Polyphenols isolated from Broussonetia kazinoki prevent cytokine-induced β-cell damage and the development of type 1 diabetes

The axis of nuclear factor κB (NF-κB)-inducible NO synthase (iNOS)-nitric oxide plays a key role in cytokine- and streptozotocin-mediated 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. Diabetes: Mulberry polyphenols may delay pancreas damage Polyphenols derived from a mulberry tree may delay damage to the pancreatic beta cells associated with type 1 diabetes. Research led by Ui-Jin Bae and Hyun-Young Jang from Chonbuk National University Medical School in Korea tested the anti-diabetic properties of two polyphenols, kazinol C and isokanizol D, isolated from the paper mulberry, Broussonetia kazinoki , which has long been used in traditional Chinese medicine for fluid retention. They found that both polyphenols protected pancreatic beta cells from damage and death in mice, and preserved the ability for clusters of the cells to secrete insulin. They suggest that the anti-diabetic effect of these kazinols could be used therapeutically to delay disease progression in humans by inhibiting pancreatic beta cell damage, or in transplantation to enhance survival of donor islets.