title: Flavonoids protect against cytokine-induced pancreatic beta-cell damage through suppression of nuclear factor kappaB activation.
abstract: OBJECTIVE
  In the past few decades, the use of natural compounds, such as flavonoids, as anti-inflammatory agents has gained much attention. Our current study focuses on the preventive effects of quercetin, apigenin, and luteolin on cytokine-induced beta-cell damage.
  
  
  METHODS
  Pancreatic beta-cells or islets were treated with cytokine mixtures in the presence or absence of flavonoids and the inhibitory effect of flavonoids against cytokine toxicity was determined.
  
  
  RESULTS
  Treatment of RINm5F (RIN) rat insulinoma cells with interleukin 1beta (IL-1beta) and interferon gamma (IFN-gamma) induced cell damage. Quercetin, apigenin, and luteolin completely protected against IL-1beta- and IFN-gamma-mediated cytotoxicity in RIN cells. Incubation with quercetin, apigenin, and luteolin resulted in a significant reduction in IL-1beta- and IFN-gamma-induced nitric oxide production, a finding that correlated well with reduced levels of the inducible form of NO synthase messenger RNA and protein. The molecular mechanism by which quercetin, apigenin, and luteolin inhibited inducible NO synthase gene expression appeared to involve the inhibition of nuclear factor kappaB (NF-kappaB) activation. The IL-1beta- and IFN-gamma-stimulated RIN cells showed increases in NF-kappaB binding activity, p50 and p65 subunit levels in nucleus, and IkappaB alpha degradation in cytosol compared with unstimulated cells. Quercetin, apigenin, and luteolin also prevented IL-1beta- and IFN-gamma-mediated inhibition of insulin secretion.
  
  
  CONCLUSIONS
  Quercetin, apigenin, and luteolin inhibited cytotoxicity in RIN cells and attenuated the decrease of glucose-stimulated insulin secretion in islets by IL-1beta and IFN-gamma.
authors: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, South Korea.
authors: Eun-Kyung
authors: EK
authors: Kim
authors: Kang-Beom
authors: KB
authors: Kwon
authors: Mi-Young
authors: MY
authors: Song
authors: Mi-Jeong
authors: MJ
authors: Han
authors: Ji-Hyun
authors: JH
authors: Lee
authors: Young-Rae
authors: YR
authors: Lee
authors: Ju-Hyung
authors: JH
authors: Lee
authors: Do-Gon
authors: DG
authors: Ryu
authors: Byung-Hyun
authors: BH
authors: Park
authors: Jin-Woo
authors: JW
authors: Park
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D047311:Luteolin / Q000494:pharmacology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D010766:Phosphorylation; D011794:Quercetin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D007004:Hypoglycemic Agents; D020672:I-kappa B Proteins; D007328:Insulin; D053583:Interleukin-1beta; D052002:NF-kappa B p50 Subunit; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D047310:Apigenin; D007371:Interferon-gamma; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005947:Glucose; D047311:Luteolin; D019331:NG-Nitroarginine Methyl Ester