Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 65, Issue 6, Pages -Publisher
WILEY
DOI: 10.1002/mnfr.202000777
Keywords
glycemia; inflammation; metabolome; polyphenols; purine metabolism
Categories
Funding
- Biotechnology and Biological Sciences Research Council (BBSRC)
- BBSRC Institute Strategic Programme Food Innovation and Health [BB/R012512/1, BBS/E/F/000PR10343, BBS/E/F/000PR10347]
- Norwich Research Park Biosciences Doctoral Training Partnership [BB/M011216/1]
- BBSRC [BBS/E/F/000PR10347, BBS/E/F/00044434, BBS/E/F/000PR10343] Funding Source: UKRI
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The study shows that quercetin can alter the balance of endothelial cell metabolites towards a less inflamed phenotype, both alone and in the presence of pro-inflammatory stimuli. Quercetin inhibits specific enzyme activities, reducing the harmful effects of high glucose or inflammation on endothelial cells.
Scope Pro-inflammatory stimuli such as hyperglycemia and cytokines have been shown to negatively affect endothelial cell functions. The aim of this study is to assess the potential of quercetin and its human metabolites to overcome the deleterious effects of hyperglycemic or inflammatory conditions on the vascular endothelium by modulating endothelial cell metabolism. Methods and results A metabolomics approach enabled identification and quantification of 27 human umbilical vein endothelial cell (HUVEC) metabolites. Treatment of HUVECs with high-glucose concentrations causes significant increases in lactate and glutamate concentrations. Quercetin inhibits glucose-induced increases in lactate and adenosine 5 '-triphosphate (ATP) and also increased inosine concentrations. Tumor necrosis factor alpha-treatment (TNF alpha) of HUVECs causes increases in asparagine and decreases in aspartate concentrations. Co-treatment with quercetin reduces pyruvate concentrations compared to TNF alpha-only treated controls. Subsequently, it was shown that quercetin and its HUVEC phase-2 conjugates inhibit adenosine deaminase, xanthine oxidase and 5 ' nucleotidase (CD73) but not ectonucleoside triphosphate diphosphohydrolase-1 (CD39) or purine nucleoside phosphorylase activities. Conclusion Quercetin was shown to alter the balance of HUVEC metabolites towards a less inflamed phenotype, both alone and in the presence of pro-inflammatory stimuli. These changes are consistent with the inhibition of particular enzymes involved in purine metabolism by quercetin and its HUVEC metabolites.
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