Ethnopharmacological Relevance: The plant Arnica montana L. has been shown to alleviate inflammation, pain and swelling associated with trauma, and post-operative clinical conditions, yet the mechanism of action is not well understood.
Aim Of The Study: The study was designed to investigate the effect of Arnica montana (A.
Microglial cells play important roles in inflammatory responses. The level of oxidative stress is a well-known marker of inflammation. Homeopathic medicines are often used clinically to alleviate inflammation.
View Article and Find Full Text PDFIntestinal mucins trigger immune responses upon recognition by dendritic cells via protein-carbohydrate interactions. We used a combination of structural, biochemical, biophysical, and cell-based approaches to decipher the specificity of the interaction between mucin glycans and mammalian lectins expressed in the gut, including galectin (Gal)-3 and C-type lectin receptors. Gal-3 differentially recognized intestinal mucins with different O-glycosylation profiles, as determined by mass spectrometry (MS).
View Article and Find Full Text PDFRuminococcus gnavus is a human gut symbiont wherein the ability to degrade mucins is mediated by an intramolecular trans-sialidase (RgNanH). RgNanH comprises a GH33 catalytic domain and a sialic acid-binding carbohydrate-binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis and binding assays to determine the structure and function of RgNanH_CBM40 (RgCBM40).
View Article and Find Full Text PDFNaturally occurring 2,7-anhydro-alpha-N-acetylneuraminic acid (2,7-anhydro-Neu5Ac) is a transglycosylation product of bacterial intramolecular trans-sialidases (IT-sialidases). A facile one-pot two-enzyme approach has been established for the synthesis of 2,7-anhydro-sialic acid derivatives including those containing different sialic acid forms such as Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). The approach is based on the use of Ruminoccocus gnavus IT-sialidase for the release of 2,7-anhydro-sialic acid from glycoproteins, and the conversion of free sialic acid by a sialic acid aldolase.
View Article and Find Full Text PDFThe major dietary flavonol quercetin, which has been shown to improve endothelial function and decrease blood pressure, is extensively metabolized during absorption. This study examined the relative abilities of quercetin and its human metabolites to modulate the expression of eNOS and ET-1, which are involved in regulating endothelial homeostasis. Quercetin aglycone significantly reduced both eNOS protein and gene expression in HUVEC, mirroring the effects of the pro-inflammatory cytokine TNFα.
View Article and Find Full Text PDFThere is accumulating evidence from epidemiological and human intervention studies that quercetin-rich diets can protect against cardiovascular diseases. Quercetin glycosides are modified during metabolism, and the forms reaching the systemic circulation are glucuronidated, sulfated, and methylated. The aim of this study was to analyse the potential beneficial effects of quercetin and its conjugated metabolites on vascular function on a co-culture model of human umbilical artery smooth muscle cells and human umbilical vein endothelial cells.
View Article and Find Full Text PDFBackground: Mitochondria mediate most of the energy production that occurs in the majority of eukaryotic organisms. These subcellular organelles contain a genome that differs from the nuclear genome and is referred to as mitochondrial DNA (mtDNA). Despite a disparity in gene content, all mtDNAs encode at least two components of the mitochondrial electron transport chain, including cytochrome c oxidase I (Cox1).
View Article and Find Full Text PDFBackground And Purpose: Quercetin is anti-inflammatory in macrophages by inhibiting lipopolysaccharide (LPS)-mediated increases in cytokine and nitric oxide production but there is little information regarding the corresponding effect on the vasculature. We have examined the effect of quercetin, and its principal human metabolites, on inflammatory changes in the porcine isolated coronary artery.
Experimental Approach: Porcine coronary artery segments were incubated overnight at 37°C in modified Krebs-Henseleit solution with or without 1µg·mL(-1) LPS.
Background And Purpose: Quercetin is a major flavonoid that contributes to the reduced risk of cardiovascular disease associated with dietary ingestion of fruits and vegetables. We have pharmacologically characterized the effect of quercetin, and its sulphate and glucuronide metabolites, on vasoconstrictor and vasodilator responses in the porcine isolated coronary artery.
Experimental Approach: Segments of the porcine coronary artery were prepared for either isometric tension recording or determination of cyclic GMP content.
The consumption of flavan-3-ols has been associated with reduced risk of cardiovascular diseases and improvements in vascular function. However, the nature of the flavan-3-ols responsible and the mechanisms underlying the vascular responses are not fully understood. We used microarrays to search for molecular changes in response to the exposure to (-)-epicatechin (EC), procyanidin dimer B2, and a mixture of oligomeric procyanidins in human umbilical vein endothelial cells (HUVECs).
View Article and Find Full Text PDFExposure of neutrophils to either lipopolysaccharide (LPS) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) is associated with changes in the expression of cell adhesion molecules and elevation of intracellular calcium ions. Although dietary flavonoids are reported to possess anti-inflammatory properties, little is known regarding the effect of their metabolites. We have investigated the effects of quercetin and its major metabolites on LPS and fMLP-stimulated human neutrophils using concentrations comparable to those reported in feeding studies on human volunteers.
View Article and Find Full Text PDFAdhesion of circulating monocytes to vascular endothelial cells, a critical step in both inflammation and atherosclerosis, is mediated by cross-linkage of adhesion molecules expressed on the surface of both cell types. Dietary flavonoids have been shown to have anti-inflammatory properties, decreasing the expression of cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. However, flavonoids are efficiently metabolised during absorption and the forms reaching the systemic circulation are glucuronidated, sulphated and methylated.
View Article and Find Full Text PDFHuman cytosolic beta-glucosidase (hCBG) is a xenobiotic-metabolizing enzyme that hydrolyses certain flavonoid glucosides, with specificity depending on the aglycone moiety, the type of sugar and the linkage between them. In this study, the substrate preference of this enzyme was investigated by mutational analysis, X-ray crystallography and homology modelling. The crystal structure of hCBG was solved by the molecular replacement method and refined at 2.
View Article and Find Full Text PDFBiochem Cell Biol
January 2001
The expression and the subcellular localizations of annexins I, II, IV, VI, and XIII in renal epithelial cells were investigated, using immunological techniques with specific monoclonal antibodies. Upon performing Western blotting experiments, no annexins VI and XIII were detected in kidney, whereas annexins I, II, and IV were. Immunofluorescence labelling procedure performed on thin frozen renal sections showed the presence of these three annexins along the plasma membrane of the collecting duct cells with a restricted expression of annexin I at principal cells.
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