Quercetin metabolites downregulate cyclooxygenase-2 transcription in human lymphocytes ex vivo but not in vivo.
Flavonoids have the potential to modulate inflammation by inhibition of cyclooxygenase-2 (COX-2) transcription. In this study, we compared the effect of the human flavonoid plasma metabolites (quercetin 3'-sulfate, quercetin 3-glucuronide and 3'-methylquercetin 3-glucuronide) on expression of COX-2 mRNA in human lymphocytes ex vivo using TaqMan real-time RT-PCR. We show that the flavonoid quercetin metabolites as detected in human plasma at physiologically significant concentrations inhibit COX-2 expression in human lymphocytes ex vivo. To examine the effect in vivo, we measured COX-2 mRNA levels in 8 subjects (5 men and 3 women) participating in a 3-way, single-blind, randomized crossover study after consumption of a single meal of white, low-quercetin onions, compared with yellow, high-quercetin onions. After consumption of high-quercetin onions, quercetin conjugates were detected in plasma (up to a maximum concentration of 4 micro mol/L at approximately 1 h). However, the expression of COX-2 mRNA in lymphocytes was unchanged by the consumption of high-quercetin onions compared with the low-quercetin group. The results show that a single high dose of the flavonoid quercetin from onions does not change COX-2 mRNA expression in human lymphocytes in vivo even though this change occurred in vitro and ex vivo.
Nutrition Division, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.
Sonia
S
de Pascual-Teresa
Kelly L
KL
Johnston
M Susan
MS
DuPont
Karen A
KA
O'Leary
Paul W
PW
Needs
Linda M
LM
Morgan
Mike N
MN
Clifford
Yongping
Y
Bao
Gary
G
Williamson
D001483:Base Sequence; D001711:Biotransformation; D051546:Cyclooxygenase 2; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008565:Membrane Proteins; D019697:Onions; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D017931:DNA Primers; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D011794:Quercetin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases