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- 2015.1
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The axis of nuclear factor κB (NF-κB)-inducible NO synthase (iNOS)-nitric oxide plays a key role in cytokine- and streptozotocinmediated pancreatic β-cell damage. In this study, we investigated the effects of kazinol C and isokazinol D isolated from Broussonetia kazinoki on the β-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-κB 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-κB pathway, thus reducing the extent of β-cell damage. Therefore, kazinol C and isokazinol D may have therapeutic value in delaying pancreatic β-cell damage in type 1 diabetes.
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참고문헌 (24)
참고문헌 신청
12 Chen RM / 2002 / Natural PTP1B inhibitors from Broussonetia papyrifera / Bioorg Med Chem Lett 12 : 3387 ~ 3390
American Diabetes Association / 2014 / Diagnosis and classification of diabetes mellitus / Diabetes Care 37 (Suppl 1) : S81 ~ S90
Bae UJ / 2011 / A prenylated flavan from Broussonetia kazinoki prevents cytokine-induced β-cell death through suppression of nuclear factor-κB activity / Biol Pharm Bull 3
Baek YS / 2009 / Tyrosinase inhibitory effects of 1,3-diphenylpropanes from Broussonetia kazinoki / Bioorg Med Chem 17 : 35 ~ 41
Cnop M / 2005 / Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes: many differences, few similarities / Diabetes 54 (Suppl 2) : S97 ~ S107
American Diabetes Association / 2014 / Diagnosis and classification of diabetes mellitus / Diabetes Care 37 (Suppl 1) : S81 ~ S90
Bae UJ / 2011 / A prenylated flavan from Broussonetia kazinoki prevents cytokine-induced β-cell death through suppression of nuclear factor-κB activity / Biol Pharm Bull 3
Baek YS / 2009 / Tyrosinase inhibitory effects of 1,3-diphenylpropanes from Broussonetia kazinoki / Bioorg Med Chem 17 : 35 ~ 41
Cnop M / 2005 / Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes: many differences, few similarities / Diabetes 54 (Suppl 2) : S97 ~ S107
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