Glucosamine

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

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.

Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 …

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

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.

Glucosamine (GlcN), also known as aminosaccharide, is an important functional monosaccharide and the first amino monosaccharide to be identified as a hydroxyl group of glucose substituted by amino ...

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Background: Osteoarthritis (OA) is a degenerative disease with complex underling mechanisms 1–3. The interactions among several factors make the study of the disease very complex and often lead to different treatment, i.e. surgical or conservative, decisions for subjects clinically and radiographically similar. Recent explorations performed at the body level pointed out that macro-factors, like overweight or gait, can influence the development of the disease 4. The number of related factors is high, and they are very likely to interact with each other. However, the literature lacks randomized and balanced studies to verify such effects of multiple factors 5. Objectives: The aim of this work was to develop a multifactorial analysis to explore whether and how gait functionality and dynamics can be related to treatment decision. Methods: A multifactorial analysis of gait dynamics in OA subjects was developed. 81 OA subjects, graded 2-3 in KL, were selected based on 4 clinical factors: Gender (male – female), Age (60-67 – 68-75), BMI (25–29.9 – 30+) and Treatment (total knee replacement (TKR) – conservative treatment). Gait analysis was performed using 8 cameras BTS Smart-DX 700, 1.5 Mpixels 250 fps and 2 force plates BTS P-6000 500 Hz sampling (BTS S.p.A., Milan, Italy). Helen Hayes marker protocol with medial markers was used for the study. Each volunteer was asked to perform a minimum of 5 valid gait sequences. Functionality and dynamics parameters were measured. Functionality : Velocity of gait and the time needed to perform a gait cycle were computed. Dynamics: The reaction forces and torques at the ankles, knees and hips were computed through inverse dynamic analyses. Analysis of variance was performed for the four factors described among the functionality and dynamics parameters. Results: The multifactorial analysis showed that functionality values are more subjective to the studied factors than the dynamics ones. Functionality seems to be directly related to the clinical treatment. Patients who selected TKR needed more time to make a step, spent more time in double stand position and walked slower (p

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.

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.

Objective To prospectively assess the association of habitual glucosamine use with risk of cardiovascular disease (CVD) events. Design Prospective cohort study. Setting UK Biobank. Participants 466 039 participants without CVD at baseline who completed a questionnaire on supplement use, which included glucosamine. These participants were enrolled from 2006 to 2010 and were followed up to 2016. Main outcome measures Incident CVD events, including CVD death, coronary heart disease, and stroke. Results During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events (hazard ratio 0.85, 95% confidence interval 0.80 to 0.90), CVD death (0.78, 0.70 to 0.87), coronary heart disease (0.82, 0.76 to 0.88), and stroke (0.91, 0.83 to 1.00). Conclusion Habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events.

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.

The present study is performed to investigate the effect of two different glucosamine containing drugs: Drug 1 and Drug 2 (D1 and D2) against CCl4 induced brain damage in male albino rats. Liverin (AM) was employed in the current study as an antioxidant reference drug. CCl4 administration caused a significant elevation in the levels of MDA and NO of brain tissue, in association with a significant decrease in the antioxidant defense system (GSH, SOD and GPX) that indicated the induction of oxidative stress in brain tissue. CCl4 administration induced brain injury as manifested by the obtained changes in neurotransmitter parameter (norepinephrine (NE), Dopamine (DA), Serotonin (5-HT), and Acetylcholinesterase AChE). The tested nutraceuticals and the antioxidant drug displayed a significant improvement against the undue effect of CCl4 via decreasing the brain tissue content of MDA, NO with the elevation of GSH content. Also, the significant increase in SOD and GPX enzymatic activity was obtained when compared to CCL4 group. In addition AM, D1, and D2 have an ameliorative effect on neurotransmitter parameter NE, DA, 5HT, and AChE. Results of this study suggest that both antioxidant drugs and tested nutraceuticals palliate the brain injuries through anti-oxidative effect, with the elimination of the deleterious effect of toxic metabolites of CCl4 on brain tissue.

Osteoarthritis is a chronic degenerative joint disease causing pain and disability. Glucosamine sulphate is a well known oral supplement for its treatment. The present pioneering study provides an overview of the accentuated transdermal delivery of glucosamine sulphate through the optimized gel formulation w

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.

Transforming growth factor-β (TGF-β) signaling plays a key role in regulating normal cell growth and differentiation, and mutations affecting members …

Glucosamine is a glycosylated amine and a slow-acting symptomatic treatment for osteoarthritis. Some experimental animal studies have shown that glucosamine can cause apoptosis in kidney tubular and mesangial cells as well as overexpression of transforming growth factor β1 (TGF-β1) and connective-ti …

UWill Discover 2018 Abstract Asma Ghafoor, Iraj Sadraei, John F. Trant Towards the synthesis of an acetal-free TF antigen from glucosamine Carbohydrates make up many of the key molecules in our body, especially those involved in signaling, and these systems are of growing interest in regard to better understanding and treating diseases. Carbohydrates are increasingly being found to play an important role in the immunogenic responses to different microbial infections and even to cancer. In terms of cancers, certain carbohydrates have been found to be expressed only on the surface of carcinomas: they are not found on healthy cells. The TF antigen, a simple disaccharide, is one such marker and is found on >85% of all carcinomas regardless of organ (ie breast, ovarian, cervical, prostate, lung, liver etc.); however, the immune system is not good at identifying carbohydrates. Consequently, we need to design new synthetic vaccines to draw attention to these targets so that the body can initiate an immune response to kill the cancer., Unfortunately, the highly biodegradable nature of carbohydrates, when exposed to various pH conditions and enzymes in the body, make it difficult to use carbohydrates in vivo. As a result, extensive and complex syntheses must be carried out to create disaccharides with better enzymatic resistance, so that they can exist long enough to initiate the immune response. The Trant Team hopes to create more stable carbohydrates by removing the unstable acetal group by replacing the exo-cyclic oxygen with a methylene group; this class of materials are known as C-glycosides. This presentation will explore our approach of using glucosamine as a starting product to produce this challenging target, and describe the potential application of this technology towards cancer therapy.

The derivatives of glucose such as glucosamine (β-D-GlcN) and N-acetyl-D-β-glucosamine (GlcNAc) are significant in several biological systems. D-GlcN …

Glucosamine is commonly used for the treatment of osteoarthritis. It is available as an over the counter preparation and also as a prescription pharmaceutical. There is concern from animal experiments that glucosamine may alter glucose metabolism through the hexosamine biosynthetic pathway. The objective of this systematic review is to determine if exogenous glucosamine adversely affects glucose metabolism in humans. This review does not separate out the effects on glucose metabolism of the various glucosamine preparations.

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...

Rheumatoid arthritis (RA) is an autoimmune disorder that affects the joint synovium. Anserine is a functional dipeptide containing methylhistidine and β-alanine, and is present in the brain and skeletal muscle of birds and mammals. Glucosamine is an amino sugar used in the synthesis of glycosylated proteins and lipids. We evaluated the effects of anserine and glucosamine on RA. Rats were assigned into the control group, RA group, anserine group (1 mg/kg), glucosamine group (200 mg/kg), or anserine plus glucosamine group (anserine, 1 mg/kg + glucosamine, 200 mg/kg). Treatment was continued for 45 consecutive days and was administered orally. The serum levels of catalase, glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), lipid peroxidation, uric acid, nitric oxide, ceruloplasmin, zinc, copper, prostaglandin E2 (PGE2), matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were assayed. The mRNA and protein levels of nuclear factor (NF)-κB and inducible nitric oxide synthase (iNOS) in synovial tissue were also determined. Anserine plus glucosamine significantly increased the catalase, SOD, Gpx, GSH, and zinc levels compared to the control, anserine, and glucosamine groups. Also, anserine plus glucosamine significantly reduced the PGE2, MMP-3, TNF-α, IL-1β, and IL-6 levels compared to the control, anserine, and glucosamine groups. Furthermore, anserine plus glucosamine significantly reduced the mRNA and protein levels of NF-κB and iNOS compared to the control, anserine, and glucosamine groups. Therefore, supplementation of anserine plus glucosamine shows therapeutic potential for RA.

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.