Effect of glucosamine and related compounds on the degranulation of mast cells and ear swelling induced by dinitrofluorobenzene in mice

Sakaï, Shota; Sugawara, Tatsuya; Kishi, Toshihiro; Yanagimoto, Kenichi; Hirata, Takashi

doi:10.1016/j.lfs.2010.01.001

Cited by 23 publications

(21 citation statements)

References 33 publications

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“…The proposed mechanism of NFkB inhibition is additionally supported by studies which have demonstrated that glucosamine and chondroitin also inhibit inflammatory factors downstream of NFkB signaling, including IL-1β, IL-6, TNF-α, and PGE 2 , as well as COX-2 expression (8, 9, 38, 40–42). These results hold in studies of glucosamine alone (8, 41), chondroitin alone (7, 38), and in studies of both supplements combined (43). In addition, a few studies have reported on the association between glucosamine and chondroitin use and biomarkers of inflammation in humans.…”

Section: Discussionmentioning

confidence: 72%

Use of glucosamine and chondroitin in relation to mortality

et al. 2012

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Background Glucosamine and chondroitin are products commonly used by older adults in the US and Europe. There is limited evidence that they have anti-inflammatory properties, which could provide risk reduction of several diseases. However, data on their long-term health effects is lacking. Objective To evaluate whether use of glucosamine and chondroitin are associated with cause-specific and total mortality. Design Participants (n = 77 510) were members of a cohort study of Washington State (US) residents aged 50–76 y who entered the cohort in 2000–2002 by completing a baseline questionnaire that included questions on glucosamine and chondroitin use. Participants were followed for mortality through 2008 (n = 5362 deaths). Hazard ratios for death adjusted for multiple covariates were estimated using Cox models. Results Current (baseline) glucosamine and chondroitin use were associated with a decreased risk of total mortality compared to never use. The adjusted hazard ratio (HR) associated with current use of glucosamine (with or without chondroitin) was 0.82 (95% CI 0.75–0.90) and 0.86 (95% CI 0.78–0.96) for chondroitin (included in two-thirds of glucosamine supplements). Current use of glucosamine was associated with a significant decreased risk of death from cancer (HR 0.87 95% CI 0.76–0.98) and with a large risk reduction for death from respiratory diseases (HR 0.59 95% CI 0.41–0.83). Conclusions Use of glucosamine with or without chondroitin was associated with reduced total mortality and with reductions of several broad causes of death. Although bias cannot be ruled out, these results suggest that glucosamine may provide some mortality benefit.

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Section: Discussionmentioning

confidence: 72%

Use of glucosamine and chondroitin in relation to mortality

et al. 2012

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“…Inhibitor E5564, which was used as a reference structure for its ability to bind to TLR4 in the initial in silico screen, has a 2-acylamidopyranoside substructure. Furthermore, the N -acetyl-glucosamine scaffold has known anti-inflammatory effects in a variety of cells, including retinal pigment epithelial cells [28], endothelial cells [29], mast cells [30] and peritoneal mesothelial cells [31], providing further evidence for the role for this class of molecules as TLR4 inhibitors. Interestingly, Lee and colleagues also recently showed that a novel aminosaccharide has anti-TLR effects in macrophages in vitro [32].…”

Section: Discussionmentioning

confidence: 97%

Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

et al. 2013

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Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases.

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“…10,11 Corroborating evidence has shown that glucosamine and chondroitin reduce factors downstream of NFkB, including: tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), interleukin-8 (IL-8), cyclooxygenase-2 (COX-2), and prostaglandin E 2 (PGE 2 ). 10,[12][13][14][15][16][17][18][19][20] Further in vitro studies have demonstrated that glucosamine and chondroitin reduces inflammation in colonic cells. 15 A number of animal studies have demonstrated that administration of glucosamine/chondroitin is associated with reduced levels of inflammatory biomarkers downstream of NFkB activation.…”

Section: Discussionmentioning

confidence: 99%

Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow‐up study

Kantor

Zhang

et al. 2016

Intl Journal of Cancer

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Recent epidemiologic evidence has emerged to suggest that use of glucosamine and chondroitin supplements may be associated with reduced risk of colorectal cancer (CRC). We therefore evaluated the association between use of these non-vitamin, non-mineral supplements and risk of CRC in two prospective cohorts, the Nurses’ Health Study and Health Professionals Follow-up Study. Regular use of glucosamine and chondroitin was first assessed in 2002 and participants were followed until 2010, over which time 672 CRC cases occurred. Cox proportional hazards regression was used to estimate relative risks (RRs) within each cohort, and results were pooled using a random effects meta-analysis. Associations were comparable across cohorts, with a RR of 0.79 (95% CI: 0.63–1.00) observed for any use of glucosamine and a RR of 0.77 (95% CI: 0.59–1.01) observed for any use of chondroitin. Use of glucosamine in the absence of chondroitin was not associated with risk of CRC, whereas use of glucosamine + chondroitin was significantly associated with risk (RR: 0.77; 95% CI: 0.58–0.999). The association between use of glucosamine + chondroitin and risk of CRC did not change markedly when accounting for change in exposure status over follow-up (RR: 0.75; 95% CI: 0.58–0.96), nor did the association significantly vary by sex, aspirin use, body mass index, or physical activity. The association was comparable for cancers of the colon and rectum. Results support a protective association between use of glucosamine and chondroitin and risk of CRC. Further study is needed to better understand the chemopreventive potential of these supplements.

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Effect of glucosamine and related compounds on the degranulation of mast cells and ear swelling induced by dinitrofluorobenzene in mice

Abstract: Our results strongly suggest that GlcN-HCl and GlcNAc have anti-inflammatory effects in vivo by suppressing the activation of mast cells.

Cited by 23 publications

References 33 publications

Use of glucosamine and chondroitin in relation to mortality

Use of glucosamine and chondroitin in relation to mortality

Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow‐up study

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