Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Regular Articles
A Prenylated Flavan from Broussonetia kazinoki Prevents Cytokine-Induced β-Cell Death through Suppression of Nuclear Factor-κB Activity
Ui-Jin BaeDa Yeon LeeMi-Young SongSang-Myeong LeeJin-Woo ParkJae-Ha RyuByung-Hyun Park
ジャーナル フリー

2011 年 34 巻 7 号 p. 1026-1031


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.

© 2011 The Pharmaceutical Society of Japan
前の記事 次の記事