Glucosamine

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.

Hypoxia-inducible factor-1 (HIF-1) is a tumor angiogenic transcription factor composed of an α and β subunit. We investigated the effect of glucosamine hydrochloride (GS-HCl) on the expression of HIF-1α and HIF-1β in serum‑treated YD-8 human tongue cancer cells. While long-term (24 h) treatment with GS-HCl strongly repressed the expression of HIF-1α and HIF-1β at both the protein and mRNA levels, short-term (4 h) GS-HCl treatment inhibited HIF-1α at the protein level. Short-term GS-HCl treatment also decreased phosphorylation of p70S6K and S6, translation-related proteins. However, the results of subsequent pharmacological inhibition and protein stability analyses indicated that HIF-1α protein downregulation induced by short-term GS-HCl treatment was not through modulation of the mTOR/p70S6K/S6 signaling pathways, the 26S proteasomal and lysosomal activities and HIF-1α protein stability. Importantly, our further analyses identified that HIF-1α protein downregulation induced by short-term GS-HCl treatment was blunted by exogenous administration of the citric acid cycle metabolites citrate and 2-oxoglutarate, but not the glycolytic end byproducts pyruvate and lactate. These findings demonstrate firstly that short-term GS treatment selectively downregulates HIF-1α at the protein level in YD-8 cells via interference of production of the citric acid cycle metabolites. It is proposed that short-term GS-HCl exposure may be applied for the treatment of oral tumors with high expression of HIF-1α.

N-acetylglucosamine, a simple sugar found in human breast milk and sold as an over-the-counter dietary supplement in the United States, promotes myelin repair in mouse models and correlates with myelination levels in multiple sclerosis patients, according to a new study.

Glucosamine sulfate (GS) has been used orally for the treatment of osteoarthritis (OA). However, it may be susceptible to the liver first pass phenomenon, which greatly affects its bioavailability, in addition to its side effects on the gastrointestinal tract. Alginate nanoparticles (Alg NPs) were investigated as a new drug carrier for transdermal delivery of GS to improve its effectiveness and reduce side effects. GS-Alg NPs were characterized by encapsulation efficiency, NP yield, particle size and surface charge properties. The in vitro release studies of GS and the ex vivo permeability through rat skin were determined using a UV-Vis spectrophotometer. GS-Alg NPs are within the nanometer range of size. High negative surface charge values are obtained and indicate the high suspension stability of the prepared formulation. The in vitro release studies showed that GS is released from Alg NPs in a sustained and prolonged manner. The ex vivo permeability of GS through rat skin is enhanced significantly after encapsulation in the negatively charged Alg NPs. We successfully reported a highly stable nanoparticlulate system using Alg NPs that permits the encapsulation of GS for topical administration, overcoming the disadvantages of oral administration.

The effect of glucosamine and vitamin E against rheumatoid arthritis (RA) in a neonatal rat model was investigated. Lipid peroxidation, superoxide dis…

Chitosan is a well-known biomaterial. D-glucosamine, which consists of a natural amino monosaccharide, is the smallest molecular weight of chitosan. D-glucosamine is widely used for relieving the...

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.

As glucosamine is presently in wide use due to its purported beneficial effects in patients with osteoarthritis, it seemed important to consider its possible adverse effects on glucose metabolism. Many subjects who take glucosamine for osteoarthritis are obese, insulin resistant, diabetic, or at risk for the development of diabetes, and it is established that glucosamine induces insulin resistance in rats and mice. Hypotheses suggest that glucosamine causes insulin resistance by directly entering the hexosamine biosynthetic pathway. It has been proposed that this provides a model for glucotoxicity-induced defects in insulin action and secretion (1), since, under hyperglycemic conditions, a larger amount of glucose flux is metabolized through the hexosamine pathway. Therefore, we undertook this study to determine if glucosamine, taken at recommended doses for the treatment of osteoarthritis, had any detrimental …

Purpose To analyze the association between glucosamine (GlcN) use and the risk of age-related macular degeneration (AMD) using claims data from the National Health Insurance Research Database (NHIRD). Methods A retrospective, population-based study was conducted with NHIRD data from a 14-year period (2000–2013). Chi-squared and Student’s t-tests were used to evaluate differences between the study and comparison cohorts for categorical and continuous variables, respectively. Risk factors for disease development were examined by the adjusted hazard ratio (aHR) with 95% confidence interval. Kaplan-Meier analysis was performed to compare the cumulative risk of AMD between the two cohorts. Results In total, 1,344 patients with GlcN treatment were enrolled in the study cohort and 5,376 patients without GlcN use were enrolled in the comparison cohort. The incidence rate of AMD was lower with GlcN use (3.65%) than without GlcN use (5.26%) (P = 0.014). GlcN use was associated with a lower risk of developing AMD among patients with hyperlipidemia, coronary artery disease, chronic obstructive pulmonary disease, stroke, other neurological disorders, or degenerative arthritis. Although the incidence of wet type AMD did not significantly differ (P = 0.91), the incidence of dry type AMD was lower in patients with GlcN use (2.9%) than those without GlcN use (4.84%) (P = 0.003). Kaplan-Meier analysis similarly revealed a lower rate of dry type AMD in patients with GlcN use compared to those without GlcN use (log-rank P = 0.004). Conclusions GlcN treatment can decrease the risk of developing dry type AMD. Further prospective controlled studies are needed to determine the effectiveness of GlcN treatment in patients with AMD and the associated mechanism.

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What's New? In this prospective study, the authors asked whether regular use of glucosamine and chondroitin supplements might reduce the risk of colorectal cancer (CRC). They found that the combinati...

Glucosamine is widely used by patients with osteoarthritis (OA) to provide symptomatic relief and to delay disease progression. However, clinical stud…