Kim Eun-Kyung, Kwon Kang-Beom, Song Mi-Young, Han Mi-Jeong, Lee Ji-Hyun, Lee Young-Rae, Lee Ju-Hyung, Ryu Do-Gon, Park Byung-Hyun, Park Jin-Woo
Department of Biochemistry, Chonbuk National University Medical School, Jeonju, South Korea.
Pancreas. 2007 Nov;35(4):e1-9. doi: 10.1097/mpa.0b013e31811ed0d2.
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.
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.
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.
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.
在过去几十年中，使用天然化合物如黄酮类作为抗炎剂已备受关注。我们目前的研究聚焦于槲皮素、芹菜素和木犀草素对细胞因子诱导的β细胞损伤的预防作用。
在存在或不存在黄酮类化合物的情况下，用细胞因子混合物处理胰腺β细胞或胰岛，并测定黄酮类化合物对细胞因子毒性的抑制作用。
用白细胞介素1β（IL-1β）和干扰素γ（IFN-γ）处理RINm5F（RIN）大鼠胰岛素瘤细胞会诱导细胞损伤。槲皮素、芹菜素和木犀草素能完全保护RIN细胞免受IL-1β和IFN-γ介导的细胞毒性。用槲皮素、芹菜素和木犀草素孵育可导致IL-1β和IFN-γ诱导的一氧化氮生成显著减少，这一发现与诱导型一氧化氮合酶信使核糖核酸和蛋白质水平的降低密切相关。槲皮素、芹菜素和木犀草素抑制诱导型一氧化氮合酶基因表达的分子机制似乎涉及对核因子κB（NF-κB）激活的抑制。与未刺激的细胞相比，IL-1β和IFN-γ刺激的RIN细胞显示出NF-κB结合活性增加、细胞核中p50和p65亚基水平升高以及细胞质中IκBα降解。槲皮素、芹菜素和木犀草素还能防止IL-1β和IFN-γ介导的胰岛素分泌抑制。
槲皮素、芹菜素和木犀草素抑制RIN细胞的细胞毒性，并减轻IL-1β和IFN-γ对胰岛中葡萄糖刺激的胰岛素分泌的降低作用。
