Quercetin supplementation and its effect on human monocyte gene expression profiles in vivo.
Quercetin has been described as having a wide range of beneficial effects in humans, ranging from anti-carcinogenic properties to reducing the risk of CVD. Nevertheless, underlying molecular mechanisms have been mostly investigated in vitro. Here, we tested whether a daily supplementation of quercetin leads to reproducible changes in human monocyte gene expression profiles. In study I, quercetin in varying dosages was given to healthy subjects for 2 weeks. RNA from monocytes isolated at the beginning and end of the study from subjects receiving 150 mg quercetin per d was subjected to transcriptome-wide microarray analysis. In study II, a double-blind cross-over study, twenty subjects exhibiting a 'cardiovascular risk phenotype' received 150 mg quercetin or placebo daily for 6 weeks each and served as the verification group. Microarray analysis revealed a number of differentially expressed genes. The most significantly represented functional groups were those of the immune system, nucleic acid metabolism, apoptosis and O-glycan biosynthesis. Twenty-four genes were chosen for technical replication and independent verification by quantitative real-time PCR. When comparing placebo and quercetin treatment, four genes showed significantly different expression changes (C1GALT1, O-glycan biosynthesis; GM2A, glycolipid catabolism; HDGF, cell proliferation; SERPINB9, apoptosis). However, these were minimal in respect to magnitude of fold change. In conclusion, although microarray analysis revealed extensive effects of quercetin on gene expression, the employment of a placebo-controlled study design showed no comparable results for twenty-four verification targets. This emphasises the need for stringent designs in nutritional intervention studies with the aim to identify relevant changes in gene expression.
Boomgaarden
Inka
I
Department of Molecular Prevention, Institute of Human Nutrition and Food Science, Christian-Albrechts University Kiel, Kiel, Germany.
Egert
Sarah
S
Rimbach
Gerald
G
Wolffram
Siegfried
S
Müller
Manfred J
MJ
Döring
Frank
F
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics*; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D007107:Immune System; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009696:Nucleic Acids / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010936:Plant Extracts / Q000494:pharmacology*; D011134:Polysaccharides / Q000096:biosynthesis / Q000235:genetics; D011794:Quercetin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D055815:Young Adult
D000975:Antioxidants; D009696:Nucleic Acids; D010936:Plant Extracts; D011134:Polysaccharides; D011794:Quercetin