protective effects of flavonoid baicalein against menadione

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1、ProtectiveEffectsofFlavonoidBaicaleinagainstMenadioneABSTRACTOxidativedamageandredoxmetalhomeostasislossaretountsofintracellularfreeironresultinFenton-typereactionoleculesandfurtherformationofnon-degradabletoxicpigmentscalledlipofuscinthatamassesinlong-livedpostmitoticcellss

2、uchasneurons.Dietaryflavonoidbaicaleincancounteractthedetrimentalconsequencesthroughexertionofamultiplicityofprotectiveactionsenadione(superoxideradicalgenerator)-treatedSK-N-MCneuroblastomacellline.Ourresultsshoentofcellsenadioneledtolipofuscinformationduetoelevatedintracel

3、lularironcontentsandaccumulationofoxidativeproductssuchasMDAandPCO.Also,menadionecausedapoptoticcelldeathinSK-N-MCcells.Hoentfuleffectsbychelatingfreeironandpreventingbiomoleculesperoxidations.Moreover,baicaleinpreventedcelldeaththroughmodulationofkeymoleculesinapoptoticpath

4、otifsinbaicaleinmakeittheappropriatecandidateinantioxidant-basedtherapyinage-relatedneurodegenerativediseases.Keyolecularoxidativedamageetabolitesofoxygen(e.g.superoxide,hydrogenperoxideandhydroxylradical)havinghigherreactivitythanmolecularoxygen[3].Theirraisond’êtreremainsu

5、nclear.Putativeexplanationsfortheiroccurrencerangefrominadvertentby-productsofaerobicmetabolismtohighlyregulatedandintricatesignalingmechanisms[4].FreeradicaloroxidativestresstheoryofagingedbyDenhamHarmandemonstratingtheroleofoxidativespeciesinagingprocessaccelerationandcell

6、death[5,6].Thistheorycanexplainmanyofthesenescentchangesincludingaccumulationofbroentsoragepigments[5,7,8].Correlationoflipofuscinountoflipofuscinelevatesoresignificantlybecausetherateoflipofuscinaccumulationnegativelycorrelatestolongevity.Highconsumptionofoxygenviabrainmake

7、sitsusceptibletooxidativedamage[9,10].Reactiveoxygenspeciesitochondriathroughdifferentesacromoleculesunderdegradationasolecularirondifferentsortsofmetalloproteins.BasedonFentonreaction,hydroxylradicalcanbegeneratedthroughthereactionofhydrogenperoxideacromoleculesandresultant

8、lipofuscinformation[7,8,10-12].Thereisadebateonthefunctionoflipofuscinpigme