Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet‐induced adipose tissue inflammation

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: AIM2;    caspase‐;    1;    diabetes;    glycyrrhizin;    IL‐;    1β;    obesity;   

DOI  :  10.1189/jlb.3A0114-005RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inflammasomeactivationinitiatesthedevelopmentofmanyinflammatorydiseases,includingobesityandtype2diabetes.Therefore,agentsthattargetdiscreteactivationstepscouldrepresentveryimportantdrugs.WereportedpreviouslythatILG,achalconefromGlycyrrhizauralensis,inhibitsLPS‐inducedNF‐κBactivation.Here,weshowthatILGpotentlyinhibitstheactivationofNLRP3inflammasome,andtheeffectisindependentofitsinhibitorypotencyonTLR4.TheinhibitoryeffectofILGwasstrongerthanthatofparthenolide,aknowninhibitoroftheNLRP3inflammasome.GL,atriterpenoidfromG.uralensis,hadsimilarinhibitoryeffectsonNLRP3activity,buthighconcentrationsofGLwererequired.Incontrast,activationoftheAIM2inflammasomewasinhibitedbyGLbutnotbyILG.Moreover,GLinhibitedNLRP3‐andAIM2‐activatedASColigomerization,whereasILGinhibitedNLRP3‐activatedASColigomerization.LowconcentrationsofILGwerehighlyeffectiveinIAPP‐inducedIL‐1βproductioncomparedwiththesulfonylureadrugglyburide.InvivoanalysesrevealedthatILGpotentlyattenuatedHFD‐inducedobesity,hypercholesterolemia,andinsulinresistance.Furthermore,ILGtreatmentimprovedHFD‐inducedmacrovesicularsteatosisintheliver.Finally,ILGmarkedlyinhibiteddiet‐inducedadiposetissueinflammationandIL‐1βandcaspase‐1productioninwhiteadiposetissueinexvivoculture.TheseresultssuggestthatILGisapotentialdrugtargetfortreatmentofNLRP3inflammasome‐associatedinflammatorydiseases...

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