acetylgalactosamine 6-O-sulfated or N-acetylgalactosamine 4-O-sulfated, correlating with the disease's severity. Additionally, we noted an increase in versican expression, a high molecular weight proteoglycan, across stages I to IV, while decorin, a small leucine-rich proteoglycan, significantly diminishes as DD progresses, both confirmed by mRNA analysis and protein detection via confocal microscopy. Coherent anti-Stokes Raman scattering (CARS) microscopy further demonstrated that collagen fibril architecture in DD varies importantly with disease stages. Moreover, the urinary excretion of both hyaluronic and sulfated glycosaminoglycans markedly decreased among DD patients.Our findings indicate that specific proteoglycans with galactosaminoglycan chains and collagen arrangements could serve as biomarkers for DD progression. The reduction in glycosaminoglycan excretion suggests a systemic manifestation of the disease.


Subject(s)
Collagen , Decorin , Dupuytren Contracture , Proteoglycans , Humans , Dupuytren Contracture/metabolism , Dupuytren Contracture/pathology , Collagen/metabolism , Proteoglycans/metabolism , Decorin/metabolism , Extracellular Matrix/metabolism , Male , Disease Progression , Female , Dermatan Sulfate/metabolism , Middle Aged , Aged , Versicans/metabolism , Versicans/genetics , Glycosaminoglycans/metabolism , Chondroitin Sulfates/metabolism , Polysaccharides
15.
Int J Mol Sci ; 25(13)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39000427

ABSTRACT

The amyloid-beta peptide (Aß) is the neurotoxic component in senile plaques of Alzheimer's disease (AD) brains. Previously we have reported that Aß toxicity is mediated by the induction of sonic hedgehog (SHH) to trigger cell cycle re-entry (CCR) and apoptosis in post-mitotic neurons. Basella alba is a vegetable whose polysaccharides carry immunomodulatory and anti-cancer actions, but their protective effects against neurodegeneration have never been reported. Herein, we tested whether polysaccharides derived from Basella alba (PPV-6) may inhibit Aß toxicity and explored its underlying mechanisms. In differentiated rat cortical neurons, Aß25-35 reduced cell viability, damaged neuronal structure, and compromised mitochondrial bioenergetic functions, all of which were recovered by PPV-6. Immunocytochemistry and western blotting revealed that Aß25-35-mediated induction of cell cycle markers including cyclin D1, proliferating cell nuclear antigen (PCNA), and histone H3 phosphorylated at Ser-10 (p-Histone H3) in differentiated neurons was all suppressed by PPV-6, along with mitigation of caspase-3 cleavage. Further studies revealed that PPV-6 inhibited Aß25-35 induction of SHH; indeed, PPV-6 was capable of suppressing neuronal CCR and apoptosis triggered by the exogenous N-terminal fragment of sonic hedgehog (SHH-N). Our findings demonstrated that, in the fully differentiated neurons, PPV-6 exerts protective actions against Aß neurotoxicity via the downregulation of SHH to suppress neuronal CCR and apoptosis.


Subject(s)
Amyloid beta-Peptides , Apoptosis , Cell Cycle , Hedgehog Proteins , Neurons , Polysaccharides , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/toxicity , Hedgehog Proteins/metabolism , Animals , Neurons/drug effects , Neurons/metabolism , Apoptosis/drug effects , Rats , Polysaccharides/pharmacology , Polysaccharides/chemistry , Cell Cycle/drug effects , Peptide Fragments , Cell Survival/drug effects , Neuroprotective Agents/pharmacology
16.
Int J Mol Sci ; 25(13)2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39000541

ABSTRACT

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and dyslipidemia. The termite fungus comb is an integral component of nests of termites, which are a global pest. Termite fungus comb polysaccharides (TFCPs) have been identified to possess antioxidant, anti-aging, and immune-enhancing properties. However, their physicochemical characteristics and their role in fighting diabetes have not been previously reported. In the current study, TFCPs were isolated and structurally characterized. The yield of TFCPs was determined to be 2.76%, and it was found to be composed of a diverse array of polysaccharides with varying molecular weights. The hypoglycemic and hypolipidemic effects of TFCPs, as well as their potential mechanisms of action, were investigated in a T2D mouse model. The results demonstrated that oral administration of TFCPs could alleviate fasting blood glucose levels, insulin resistance, hyperlipidemia, and the dysfunction of pancreatic islets in T2D mice. In terms of mechanisms, the TFCPs enhanced hepatic glycogenesis and glycolysis while inhibiting gluconeogenesis. Additionally, the TFCPs suppressed hepatic de novo lipogenesis and promoted fatty acid oxidation. Furthermore, the TFCPs altered the composition of the gut microbiota in the T2D mice, increasing the abundance of beneficial bacteria such as Allobaculum and Faecalibaculum, while reducing the levels of pathogens like Mailhella and Acetatifactor. Overall, these findings suggest that TFCPs may exert anti-diabetic effects by regulating hepatic glucose and lipid metabolism and the composition of the gut microbiota. These findings suggest that TFCPs can be used as a promising functional ingredient for the prevention and treatment of T2D.


Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Hyperglycemia , Hyperlipidemias , Lipid Metabolism , Liver , Animals , Gastrointestinal Microbiome/drug effects , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Mice , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Lipid Metabolism/drug effects , Hyperglycemia/drug therapy , Hyperglycemia/metabolism , Liver/metabolism , Liver/drug effects , Fungal Polysaccharides/pharmacology , Male , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Glucose/metabolism , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Termitomyces/metabolism , Blood Glucose/metabolism , Polysaccharides/pharmacology , Mice, Inbred C57BL
17.
Molecules ; 29(13)2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38998935

ABSTRACT

This article systematically reviews the extraction and purification methods, structural characteristics, structure-activity relationship, and health benefits of C. speciosa polysaccharides, and their potential application in food, medicine, functional products, and feed, in order to provide a useful reference for future research. Chaenomeles speciosa (Sweet) Nakai. has attracted the attention of health consumers and medical researchers as a traditional Chinese medicine with edible, medicinal, and nutritional benefits. According to this study, C. speciosa polysaccharides have significant health benefits, such as anti-diaetic, anti-inflammatory and analgesic, anti-tumor, and immunomodulatory effects. Researchers determined the molecular weight, structural characteristics, and monosaccharide composition and ratio of C. speciosa polysaccharides by water extraction and alcohol precipitation. This study will lay a solid foundation for further optimization of the extraction process of C. speciosa polysaccharides and the development of their products. As an active ingredient with high value, C. speciosa polysaccharides are worthy of further study and full development. C. speciosa polysaccharides should be further explored in the future, to innovate their extraction methods, enrich their types and biological activities, and lay a solid foundation for further research and development of products containing polysaccharides that are beneficial to the human body.


Subject(s)
Polysaccharides , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Polysaccharides/pharmacology , Humans , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , Rosaceae/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Medicine, Chinese Traditional , Monosaccharides/chemistry , Monosaccharides/analysis , Structure-Activity Relationship , Animals
18.
Molecules ; 29(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38998999

ABSTRACT

Phellinus is a precious perennial medicinal fungus. Its polysaccharides are important bioactive components, and their chemical composition is complex. The polysaccharides are mainly extracted from the fruiting body and mycelium. The yield of the polysaccharides is dependent on the extraction method. They have many pharmacological activities, such as antitumor, immunomodulatory, antioxidant, hypoglycemic, anti-inflammatory, etc. They are also reported to show minor toxic and side effects. Many studies have reported the anticancer activity of Phellinus polysaccharides. This review paper provides a comprehensive examination of the current methodologies for the extraction and purification of Phellinus polysaccharides. Additionally, it delves into the structural characteristics, pharmacological activities, and mechanisms of action of these polysaccharides. The primary aim of this review is to offer a valuable resource for researchers, facilitating further studies on Phellinus polysaccharides and their potential applications.


Subject(s)
Fungal Polysaccharides , Humans , Fungal Polysaccharides/chemistry , Fungal Polysaccharides/pharmacology , Fungal Polysaccharides/isolation & purification , Basidiomycota/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification , Animals , Phellinus/chemistry
19.
Molecules ; 29(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38999001

ABSTRACT

The root of Adenophora tetraphylla (Thunb.) Fisch. is a common Chinese materia medica and the polysaccharides which have been isolated from the plant are important active components for medicinal purposes. The objective of the current study was to optimize the extraction parameters and evaluate the glucose consumption activity for Adenophorae root polysaccharides (ARPs). The optimization of ARP extraction was evaluated with preliminary experiments and using response surface methodology (RSM). The conditions investigated were 35-45 °C extraction temperature, 20-30 (v/w) water-to-solid ratio, and 3-5 h extraction time. The antidiabetic effects of ARPs for the glucose consumption activity were evaluated in HepG2 cells. The statistical analyses of the experiments indicated that temperature, water-to-solid ratio, and extraction time significantly affected ARP yield (p < 0.01). The correlation analysis revealed that the experimental data were well-aligned with a quadratic polynomial model, as evidenced by the mathematical regression model's fit. The optimal conditions for maximum ARP yield were 45 °C extraction temperature and 28.47:1 (mL/g) water-to-solid ratio with a 4.60 h extraction time. Extracts from these conditions showed significant activity of promoting cell proliferation from 11.26% (p < 0.001) to 32.47% (p < 0.001) at a dose of 50 µg/mL to 800 µg/mL and increasing glucose consumption to 75.86% (p < 0.001) at 250 µg/mL on HepG2 cells. This study provides a sustainable alternative for the industry since it allowed simplified handling and a specific quantity of ARPs. Furthermore, ARPs might directly stimulate the glucose consumption in the liver and showed no cytotoxicity; therefore, ARPs probably could be taken as a potential natural source of antidiabetic materials.


Subject(s)
Glucose , Plant Roots , Polysaccharides , Water , Humans , Hep G2 Cells , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Glucose/metabolism , Plant Roots/chemistry , Water/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Solubility , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification
20.
Molecules ; 29(13)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38999153

ABSTRACT

BACKGROUND: Ophiocordyceps sinensis has long been recognized as a mysterious and valuable traditional Chinese medicine but there has been little research on quality markers for O. sinensis. PURPOSE: This study looked into the potential of using powder X-ray diffractometry (PXRD) to analyze polysaccharides as a quality marker for O. sinensis. STUDY DESIGN: There were 16 different habitats of O. sinensis collected in Qinghai, Gansu, Sichuan, Yunnan, and Tibet. In addition, five different types of Cordyceps species were collected. The characteristic diffraction peaks of O. sinensis were determined and then matched with the characteristic diffraction peaks of intracellular polysaccharides obtained from O. sinensis to determine the attribution relationship of the characteristic diffraction peaks. METHODS: O. sinensis powder's X-ray diffraction pattern is determined by its composition, microcrystalline crystal structure, intramolecular bonding mechanism, and molecular configuration. After fractionation and alcohol precipitation of crude intracellular polysaccharide, mycelium crude intracellular polysaccharide (MCP) and fruiting body crude intracellular polysaccharide (FCP) were obtained and the fingerprint of O. sinensis was identified by the specific characteristic peaks of the X-ray diffraction pattern from intracellular polysaccharide. RESULTS: The results indicated that the PXRD patterns of different populations of O. sinensis were overlaid well with 18 characteristic diffraction peaks obtained by microcrystalline diffraction. Moreover, the powder diffractograms as a fingerprint provided a practical identification of O. sinensis from other Cordyceps species. In addition, we detected that the powder diffractograms of intracellular polysaccharide MCP and MCP75 could be coupled with the PXRD of O. sinensis. Specifically, 18 characteristic diffraction peaks were identified as coming from MCP and MCP75 according to those interplanar crystal spacing, which matched well with those of PXRD of O. sinensis. CONCLUSIONS: PXRD spectra combined with an updated multivariable discriminant model were found to be an efficient and sensitive method for O. sinensis quality control. According to the findings of this study, PXRD should be further investigated for quality control assessments and plant extract selection trials.


Subject(s)
Cordyceps , Polysaccharides , X-Ray Diffraction , Cordyceps/chemistry , Polysaccharides/chemistry , Polysaccharides/analysis , Medicine, Chinese Traditional , Hypocreales/chemistry
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