Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Polyphenols isolated from Broussonetia kazinoki prevent cytokine-induced β-cell damage and the development of type 1 diabetes

  • Bae, Ui-Jin (Department of Biochemistry, Chonbuk National University Medical School) ;
  • Jang, Hyun-Young (Department of Biochemistry, Chonbuk National University Medical School) ;
  • Lim, Jung Min (Department of Anatomy, Chonbuk National University Medical School) ;
  • Hua, Li (Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University) ;
  • Ryu, Jae-Ha (Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University) ;
  • Park, Byung-Hyun (Department of Biochemistry, Chonbuk National University Medical School)
  • Received : 2014.11.11
  • Accepted : 2015.01.12
  • Published : 2015.04.30
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Abstract

The axis of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$)-inducible NO synthase (iNOS)-nitric oxide plays a key role in cytokine- and streptozotocin-mediated pancreatic ${\beta}$-cell damage. In this study, we investigated the effects of kazinol C and isokazinol D isolated from Broussonetia kazinoki on the ${\beta}$-cell viability and function. RINm5F cells and primary islets were used for in vitro and ex vivo cytokine toxicity experiments, respectively. For type 1 diabetes induction, mice were injected with multiple low-dose streptozotocin (MLDS). Cytokine-induced toxicity was completely abolished in both RINm5F cells and islets that were pretreated with either kazinol C or isokazinol D. Both kazinols inhibited the $NF-{\kappa}B$ signaling pathway, thereby inhibiting cytokine-mediated iNOS induction, nitric oxide production, apoptotic cell death and defects in insulin secretion. Moreover, the occurrence of diabetes in MLDS-treated mice was efficiently attenuated in kazinol-pretreated mice. Immunohistochemical analysis revealed that the numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic cells and nuclear p65-positive cells were significantly decreased in kazinol-pretreated mice. Our results suggest that kazinol C and isokazinol D block the $NF-{\kappa}B$ pathway, thus reducing the extent of ${\beta}$-cell damage. Therefore, kazinol C and isokazinol D may have therapeutic value in delaying pancreatic ${\beta}$-cell damage in type 1 diabetes.

Keywords

Acknowledgement

Supported by : National Research Foundation

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