Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155.
In the present study the effect of quercetin and its major metabolites quercetin-3-glucuronide (Q3G) and isorhamnetin on inflammatory gene expression was determined in murine RAW264.7 macrophages stimulated with lipopolysaccharide. Quercetin and isorhamnetin but not Q3G significantly decreased mRNA and protein levels of tumor necrosis factor alpha. Furthermore a significant decrease in mRNA levels of interleukin 1β, interleukin 6, macrophage inflammatory protein 1α and inducible nitric oxide synthase was evident in response to the quercetin treatment. However Q3G did not affect inflammatory gene expression. Anti-inflammatory properties of quercetin and isorhamnetin were accompanied by an increase in heme oxygenase 1 protein levels, a downstream target of the transcription factor Nrf2, known to antagonize chronic inflammation. Furthermore, proinflammatory microRNA-155 was down-regulated by quercetin and isorhamnetin but not by Q3G. Finally, anti-inflammatory properties of quercetin were confirmed in vivo in mice fed quercetin-enriched diets (0.1 mg quercetin/g diet) over 6 weeks.
Boesch-Saadatmandi
Christine
C
Institute of Human Nutrition and Food Science, Christian Albrechts University Kiel, 24098 Kiel, Germany.
Loboda
Agnieszka
A
Wagner
Anika E
AE
Stachurska
Anna
A
Jozkowicz
Alicja
A
Dulak
Jozef
J
Döring
Frank
F
Wolffram
Siegfried
S
Rimbach
Gerald
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D044948:Flavonols / Q000097:blood / Q000494:pharmacology*; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000893:Anti-Inflammatory Agents; D044948:Flavonols; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D014409:Tumor Necrosis Factor-alpha; C443401:quercetin 3-O-glucuronide; C047368:3-methylquercetin; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1