Glucosamine Compounds Research Articles

Diosgenyl glucosamine conjugates increase pro-apoptotic and selective activities in cancer cell lines.

Antiproliferative and apoptotic activities have been attributed to the phytosteroid diosgenin ((25R)-spirost-5-en-3β-ol; 1). It is known that combining glucose with two rhamnoses (the chacotrioside framework) linked to diosgenin increases its apoptotic activity. However, the effects of diosgenin glucosamine glycosides on different cancer cell types and cell death have not been entirely explored. This study reports the antiproliferative, cytotoxic, and apoptotic activities of diosgenin and its glycosylated derivative ((25R)-spirost-5-en-3β-yl β-D-glucopyranoside; 2). It also explores the effects of two diosgenin glucosamine derivates, diosgenin 2-acetamido-2-deoxy-β-D-glucopyranoside (3), and diosgenin 2-amino-2-deoxy-β-D-glucopyranoside hydrochloride (4), on different cancer cell lines. We found that all the compounds affected proliferative activity with minimal toxicity. In addition, all cancer cell lines showed morphological and biochemical characteristics corresponding to an apoptotic process. Apoptotic cell death was higher in all cell lines treated with compounds 2, 3 and 4 than in those treated with diosgenin. Moreover, compounds 3 and 4 induced apoptosis better than compounds 1 and 2. These results suggest that combining glucosamine with modified glucosamine attached to diosgenin has a greater apoptotic effect than diosgenin or its glycosylated derivative (compound 2). Furthermore, diosgenin and the abovementioned glycosides had a selective effect on tumour cells since the proliferative capacity of human lymphocytes, keratinocytes (HaCaT) and epithelial cells (CCD841) was not significantly affected. Altogether, these results demonstrate that diosgenin glucosamine compounds exert an antiproliferative effect on cancer cell lines and induce apoptotic effects more efficiently than diosgenin alone without affecting non-tumour cells. This study evidences the pro-apoptotic and selective activities of diosgenyl glucosamine compounds in cancer cell lines.

Risk of bias and brand explain the observed inconsistency in trials on glucosamine for osteoarthritis:a meta-analysis of placebo-controlled trials

Purpose: the aim of this study was to determine whether study sponsor, chemical formulation, brand of glucosamine, and/or risk of bias explain observed inconsistencies in trial findings of glucosamine’s efficacy for treating pain in osteoarthritis (OA) clinical trials. Furthermore, we determined the effect of glucosamine on pain in OA and how the aforementioned factors play a role in regards to the efficacy of the preparation on pain in OA. Methods: A systematic review and stratified meta-analysis of randomized placebo-controlled trials (RCTs) were conducted. Inclusion criteria consisted of RCTs testing glucosamine compounds vs. placebo in humans with combined treatment regimens as an exclusion criterion (i.e. glucosamine combined with other intervention vs. placebo). Random effects models were applied with inconsistency (I-squared) and heterogeneity (Tau-squared) using Review Manager and SAS, respectively. The major outcome measure was reduction of pain. Selecting outcome-measuring scale for data extraction was done after a predefined verified hierarchy of pain scales; the standardized mean difference (SMD and [95%CI]) served as effect size. Results: The inclusion criteria yielded 25 trials (3,458 patients). Compared with a placebo, glucosamine reduced pain (SMD = -0.51 [-0.72 to -0.30]), although expected high level of between-trial inconsistency was observed (I-sq=88%). The single most important explanation (i.e., covariate) was brand (reducing heterogeneity by 41%, p=(0.00032): Twelve trials (1,437) using the Rottapharm|Madaus product apparently resulted in significant pain reduction (-1.05 [-1.43 to -0.68],), with a large amount of inconsistency(I-sq=92%); whereas 13 trials (1,963 patients) using non-Rottapharm|Madaus products consistently failed to show a reduction in pain when compared with placebo (-0.11 [-0.46 to 0.24], I-sq=10%) - Tau-sq reduced from 0.601 to 0.359 (p<0.001). The second most important explanation was overall risk of bias (reducing Tau-sq by 32%). Conclusions: Trials using the Rottapharm|Madaus glucosamine product had a superior outcome on pain in OA compared to other preparations of glucosamine, though Rottapharm|Madaus trial showed large inconsistency in their results and therefore confidence in the results in limited. We did not find an effect of other brands of glucosamine. Most of the observed heterogeneity in trials on glucosamine for (OA) can be explained by brand and risk of bias.Tabled 1Stratified meta-analysisVariableTrialsEffect size95%CItau-squaredp-value for interactionAll trials25−0.58(−0.90 to −0.26)0.601Label:0.3590.00032Other label13−0.11(−0.46 to 0.24)Rottapharm|Madaus12−1.05(−1.43 to −0.68)Chemical structure:0.54670.082HCl40.03(−0.72 to 0.77)SO421-0.7(−1.04 to −0.36)Risk of bias (overall)0.40790.004Low RoB8−0.09(−0.54 to 0.36)Unclear RoB7−0.39(−0.90 to 0.12)High RoB10−1.14(−1.59 to −0.69)Industry funding0.54990.0767Yes14−0.83(−0.41 to 1.24)No11−0.26(−0.73 to 0.20) Open table in a new tab

Genomic expression changes induced by topical N‐acetyl glucosamine in skin equivalent cultures in vitro

N-acetyl glucosamine (NAG) has been shown to be effective in reducing the appearance of hyperpigmented spots. From published in vitro mechanistic testing, glucosamine inhibits enzymatic glycosylation, a required processing step in converting inactive human pro-tyrosinase to the active tyrosinase, a key enzyme in the production of melanin. There is also published literature discussing the anti-inflammatory and antioxidant properties of glucosamine compounds. To identify additional mechanisms by which NAG might affect melanin production, an in vitro genomics experiment was conducted in SkinEthic skin equivalent cultures, which were topically dosed with NAG vs. a vehicle control. Relative to vehicle, NAG reduced melanin production, and the expression of several pigmentation-relevant genes were affected (down-regulated or up-regulated) by NAG treatment. Thus, there are several mechanisms that may be operative in the observed pigmentation effects.

Glucosamine: an ingredient with skin and other benefits

Both glucosamine and its derivative N-acetyl glucosamine are amino-monosaccharides that serve key biochemical functions on their own and as substrate precursors for the biosynthesis of polymers such as glycosaminoglycans (e.g., hyaluronic acid) and for the production of proteoglycans. Glucosamine has an excellent safety profile and has been shown to provide benefits in several clinical disorders. Glucosamine compounds have been reported to have several beneficial effects on the skin or skin cells. Because of its stimulation of hyaluronic acid synthesis, glucosamine has been shown to accelerate wound healing, improve skin hydration, and decrease wrinkles. In addition, as an inhibitor of tyrosinase activation, it inhibits melanin production and is useful in treatment of disorders of hyperpigmentation. Mechanistically, glucosamine also has both anti-inflammatory and chondroprotective effects. Clinical trials have shown benefit in using oral glucosamine supplementation to improve symptoms and slow the progression of osteoarthritis in humans. Glucosamine has also been used to prevent and treat osteoarthritis in animals. Based on other observations, glucosamine has been suggested for additional clinical uses, including treatment of inflammatory bowel disease, migraine headaches, and viral infections. The current clinical uses for topical and oral glucosamine compounds and the mechanistic rationale for these uses are reviewed here.

Efficient Routes to Ethyl‐2‐Deoxy‐2‐phthalimido‐1‐β‐D‐thio‐galactosamine Derivatives via Epimerization of the Corresponding Glucosamine Compounds

Short synthetic routes to protected ethyl 2‐deoxy‐2‐phthalimido‐1‐β‐D‐thio‐galactosamine derivatives via epimerization of the corresponding glucosamine compounds are described. Starting from D‐glucosamine hydrochloride, the epimerizations were performed by displacement of presynthesized triflates with nitrite anions and by an oxidation/reduction route. The latter method involved Moffatt oxidation to the corresponding 4‐ketohexoses and subsequent reduction using sodium borohydride/tetrabutylammonium borohydride, zinc borohydride, or lithium tri‐sec‐butyl borohydride in THF. The displacement route was found to be the preferred method for epimerization of 3‐O‐acyl (benzoyl) derivatives. For glucosamine compounds with 3‐O‐etheral‐ (allyl or benzyl) and 6‐O‐benzyl protecting groups, the oxidation/reduction route was the most convenient procedure to achieve corresponding galactosamine compounds. The produced galactosamine derivatives will be useful building blocks in the synthesis of antifreeze glycoproteins substances and analogues thereof.