期刊
PHARMACOLOGICAL RESEARCH
卷 76, 期 -, 页码 41-48出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2013.07.001
关键词
Caenorhabditis elegans; Quercetin; Lifespan; Absorption; Deglycosylation; Mutant worms; klo-1; klo-2; beta-Glucosidases
资金
- Spanish Government [BFU2012-35228, AGL2009-12001, CSD2007-00063]
- Spanish Ministry of Science and Innovation [BFU2010-21794]
- Rioja Salud Foundation
- Spanish Ramon y Cajal Programme
Due to their purported healthful activities, quercetin and other flavonoids are being increasingly proposed as nutraceuticals. Quercetin occurs in food as glycosides; however, most assays on its activity have been performed with the aglycone, despite glycosylation deeply affects compound bioavailability. In this work, the uptake and lifespan effects of quercetin-3-O-glucoside (Q3Glc) and quercetin have been assessed in Caenorhabditis elegans. Q3Glc was taken up by this nematode in a concentration-dependent manner and rapidly deglycosylated to quercetin, which was accumulated in the worm and partially biotransformed to conjugated metabolites. Significant mean lifespan extension up to 23% compared to controls was observed in wild type worms cultivated in the presence of low concentrations of Q3Glc (10 mu M and 25 PM), whereas exposure to greater concentrations of Q3Glc (50-200 mu M) caused a reduction in mean and maximum lifespan compared with the control. By contrast, treatment of klo-1 and klo-2 mutant worms lacking p-glucosidase activity with 200 pM of Q3Glc led to extended mean lifespan (up to 39%), similar to quercetin aglycone at the same concentration levels. In those mutants, Q3Glc was accumulated without important deglycosylation to quercetin was produced. Taken together, these findings indicated that Q3Glc was taken up by the nematode in greater extent than quercetin, and that deglycosylation and subsequent aglycone accumulation in the worm appeared as key points to explain the observed lifespan effects. The obtained results also suggested that facilitated absorption should be more important for the uptake of quercetin derivatives than passive diffusion. (C) 2013 Elsevier Ltd. All rights reserved.
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