KMID : 0620920150470040003
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Experimental & Molecular Medicine 2015 Volume.47 No. 4 p.3 ~ p.3
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Polyphenols isolated from Broussonetia kazinoki prevent cytokine-induced ¥â-cell damage and the development of type 1 diabetes
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Bae Ui-Jin
Jang Hyun-Young Lim Jung-Min Li Hua Ryu Jae-Ha Park Byung-Hyun
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Abstract
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The axis of nuclear factor ¥êB (NF-¥êB)-inducible NO synthase (iNOS)-nitric oxide plays a key role in cytokine- and streptozotocin-mediated pancreatic ¥â-cell damage. In this study, we investigated the effects of kazinol C and isokazinol D isolated from Broussonetia kazinoki on the ¥â-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-¥êB 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-¥êB pathway, thus reducing the extent of ¥â-cell damage. Therefore, kazinol C and isokazinol D may have therapeutic value in delaying pancreatic ¥â-cell damage in type 1 diabetes.
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