Glucosamine

Background Transforming growth factor (TGF) family members play important roles in the regulation of corneal integrity, and the pathogenesis of corneal fibrosis. Currently, there are no effective agents targeting TGF-β signaling to diminish corneal fibrosis. Glucosamine (GlcN), which is widely used in the treatment of osteoarthritis, abrogates the morphologic effects of TGF-β2 on retinal pigmented epithelial cells in a mouse disease model. Here, we sought to determine whether GlcN would exert beneficial effects against TGF-β1-induced corneal fibrosis. Methods In human corneal fibroblasts (HCFs) treated with GlcN, the expression of Krüppel-like factor 4 (KLF4) and its downstream signaling effects were determined in the presence and absence of TGF-β1 using immunoblot analysis. We further explored GlcN inhibition of fibroblast-to-myofibroblast differentiation via KLF4 siRNA. The effect of cycloheximide on KLF4 protein levels with or without GlcN administration was assessed to determine whether GlcN affects the stability of the KLF4 protein. Results In HCFs, GlcN induced the expression of KLF4, which regulated the maturation and maintenance of the ocular surface. GlcN partially suppressed the TGF-β1-induced expression of alpha-smooth muscle actin (α-SMA) and reduced the collagen contraction capacity in HCFs, suggesting a decrease in fibroblast-to-myofibroblast differentiation. This effect appeared to be mediated through suppression of Smad2 phosphorylation and ERK-dependent signaling. The levels of KLF4 mRNA were increased by GlcN and decreased by TGF-β1 and the TGF-β1-induced α-SMA mRNA expression was upregulated when the KLF4 gene was silenced. GlcN also appeared to stabilize the KLF4 protein, reducing its turnover in corneal fibroblasts. Conclusion These findings shed light on a novel mechanism by which GlcN suppresses TGF-β1-induced fibroblast-to-myofibroblast differentiation through the upregulation of KLF4 expression. Current strategies for treating corneal fibrosis were not effective. Elevating KLF4 levels through the use of GlcN might provide an effective alternative to alleviate the development and progression of corneal fibrosis.

The aim of the current study was to investigate the effects of glucosamine (GlcN) on septic lethality and sepsis-induced inflammation using animal models of mice and zebrafish. GlcN pretreatment improved survival in the cecal ligation and puncture (CLP)-induced sepsis mouse model and attenuated lipo …

Glucosamine is an essential substrate for N-linked protein glycosylation. However, elevated levels of glucosamine can induce endoplasmic reticulum (ER) stress. Glucosamine-induced ER stress has bee...

Glucosamine is an essential substrate for N-linked protein glycosylation. However, elevated levels of glucosamine can induce endoplasmic reticulum (ER) stress. Glucosamine-induced ER stress has bee...

The NLRP3 inflammasome promotes the pathogenesis of metabolic, neurodegenerative and infectious diseases. Increasing evidences show that the NLRP3 inflammasome is a promising therapeutic target in inflammatory diseases. Glucosamine is widely used as a dietary supplement to promote the health of cartilage tissue and is expected to exert anti-inflammatory activity in joint inflammation, which is a nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome-associated complication. Here, we investigated whether GlcN inhibits the NLRP3 inflammasome and dissected the underlying molecular mechanisms. We found that GlcN suppressed the NLRP3 inflammasome in mouse and human macrophages. A mechanistic study revealed that GlcN inhibited the expression of NLRP3 and IL-1β precursor by reducing reactive oxygen species generation and NF-κB activation in lipopolysaccharide-activated macrophages. GlcN also suppressed mitochondrial reactive oxygen species generation and mitochondrial integrity loss in NLRP3-activated macrophages. Additionally, GlcN disrupted NLRP3 inflammasome assembly by inhibiting NLRP3 binding to PKR, NEK7 and ASC. Furthermore, oral administration of GlcN reduced peritoneal neutrophils influx and lavage fluids concentrations of IL-1β, IL-6 MCP-1 and TNF-α in uric acid crystal-injected mice. These results indicated that GlcN might be a novel dietary supplement for the amelioration of NLRP3 inflammasome-associated complications.

Glucosamine (GlcN) is a naturally occurring derivative of glucose and an over-the-counter food additive. However, the mechanism underlying GlcN action on cells is unknown. In this study, we investigated the effect of GlcN on natural killer (NK) cells. We demonstrate that GlcN affects NK-92 cell cytotoxicity by altering the distribution of cathepsin C, a cysteine protease required for granzyme processing in cytotoxic granules. The relocation of cathepsin C due to GlcN was shown to be accompanied by a decrease in the intracellular enzyme activity and its extracellular secretion. Similarly, the relocation of endosomal aspartic cathepsin E was observed. Furthermore, we elucidated that repositioning of cathepsin C is a consequence of altered signaling pathways of cytotoxic granule movement. The inhibition of phosphorylation upstream and downstream of ERK by GlcN disturbed the polarized release of cytotoxic vesicles. Considerable changes in the ERK phosphorylation dynamics, but not in those of p38 kinase or JNK, were observed in the IL2-activated NK-92 cells. We found decreased phosphorylation of the transcription factor FOXO1 and simultaneous prolonged phosphorylation of ERK as well as its nuclear translocation. Additionally, a protein downstream of the ERK phosphorylation cascade, paxillin, was less phosphorylated, resulting in a diffuse distribution of cytotoxic granules. Taken together, our results suggest that dietary GlcN affects signaling pathway activation of NK-92 immune cells.

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Glucosamine (GlcN), a dietary supplement widely utilized to promote joint health and effective in the treatment of osteoarthritis, is an effective macroautophagy/autophagy activator in vitro and in vivo. Previous studies have shown that autophagy is required for hepatitis B virus (HBV) …

Glucosamine is effective in the treatment of osteoarthritis; however, its effect on osteoporosis remains unclear. Decreased activity of osteoblasts is the main cause of osteoporosis. Here, we examined the effects of glucosamine on osteoblasts. The potential underlying mechanisms were explored. The r …

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Background We assessed whether local anaesthetics caused inhibition of proteoglycan metabolism in human articular cartilage and whether the addition of Glucosamine sulphate could prevent or allow recovery from this adverse effect on articular cartilage metabolism. Methods Cartilage explants obtained from 13 femoral heads from fracture neck of femur patients (average age 80 years, 10 female) were exposed to either 1% Lidocaine, 2% Lidocaine, 0.25% Bupivacaine, 0.5% Bupivacaine, 0.5% Levo-bupivacaine or a control solution (M199 culture medium). Glucosamine-6-Sulphate was added during or 1 h after exposure to 0.5% Bupivacaine to assess its protective and reparative effects. After exposure, the explants were incubated in culture medium containing radio labelled 35-sulphate and uptake was measured after 16 h to give an assessment of proteoglycan metabolism. Results The reduction in 35-S uptake compared to control was 65% for 1% Lidocaine (p < 0.001), 79% for 2% Lidocaine (p < 0.001), 61% for 0.25% Bupivacaine (p < 0.001), 85% for 0.5% Bupivacaine (p < 0.001) and 77% for 0.5% Levobupivacaine (p < 0.001). Glucosamine was able to protect the articular cartilage by reducing the inhibition of proteoglycan metabolism of 0.5% Bupivacaine from 85 to 30% (p < 0.001). When added after 0.5% Bupivacaine exposure, Glucosamine allowed some recovery with inhibition of metabolism to 70% (p = 0.004). Conclusion Our results showed that all local anaesthetic solutions inhibited proteoglycan metabolism in articular cartilage and the addition of Glucosamine was able to reduce the inhibition of metabolism caused by 0.5% Bupivacaine. Intra-articular injection of local anaesthetics requires careful consideration of risks and benefits.

Obesity is associated with metabolic disorders. Fibroblast growth factor 21 (FGF21) has been recognized as important in metabolism. Glucosamine (GLN) …

Glucosamine (GlcN), a natural amino sugar in human body, was reported to exhibit anticancer activity against some tumors. In the present study, we eva…

(2020). Glucosamine Reverses P-Glycoprotein-Mediated Multidrug Resistance in the Daunorubicin-Resistant Human Gastric Cancer Cells. Nutrition and Cancer: Vol. 72, No. 3, pp. 522-527.

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.