title: Dose-dependent induction of signaling pathways by the flavonoid quercetin in human primary hepatocytes: A transcriptomic study.
abstract: METHODS
  Quercetin is widespread in plant kingdom and consumed regularly with human diet (16 mg/day). Due to reported positive effects on health, quercetin supplements with recommended doses up to 2 g/day are offered. However, molecular effects of such high doses on human liver have not been assessed yet. Therefore, molecular effects on human hepatocytes were analyzed to help assessing the risk of quercetin supplementation.
  
  
  RESULTS
  Molecular effects of three different quercetin concentrations on gene expression in human hepatocytes were investigated by microarray analysis. Possible new signaling pathways were investigated using reporter gene assays. Quercetin concentrations representing the normal intake showed weak effects on mRNA expression in liver cells. In contrast, supplemental doses affect immune response and p53 signaling and might be associated with cancer. Additionally, quercetin showed inhibition of transcriptional activation and mRNA-expression of HNF4α and its target genes. Inhibitory effects were also found for FXR, LXRα, and PXR.
  
  
  CONCLUSIONS
  Normal intake of quercetin seems to play a minor regulatory role, while supplement doses may have great effects on gene expression in hepatocytes. However, since it is not clarified whether such high doses of quercetin exert positive or negative effects, a careful handling of quercetin supplements is advised.
authors: Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany.|Biochemical Institute for Environmental Carcinogens, Grosshansdorf, Germany.
authors: Julia
authors: J
authors: Waizenegger
authors: Institute of Pathology, Charité - University Hospital Berlin, Berlin, Germany.
authors: Dido
authors: D
authors: Lenze
authors: Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany.
authors: Claudia
authors: C
authors: Luckert
authors: Biochemical Institute for Environmental Carcinogens, Grosshansdorf, Germany.
authors: Albrecht
authors: A
authors: Seidel
authors: Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany.
authors: Alfonso
authors: A
authors: Lampen
authors: Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany.
authors: Stefanie
authors: S
authors: Hessel
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D057809:HEK293 Cells; D056945:Hep G2 Cells; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011794:Quercetin
keywords: Flavonoid; Liver; Molecular effects; Quercetin; Supplementation