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A Prenylated Flavan from Broussonetia kazinoki Prevents Cytokine-Induced beta-Cell Death through Suppression of Nuclear Factor-kappa B Activity

Authors
Bae, Ui-JinLee, Da YeonSong, Mi-YoungLee, Sang-MyeongPark, Jin-WooRyu, Jae-HaPark, Byung-Hyun
Issue Date
Jul-2011
Publisher
PHARMACEUTICAL SOC JAPAN
Keywords
beta-cell; Broussonetia kazinoki; cytokine; nuclear factor-kappa B; reactive oxygen species
Citation
BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.34, no.7, pp 1026 - 1031
Pages
6
Journal Title
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume
34
Number
7
Start Page
1026
End Page
1031
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/12546
DOI
10.1248/bpb.34.1026
ISSN
0918-6158
1347-5215
Abstract
The generation of nitric oxide (NO) via inducible NO synthase (iNOS) and reactive oxygen species plays a key role in cytokine-mediated pancreatic beta-cell damage. Oxidative stress due to reactive oxygen species activates the nuclear factor-kappa B (NF-kappa B) transcription factor, which regulates iNOS expression. In this regard, suppression of the NF-kappa B pathway is a novel strategy for protecting beta-cells from damage. This study was performed to explore the effects of kazinol U, a prenylated flavan from Broussonetia kazinoki, on the NF-kappa B activation pathway in interleukin-1 beta (IL-1 beta)- and interferon-gamma (IFN-gamma)-treated beta-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-kappa B subunits, which correlated with the inhibitory effects on I kappa B kinase (IKK) phosphorylation and I kappa B alpha 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-kappa B pathway in pancreatic beta-cells reduces cell damage. Therefore, kazinol U may have therapeutic value in delaying pancreatic beta-cell destruction in type 1 diabetes.
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