Effects of physiological quercetin metabolites on interleukin-1β-induced inducible NOS expression.
Cytokines released by inflammatory cells around the pancreatic islets are implicated in the pathogenesis of diabetes mellitus. Specifically, interleukin-1β (IL-1β) is known to be involved in islet β-cell damage by activation of nuclear factor-κB (NF-κB)-mediated inducible nitric oxide synthase (iNOS) gene expression. Though most flavonoids are shown to have various beneficial effects, little is known about the anti-inflammatory effects of their metabolites. Therefore, we investigated the effects of quercetin and its metabolites quercetin 3'-sulfate, quercetin 3-glucuronide and isorhamnetin 3-glucuronide on IL-1β-stimulated iNOS gene expression in RINm5F β-cells. The nitrite level, iNOS protein and its mRNA expression levels and iNOS promoter activity were measured. In addition, IκBα protein phosphorylation, nuclear translocation of nuclear factor-κB (NF-κB) and NF-κB DNA binding activity were determined. Adenosine 5'-triphosphate disodium salt-induced insulin release was also measured. Quercetin significantly reduced IL-1β-induced nitrite production, iNOS protein and its mRNA expression levels, and it also inhibited IL-1β-induced IκBα phosphorylation, NF-κB activation and iNOS promoter activity. Additionally, quercetin significantly restored the inhibition of insulin secretion by IL-1β. Meanwhile, quercetin metabolites did not show any effect on IL-1β-induced iNOS gene expression and also on insulin secretion. Therefore, in terms of iNOS expression mechanism, dietary ingestion of quercetin is unlikely to show anti-inflammatory effects in rat islet β-cells exposed to IL-1β.
Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
Jae Min
JM
Cho
Seo-Yoon
SY
Chang
Dong-Bin
DB
Kim
Paul W
PW
Needs
Yang-Hyeok
YH
Jo
Myung-Jun
MJ
Kim
D000818:Animals; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D053583:Interleukin-1beta / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011794:Quercetin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats
D020672:I-kappa B Proteins; D007328:Insulin; D053583:Interleukin-1beta; D016328:NF-kappa B; D009573:Nitrites; C531389:quercetin 3'-sulfate; C443401:quercetin 3-O-glucuronide; C047368:3-methylquercetin; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat