Flavonoids protect against cytokine-induced pancreatic beta-cell damage through suppression of nuclear factor kappaB activation.
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.
Kim
Eun-Kyung
EK
Department of Biochemistry, Chonbuk National University Medical School, Jeonju, South Korea.
Kwon
Kang-Beom
KB
Song
Mi-Young
MY
Han
Mi-Jeong
MJ
Lee
Ji-Hyun
JH
Lee
Young-Rae
YR
Lee
Ju-Hyung
JH
Ryu
Do-Gon
DG
Park
Byung-Hyun
BH
Park
Jin-Woo
JW
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*
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