Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPbeta.

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Shimizu M, Li J, Inoue J, Sato R

Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPbeta.

PLoS One. 2015 Apr 15;10(4):e0121784. doi: 10.1371/journal.pone.0121784. eCollection 2015.

PubMed ID

25875015 [ View in PubMed

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Abstract

Quercetin is one of the most abundant polyphenolic flavonoids found in fruits and vegetables and has anti-oxidative and anti-obesity effects. Because the small intestine is a major absorptive organ of dietary nutrients, it is likely that highly concentrated food constituents, including polyphenols, are present in the small intestinal epithelial cells, suggesting that food factors may have a profound effect in this tissue. To identify novel targets of quercetin in the intestinal enterocytes, mRNA profiling using human intestinal epithelial Caco-2 cells was performed. We found that mRNA levels of some apolipoproteins, particularly apolipoprotein B (apoB), are downregulated in the presence of quercetin. On the exposure of Caco-2 cells to quercetin, both mRNA and protein levels of apoB were decreased. Promoter analysis of the human apoB revealed that quercetin response element is localized at the 5'-proximal promoter region, which contains a conserved CCAAT enhancer-binding protein (C/EBP)-response element. We found that quercetin reduces the promoter activity of apoB, driven by the enforced expression of C/EBPbeta. Quercetin had no effect on either mRNA or protein levels of C/EBPbeta. In contrast, we found that quercetin inhibits the transcriptional activity of C/EBPbeta but not its recruitment to the apoB promoter. On the exposure of Caco-2 cells to quercetin 3-O-glucuronide, which is in a cell-impermeable form, no notable change in apoB mRNA was observed, suggesting an intracellular action of quercetin. In vitro interaction experiments using quercetin-conjugated beads revealed that quercetin binds to C/EBPbeta. Our results describe a novel regulatory mechanism of transcription of apolipoprotein genes by quercetin in the intestinal enterocytes.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Quercetin	CCAAT/enhancer-binding protein beta	Protein	Humans	Unknown	Inhibitor	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Quercetin	Experimental Investigational	APOA1	335	downregulated	Quercetin results in decreased expression of APOA1 mRNA	11q23.3
Quercetin	Experimental Investigational	APOB	338	downregulated	Quercetin results in decreased expression of APOB mRNA	2p24.1
Quercetin	Experimental Investigational	MTTP	4547	downregulated	Quercetin results in decreased expression of MTTP mRNA	4q23