Apple Peel Polyphenols and Their Beneficial Actions on Oxidative Stress and Inflammation.docVIP

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Apple Peel Polyphenols and Their Beneficial Actions on Oxidative Stress and Inflammation.doc

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Apple Peel Polyphenols and Their Beneficial Actions on Oxidative Stress and Inflammation

ApplePeelPolyphenolsandTheirBeneficialActionson OxidativeStressandInflammation MarieClaudeDenis1,2,AlexandraFurtos3,Ste′phanieDudonne′4,AlainMontoudis1,CaroleGarofalo1, YvesDesjardins4,EdgardDelvin1,3,EmileLevy1,2,4 * 1ResearchCentre,Sainte-JustineHospital,Montreal,Quebec,Canada,2DepartmentofNutrition,FacultyofMedicine,Universite′deMontre′al,Montreal,Quebec,Canada, 3DepartmentofBiochemistry,FacultyofMedicine,Universite′deMontre′al,Montreal,Quebec,Canada,4InstituteofNutraceuticalsandFunctionalfoods,Universite′Laval, Quebec,Quebec,Canada Abstract Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sources, the presence of antioxidantsmaycontributetothebody’snaturaldefensesagainstinflammatorydiseases. Hypothesis:Todefinethepolyphenolsextractedfromdriedapplepeels(DAPP)anddeterminetheirantioxidantandanti- inflammatory potential in the intestine. Caco-2/15 cells were used to study the role of DAPP preventive actions against oxidativestress(OxS)andinflammationinducedbyiron-ascorbate(Fe/Asc)andlipopolysaccharide(LPS),respectively. Results:ThecombinationofHPLCwithfluorescencedetection,HPLC-ESI-MSTOFandUPLC-ESI-MS/MSQQQallowedusto characterizethephenoliccompoundspresentintheDAPP(phenolicacids,flavonolglycosides,flavan-3-ols,procyanidins). TheadditionofFe/AsctoCaco-2/15cellsinducedOxSasdemonstratedbytheriseinmalondialdehyde,depletionofn-3 polyunsaturated fatty acids, and alterations in the activity of endogenous antioxidants (SOD, GPx, G-Red). However, preincubationwithDAPPpreventedFe/Asc-mediatedlipidperoxidationandcounteractedLPS-mediatedinflammationas evidencedbythedown-regulationofcytokines(TNF-aandIL-6),andprostaglandinE2.Themechanismsofactiontriggered by DAPP induced also a down-regulation of cyclooxygenase-2 and nuclear factor-kB, respectively. These actions were accompaniedbytheinductionofNrf2(orchestratingcellularantioxidantdefensesandmaintainingredoxhomeostasis),and PGC-1a(the‘‘mastercontroller’’ofmitochondrialbiogenesis). Co