A prenylated flavan from Broussonetia kazinoki prevents cytokine‐induced ‐ [beta]cell death through suppression of NF‐[kappa]B activity

Abstract

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 IL‐1β‐ and IFN‐γ‐treated β‐cells. 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.