Protective Effect of Monoterpene Isoespintanol in a Rat Model of Prediabetes Induced by Fructose

DI SARLI, LUCIANA; CASTRO, MARÍA CECILIA; FARROMEQUE VÁSQUEZ, SHERLEY; VILLAGARCIA, HERNAN; GONZALEZ ARBELAEZ, LUISA; ROJANO, BENJAMIN; SCHINELLA, GUILLERMO; MAIZTEGUI, BARBARA; FRANCINI, FLAVIO

Pharmaceuticals

MDPI

Año: 2023 vol. 17

1424-8247

Ahigh-fructosediet (HFD) inducesmurinealterations likethoserecordedinhuman prediabetes.Protectiveeffectsofisoespintanol(monoterpeneisolatedfromOxandracf.xylopioides) onchangesinducedbyHFDwereevaluated.Animalsweremaintainedfor21dayswithastandard diet(C),10%fructose(F),andFplusisoespintanol(FI,10mg/kg,i.p.).Glycemia,triglyceridemia,total andHDL-cholesterol,andinsulinresistanceindex(IRX)weredetermined. Intraperitonealglucose tolerancetest(IGTT)wasperformed. Intheliver,wemeasuredglycogen,lipogenicgeneexpression (SREBP-1c,GPAT,FAS,andCPT1),oxidativestress(GSHand3′-nitrotyrosinecontent),inflammation markers(iNOS,TNF-α,andPAI-1geneexpression;iNOSandCOX-2proteinlevels),p-eNOS,p-Akt, andp-GSK3βproteinlevels. Isoespintanolcorrectedenhancedtriglycerides,lipogenicgenes,and IRX,andreducedHDL-cholesterol inducedbyHFD. Increasedliverglycogenandinflammatory markersanddecreasedGSH,p-Akt,andp-GSK3βmeasuredinFratswerereversedbyisoespintanol, andp-eNOS/e-NOSandiNOS/GADPHratioswerenormalized. Isoespintanolrestoredglucose tolerance(IGTT)comparedtoFrats.Theseresultsdemonstrateforthefirsttimethatisoespintanol preventsendocrine–metabolicalterationsinducedbyHFDinprediabeticrats.Theseeffectscouldbe mediatedbyAkt/eNOSandAkt/GSK3βpathways,suggestingitspossibleuseasatherapeutictool forthepreventionofdiabetesatearlystagesofitsdevelopment(prediabetes).