A Prenylated Flavan from Broussonetia kazinoki Prevents Cytokine-Induced β-Cell Death through Suppression of Nuclear Factor-κB Activity
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概要
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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.
- 公益社団法人 日本薬学会の論文
著者
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Song Mi-Young
Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University
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Park Byung-Hyun
Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University
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Park Jin-woo
Department Of Dermatology Hanyang University College Of Medicine
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Park Jin-woo
Department Of Biochemistry Chonbuk National University Medical School And Institute For Medical Scie
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Park Byung-hyun
Department Of Biochemistry Chonbuk National University Medical School And Institute For Medical Scie
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RYU Jae-Ha
College of Pharmacy, Sookmyung Women's University
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Ryu Jae-ha
College Of Pharmacy Sookmyung Women's University
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Bae Ui-Jin
Department of Biochemistry, Research Institute for Endocrine Sciences, and Diabetes Research Center,
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Lee Da
College of Pharmacy, Sookmyung Womens University
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Lee Sang-Myeong
Division of Biotechnology, College of Environmental and Bioresource Sciences, Chonbuk National Unive
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Song Mi-Young
Department of Biochemistry, Research Institute for Endocrine Sciences, and Diabetes Research Center, Chonbuk National University Medical School
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Lee Da
College of Pharmacy, Sookmyung Women's University
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Bae Ui-Jin
Department of Biochemistry, Research Institute for Endocrine Sciences, and Diabetes Research Center, Chonbuk National University Medical School
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Lee Sang-Myeong
Division of Biotechnology, College of Environmental and Bioresource Sciences, Chonbuk National University
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Park Jin-Woo
Department of Biochemistry, Research Institute for Endocrine Sciences, and Diabetes Research Center, Chonbuk National University Medical School
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