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

Bae UJ, Jang HY, Lim JM, Hua L, Ryu JH, Park BH - Exp. Mol. Med. (2015)

Bottom Line: In this study, we investigated the effects of kazinol C and isokazinol D isolated from Broussonetia kazinoki on the β-cell viability and function.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.Our results suggest that kazinol C and isokazinol D block the NF-κB pathway, thus reducing the extent of β-cell damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.

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.

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High-performance liquid chromatography (a) and chemical structures (b) of kazinol C and isokazinol D.
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fig1: High-performance liquid chromatography (a) and chemical structures (b) of kazinol C and isokazinol D.

Mentions: The purities of B. kazinoki-derived preparations of kazinol C and isokazinol D were assessed by high-performance liquid chromatography (Figure 1a). The clean peaks at retention times of 15.2 and 16.25 min in the high-performance liquid chromatography indicate pure preparations of kazinol C and isokazinol D, respectively. The purities were determined to be >95% (kazinol C) and >93% (isokazinol D). Kazinol C and isokazinol D were elucidated by spectroscopic analysis to be 1,3-diphenyl propane derivatives, structures which are common among phenolic compounds isolated from B. kazinoki (Figure 1b).


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

Bae UJ, Jang HY, Lim JM, Hua L, Ryu JH, Park BH - Exp. Mol. Med. (2015)

High-performance liquid chromatography (a) and chemical structures (b) of kazinol C and isokazinol D.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4418042&req=5

fig1: High-performance liquid chromatography (a) and chemical structures (b) of kazinol C and isokazinol D.
Mentions: The purities of B. kazinoki-derived preparations of kazinol C and isokazinol D were assessed by high-performance liquid chromatography (Figure 1a). The clean peaks at retention times of 15.2 and 16.25 min in the high-performance liquid chromatography indicate pure preparations of kazinol C and isokazinol D, respectively. The purities were determined to be >95% (kazinol C) and >93% (isokazinol D). Kazinol C and isokazinol D were elucidated by spectroscopic analysis to be 1,3-diphenyl propane derivatives, structures which are common among phenolic compounds isolated from B. kazinoki (Figure 1b).

Bottom Line: In this study, we investigated the effects of kazinol C and isokazinol D isolated from Broussonetia kazinoki on the β-cell viability and function.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.Our results suggest that kazinol C and isokazinol D block the NF-κB pathway, thus reducing the extent of β-cell damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.

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.

Show MeSH
Related in: MedlinePlus