2015-prevent cytokine-induced β-cell damage and the

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1、OPENExperimental&MolecularMedicine(2015)47,e160;doi:10.1038/emm.2015.16&2015KSBMB.Allrightsreserved2092-6413/15www.nature.com/emmORIGINALARTICLEPolyphenolsisolatedfromBroussonetiakazinokipreventcytokine-inducedβ-celldamageandthedevelopmentoftype1diabe

2、tesUi-JinBae1,4,Hyun-YoungJang1,4,JungMinLim2,LiHua3,Jae-HaRyu3andByung-HyunPark1TheaxisofnuclearfactorκB(NF-κB)-inducibleNOsynthase(iNOS)-nitricoxideplaysakeyroleincytokine-andstreptozotocin-mediatedpancreaticβ-celldamage.Inthisstudy,weinvestigatedth

3、eeffectsofkazinolCandisokazinolDisolatedfromBroussonetiakazinokiontheβ-cellviabilityandfunction.RINm5Fcellsandprimaryisletswereusedforinvitroandexvivocytokinetoxicityexperiments,respectively.Fortype1diabetesinduction,micewereinjectedwithmultiplelow-do

4、sestreptozotocin(MLDS).Cytokine-inducedtoxicitywascompletelyabolishedinbothRINm5FcellsandisletsthatwerepretreatedwitheitherkazinolCorisokazinolD.BothkazinolsinhibitedtheNF-κBsignalingpathway,therebyinhibitingcytokine-mediatediNOSinduction,nitricoxidep

5、roduction,apoptoticcelldeathanddefectsininsulinsecretion.Moreover,theoccurrenceofdiabetesinMLDS-treatedmicewasefficientlyattenuatedinkazinol-pretreatedmice.ImmunohistochemicalanalysisrevealedthatthenumbersofterminaldeoxynucleotidyltransferasedUTPnicken

6、dlabeling-positiveapoptoticcellsandnuclearp65-positivecellsweresignificantlydecreasedinkazinol-pretreatedmice.OurresultssuggestthatkazinolCandisokazinolDblocktheNF-κBpathway,thusreducingtheextentofβ-celldamage.Therefore,kazinolCandisokazinolDmayhavethe

7、rapeuticvalueindelayingpancreaticβ-celldamageintype1diabetes.Experimental&MolecularMedicine(2015)47,e160;doi:10.1038/emm.2015.16;publishedonline24April2015INTRODUCTIONMLDS-inducedβ-celldysfunctionanddestructionhasbeenType1diabetesisaTcell-mediateddise

8、asethatultimatelyshowntobemediatedbyNO.4Interestingly,miceharboringadestroysthecapacityofthebodytoproduceandsecretemutationineitherNF-κBoriNOSareresistanttoMLDS-insulin.1Immunecellinfiltrationandthesubsequentapoptoticinduceddiabetes.5,6destruct