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.
de Pascual-Teresa
Sonia
S
Nutrition Division, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.
Johnston
Kelly L
KL
DuPont
M Susan
MS
O'Leary
Karen A
KA
Needs
Paul W
PW
Morgan
Linda M
LM
Clifford
Mike N
MN
Bao
Yongping
Y
Williamson
Gary
G
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