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标题：A Prenylated Flavan from Broussonetia kazinoki Prevents Cytokine-Induced β-Cell Death through Suppression of Nuclear Factor-κB Activity
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作者：Ui-Jin Bae ; Da Yeon Lee ; Mi-Young Song 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2011
卷号：34
期号：7
页码：1026-1031
DOI：10.1248/bpb.34.1026
出版社：The Pharmaceutical Society of Japan
摘要：The generation of nitric oxide (NO) via inducible NO synthase (iNOS) and reactive oxygen species plays a key role in cytokine-mediated pancreatic β-cell damage. Oxidative stress due to reactive oxygen species activates the nuclear factor-κB (NF-κB) transcription factor, which regulates iNOS expression. In this regard, suppression of the NF-κB pathway is a novel strategy for protecting β-cells from damage. This study was performed to explore the effects of kazinol U, a prenylated flavan from Broussonetia kazinoki , on the NF-κB activation pathway in interleukin-1β (IL-1β)- and interferon-γ (IFN-γ)-treated β-cells. The cytotoxic effects of cytokines were completely abolished when RINm5F cells or islets were pretreated with kazinol U. Kazinol U inhibited the nuclear translocation and DNA binding of NF-κB subunits, which correlated with the inhibitory effects on IκB kinase (IKK) phosphorylation and IκBα degradation. In addition, kazinol U suppressed NO and hydrogen peroxide production and apoptotic cell death by cytokines in RINm5F cells. The protective effects of kazinol U were further demonstrated by normal insulin secretion of cytokine-treated islets in response to glucose. Taken together, these results suggest that using kazinol U to block the NF-κB pathway in pancreatic β-cells reduces cell damage. Therefore, kazinol U may have therapeutic value in delaying pancreatic β-cell destruction in type 1 diabetes.
关键词：β-cell;Broussonetia kazinoki;cytokine;nuclear factor-κB;reactive oxygen species