Effect of quercetin on paraoxonase 2 levels in RAW264.7 macrophages and in human monocytes--role of quercetin metabolism.
There is increasing evidence that the intracellular antioxidant enzyme paraoxonase 2 (PON2) may have a protective function in the prevention of atherogenesis. An enhancement of PON2 activity by dietary factors including flavonoids is therefore of interest. In the present study we determined the effect of quercetin on paraoxonase 2 levels in cultured murine macrophages in vitro and in overweight subjects with a high cardiovascular risk phenotype supplemented with 150 mg quercetin/day for 42 days in vivo. Supplementation of murine RAW264.7 macrophages in culture with increasing concentrations of quercetin (1, 10, 20 micromol/L) resulted in a significant increase in PON2 mRNA and protein levels, as compared to untreated controls. Unlike quercetin, its glucuronidated metabolite quercetin-3-glucuronide did not affect PON2 gene expression in cultured macrophages. However the methylated quercetin derivative isorhamnetin enhanced PON2 gene expression in RAW264.7 cells to similar extent like quercetin. Although supplementing human volunteers with quercetin was accompanied by a significant increase in plasma quercetin concentration, dietary quercetin supplementation did not change PON2 mRNA levels in human monocytes in vivo. Current data indicate that quercetin supplementation increases PON2 levels in cultured monocytes in vitro but not in human volunteers in vivo.
Institute of Human Nutrition and Food Science, Christian Albrechts University Kiel, Olshausenstrasse 40, D-24118 Kiel, Germany.
Christine
C
Boesch-Saadatmandi
Institute of Human Nutrition and Food Science, Christian Albrechts University Kiel, Olshausenstrasse 40, D-24118 Kiel, Germany.
Renata Toedter
RT
Pospissil
Institute of Human Nutrition and Food Science, Christian Albrechts University Kiel, Olshausenstrasse 40, D-24118 Kiel, Germany.
Anne-Christin
AC
Graeser
National Research Institute for Food and Nutrition (INRAN), 00178 Roma, Italy.
Raffaella
R
Canali
Institute of Human Nutrition and Food Science, Christian Albrechts University Kiel, Olshausenstrasse 40, D-24118 Kiel, Germany.
Inka
I
Boomgaarden
Institute of Human Nutrition and Food Science, Christian Albrechts University Kiel, Olshausenstrasse 40, D-24118 Kiel, Germany.
Frank
F
Doering
Institute of Animal Nutrition and Physiology, Christian Albrechts University Kiel, 24118 Kiel, Germany.
Siegfried
S
Wolffram
Institute of Human Nutrition and Food Science, Christian Albrechts University Kiel, Olshausenstrasse 40, D-24118 Kiel, Germany.
Sarah
S
Egert
Institute of Human Nutrition and Food Science, Christian Albrechts University Kiel, Olshausenstrasse 40, D-24118 Kiel, Germany.
Manfred James
MJ
Mueller
Institute of Human Nutrition and Food Science, Christian Albrechts University Kiel, Olshausenstrasse 40, D-24118 Kiel, Germany.
Gerald
0000-0001-7888-4684
G
Rimbach
D000818:Animals; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D009765:Obesity / Q000150:complications; D010865:Pilot Projects; D011794:Quercetin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D011794:Quercetin; D043303:Aryldialkylphosphatase; C468411:PON2 protein, human