Glyconutrients

Author summary Cryptococcal meningitis claims half a million lives each year. There is no clinically available vaccine and the current antifungal therapies have serious limitations. Thus identifying cryptococcal specific programs that can be targeted for antifungal or vaccine development is of great value. We have shown previously that switching from the yeast to the hypha form drastically attenuates/abolishes cryptococcal virulence. Cryptococcal cells in the filamentous form also trigger host immune responses that can protect the host from a subsequent lethal challenge. However, self-filamentation is rarely observed in serotype A isolates that are responsible for the vast majority of cryptococcosis cases. In this study, we found that glucosamine stimulated self-filamentation in genetically distinct strains of the Cryptococcus species complex, including the most commonly used serotype A reference strain H99. We demonstrated that filamentation elicited by glucosamine did not depend on the pheromone pathway, but it requires the calcineurin transcription factor Crz1. Glucosamine promotes nuclear translocation of Crz1, which is positively controlled by the phosphatase calcineurin and is suppressed by the HOG pathway. These findings raise the possibility of manipulating genetic pathways controlling fungal morphogenesis against diseases caused by the Cryptococcus species complex.

Background During late gestation the placental epithelial interface becomes highly folded, which involves changes in stromal hyaluronan. Hyaluronan is composed of glucoronate and N-acetyl-glucosamine. We hypothesized that supplementing gestating dams with glucosamine during this time would support placental folded-epithelial-bilayer development and increase litter size. In Exp. 1, gilts were unilaterally hysterectomized-ovariectomized (UHO). UHO gilts were mated and then supplemented daily with 10 g glucosamine (n = 16) or glucose (control, n = 17) from d 85 of gestation until slaughter (d 105). At slaughter, the number of live fetuses was recorded and each live fetus and its placenta was weighed. Uterine wall samples adjacent to the largest and smallest fetuses within each litter were processed for histology. In Exp. 2, pregnant sows in a commercial sow farm were supplemented with either 10 g glucosamine or glucose daily from d 85 of gestation to farrowing. Total piglets born and born alive were recorded for each litter. In Exp. 3, the same commercial farm and same protocol were used except that the dose of glucosamine and glucose was doubled to 20 g/d. Results In Exp. 1, the number of live fetuses tended to be greater in glucosamine-treated UHO gilts (P = 0.098). Placental morphometry indicated that the width of the folded bilayer was greater (P = 0.05) in glucosamine-treated gilts. In Exp. 2, litter size did not differ between glucosamine- and glucose-treated sows. However in Exp. 3, the increased dose of glucosamine resulted in a significant treatment by parity interaction (P ≤ 0.01), in which total piglets born and born alive were greater in glucosamine treated sows of later parity (5 and 6). Conclusions These results indicated that glucosamine supplementation increased the width of the folds of the placental bilayer and increased litter size in later parity, intact pregnant commercial sows.

Osteoclasts represent the only bone resorbing cells in an organism. In this study, we investigated the effect of glucosamine (GlcN), a nutrient used t …

OBJECTIVE Glucosamine is a widely used supplement typically taken for osteoarthritis and joint pain. Emerging evidence suggests potential links of glucosamine with glucose metabolism, inflammation, and cardiometabolic risk. We prospectively analyzed the association of habitual glucosamine use with risk of type 2 diabetes (T2D) and assessed whether genetic susceptibility and inflammation status might modify the association. RESEARCH DESIGN AND METHODS This study analyzed 404,508 participants from the UK Biobank who were free of diabetes, cancer, or cardiovascular disease at baseline and completed the questionnaire on supplement use. Cox proportional hazards models were used to evaluate the association between habitual use of glucosamine and risk of incident T2D. RESULTS During a median of 8.1 years of follow-up, 7,228 incident cases of T2D were documented. Glucosamine use was associated with a significantly lower risk of T2D (hazard ratio 0.83, 95% CI 0.78–0.89) after adjustment for age, sex, BMI, race, centers, Townsend deprivation index, lifestyle factors, history of disease, and other supplements use. This inverse association was more pronounced in participants with a higher blood level of baseline C-reactive protein than in those with a lower level of this inflammation marker ( P -interaction = 0.02). A genetic risk score for T2D did not modify this association ( P -interaction = 0.99). CONCLUSIONS Our findings indicate that glucosamine use is associated with a lower risk of incident T2D.

There may be good reason to take glucosamine supplements for symptoms other than joint problems.

About Authors: Priya M. Padalia*, Manthan A. Padalia Dagon Pharmaceuticals Pvt. Ltd. *modiyapriya@gmail.com ABSTRACT Of the truly abundant polysaccharides in Nature, only glucosamine has yet to find utilization in large quantity. It is the content of exoskeletons of crustaceans and also from cell walls of fungi and insects. The linear β- 1,4 linked polymer of N-acetyl-D-glucosamine (GlcNAc) is known as chitin, whereas chitosan, a copolymer of GlcNAc (~20%) and glucosamine (GlcN, 80%) residues, is a product derived from de-N-acetylation of chitin in the presence of hot alkali. Glucosamine and their modified derivatives find extensive applications in medicine, agriculture, food, and non-food industries as well. Glucosamine derivative have emerged as a new class of physiological materials of highly sophisticated functions. The development of technologies based on the utilization of its derivatives is caused by their polyelectrolite properties, the presence of reactive functional groups, gel-forming ability, high adsorption capacity, biodegradability and bacteriostatic, fungistatic, antitumour influence, anti inflammatory, wound healing property, lubricating material in joints to provide strength. It is having ability to form self assembly nenoparticles. All these are the result of their versatile biological activity, excellent biocompatibility, and complete biodegradability in combination with low toxicity. With more and more useful and specific properties have led to an unlimited R&D efforts on this most versatile amino polysaccharide, to find new applications, which are necessary to realize its full potential. Incidentally, this too has become an environmental priority. No doubt, glucosamine is surely an undisputed biomolecule of great potential.

Growing evidence suggests that galectin-3 (Gal-3) is instrumental in orchestrating innate immune response and microglia activation following different…

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This study investigated changes in neuroinflammation and cognitive function in adult zebrafish exposed to acute hypoxia and protective effects of glucosamine (GlcN) against hypoxia-induced brain damage. The survival rate of zebrafish following exposure to hypoxia was improved by GlcN pretreatment. Moreover, hypoxia-induced upregulation of neuroglobin, NOS2α, glial fibrillary acidic protein, and S100β in zebrafish was suppressed by GlcN. Hypoxia stimulated cell proliferation in the telencephalic ventral domain and in cerebellum subregions. GlcN decreased the number of bromodeoxyuridine (BrdU)-positive cells in the telencephalon region, but not in cerebellum regions. Transient motor neuron defects, assessed by measuring the locomotor and exploratory activity of zebrafish exposed to hypoxia recovered quickly. GlcN did not affect hypoxia-induced motor activity changes. In passive avoidance tests, hypoxia impaired learning and memory ability, deficits that were rescued by GlcN. A learning stimulus increased the nuclear translocation of phosphorylated cAMP response element binding protein (p-CREB), an effect that was greatly inhibited by hypoxia. GlcN restored nuclear p-CREB after a learning trial in hypoxia-exposed zebrafish. The neurotransmitters, γ-aminobutyric acid and glutamate, were increased after hypoxia in the zebrafish brain, and GlcN further increased their levels. In contrast, acetylcholine levels were reduced by hypoxia and restored by GlcN. Acetylcholinesterase inhibitor physostigmine partially reversed the impaired learning and memory of hypoxic zebrafish. This study represents the first examination of the molecular mechanisms underlying hypoxia-induced memory and learning defects in a zebrafish model. Our results further suggest that GlcN-associated hexosamine metabolic pathway could be an important therapeutic target for hypoxic brain damage.

The significant place in the menopausal syndrome and deficiency of estrogens takes psycho-emotional disorders. Psychosomatic disorders, difficulty of adequate evaluation and correction in menopausal women evidence the fact that this issue is important today. Severe symptoms of menopausal syndrome at violation of psycho-vegetative sphere appear in the early post-menopause, due to final termination of ovarian function and sharply deficiency of estrogens during this period. Intravaginal administration of glucosamine hydrochloride to spay female rats has moderate anti-depressant and anxiolytic effects, accompanied by reduction of the psycho-emotional behavioral reactions, normalization of locomotor activity of animals. As of totality of effects, the estriol reference drug is better than glucosamine hydrochloride. The data reveal prospects of vaginal gel glucosamine hydrochloride in the treatment of menopausal disorders of various origins.

Breast cancer is a common cancer leading to many deaths among females. Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two highly expressed inflammatory mediators to be induced by the protein ...

Background Glucosamine hydrochloride (GAH) and N-acetyl glucosamine (NAG) are chitin derivatives. Owing to their excellent biological activity, they have long been used as pharmaceuticals and nutraceuticals. However, both of them exist simultaneously in chitin hydrolyzate or fermentation production. The aim of this study is to identify the feasibility of separating GAH and NAG by nanofiltration on the basis of appropriate adjustments of physical conditions. Methods One commercial spiral nanofiltration membrane (QY-5-NF-1812) was used. Experiments were carried out in full recycle mode and the membrane separation performance was investigated at various mass ratios (mass ratios of GAH to NAG were from 1:14 to 1:2), pressures (4–22 bar), temperatures (15–35 °C), and electrolytes (NaCl, MgSO4, and MgCl2). The influence of temperature on molecular characteristics that play an important role in the separation process was also studied. Results Owing to the steric-hindrance effect, electrostatic effect, and different solute permeability, the GAH separation factor increased with increasing GAH concentration. Furthermore, upon temperature increasing, the permeability difference between GAH and NAG decreased, thus decreasing the GAH separation factor. Simultaneously, with increasing temperature, the polarities and calculated molecular diameters for both GAH and NAG increased evidently. The calculated reflection coefficients for both GAH and NAG can be well fitted by the steric-hindrance pore (SHP) model, suggesting that steric-hindrance effect played an important role on the separation process. Furthermore, owing to Donnan repulsion and solute diffusion effects, three electrolytes had noticeable effects on nanofiltration separation efficiency. Conclusions The nanofiltration separation efficiency of GAH and NAG was significantly affected by their physical properties in this system, and the mechanisms for GAH and NAG separation were elucidated. The current study could provide a certain basis for the nanofiltration separation of GAH and NAG on an industrial scale.

Objective To examine the long-term (6-year) effect of combined glucosamine (Glu) and chondroitin sulfate (CS) treatment on cartilage volume in knee osteoarthritis (OA). Methods Participants were f...

Background: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells in cancer patients. However, patients often develop TRAIL resistance; thus, agents that can sensitize cells to TRAIL therapy would be beneficial clinically. Methods: Immunoblotting, flow cytometry, confocal microscopy, qPCR and caspase 8 activity assays were used to investigate whether glucosamine (GlcN) can sensitize cancer cells to TRAIL thereby enhancing apoptosis and potentially improving clinical response. Results: GlcN sensitized DU145 cells to TRAIL-induced apoptosis but did not increase death receptor 5 (DR5) cell surface expression. Once treated, these cells responded to TRAIL-induced apoptosis through both extrinsic and intrinsic apoptotic pathways as evidenced by the cleavage of both caspases 8 and 9. The combination of GlcN and TRAIL suppressed the expression of key anti-apoptotic factors cFLIP, BCL-XL, MCL-1 and XIAP and translocated BAK to the mitochondrial outer membrane thereby facilitating cytochrome C and SMAC release. In addition to the activation of apoptotic pathways, TRAIL-mediated inflammatory responses were attenuated by GlcN pretreatment reducing nuclear NF-kB levels and the expression of downstream target genes IL-6 and IL-8. Conclusions: GlcN/TRAIL combination could be a promising strategy for treating cancers by overcoming TRAIL resistance and abrogating TRAIL-induced inflammation.

Glucosamine and chondroitin (G&C), typically taken for joint pain, are among the most frequently used specialty supplements by US adults. More recently, G&C have been associated with lower incidence of colorectal cancer in human observational studies and reduced severity of experimentally-induced ulcerative colitis in rodents. However, little is known about their effects on colon-related physiology. G&C are poorly absorbed and therefore metabolized by gut microbiota. G&C have been associated with changes in microbial structure, which may alter host response. We conducted a randomized, double-blind, placebo-controlled crossover trial in ten healthy adults to evaluate the effects of a common dose of G&C compared to placebo for 14 days on gut microbial community structure, measured by 16S rRNA gene sequencing. Linear mixed models were used to evaluate the effect of G&C compared to placebo on fecal microbial alpha and beta diversity, seven phyla, and 137 genera. Nine genera were significantly different between interventions (False Discovery Rate < 0.05). Abundances of four Lachnospiraceae genera, two Prevotellaceae genera, and Desulfovibrio were increased after G&C compared to placebo, while Bifidobacterium and a member of the Christensenellaceae family were decreased. Our results suggest that G&C affect the composition of the gut microbiome which may have implications for therapeutic efficacy.

Glucosamine and its acetylated derivative, N-acetyl glucosamine, are naturally occurring amino sugars found in human body. They are important componen…

Glucosamine is an amino sugar that is produced naturally in human body. It is an essential carbohydrate component of many cellular glycoproteins, glyc…

The use of lectins can play an important role for tracking modification on cell surface components, since lectins can be easily complexed with radioisotopes, biotin or fluorescein, facilitating the evaluation of carbohydrates distribution in the cell and mitochondrial activity. The aim of this study was to evaluate photodynamic therapy effects on indirect distribution of N-acetyl-glucosamine terminal glycoproteins, in human laryngeal carcinoma HEp-2 cell line surface, using lectin wheat germ agglutinin (WGA) and on mitochondrial activity, for the same cell line, using MitoTracker. The photosensitizer Aluminum Phthalocyanine Tetrasulfonate (AlPcS4) was administrated at 10 μM/mL, followed by an incubation period for its accumulation in the tumor cells, which were irradiated with laser diode λ = 685 nm and energy density of 4.5 J/cm2. Our results indicated that, after Photodynamic Therapy (PDT), it was observed N-acetyl glucosamine terminal glycoprotein expression and mitochondrial O2 production, compared to the control group. Based on these results, we suggest that PDT influences the O2 mitochondrial production and the presence of surface glycoproteins N-acetyl glucosamine terminals.

Background/Aims: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity. However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application. Therefore, there is a need for the development of novel adjuvant th

AbstractBackground: Inflammatory bowel disease (IBD) is associated with a widespread breakdown of glycosaminoglycans, which are normally attached to mucin and help to form a protective barrier separating bacteria from the intestinal epithelium. N-acetylglucosamine (NAG) is a naturally occurring amino sugar precursor for epithelial glycosaminoglycan synthesis. We hypothesize that NAG administration can alleviate IBD-related inflammation by increasing glycosaminoglycan synthesis, which would result in more glycosaminoglycan attachments to the protective mucin layer.

Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.

Osteoarthritis (OA) is one of the major joint diseases, and the synovial inflammation is involved in the pathogenesis and progression of OA. Glucosamine (GlcN) is widely used as a dietary supplement for OA, and is expected to exert the antiinflammatory action in OA. However, the detailed mechanism for the antiinflammatory action of GlcN remains poorly understood. In this study, to elucidate the molecular mechanism involved in the GlcN-medicated regulation of synovial cell activation, we comprehensively analyzed the effect of GlcN on the gene expression using a human synovial cell line MH7A by DNA microarray. The results indicated that GlcN significantly downregulates the expression of 187 genes (≤1/1.5-fold) and upregulates the expression of 194 genes (≥1.5-fold) in IL-1β-stimulated MH7A cells. Interestingly, pathway analysis indicated that among the 10 pathways into which the GlcN-regulated genes are categorized, the 4 pathways are immune-related. Furthermore, GlcN suppressed the expression of proinflammatory cytokine genes (such as IL-6, IL-8, IL-24 and TNF-α genes). In addition, GlcN-mediated O-GlcNAc modification was involved in the downregulation of TNF-α and IL-8 genes but not IL-6 and IL-24 genes, based on the effects of alloxan, an O-GlcNAc transferase inhibitor. Thus, GlcN likely exerts an antiinflammatroy action in OA by suppressing the expression of proinflammatory cytokine genes in synovial MH7A cells by O-GlcNAc modification-dependent and -independent mechanisms.

A safe and effective colorectal cancer (CRC) chemoprevention agent remains to be discovered. We aim to evaluate the association between the use of glucosamine and/or chondroitin sulphate and risk of colorectal cancer (CRC) in the MCC-Spain study, a case-control study performed in Spain that included 2140 cases of CRC and 3950 population controls. Subjects were interviewed on sociodemographic factors, lifestyle, family and medical history and regular drug use. Adjusted odds ratios and their 95% confidence intervals were estimated. The reported frequency of chondroitin and/or glucosamine use was 2.03% in controls and 0.89% in cases. Users had a reduced risk of CRC (OR: 0.47; 95% CI: 0.28–0.79), but it was no longer significant when adjusted for NSAID (nonsteroidal anti-inflammatory drugs) use (OR: 0.82; 95% CI: 0.47–1.40). A meta-analysis with previous studies suggested a protective effect, overall and stratified by NSAID use (OR: 0.77; 95% CI: 0.62–0.97). We have not found strong evidence of an independent preventive effect of CG on CRC in our population because the observed effects of our study could be attributed to NSAIDs concurrent use. These results merit further research due to the safety profile of these drugs.