title: Polyphenols isolated from Broussonetia kazinoki prevent cytokine-induced β-cell damage and the development of type 1 diabetes.
abstract: 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.
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Ui-Jin
authors.initials: UJ
authors.lastname: Bae
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Jang
authors.affiliation: Department of Anatomy, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lim
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Li
authors.initials: L
authors.lastname: Hua
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D031623:Broussonetia / Q000737:chemistry*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D045782:Hemiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology; D051381:Rats; D012118:Resorcinols / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D045782:Hemiterpenes; D016328:NF-kappa B; D012118:Resorcinols; C000599716:kazinol C; D009569:Nitric Oxide