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Published on: May 2, 2025
Flavonoids protect against cytokine-induced pancreatic beta-cell damage through suppression of nuclear factor kappaB
Eun-Kyung Kim1, Kang-Beom Kwon, Mi-Young Song
1Department of Biochemistry, Chonbuk National University Medical School, Jeonju, South Korea.
Objectives:
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.
Conclusion:
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.
Insights
Quercetin, apigenin, and luteolin protect pancreatic beta-cells from cytokine damage by inhibiting nitric oxide production and nuclear factor kappaB activation. These flavonoids also prevent reduced insulin secretion, offering potential therapeutic benefits.
Area of Science:
- Biochemistry
- Immunology
- Endocrinology
Background:
- Natural compounds, particularly flavonoids, are increasingly recognized for their anti-inflammatory properties.
- Cytokine-induced damage to pancreatic beta-cells is a significant concern in various pathological conditions.
Purpose of the Study:
- To investigate the protective effects of quercetin, apigenin, and luteolin against cytokine-induced damage in pancreatic beta-cells.
- To elucidate the molecular mechanisms underlying the protective actions of these flavonoids.
Main Methods:
- Pancreatic beta-cells (RINm5F cells) were exposed to a mixture of interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) with or without quercetin, apigenin, or luteolin.
- Assays were performed to measure cytotoxicity, nitric oxide production, inducible nitric oxide synthase (iNOS) expression, nuclear factor-kappaB (NF-kappaB) activation, and insulin secretion.
Main Results:
- Quercetin, apigenin, and luteolin completely protected RIN cells from IL-1beta and IFN-gamma-induced cytotoxicity.
- These flavonoids significantly reduced nitric oxide production and iNOS expression by inhibiting NF-kappaB activation.
- The compounds also prevented the inhibition of glucose-stimulated insulin secretion caused by the cytokines.
Conclusions:
- Quercetin, apigenin, and luteolin demonstrate potent protective effects against cytokine-induced beta-cell damage.
- Inhibition of iNOS and NF-kappaB pathways, along with preservation of insulin secretion, are key mechanisms of action.
- These findings highlight the therapeutic potential of these flavonoids in managing conditions involving beta-cell inflammation.
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