title: A prenylated flavan from Broussonetia kazinoki prevents cytokine-induced β-cell death through suppression of nuclear factor-κB 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 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.
authors: Department of Biochemistry, Research Institute for Endocrine Sciences, and Diabetes Research Center, Chonbuk National University Medical School, Jeonju, Jeonbuk 561–756, Republic of Korea.
authors: Ui-Jin
authors: UJ
authors: Bae
authors: Da Yeon
authors: DY
authors: Lee
authors: Mi-Young
authors: MY
authors: Song
authors: Sang-Myeong
authors: SM
authors: Lee
authors: Jin-Woo
authors: JW
authors: Park
authors: Jae-Ha
authors: JH
authors: Ryu
authors: Byung-Hyun
authors: BH
authors: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D031623:Broussonetia / Q000737:chemistry*; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000502:physiology; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D054876:Prenylation; D051381:Rats
chemical_list: D016207:Cytokines; D005419:Flavonoids; D016328:NF-kappa B