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Truth Publishing International, Ltd P. O. Box 29-99 Taichung, Taichung City 40899 Taiwan

Resveratroland its Effects on Human Healthand Longevity - Myth or Miracle?

JaMEs BETzFounder and CEO of Biotivia Bioceuticals, LLC

All information contained in this book is copyright © 2011 by Truth Publishing, Inc. All rights reserved. All information contained in this publication may not be copied, published, distributed, broadcast, posted on the internet, or otherwise used for any purpose whatsoever without the prior written consent of Truth Publishing, Inc.

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Disclaimer: This book is offered for information purposes only and is protected under freedom of speech. It is not medical advice nor should it be construed as such. Nothing in this book is intended to diagnose or treat any disease. Always work with a qualified health professional before making any changes to your diet, prescription drug use, lifestyle or exercise activates. This information is provided as-is, and the reader assumes all risks from the use, non-use or misuse of this information. The information in this book is not supported by conventional medicine or most physicians. It is, however, the truth.

Contents

Introduction 1

Resveratrolversuspenicillin 3

Thescientificcommunityrecognizesresveratrol’spotential 4

Vintagewineversusalowlyweed 6

Canamoleculethatprotectsplantsalsoprotecthumans? 9

Whysmallerisbetter 12

Resveratrolandaging,lifespanversushealthspan 13

Mostofwhatyouthinkyouknowaboutagingiswrong 15

Whyareweagingfasterbutlivinglonger? 22

Aprescriptionforlongevity 24

Whatthesciencesays 27

Resveratrolhumanclinicaltrials 27

Aguidetoselectingaqualityresveratrolsupplement 33

Gimmickstowatchourfor 39

Fiveessentialcriteriontopickaresveratrolprovider 41

FutureProspects 44

Scientificstudiesconfirmingstatementsandclaims… 47

Resveratrol and its effects on human health and longevity - Myth or miracle?

Distributed by www.NaturalNews.com

Introduction

Is resveratrol, as many scientists believe, a breakthrough discoverydestinedtomakeagreatercontributiontohumanhealthandthepre-ventionandtreatmentofage-relateddiseasethanantibiotics;or is itonlyanotherfalsepromisewhichistakingscarceresearchdollarsandtalentawayfromthedevelopmentofpharmaceuticalstheworldneedsnowtotreatanagingpopulation?

With obesity, diabetes, coronary disease, Alzheimer’s disease andcancerreachingnearpandemiclevelsinthedevelopedworld,surelyacompoundwiththeputativediseasepreventionandtreatmentpowersofresveratrolcannotbedismissedwithoutextensivescientific inves-tigation. Only five years ago physicians, scientists and pharmaceuti-calcompanieshadbarelyheardofthisnaturalcompound,andonlyahandfulofscientistsandphysicianspossessedanyrealknowledgeofthemolecule’spotentialhealthandwellnesseffects.

Thefirsthigh-strengthresveratrolsupplement,Bioforte,wasnotevenontheconsumers’radar.Afewanimalstudieshadshownthepotentialfor increasesin lifespan,andafewhundredinvestigations—primar-ilybyresearchersatuniversitiesinJapan,IndiaandChina—elucidatedresveratrol’schemoprotectiveproperties,particularlywithrespecttocancer and diabetes. However, the same could be said for hundredsofotherphytochemicalsandsyntheticdrugs thathadatone timeoranothershownpromisingresultsinthelab,onlytobeshuttledofftooblivionwhenscientistswereunable toreplicate thesameeffects inmammals,especiallyhumans.

Oneintriguingandratheruniqueaspectofresveratrolthatcaughttheattentionofbothresearchersandthepublicwas itsabilitytoextend

thelifespanofsomeanimals.Fishfedresveratrol,forexample,lived59percentlongerthanthesamespecieswithoutresveratrol.Obesemicelived31percentlongerandmanagedtoavoidallofthediseasesnor-mallyassociatedwithagingandobesity.

Thebigmissingelement in the resveratrol equation,however,wasalackofpublishedhumanclinical trialsbymajormedicalschoolsandresearchinstitutions.Verylittlewasthenknownalsoaboutthepoten-tialtoxicityofresveratrolinhumansorwhatmightconstituteacorrectdose;andtherewereconcernsaboutthelowbioavailabilityofresve-ratrol,aswellasquestionsaboutitspossibleestrogeniceffects.Somescientistsspeculatedthatwomenmightbebestadvisedtoavoidres-veratrol for this reason.Wenowknow thatprecisely theopposite istrue.Resveratrolhasbeenshowninawealthofstudiestobeapowerfulchemoprotectorantandchemotherapeuticagentagainstbreastcancer.Itseemsthat,asmoreresourcesaredevotedtothestudyofthispotentmolecule,newmedicalandqualityoflifeapplicationscometolightonaregularbasis.

As theresultsof theearlierstudiesweresuccessfullyreplicated,andnew investigationsbyresearch teamsaround theworlduncoveredavirtuallaundrylistofcriticaltranscriptionfactors,signalingpathwaysandotherimportantpharmacokineticeffectsofthisverysmallmole-cule,interestinresveratrolincreasedexponentiallyinAsia,theUSandEurope.Bylate2010,therewereover4,000publishedstudiesonres-veratrol anda remarkable consensuswasdeveloping.Notonlywerescientistsfindingunusuallyconsistentandreplicablepositiveresults,asoneinstitutionaftertheotherexaminedthemoleculeusingdifferentapproachesandtechnologies,butfundamentalneweffectsandmodesofactionwerebeingdiscoveredatanastonishingrate.Manyofthesediversepropertiesofresveratrolhavepotentiallyhugeimplicationsforthepreventionandtreatmentofhumandisease.

Onlytimewilltellifresveratrolmanagestounseatantibioticstotakethetopspotasthemost importantcontributortohumanhealth,butatthispointintimeitcannotbecountedout.Intermsofitsbeneficialpropertiesrelative tochronicconditionssuchasdiabetes, cardiovas-culardiseases,manycancersand fitness, resveratrol isastrongcon-tender—andforresveratroltheracehasjustbegun.

Resveratrolversuspenicillin

Inaninterviewwithawell-knowninternationaltechnologymagazineinMarch2009,Itoldthejournalist;“Inmyopinion,resveratrolwill,inthespaceof20or30years,cometoberegardedasamoreimportantscientificdevelopmentthanpenicillin.” InthispredictionIwasrefer-ringtothissmallmolecule’spotentialtopositivelyimpactthehealth,longevity,andqualityoflifeofthehumanrace.Sevenmonthsaftermyinterview,ascientistresearchingresveratrolatHarvardUniversitytookthispredictiononestepfurtherbyproclaimingthatresveratrolwillbemoreimportantthanallantibiotics.

Penicillinwasdiscovered in1928andhasbeen creditedwith savingmanythousands,ifnotmillions,oflives.Resveratrolwasfirstisolatedfromaplantsourcein1940intheWest,buthasbeenusedasatradi-tionalmedicineinAsiaformorethan2,000years.In1970itwasfirstcharacterizedasachemopreventive,asubstancethatprotectshealthyhumantissuefromthedisease-causingeffectsofvariousagentssuchaspoordiet,bacteria,virusesandaging.Anexampleofachemopreventivewouldbetheuseoflowdoseaspirintoprotectagainstheartattacks.

Bothpenicillinandresveratrol,likemostdrugswithalonghistoryofeffi-cacy,arederivedfromnaturalsources;penicillincomesfromacommonfungus,andresveratrolisfoundinavarietyofplantsincludinggrapes,

peanutsandcranberries,butmost importantly in the JapaneseGiantKnotweed plant, also known as Polygonum-cuspidatum. Giant knot-weedhasbeenusedinAsiaasatraditionalmedicinetotreatimmunedisorders, cancer, and neurological conditions. The plant acquired aratherunsavoryreputationasaforeigninvaderthroughoutSoutheastAsiaandJapan,owingtoitsabilitytosurviveintheharshestconditionsandtocrowdoutotherplantsandcrops.FiveyearsagoaGooglesearchforgiantknotweedwouldreturnhundredsofarticlesonhowtoexter-minateit.Thesamesearchtodaywouldbefilledwithscientificstudieselucidatingitsastonishingmedicalandhealthapplications.

Thescientificcommunityrecognizesresveratrol’spotential

InSeptember2010thefirstinternationalconferenceofresveratrolre-searcherswasheldaboutaone-hourtrainrideoutsideofCopenhagen,Denmark.Atthismilestoneevent,over120oftheworld’sleadingsci-entists from prestigious research institutions in the US, Asia, India,EuropeandAustraliamettopresenttheirfindingsonresveratrol.Afterattending this conferenceand listening to thepresentationsof thesedistinguishedandhighlyaccomplishedscientists,Iamnowconvincedthat,ifanything,mycomparisonofresveratrolwithpenicillinwasex-tremelyconservative.

Resveratrol and the drugs, treatments, supplements and functionalfoodsthatcontainthistinybutincrediblypotentmolecule,willeclipsepenicillin’s importancewithinonegeneration.From1940until2005,thereweresome800publishedstudiesonresveratrol’sbiologicalprop-ertiesanditshealthbenefits.From2005untilthemiddleof2010,therehavebeenmorethan3,000newstudiesoncells,animals,andhumans.New and surprising revelations are being announced almostweekly

nowbytheleadinguniversities,medicalschoolsandresearchorganiza-tionsaroundtheworld.Allofthesediscoveriesaddtoourknowledgeofresveratrol’sremarkablerangeofhealthanddiseasepreventioneffectsandgivesusnewideasonhowtoapplythisknowledgeforthegoodofmankind.

The reservations expressedby somephysicians and science journal-istsafewyearsagoaboutpossiblesideeffects,oroverestimationofthebenefitsofresveratrol,havebeenalmostentirelyrefuted;andnewpreviouslyunimaginedbenefitsarebeingrevealedasmorefundingisdevotedtoanimalandhumanclinicaltrialsofthisremarkablenaturalchemical.Atatimewhenwefacemultipledrugresistantbacteria,anexplosionintheincidenceofdiabetes,pandemiclevelsofobesity,de-bilitatingincreasesinAlzheimer’sdiseaseandotherformsofdementia,andmanyotherdiseasesofaging,itisclearthatresveratrolisachemo-preventivewhosetimehascome.

Nosinglemoleculeordrugknowntomedicalsciencehasshownthewide range of potential preventative, therapeutic, and quality of lifeenhancement properties of resveratrol. It has been shown to inhibitcancer,killbacteria,virusesandfungal infections,extend lifespan inanimals, improve energy production in cells, quench damaging freeradicals,increaseglucosetoleranceindiabetics,improvecardiacfunc-tion, enhance physical and mental fitness and concentration, repairdamagedDNA,preventcelldamagefromnuclearradiation,andmuchmore.

Penicillinhasbeenshowntohaveoneuse:tocombatbacterialinfec-tions.Itseffectivenesshasbeengreatlydiminishedoverthepasttwentyyearsasmanystrainsofharmfulbacteriahaveacquiredresistancetoit.Timewilltellifresveratroldoesfulfillitspromiseasaso-calledmiraclemolecule,butifitonlyprovestopossess10percentofthehealthandmedicalbenefitsresearchershaveattributedtoitsofar,itwillindeed

make a greater contribution to human health then penicillin, andperhapsevenallantibiotics.

Vintagewineversusalowlyweed

Givenalloftherecentpublicityaboutthehealthbenefitsofdrinkingwine and the so-calledFrenchParadox, onewouldnaturally assumethattheprincipalsourceofresveratrolusedbyscientistsandsupple-mentmakers is the redwine grape.Although the skinof redgrapesdoescontainsmallamountsofresveratrol,theconcentrationismuchtoolowtomakegrapesaneconomicalsourceofthiscompound.

Anotherproblemwiththeextractionofresveratrolfromgrapesisthedifficultyinremovingtheresiduesfrompesticides,fungicides,andotheragriculturalchemicalsneededtoprotectthefruitwhileitripens.Theapplicationofagriculturalchemicalsnotonlyposesaseriousproblemfromcontaminationbytoxins,butalsotendstoreducethenaturalpro-ductionofresveratrolandotherantioxidantsbythegrape.Thehighestconcentrationofresveratrolisfoundinorganicgrapesthatarestressedbyfungus,unfavorableweather,toolittleortoomuchwaterandalackofpesticides.Theseconditionsalso lowerthewineproductionlevelsbutoftenresultinawineofoutstandingquality.

If theamountof resveratrol inredwine is inadequate toexplain theFrenchParadoxthenwhatisthereasontheFrenchsuffer40percentless heart disease than the averagewesterner? As anyonewho hasspent time inFranceknows, the typical Frenchurbandiet ishigh infatsandsaltandotherless-than-idealingredientsfromahealthstand-point. In spite of this fact, the French people tend to have far lowerrates of cancer and cardiovascular disease than do Americans. Evenlungcancerratesarerelativelylowamongstthetobacco-lovingFrench

citizens.Furthermore,Francehasmorepeopleovertheageof100thananyotherEuropeancountry.Manyscientistsnowbelievethatitisthefullrangeofpolyphenols,notonlyresveratrol,whichaccountsforthechemopreventiveeffectsofdrinkingwine.

Thereisanotherparadox,whichiscalledtheAmericanParadox.TheAmericanParadox refers to the fact that even thoughAmericansareamongstthebestfedandmostaffluentpeopleintheworld,theirrateofmortalityfromcancerandheartdisease,andmorerecently,diabe-tesandtheeffectsofobesity,isextraordinarilyhighcomparedtomanyotherdeveloped countries.Wine consumption in theUS is relativelylowandthetypicalAmericanandUKdietisheavyonbadfats,redmeatraisedonantibiotics,growthhormonesandotherchemicals,highfruc-tosecornsyrup,processedfoodsandchemicalladenburgersandotherfastfoods.Thesefactors,alongwithtoolittleexercise,toomuchstress,notenoughsoundsleep,andaheavyrelianceonpharmaceuticals totreatchronicconditions,surelyaccountformuchoftheseriousdiseas-esintheUS.Theyalsoresultinashorterhealthspan.

Healthspanisthenumberofyearsapersonlivesfreeoftheso-calleddiseasesofaging.Apersonwhodiesattheageof85whomanagestoavoidcancer,diabetes,heartdiseaseandneurologicalconditionssuchasAlzheimer’sanddementiahasafarlongerhealthspanthanapersonwhodiesatthesameageaftermanyyearsofintensivemedicaltreat-mentandadramaticallyimpairedqualityoflifeduetochronicdiseaseandincapacity.

So,ifgrapeskinsarenotthepreferredsourceofresveratrol,thenwhatis?TheansweristheJapaneseGiantKnotweedplant,akaPolygonum-cuspidatum.Iftherewereamasterninjaoftheplantkingdom,itwouldsurelybeJapaneseGiantKnotweed.

This voracious predator is one of the toughest andmost aggressiveplants inexistence.Abovetheground itappearstobemuch likeanyotherdocilefloweringgreenperennialbutunderthesurfaceitsrootstell a different story. If you can imagine a gnarly, hard, dense, thickbrownmassthatresemblestherootsofamatureoaktree,youhaveagoodideaofwhattherootsofthisplantlooklike.Itthrivesjustaswellinhighandlowaltitudes,inhotandcold,andinwetoraridclimates.Itseemstoactuallygrowstrongerinmorehostileenvironments.Itisanaggressiveinvaderand,onceestablishedinanarea,willoverwhelmexistingvegetationwithinafewyears.Itissotoughithasbeenknowntogrowupthroughconcretebuildingfoundations.

InJapanandpartsofEurope,afiercebattleiswagedbyfarmersandlocalcouncilstoeliminateoratleastcontrolit.Inmid-2010,thegovern-mentoftheUnitedKingdomtooktheextrememeasureofapprovingtheimportationofawormknowntothriveontherootsofthePolygonum-cuspidatum plant in a rather desperate attempt to rid England andWalesoftheinvasiveweed.BritishandAsianfarmerswhohavetriedtoremoveinfestationsofJapaneseGiantKnotweedwilltellyouthatifevenonecentimeteroftherootofoneplant is left inthegroundtheplantwillreturnwithavengeancewithinayearortwo.

Thisobnoxiousplantistheprincipalsourceoftheresveratrolusedinthousandsofstudiesoncells,animalsandhumans.It isalsoa2,000-year-oldtraditionalmedicineinChinaandTibet.

Resveratrolfunctionsastheimmuneanddefensesystemsforthisplantandmanyothers.Althoughresveratrolisfoundinpeanuts,blueberries,andmanyotherplants, theconcentrationof resveratrol ishighest inKnotweed.Notonlyistheplantrichinresveratrol,itisalsoasourceofothernaturalprotectivecompoundswithnameslikepolydatin,pteros-tilbene,andemodin,whichwesternscientistsareonlybeginningtoin-vestigate.Someoftheseso-calledresveratrolanalogsappeartobeeven

morepotentthanresveratrolinfightingspecificdiseasesandimprov-inghealth.

Pterostilbene, forexample, a compoundclosely relatedchemically toresveratrol,hasbeenshown to reversedecline inmental function inratswhosecerebrumswerechemicallydamagedevenbetterthanres-veratroloranypharmaceutical.Italsohaspotentcholesterolloweringproperties.Manyscientistsbelievethattheoptimumhealthandmedicaleffectswillfollowfromcombiningresveratrolwithotherchemopreven-tiveplantextractssuchaspterostilbene,fruit-basedpolyphenols,andotherphytochemicals.Asonephysicianandresearcherrecentlystated,“Antioxidantsarenotsoloacts,theyperformbestasplayersinadiversesymphonyorchestra.”

Canamoleculethatprotectsplantsalsoprotecthumans?

In2006, scientistsworkingatHarvardbeganreferring toresveratrolasahormetic.Ahormetic isa substance that isproducedbyaplantinresponsetostressessuchasfungus,bacteria,insects,heat,andtoomuchsunlight,whichprotects theplantagainstdamageor infection.Thetheoryofzenohormesisisthatthesesubstancesalsoprovidepro-tectionandearlywarningofenvironmental threats totheanimals intheirvicinitywhoconsumethem,eitherbyeatingthewholeplantor,inthecaseofhumans,aconcentratedformoftheplantcompounds,suchasinasupplement.

Hormetics, such as resveratrol, do not normally act directly on theillnessorbiologicalstressor,asdomostdrugs.Theydonotfunctionlikeconventionalmedicinessuchasantibiotics,painkillers, cancerdrugs,andbloodpressureregulators;nordotheygenerallypossessthetoxic-

ityofsyntheticdrugs.Thesenaturalplant-derivedcompoundsworkbykick-startingprocesseswithintheanimals’owncellsandorgans,whichattackdiseaseorprotectagainstthestressandharmfulenvironmentalfactors.

One example of a way in which resveratrol protects animals is itsabilitytopreventandreduceinflammationbysuppressingcertainpro-teinsproducedbythebodyinresponsetoinfection,injury,andotherstresses.

It is nowwell known that inflammation, rather then simply being asymptomofdiseaseasoncethought,isitselfthecauseofmanyhumanafflictions.Wehaveverycompellingevidence,forexample,thatinflam-mationplaysakeyroleinautoimmunediseasessuchasarthritis,aller-giesandmultiplesclerosis,aswellasmanyother illnesses includingheartdisease,diabetesandAlzheimer’sdisease.

When resveratrol is consumed itdoesnotdirectly reduce inflamma-tion.Instead,itactivatessystemsinthebody’scellsandproteinsthatreduceinflammationnaturally.Thisiswhyresveratroliscalledaregu-latororapotentiator,andnotadrug.Aregulatorworksbyactivatingordeactivatingvariousenzymes,proteinsandevengenestopreventortreatthecauseofaproblem,notsimplymaskitssymptoms.

Whenisthelasttimeyouheardofasyntheticdrugthatactuallycuredanydisease?Resveratrol inhibits inflammationbyactivatingmanyofthesameprocessesthatareactivatedbyanti-inflammatorydrugs,butinamoresophisticatedandpreciselytargetedmanner.Comparingres-veratrolwithNSAIDS,non-steroidalanti-inflammatorydrugs,isanalo-goustocomparingascalpel toabreadknife.Resveratrolreduces in-flammationwithoutalsointerferingwiththebeneficialprocessesthattheanti-inflammatorydrugsinhibit.Italsodoesnothavetheunwanted

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sideeffectsofdrugssuchasaspirin,ibuprofen,andthemorerecentlyreleasednextgenerationanti-inflammatorydrugs.

Themannerinwhichresveratrolattackscancerisanotherexampleofitsselective,almostintelligenteffectsoncells.Resveratrolinhibitsthegrowthofcancerouscellsthroughanumberofdifferentactions.Itin-hibitsthegrowthofsmallbloodvesselsthatfeedatumor,butdoesnotstimulatethespreadofthetumortootherareasofthebody,aprocessreferred to asmetastasis,which is one side effect of the anti-cancerdrugs,whichalsoinhibitthesupplyofbloodtoacanceroustumor.ItalsoworksbyactivatingordeactivatingcertainproteinssuchasTumorNecrosisFactor,TNF,animportantimmunesystemmoleculethatchar-acterizesmanytumors,andbysuppressingNF-kB,aproteinwhichislinkedtoalmostallcancersinhumans.

Many of these anti-cancer effects of resveratrol are the same effectsthatthepharmaceuticalcompaniesarespendingbillionsofdollarstoreproduceinnewpharmaceuticals.Unfortunately,manyofthemoreef-fectivedrugsbeingusedtodayarealsohighlypoisonoustothepatientaswellastothetumor.Oftenitisadeathraceforthepatientbetweenthedrugs’toxiceffectsandthegrowthandspreadofthecancer.

OneoncologistIspoketoatM.D,AndersonHospitalinHoustonsaid;“Veryfewpeopleareactuallydyingofcancerthesedays.Withaggres-sivetreatmentssuchaschemo,radiationandsurgerymostdieofthetherapyfirst,oriftheyareluckytheysurviveboththecancerandthetreatment.”

Thisisnottoproposetheuseofresveratrolasatreatmentforcancer,oranyotherdiseaseforthatmatter.Weneedmuchmoreactualhumanclinical data and confirmation of the results seen in the 4000 plusstudies,trialsandinvestigationsalreadycompletedbeforewecansaywithconfidencethatresveratrolisaseffectiveasthelaboratorystudies

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indicateitshouldbeagainstanyspecificdisease.Itmaywellturnoutthatsomecombinationofresveratrolandthemoreeffectiveanti-cancerdrugswillbethebeststrategytopursue.Weknowforexamplethat,inthecaseofsomechemotherapyagents,resveratrolimprovestheiref-fectivenessand reduces the severityof their sideeffects. Itmayalsoturnoutthatsomeotherphytochemical,suchasPterostilbene,maybeevenmoreeffectivethanresveratrol.Thereispresentlyanenormousamountofresearchbeingundertakentoanswerthesequestions.

Whysmallerisbetter

The largerandmorecomplexamolecule is, theharder it is for themolecule,beitadrugornutrient,tobetakenupbythecell.It’salsoveryoftenlesseffectiveagainstthebasicprocessordiseasebeingtar-geted. Largermolecules are alsomore likely to have unpredictablesideeffects.

Smallermoleculesarebetterabletopassthroughthecellmembranes,whichactasbarrierssurroundingallcells.Theyarealsobetterabletopreciselytargetindividualdiseasecomponentsatthecellularlevel.Theeffectsoflargemolecules,whichconstitutemostpharmaceuticaldrugsonthemarkettoday,versussmallmolecules,suchasresveratrol,isthedifferencebetweenusingalasertoremoveatumorversusremovingtheentireorganorlimbsurgically.

Themajordrugcompanies,suchasBioticaandGenentech,aswellasresearchorganizations,includingtheNationalInstitutesofHealth,con-sidersmallmoleculedrugcandidatestohavethegreatestpotentialastreatmentsfordiseasessuchasarthritis,Alzheimer’sdisease,cancer.Intheareasofgenetherapy,andneurologicaldiseasessuchasAlzheimer’sdisease,largermoleculesareessentiallyineffectiveduetotheirinabil-

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itytopassthroughthebloodbrainbarrier,theprotectivebarrierwhichpreventspotentiallydamagingchemicalsfromenteringthebrain.Onlysmallmoleculescanpassthroughthisprotectivefilter.

Resveratrol isanexceptionallysmallmoleculethathasshownaston-ishingeffectsinthousandsofanimalandlaboratorystudies.Inthepastfewyears,manyofthehealthandlongevityeffectsseeninthelabora-toryhavealsobeenconfirmedinhumanclinicaltrials.Wenowknowinmuch finerdetail how resveratrol operates at the cellular level toaffectthebody’ssystemsandfunctions.Goingforward,theemphasisofresearcherswillshiftfromcellandanimaltrialstoclinicaltrialsonhumans. Results from these limited human studies so far have beennothingshortofastonishing.Itisexpectedthatprogressindiscoveringnewmedicalandhealthenhancementapplicationsforresveratroloverthecomingdecadewillberapidanddramatic.

Resveratrolandaging,lifespanversushealthspan

Increasesinthemaximumandaveragelifespanofhumansfromthebe-ginningofthetwentiethcenturyuntilnowhavenotbeenparticularlyimpressivecomparedtotheadvancesmadeinotherareasofscienceandtechnology;andinsomecountries,suchasRussia,lifespanshaveactuallydeclined.PredictionsbydemographersofadropintheaverageUSlifespaninthiscenturyarebaseduponcompellingevidenceofde-clining health amongst the present generation of teens and twenty-somethings,madeworsebytherisingcostofhealthcare.

Our poor record in extending maximum life span is attributable tothe fact thatmedical technologiesandpharmaceutical researchhavefocusedmoreonkeepingsickpeoplealiveratherthanonpreventing

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thediseasesanddisabilitiesrelatedtoaging.Drugcompaniesmakefarmoremoneysellingdrugsthat treatdiseasethanoncurestodiseas-es.Thisisonereasonwhyvirtuallynocureshavebeenofferedbyanymajorpharmaceuticalcompanyinthelast25years.

Oneresultofcorporategreed-drivenmedicinehasbeenthattheaveragepersonspendsmorethan90percentofhisorherlifetimemedicalex-pendituresduringthelastfiveyearsoflife.Althoughaveragelifespanshaveincreasedmoderatelyoverthepasttwodecades,healthspan,thenumberofyearsoneenjoysahealthy,independent,andproductivelife,hasnotkeptpace.Infact,healthspanappearstobedecreasingintheUS,theUKandinmuchofAsia,asthecitizensofthesecountriesforsaketraditionaldietandremediesforthewesternlifestyle.

Oneratheralarmingpredictionisthatparentsnowaged45to60maycommonly outlive their children for the first time in history. At thecurrentrateofincreaseofmedicalcosts,thepolicyoftreatingdiseaseratherthenpreventingdiseaseisunsustainable.Atsomepointduringthenext ten to twentyyears the resultwill be thathealth care, andconsequentlylifespan,willbeseverelyrationed,ornationalbudgetsforhealthcarewillconsumemorethanthetotalgovernmentrevenuesforallpublic services.Preventablediseasessuchas type2diabetes,manycancers,andcardiovasculardiseasesareincreasinginincidenceatunprecedentedratesinthedevelopedworld.Manyphysiciansandscientistsbelieve that resveratrolcanplayacritical strategicrole inreducingrunawayhealthcarecostsbypreventing,delayingortreat-ingmanyof thehealth conditionsassociatedwithpoordiet, lackofexercise,andobesity.

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Mostofwhatyouthinkyouknowaboutagingiswrong

This applies whether you are a laymen, physician, political leader,sciencejournalist,socialscientistorauthorofbooksandarticlesonthesubject.Tobegintheprocessofdismantlingtheprevailingmythsandmisconceptionshereareafewfactstoconsider.

“Aging and the widely recognized diseases of aging are the inevitable consequences of living longer.”

False:Agingisnotinitselfthecauseofdiabetes,obesity,heartdisease,cancerorAlzheimer’s.Nordoesagingnecessarilyleadtoimpairmentofemotionalhealth,physicalcapacity,libido,cognition,memoryorintel-ligence.Agingismerelythenamegiventotheconstellationofadversehealthandmedicalconditionsnormallyassociatedwiththeelapseoftime sinceone isborn.Thediseases anddisabilities associatedwithadvancingageallhavespecificcauses.One’sageissimplyameasure-mentoftimelived,andtimeisnotinitselfacauseofanydisease.Bymodifyingone’sdietanddailyroutine,stayingphysicallyandmentallyactive,adoptingpreventativelifestylepractices,andseekingappropri-atemedicalinterventionstorepair,replaceandrenovatedeterioratedbodyparts and capabilities, virtually all of thediseasesnormally as-sociatedwithchronologicalagingcanbeeitherdelayed,preventedorevenreversed.

Adopting preventative strategies at the individual level can radicallylowerthemortalityratefromdisease,andonesuchstrategyisthein-telligentuseofsupplementssuchasresveratrol.Unfortunately,thein-stitutionalizedprofitmotivedrivingtheemphasisontreatmentversus

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preventiondeprivesthemajorityoftheworld’spopulationoftheben-efitsofincreasedlongevityandimprovedhealthduringlaterlife.Onlythoseindividualswhotakepersonalresponsibilityfortheirhealthcanexpecttoachieveimprovedhealthandlifespans.

“An aging population will be a drag on society, the young, and the economy.”

False:Preciselytheoppositescenariotothisalmostuniversallypre-dictedcalamitywillactuallyensue.

Thesciencecommentatorsandsocialscientistswhocontendthatanincreasedpopulationofoldercitizenswillbeaburdenontheyoungermembers of society fail to understand one very simple fact; manypeoplewill live longerbecausetheyarefreeofthedisablingmedicalconditionswhichpresentlydrainthewealth,vitality,andproductivityfromsociety.

It isfoolishtopresumethatpeoplewillsomehowmagically livesub-stantiallylongerwithoutconcurrentimprovementsintheirhealthandvitality. An elderly professionalman orwoman, for example,who isstillhealthy,energetic,andmentallysharpisgreatlyadvantagedoverayoungercolleaguebyvirtueofhisorheradditionalyearsofworkexpe-rience,judgment,andmaturity.

Thinkaboutit.Giventhechoicebetweentwosurgeons,bothofwhomarefitandhealthy,wouldyoupreferthedoctorwith40yearsofexperienceandthousandsofoperationsunderhisbelt toremoveyourrupturedappendixorthesurgeonwithfiveyearsandonly100operations?

Industryandtheprofessionsarealreadyseeingasurgeindemandforolderworkersovertheirlessexperiencedcolleaguesinalldeveloped

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countries.Asaveragehealthspanincreaseswewillseepeopletakingupnewcareersandstartinguniversityattheageof50andgreater,pro-fessionalathletesintheir40sand50swillchallengecompetitorswhoaredecadesyounger,andtheaverageretirementagewillincreasedra-matically,whichmeansthatmanymorepeoplewillbepayingtaxesandcontributingtotheeconomyforfivetotwentyyearslongerduringtheirlifetimes.Importantly,manyfewerpeoplewillbedrawingretirementanddisabilitypaymentsorrequiringcostlymedicaltreatments.

Ifpreventionandpersonalresponsibility forhealthbecomeareality,theimprovementsinhealthspancouldbethesinglelargestcontribu-tortotheUSandUKeconomiestwentyyearsfromnow.Resveratrolandothernaturalcompoundsrelatedtoresveratrolmayhavethepotentialto addmanyproductive years to the life ofwesternersby extendinghealthspanandinhibitingconditionssuchasdementia,diabetes,car-diovasculardiseaseandcancer.

“There is an intrinsic biological limit to the number of years humans can live healthy, vital, independent lives.”

False:Scientistshaveyet to identifya ticking“biologicalclock” thatpredetermines themaximum life span forahuman.Humansarenot“programmed” to die at a certain age. We knowwhat the principalcausesofagingare,andwearerapidlyclosinginonsolutionstothesecauses.Some,suchasthecorruptionofone’sDNA,anddecreasingtelo-merelength,whichoccursascellsdivide,areabitmorecomplexthanothers,butnoneare impossibletosolvegiventheapplicationofsuf-ficientresources.

AManhattanProjectstyleattackonagingwouldprobablysolveallofthesechallengesinfewerthantenyears.Nowthatthemedicalandre-searchcommunitiesarebeginningtotreatagingasanyotherdisease,

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ratherthenacceptingitasinevitable,andsimplyfocusingonmakingolderpeoplemorecomfortable,wecanexpectdramaticbreakthroughsinlifeextension.Eachnewbreakthroughwillgivehumansabitmoretimeduringwhichnewdiscoverieswillbemadethatwillcreatestep-pingstonestothefinalgoalofindefinitelifespan.

Resveratrolisknowntobeachemoprotectiveagent,whichcanplayacriticalrole indelayingorpossiblyevenpreventingthemostseriouscauses of mortality in the developed world. Serious considerationshouldbegiventoincorporatingresveratrolandothernaturalchemo-preventivesupplementsintoamorerational,humaneandeffectivena-tionalhealthplanineverydevelopedcountry.Unlessthepriorityshiftsfromtreatmenttoprevention,thehealth,wealthandlifespanofciti-zenswillcontinuetodeclineandnationalhealthcarebudgetswillbeunabletokeeppace.

“A silver bullet is just over the horizon that will dramatically extend human life span.”

False:Theincreaseinhumanlongevitywillcomeinsmallstepswhichwillturnagingfromadebilitatingterminaldiseaseintoatreatablecon-dition just as the casehasbeenwithdiseases suchasdiabetes,HIV-AIDS,malaria,andmanyothers.

Resveratrolisnotamagicelixirthatwillpreventthediseasesofagingorcompensate forpoorhealthhabits.Likestemcell therapy,geneticengineering,organreplacement,naturalandsyntheticdrugs,exercise,dietandmedicaltechnology,ithasanimportantparttoplayinanylon-gevityprogram.Aswecollectmoredatafromhumanclinicaltrialswewillbebetterabletodefinejustwhatthisroleshouldbe.

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Resveratrolisonlythefirstinwhatwilllikelybealonglistofsimilarcompoundswithextensivehealthbenefits.Othercompoundsrelatedtoresveratrol,suchasPterostilbene,Polydatin,andvariousotheranalogsof resveratrol, will be intensively investigated over the coming fewyears,anditisalmostcertainthatresearcherswillfindatreasuretroveofgeneticandotherbiologicaleffectsevenmoreimpressivethanthoseofresveratrol.

Pterostilbene,anaturalcompoundfoundinblueberries, forexample,hasbeenshowninratstoactuallyreversedeclinesindecision-makingabilitiesandappearsto improve intelligence. Italso lowersLDLcho-lesterolmoreeffectivelythanresveratroldoes.Polydatinismoreeffec-tivethanresveratrolinpreventingthedamagetohearttissueoccurringwhenaheartattackvictimisresuscitatedoraheartisrestartedfollow-ingsometypesofcardiacsurgery.Emodin,anantioxidantfoundintheJapaneseGiantKnotweedplant,isapotentanti-canceragent.

Themorewelearnabouttheseastonishingmolecules,themoreweareawedbytheirbenefitstohumanhealth.Manyresearchershavenotedasynergisticeffectwhenresveratroliscombinedwithotherpolyphe-nols suchas curcumin,howevernotall combinationsofpolyphenolsaresynergistic.Forexample,anegativeeffectonSirtgeneactivationhasbeenobservedwhenresveratroliscombinedwiththeantioxidantquercetin.

Health span and life spanwill increase as discoveries aremade andknowledgeiscreatedthatwillleadtocuresandtherapiestotreattheso-calleddiseasesofaging.Naturalchemoprotectivessuchasresvera-trol, curcuminandawiderangeofotherpolyphenolsmay takeovermuchoftherolesyntheticdrugsnowplayintreatingdiseaseafterthefactratherthanfocusingonpreventingdiseasenaturally.

“Technology advances will lead to longer life spans and elimination of many diseases.”

True:Dr.SinclairatHarvardUniversitydiscoveredthegeneactivationpropertiesofresveratrolonlybecausehehadthehelpofanewcom-puterizedchemicalscreeningsystemthatcouldexaminethousandsofmoleculesfortheiranti-aginggeneactivationpropertiesinthetimeitpreviouslytooktoinvestigateonlyahandfulofcompounds.

Advances in computing power are rapidly increasing our ability tocomprehendtheintricaciesofthemetabolicprocessandtorealisticallysimulatecriticalbiologicalpathways.Thepastdecadesawthedevelop-mentofgenomics.Thecomingtenyearswillconsolidatethisknowledgeandmoveontounravelingtheroleoftheproteinswhichareencodedbyourgenes.Thiswillrepresentanenormousadvanceinourabilitytodesigndrugsthatturnonbeneficialgenesandswitchoffthegenesresponsible fordiseases such asmultiple sclerosis, asthma, cystic fi-brosis,thalassemia,mentalillnessandhundredsofotherdiseasesthatarecausedbyeitheraspecificgeneticabnormalityoracombinationofgeneticfactors.

Wewillalsobegintosolvethemysteryofwhatfunctionthe95percentof thegenomewhichdoesnotcode forproteinsplays inhumande-velopment.Thiswill lead to thedesignofnewstrategies topreventorreverseagingandresultinquantumleapsinhumanlongevity.By2020computersandothermedicaldeviceswillbepowerfulandcheapenoughtogivescientiststhetoolstheyhaveneededtovirtuallystoptheagingprocessinanimals.Thisgoalhasalreadybeenachievedinthelab.

Theconvergenceof thousandsof independentdiscoveriesand incre-mentalbreakthroughsbydedicatedprofessionalsworking indiverse

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fieldsarecreatingsynergiesandmutuallyreinforcingdiscoveriesthatarethekeytoextendinglifespanandeventuallyeliminatingagingal-together. Developments in advanced prosthetics, stem cell therapy,organreplacement,andthepreventionandtreatmentofcancer,heartdisease,andneurologicalconditionssuchasAlzheimer’sanddementiawillmeanthatthosepersonswhoarepresentlyunder60yearsofageandinexcellenthealthwillhaveareasonablygoodchanceoflivingin-definitely.Thisassumesthattheyarefinanciallyabletoaffordthetreat-ments,drugs,andtherapeuticprocedures,whichwillbecomeavailableoverthenext30years.

Beyond2040,agingwillbesimplyachronicconditiontreatableorpre-ventableatareasonablecosttothepatient.Thetimingofone’sdeathwillbecomeformanypeopleamatterofindividualchoice.Accidentsandneedlesswarsoverresourceswillbecomethemaincausesofdeathinthedevelopedworld.Unlesswestopdestroyingourplanetthroughtheplunderingofitsresourcesandpoisoningitsairandwater,climatechangeandscarcityofusablewaterandbreathableairwillrenderanyincreaseswemakeinaveragelifespansawasteoftimeandeffort.Ifwedestroythevitalbalance,whichsustainslifeonthisplanet,nothingelsewillmatter.

“We must first fully understand the cell’s incredibly complex metabolic process before we can develop effec-

tive drugs and other preventatives and treatments for the disease we call aging.”

False: Many of the safest and most successful drugs in use todaywork by targeting unidentified biological processes they werenot initially designed to attack. Luck plays a big part in drugdiscovery.Serendipityandpersistenceonthepartofresearchersandphysiciansresulted in thediscoveryofpenicillin,aspirin,painkillers

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andmanyothervaluabledrugs.Partialknowledgeofthecellular-levelbiologicalprocessesbeingtargeted,coupledwiththeintelligentappli-cationoftrialanderror,isaneffectiveandrationallifeextensionstrat-egy. It probably offers the greatest potential to conquer aging in thenear-tomid-term.

WhenDr.Sinclairdiscovered theabilityof resveratrol toactivate theso-called anti-aging genes, it was due to serendipity as much as toscience.Sinclairdiscoveredthispreviouslyunknownabilityofresvera-trolbecausehewasabletoquicklyscreenthousandsofchemicalsforthispropertyduetoadvanceswhichhadjustbeenmadeinlaboratoryanalysistechnology.Hisdiscoverydidnotcomeaboutbecausehehadsomereasontobelievethatresveratrolmightfitanyreceptoronacellor itmighthaveanti-inflammatoryorantioxidantproperties. In fact,so called rational drugdevelopment, inwhich computers attempt tomatchchemicalstocellreceptorsinasearchfordrugcandidates,hasfailedtoliveuptoitspromise.

Whyareweagingfasterbutlivinglonger?

The decline in the health status of the average British or Americancitizenisnotprincipallyanaturalorinevitableconsequenceofhumanevolutionnorisitduetotheriseofnewdiseasesorthedeteriorationofthequalityoftheenvironmentinwhichwelive,althoughenvironmen-tal factorsdomilitateagainst increasing life spans.The fundamentalcausesaresimpleandwellknown.

Life span increases so far have come about only because advancesinmedical technology and pharmaceuticals are keeping sick peoplealive longer, but at a very high and untenable cost, not because dis-

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easesanddisabilitiesarebeingpreventedor thatpeoplearestayinghealthylonger.Furtherincreasesinbothhealthspanandlifespanmustcomefromadoptingpreventionasourprimaryfocus.Wehaveyettobegintoexploittheadvantagesofpreventionattheinstitutionallevel.Resveratrol isonemolecule thatmayplayan importantpart inbothpreventionandtreatmentofdisease.

Obesityandlifestylefactors,notaging,aretheprincipalcauseofdiabe-tes,hypertension,mostheartconditions,andmostcancers.Obesityisalsoamajorcausalfactorforgastricrefluxdisease,gallbladderdisease,degenerationofL-sacralspineandweight-bearingjoints,asthmaandhundredsofotheradversemedicalconditions.Resveratrolwasshownto increase the life span and health span in obesemammals. In Dr.Sinclair’s now famous study published in the journal Nature, obeseratsfedresveratrollived31percentlonger.Whenthevitalorgansoftheresveratrol-fedratswereexaminedbyapathologist theyresem-bledthoseofyoung,lean,healthyrats.

Lackofregularexercisecompoundsthenegativemedicalconsequencesofobesity,andisariskfactorforosteoporosisaswellasawiderangeofadversephysical,emotionalandneurologicalconditions.Mitochondriaare the cells’ energy factory. Resveratrol increases mitochondrialdensityandenhancesmitochondrial function.Rats fed resveratrol inthestudybyDr.Auerandpublished in the journalCell,wereable toruntwiceasfarasratsnotfedresveratrol.Whenthemuscletissueofresveratrol-fedanimalsisexaminedunderamicroscope,theincreasednumberandhealthofthemitochondriaisevident.

Probably the largest contributor to early aging and the diseases as-sociatedwithaging ispoordiet.Excessiveconsumptionof redmeat,processedfoods,sugarsandhighfructosecornsyrup,aswellastransfats and the lack of omega-3 rich foods and polyphenols from fruitsandgreenleafyvegetables,andovereatingingeneralareallenemies

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of human health span and longevity. Resveratrol has been shown tocountermanyoftheadverseeffectsofpoordiet.WeknowthatobeseratsfedresveratrolinDr.Sinclair’sstudyoutlivedtheratsnotfedresve-ratrol,butitislesswellknownthattheresveratrol-fedratsalsoavoidedallofthenormaldiseasesassociatedwithagingandobesity.

Chronic unresolved stress results in endocrine imbalances, immunesystem dysfunction, inflammation, sleep disorders and neurologi-cal impairment.Resveratrol isanaturalanti-inflammatoryagentandmay have important neuroprotective properties. In a study done atNorthumbriaUniversityintheUK,studentswhoweregiveneitheroneortwoBiofortecapsulescontaining250mgoftrans-resveratrolexperi-enceda100percenttoover200percentincreaseinbrainbloodflow.

Aprescriptionforlongevity

Anyone can substantially increase both health span and life spanbyadoptingthefollowingmeasures:

• Stopusingtobaccoproductsofalltypesandlimitalcoholusetonomorethanthreeglassesofwineorthreeouncesofspiritsperday.

• Reduce,orbetteryeteliminate,allprocessedfoods,fastfoods,andsweetened beverages.Make green leafy vegetables your primaryfoodgroup.Reduceoreliminateredmeatfromyourdiet.

• Takeapill.Addthebelowsupplementstoyourdailyroutine:

• Biotiviaorotherqualityresveratrol,250mgto1,000mg

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• Pterostilbene, a molecule closely related to resveratrol, 100mgdaily.

• Non-fishsourcedomega-3,suchasGreenOmega3,withEPAandDHA,atleast500mg.

• Amulti-antioxidant(notmultivitamin)complexsuchasBioQuench,500mgto1,000mg

• VitaminD,10,000 IU.Mostpeoplearedeficient in this importantnutrient.

• AcetylL-CarnitineandAlphaLipoicAcidsupplements,250mgofeach.

• Curcumin,alsoknownasthespiceturmeric,1to2gramsperday.

• VitaminC,preferablytheoilsolubleformcalledascorbylpalmitate,1gramperday.

Thereare,ofcourse,manyothersupplementsthatmayhaveabenefi-cial impactonhealthspanand longevity,but thepublishedscientificevidencebestsupportstheabovenutrients.Themajorityofover-the-countersupplementsareofverylittlechemoprotectivevalue.

Inadditiontotheabovesupplementregime,incorporatethefollowingintoyourdailyroutine:

• Incorporateatleast30minutesofmoderatetointenseexercise,atleast three timeseachweek, intoyour routine.Getup fromyourcomputer,videogames,iPad,email,andFacebookaccountsanddosomethingphysical,preferablyoutdoors.Evenifyouareoverweight

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youcanbefit.Infact,itishealthiertobefitandfatthenunfitandthin.

• Meditate,oratleasttakeaone-hourmentalandphysicalbreakfromyourdailygrind,onceeachday.Middaynapsof20to45minutesarealsoextremelybeneficial.

• Maintainahealthyweight,whichisbestmeasuredbydividingyourheightininchesbyyourwaistcircumference.Theresultshouldbenolessthan2.0.ThepopularBMImeasurementisbasicallyworth-less,asitmakesnodistinctionbetweenleanandfatbodymass.

• Usehighquality air andwaterpurifiers inyourhomeandoffice.Lobbyyourpoliticalleaderstotakeenvironmentalprotectionandcleanenergyseriously.AtsomepointthelimitonlifespanwillbethedeterminedbytheabilityoftheEarth’sclimateandresourcestosupporthumanlife.

• Seeyourphysicianat leastonceperyearandrepair failingpartsjustasyoudowithyourautomobileoranyothercomplexmachine.Ifyoureyesightisdeteriorating,considerhavingacorrectivepro-cedurebyaneyesurgeon,Ifyouhavedentalorperiodontalissues,see yourdentist and get them sortedbefore they lead to seriousdisease.Teethandguminfectionscancausefatalheartdiseaseandotherlifethreateningconditions.

• Donotignoresymptomsofanunderlyingproblem.Yourchancesofsurvivingcancer,asweallknow,aredramaticallyenhancedifyoubegintreatmentearly.Thesameruleappliestodiabetesandmostotherchronicdiseases.

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• Drive sensibly, wear seat belts and control your stress. It wouldbeapitytoliveahealthylifeandthendieattheageof40onthemotorway.

• UseanadvancedUVprotectionproduct tocontrolphotoagingoftheskin.ResveratrolhasbeenshowntobothpreventandreversetheDNAdamage,whichagestheskin.Onecreamthatcontainsres-veratrolinhighconcentrationalongwithotherpolyphenolsisCellebyBiotivia.

Whatthesciencesays

ThemostrecentresearchresultsbyscientistsandphysiciansworkingatprestigiousmedicalschoolsandotherinstitutionsaroundtheworldwerepresentedinSeptemberofthisyearattheResveratrol2010,thefirstinternationalscienceconferenceonresveratrolandhealth.Thereisnotenoughspaceinthispapertodiscussalloftheremarkableresultspresentedbytheexpertsatthisconference.Ihavechosentosumma-rizethehighpointsofsomeofthemoreinterestingandauthoritativestudiesbelow.Itshouldbenotedthatnostudywaspresentedinwhichanytoxicorseriousadverseeffectoforaladministrationofresveratroltoanimalsorhumanswasobserved,andnostudyortrialwasstoppedduetothepresenceofsuchnegativeeffects.

Resveratrolhumanclinicaltrials

Overthepastthreeyearsasubstantialnumberofmedicalschoolsandresearchinstitutionshaveundertakenstudiesofresveratrol’sabilitytoprevent or treatdisease inhumans.Thenumberof such clinical

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trialsisincreasingweekly.Afewofthemoreimportantonesarede-scribedbelow.

DiabetesAlbertEinsteinMedicalCollegeconductedtwohumanclinicaltrialsinwhichtheabilityofresveratroltoenhancemitochondrialfunctionandimproveinsulinsensitivity,twoimportantfunctionsthedrugcompa-niesareattemptingtotargetwithanewgenerationofdiabetesdrugs.

Theresultsof thisstudywereextremelypositiveand itwasrecentlyannouncedthatthissmall-scalestudyusingBioforteresveratrolwillbeexpandedlaterthisyearbyAlbertEinsteinMedicalCollegeincollabora-tionwiththeMayoClinic.Althoughthereareseveralotherhumanclini-cal trialseitherunderwayorabout tocommence, theEinstein/MayoClinicstudyistheonetolookoutfor.Theresultsofthisrelativelylarge-scaledouble-blindtrialwilllikelyanswerthequestionofresveratrol’spotentialusefulnessasanalternativetosomeofthepresentsideeffectladenpharmaceuticals.

Onesuchnewgenerationdiabetesdrugannouncedattheannualscienceconference of the AmericanDiabetes Association in Orlando FloridawarnedthattwoadverseeffectshadbeenseenintheFDAmandateddrugtrialsofthiscompound.ThefirstwasthatthedrugcanactuallycausesomeonewhodoesnotsufferfromType2Diabetestocontractthedisease,andthesecondwasthatithadthenastytendencytolowerbloodglucoselevelssoseverelythatthepatientcoulddie.Otherdia-betesdrugshavebeentakenoffthemarketafterlife-threateningsideeffectswerediscovered.

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HeartDiseaseStonyBrookUniversityMedicalCenter,arenownedcardiaccenter inNewYork,hasbegunalong-termhumanstudyofresveratrol’spoten-tialabilitytopreventpatientswhohavesufferedoneheartattackfromhavingasecondone,orincreasingthechancesthat,ifthepatientdoeshaveasubsequentinfarct,heorshewillsurviveit.

Theabilityofresveratrolandpterostilbeneandpolydatin,analogsofres-veratrol,topreventthecardiactissuedamagethatoccurswhenaheart,whichstoppedbeatingduetoaheartattackoropenheartsurgery,isperfusedwithoxygen.Interestinglyenough,thetissuedamage,,whichheartattackvictimssuffer,doesnothappenwhiletheheartisstopped,evenforconsiderablelengthsoftime.Thedamageoccursduetoafloodof destructive free radicals, which occurs when oxygen again flowsthrough the tissue. This finding suggests that paramedicsmight onedaybeequippedwithinjectableresveratroltoadministertopatientswhoseheartshavestoppedpriortoperfusingtheheartwithoxygen.

COPD,ChronicObstructivePulmonaryDiseaseCOPDisacommonbutseriousanddebilitatingconditioncausedbyin-flammationofthetissuesofthelungandtheresultinginabilitytodeliversufficientamountsofoxygentothebloodandtoremoveaccumulatedcarbondioxide.Sufferersofthisconditionconstantlyfeelthattheyaresuffocating.COPDaffectsmillionsofpeopleandisacommondiseaseof smokersandpeoplewhohaveworked formanyyears inahighlypolluted environment, such as a chemical factory or mine. ImperialCollegeofLondonhasobtainedaninternationalpatentontheuseofresveratroltotreatCOPD.Asofthispublicationnomedicinehasbeendevelopedbyanypharmaceuticalcompanyonthebasisofthispatent,howevertheUniversityofTorino,foundedin1404andthehomeoftwo

recentNobelPrizewinners,isabouttoembarkonastudyofsmokerstostudyresveratrol’sabilitytoalleviatethepulmonaryinflammationcausedbytheirhabit.

Metabolicsyndrome,prediabetesandnon-alcoholicfattyliverdisease

A study funded by theDanish government is about to begin in June2011.TheleadresearcherisDr.SteenBønløkkePedersenfromAarhusUniversity. The project will include a one year randomized double-blindedstudyof50subjects.AsidefromAarhusUniversityandFluxome,the Aarhus University Hospital, University of Southern Denmark,RoskildeUniversityandPennsylvaniaStateUniversitywillcontributetotheclinicaltrial.This$3.5millionhumanclinicaltrialwillinvestigateresveratrol’s potential to treat andprevent a constellation of humanhealthconditionswhichareknowntoaccompanyaging.Thiswillbethemostextensiveandbest-fundedlong-termhumanclinical trial todate.Theknowledgegleanedfromthisinvestigationwillbeinvaluableinassessingthepotentialofresveratroltoalleviatearangeofadversehealthconsequenceswhichafflictmillionsofpeopleworldwide.

“Weexpecttoprovethatresveratrolinhumanscanneutralizethedet-rimental effect of obesityonwholebodymetabolism, like low-gradechronic inflammation, insulin resistanceand lipid infiltration in liverandskeletalmuscle,”Dr.Pedersensaid.

ThalassemiaBetaThalassemiaisaninheriteddisorderinwhicheitherveryfewornoredbloodcellsareproducedbythebonemarrowafterinfancy.Thetreatmentismonthlywholebloodtransfusionsandtheuseofadrug

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whichisextremelytoxicandcannotbeusedwithchildren.Thediseasedramatically impacts thesufferers’qualityof lifeandoftenresults indeatharound theageofpuberty.Because it ismorecommon in lessdevelopedcountrieswhereitisvirtuallyimpossibleforanyoneotherthantheverywealthytoobtainregularsuppliesofcleanwholebloodfortherequiredtransfusions,thefatalityrateishigh.Evenifthepatientisabletoobtainmonthlytransfusionsandisabletoaffordthedrugstotreatthedisease,heorsheisconstantlyanemicandlackingofenergy.

Dr. Roberto Gambari, physician and molecular biologist, and well-known authority on Beta Thalassemia, at the University of Ferrara,discoveredthatTransmaxresveratrol,theconcentratedpureresvera-trolsupplementusedbyresearchers inmostclinical trials,wasabletostimulatetheproductionofembryonicredbloodcells,thetypethatareproducedwhenababyisstillinthemother’swomb,butsoonafterbirth cease being produced. This is an extremely important findingandone that has led to a human clinical trial nowunderway at theUniversityofFerrara.Thesubjectsinthisclinicaltrialarehospitalized,adolescentBetaThalassemiapatients.Hopefullyresveratrolwillgiveanewleaseonlifetothosewhosufferadiseasethatthepharmaceuticalcompaniesdonotconsiderpotentiallyprofitableenoughtodevelopanewdrugfor.

BrainbloodflowandcognitionIn2010NorthumbriaUniversity,locatedinnortheasternEngland,con-ductedahumanclinicaltrialinwhichuniversitystudentsweregiveneitheroneortwoBiofortecapsules,eachcontaining250mgof trans-resveratrol.Theobjectiveofthisstudywastoassesstheeffectsoforalresveratroloncognitiveperformanceandlocalizedcerebralbloodflowvariablesinhealthyhumanadults.

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Inthisrandomized,double-blind,placebo-controlled,crossoverstudy,22healthyadults receivedplaceboand2doses (250and500mg)oftrans-resveratrol in counterbalanced order on separate days. After a45-minuterestingabsorptionperiod,theparticipantsperformedase-lectionof cognitive tasks that activate the frontal cortex foranaddi-tional36minutes.Cerebralbloodflowandhemodynamics,asindexedbyconcentrationchanges inoxygenatedanddeoxygenatedhemoglo-bin,wereassessedinthefrontalcortexthroughouttheposttreatmentperiodwiththeuseofnear-infraredspectroscopy.Thepresenceofres-veratrolanditsconjugatesinplasmawasconfirmedbyHPLCafterthesamedosesinaseparatecohort(n=9).

Resveratroladministrationresultedindose-dependentincreasesince-rebralbloodflowduringtaskperformance,asindexedbytotalconcen-trationsofhemoglobin.Therewasalsoanincreaseindeoxyhemoglobinafterbothdosesofresveratrol,whichsuggestedenhancedoxygenex-tractionthatbecameapparenttowardtheendofthe45-minuteabsorp-tionphaseandwassustainedthroughouttaskperformance.Cognitivefunction was not affected. Resveratrol metabolites were present inplasmathroughoutthecognitivetaskperiod.Thesecondphaseofthistrial iscurrentlyunderway. In thishumanclinicalstudythestudentswillbegivendailydosesofBioforteresveratroloveraperiodofonemonthversusthesingledoseregimenofthefirsttrial.Additionalpa-rameters,suchasresveratrol’seffectonthestudents’weight,sleeppat-ternsandmoodwillbeexaminedinthistrial.

FitnessandphysicalperformanceTheUniversityofTexasisconductingahumantrialtoinvestigateresve-ratrol’seffectonhumanathleticperformanceandphysicalendurance.Thetrial,alsousingTransmax,ispresentlyunderwayandresultsareexpectedinabouttwomonths.DaveNoble,a64-year-oldAmericanwho

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participated incompetitiveswimmingeventsasa twentysomething,startedtocompeteagainaftera40-yearsabbaticalfromthesport.Davebeganusingaresveratrolsupplement,thesameoneusedinmostofthemedicalschooltrials,aftersixmonthsoftraining.WithintwomonthsofbeginningsupplementationwithresveratrolDavewasbreakingper-sonalrecordsthathesetwhenhewasinhisearlytwenties.Asof1May2011Davewaswithinthetopfiveamateurswimmersworldwideforhiseventandcategory.Davecreditsresveratrolforhisathleticimprove-ment.Hetakes500mgofresveratrolabout45minutespriortotrainingandcompeting,andcreditsthecompoundforhissuccess.Hehasbeencompetingnowforaboutthreeyearssincestartingagainattheageof61,andeachmonthhistimesimproveandhisendurance,asmeasuredbymaximumoxygenuptake,knownasVO2Max,isincreased.

Aguidetoselectingaqualityresveratrolsupplement

SincethestudybyDr.DavidSinclairwaspublishedinthejournalNature,aplethoraofnewcompanieshavesprungintoexistenceofferingresve-ratrol supplements.Evaluating resveratrol sellers and theirproductshasbecomeaconfusingandfrustratingprocess.Thisguideismeanttoelucidatethemostimportantfactorsoneshouldusetodistinguishoneresveratrolsupplementfromanotherbasedupontheirrelativequality,valueandlikelihoodofbeingeffective.

Unlikemostdietarysupplements,thousandsofwellmanagedauthori-tative scientific studies and trials have highlighted resveratrol’s po-tentiallycriticalhealthpropertiesasatreatmentfordiabetes,cancer,inflammatoryandautoimmunediseasesandneurologicalconditions.Withoutpassingjudgmentonresveratrol’sactualcurativepowers,itisclearthatmanypeoplepurchaseresveratrolasapreventativeortreat-

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mentforaseriousmedicalcondition.Iftheresveratroltheseconsumerspurchaseisnotahighquality,properlymanufactured,bioactivecom-poundthentheyarenotonlywastingtheirmoneybutarealsofailingtoobtainwhateverbenefitsresveratrolmayofferforthepreventionortreatmentofdisease.

The criteria belowarebaseduponvalid scientific principals and ac-ceptedstandardsfortheevaluationofafunctionaldietarysupplementsuchas resveratrol.Thestandardscanalsobeused in judgingothersupplements.

YoursupplierAftertheDr.SinclairstudywaspublishedinthejournalNature,afloodofnew,inexperiencedandillequippedonlineresveratrolsupplierssud-denlystartedtopromotethiscompound.Manyofthesecompaniesandindividualsengagedinunethicalanddeceptivemarketingcampaigns,whichluredcustomersinwithphoney“freeoffers”andotherinduce-ments. Their products often did not containmeasurable amounts ofresveratroland,inmanycases,theoperatorsandownersofthesecom-panieshadahistoryoffraud.Thelessonhereisthatoneiswelladvisedtoselectacompanywithahistoryofatleasttenyearsintheindustry,andonewhichspecializesinadvancednutraceuticals,versusagenericsupplementmaker.Resveratrolisadifficultcompoundtoprocessand,unlessspecialcareistakenthroughoutthemanufacturingprocess,caneasilydegradeintoaworthlesspowder.

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EthicallabelingThelabelsofmanyresveratrolsuppliersdonotdisclosetheexactformof resveratrol or the quantity contained in their supplement. Somesimplycalltheirmainingredient“redwinecomplex”ora“proprietaryblend.”Giventhatredwinecontainslessthan1percentresveratrol,itseemsabitstrangethatacompanywouldusethisdescriptiontolabelaresveratrolproductunlessthepurposewastoconcealtheactualingre-dientsintheproduct.Aproprietaryblendcanbealmostanything,butisunlikelytoconsistofpureresveratrolgiventherelativelyhighcostofqualityresveratrolversusotherpossibleingredients.

Resveratroliscomposedoftwoprincipalisomers:trans-resveratrolandcis-resveratrol.Onlythetrans-isomerhasbeenassociatedwithhealthbenefits.Thecisisomeractuallyactstonullifytheeffectsoftrans-res-veratrol.Unlessthesellerstatesonthelabelthattheproductconsistsentirelyofthetrans-resveratrolformitishighlylikelythatitcontainseithersomeorallofcis-resveratrol,whichis,byanorderofmagnitude,thelesscostlyformofresveratrol.

Dosage The appropriate dosage of trans-resveratrol is a highly contentiousissue,withrespecttotherhetoricofresveratrolsuppliers,thatis.Thescienceregardingdosageisrelativelyclearhowever.Althoughdosesofaround50mgto100mgappearfromsomestudiestohavepotentiallyimportantpreventativeeffects,theconsensusisthatatleast250mgisrequiredtoreachthethreshold forefficacyasdemonstrated inmostanimal and in vitro studies undertaken to date. This equates to thehumanequivalentofthedosageusedintheDr.Sinclairstudyandmanyotherstudies.Thedoserecommendedbymostcliniciansfortreatmentofanexistingconditionrangesfrom1,000mgto4,000mg.Howeverit

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isrecommendedthatoneconsultaphysicianbeforetakingadoseover1,000mgdaily.Notoxicityorseriousadverseeffectswereobservedinseveralanimalandhumanstudiesinwhichupto5,000mgwasgivenonadailybasisforanextendedperiodoftime.Inanimalstudies,dosagesuptothehumanequivalentof30,000mghavebeentoleratedwithonlyminoradverseeffects.Productswhichoffer less than250mgofpuretrans-resveratrolareofdubiousvalue.

SourceofresveratrolAlthoughmuchof thenewsaboutresveratrolmentionstheredwinegrapeasitssource,winegrapesarenotapracticalordesirablesourceofresveratrolfortwoimportantreasons.Firstgrapesaresubjectedtoawiderangeoftoxicchemicalsinthecultivationprocess.Fungicides,pesticides,chemicalfertilizersandmanymorechemicalsaresprayeddirectlyonwinegrapes.Sinceresveratrolcomes fromtheskins, it isverydifficulttoeliminatecontaminationintheresveratrolconcentrate.The second reasonwinegrapesarenotagoodsourceof resveratrolis that it is impossible to produce a high potency supplement usinggrapeextract.Theconcentrationofresveratrolingrapeskinsissimplytoolow.Thisiswhy,invirtuallyalloftheanimalandtissuestudiesonthehealthbenefitsofresveratrol,thesourceoftheresveratrolwastheJapaneseGiantKnotweedplant,whichgrowswithoutfertilizersorag-riculturalchemicalsinthewild.

NaturalversussyntheticSyntheticresveratrolcanbeproducedusingoneoftwomethods,fer-mentationandchemicalengineering.Inthecaseoffermentation,ayeastorbacteria isgeneticallymodifiedtoproduceresveratrol.Chemicallyengineeredresveratrolisconstructedfromabrothofcompoundsusing

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organicchemistrytoengineerthemolecule.Bothprocessesarefraughtwithpotentialpitfalls.

In the case of fermentation oftenwhatmay occur is that bits of thebacteriaoryeastDNAusedtoproducetheresveratrolshowupinthefinishedmaterial.Thismeansthatifyouusethisproduct,youarecon-suminganovelsubstance—acompoundthathasneverbeenpreviouslyconsumedbyahuman,withpotentiallytoxicorotherotherunknowneffects. In the case of a chemically engineered resveratrol product,theissueiscontaminationbysmallamountsofthechemicalsusedtoproducethesyntheticresveratrol.

On a typicalHPLC graphof a synthetic resveratrol therewill almostalwaysbespikesonthechartofwhatarereferredtoas“unknowns.”Thesetracechemicalsareby-productsofthecreationoftheresvera-trolwhich are unidentified and assumed, or hoped, to be non-toxic.Furthermore,naturallyextractedresveratrolfromthepolygonumcus-pidatumplantisknowntobeeffectiveandnon-toxic.Neitherproper-tieshavebeendefinitivelyverified inregard tosynthetic resveratrol.Whenanaturalcompoundsuchasresveratroliscopiedusingchemi-cals,yeastorbacteriaoftenthefinalproductisnottrulyidenticaltothenaturalcompound.Thereisonlyonereasonwhysomesuppliersusesynthetic resveratrol inplace of natural resveratrol frompolygonumcuspidatum.Thereasonisthefarlowercostofsyntheticresveratrol.Ifasupplierdoesnotdisclosewhichtypeofresveratroliscontainedinitsproductsyoucannormallyassumethatitisthesyntheticvariety.

CapsulesizeAsizezerocapsuleisabletocontainabout500mgofresveratrol,butonlyifthebasematerialisprocessedusingpharmaceuticaltechnologyandequipment.Thisisthelargestsizecapsulethatisquiteeasilyswal-

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lowedbymostpeople.Sellerswhouselargercapsulesdosotocom-pensate for the fact that they are simply stuffing lowerpotency rawmaterialintoacapsulewithoutgoingthroughthetimeandexpenseofpurifyingandgranulatingtheresveratrolextract.Alargercapsulesizealsoallowsfortheuseofvariousfillersandchemicalssuchassilicon,magnesiumsterate,celluloseandotheradditives.Thebestqualityres-veratrolsupplementsarecontainedinasizezero,all-vegetablecapsuleandcontainnoadditivesor fillersatall.There isnoreasonwhyyoushouldhavetoconsumesand,chemicals,andotherunwantedingredi-entsinyoursupplementsimplybecauseyoursuppliercannotbeboth-eredwithusingmoresophisticatedprocessingandfillingtechnology.

Resveratrolishighlysusceptibletodeteriorationbyoxidationandexposuretoultravioletlight

Aquality supplementwill beprotected fromoxidationduringman-ufacture through the use of nitrogen gas-filled processing lines. Thebottle inwhichthesupplement iscontainedshouldalsousean inertgastopreventoxidationduringshipment.Howeveroncethebottleisopenedoxygenisallowedtoenter.Ifactivepackagingtechnologyisnotemployedtoprotectagainstthisdamage,theshelflifeoftheproductwillbeseriouslydegraded.Manyresveratrolsupplementsarealreadyoxidizedwhenpurchased.Onlyonecompanyusesanactivepackagingoxygenabsorbersystemtocapturetheoxygenwhichentersthebottlewhenacapsuleisretrieved.

CapsulesandpackagingThe capsules themselves shouldbemade fromhighquality, all-veg-etablematerialssuchasPfizerVcaps.Cheapercleargelatincapsules,whicharemadefromanimalby-products,havenoplaceinaresveratrol

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supplement.Notonlyisanall-vegetablecapsulehealthiertoconsumethanagelatincapsule,butitisdesignedtobetterregulatethereleaseof theactive ingredients intoyourdigestive tract.What is theuseoftakingahighqualitynaturalsupplementifthecapsuleitiscontainedinismadefromthecollageninsideanimals’skinandbones?

Gimmickstowatchourfor

MicronizedornanoresveratrolThereisabsolutelynopublishedscientificevidencethatshowsmicron-izationimprovesthebioavailabilityofresveratrol.Infact,itmayhaveanegativeeffectbyreducingthehalf-lifeofresveratrolinbloodplasma.Thereisnoreasontopayextraforamicronizedresveratrolproduct,whichoffersnopracticaladvantagetotheuser,andmaynotbeaseffec-tiveasagoodqualitygranulatedresveratrol.

ResveratrolwithquercetinQuercetinisapotentantioxidantinitsownright,howeveritshouldnotbecombinedwithresveratroloreventakenwithinat leasteighthoursoftakingaresveratrolsupplement.Thereason,whichwasonlyrecentlydiscovered,isthatquercetinblocksthemetabolitesofresvera-trolfromenteringyourbloodstream.Quercetinalsodeactivatessirtu-ins,preciselytheoppositeeffectofresveratrol.

Untilafewyearsagoitwasassumedthataddingquercetinwasagoodthing since the importance of the metabolites was not understood.Before the latest studiesrevealedotherwise itwasassumedthat themetaboliteswerenotresponsibleforthebiologicalandlongevitygene

activation effects of resveratrol. Based upon several highly regardedstudies,wenowknowthatitisverylikelythatthebeneficialeffectsofresveratrolactuallyderivemainlyfromthesemetabolitesratherthanfromthefreeresveratrol.

Thesemetabolitesarebioactiveproductsofthebreakdownofresvera-trolbytheliverandlayerofcellsliningthesmallintestine.Byblockingthesesulphatesandglucordinates,quercetininterfereswiththeabilityof resveratrol toactivate thesirtuins, specificallySirt-1and2, thesocalledanti-aginggenes,andblocksothersignalingpathwaysthroughwhichresveratroloperates,andwhichareresponsibleformanyofthedesirablehealtheffectsofresveratrol.Moreover,thehalf-lifeoftheme-tabolitesinhumantissueisseveralhourswhereasthehalf-lifeoffreeresveratrolisonlyabout12minutes.

Ina2009studyofresveratrol’seffectsoninducingthecreationofhe-moglobin cells in patients’ blood it was found that quercetin totallyblocked the ability of resveratrol to create the new red blood cells.Quercetinalsonullifiedtheanti-inflammatorypropertyofresveratrolinaninformaltrialofresveratrol’spalliativeeffectonarthritis.Thereisnoscientificjustificationforaddingquercetintoaresveratrolsupple-ment.Ifonewishestotakequercetinitisreadilyavailableasalowcostsupplementthatmaybetakenbyitself.

RedwinecomplexSomesupplementmakersattempttoconfusethebuyerintothinkingthatheisbuyingaresveratrolproductbyusingthismisleadingdescrip-tion.Thereisnostandardfor“RedWineComplex.”Redwinecontainsonlyverysmallamountsofresveratrol, lessthan5percentasarule.Companieswhodonotdisclosetheamountoftrans-resveratrolintheirproductsshouldbeavoided.

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Dr. Oz or Oprah recommended resveratrol

NeitherDr.OznorOprahrecommendanybrandofresveratrol.Ifyouareinterestedinknowingwhichbrandtheyuseintheirpresentationsonresveratrolyoucan find thisbysearching forresveratrolon theirrespectivewebsites.Thelawyersforbothoftheserespectedpersonali-tieshavetakenaggressivelegalactionagainstthecompaniesandindi-vidualswhoclaimthattheyrecommendtheirproducts.

Fiveessentialcriteriontopickaresveratrolprovider

CredentialsThemediacoverageofthestudiesdemonstratingthepotentialbenefitsofresveratrolhasattractedafloodofnewandclearlydisreputableres-veratrolsellerstothemarket.Thesecompanieshavenoexperienceinproducingafoodorhealthsupplement,noscientificstaffs,testinglabs,orothertechnicalresources.Mosthavenoestablishedqualitycontrolstandardsandnohistorybywhichonecanjudgetheirreliabilityandintegrity.Manyofthesecompaniesuseaformofthewordresveratrolintheirnamesandsellonlyviaawebsite.ThelawyersforDr.MehmetOzandOprahWinfreyrecentlyfiledfederallawsuitsagainstover50ofthesecompaniesforillegallyusingtheirtrademarksandmakingfalseclaimsthattheirproductswereendorsedbythesewell-knownperson-alities.Acopyofthelitigationcanbedownloadedbyvisitingthefol-lowinglink:

http://www.scribd.com/doc/19144074/Harpo-Productions-versus-MonavieOprah-Dr-Oz-Suing-More-Than-50-Companies

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AmanufacturerratherthansimplyaresellerMany suppliers buy rawmaterial fromAsian sources at the lowestpossible price and simply fill capsules, rather then collect the plantandprocess it intheirownGMP-certifiedfacility.Legitimateresvera-trol supplementswill have passedConsumer Lab’s recently updatedevaluationofresveratrolbrands,anditswebsiteshouldprovideeasymethodstocontactthecompanyifyouhaveanyquestions,complaintsorarequestforarefund.

Tenyears,preferablymore,ofethicalbusinessoperationswithnounresolvedBetterBusiness

BureaucomplaintsItshouldofferarangeofproductsnotonlyoneortwovirtuallyidenti-calproducts.Ifthecompanyoffersamonthlyrecurringorderprogramaclearandconvenientmeansofcancelingyoursubscriptionshouldbeoffered.Beforeyougiveyourcreditcardinformationtoanonlinesellerbesurethatthecompanyislegitimate.ThiscanusuallybeestablishedbycontactingyourlocalBBBanddoingabitofonlineduediligence.

Thesupplementissoldretailshops,notonlythroughwebsites

Ifthecompany’sproductsarenotavailableinbrickandmortarstoressuch as GNC,Walgreens, The Vitamin Shop and other reputable re-sellersitshouldprobablybeavoided.AnyonecansellaproductovertheInternetbuttohaveone’sproductsacceptedbymajorHealthandSupplement stores requires liability insurance, thorough testing ofthe products’ quality and vetting of the company and its principals.Shopsthatcarrysupplementscarryoutthoroughduediligenceofboth

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theproduct itselfandthecompanysupplyingandmanufacturingtheproduct.Youhavenosuchassurancewithmostonlinesuppliers.

Thisisnottosaythatallonlinesupplierssellinferiorqualitysupple-ments.TherearesomeveryreputableandethicalInternetmerchantsandmanufactures.Unfortunatelyhowever,withanynewsupplementcomesaraftofbrandnewsupplierswithnohistoryorexperienceinmanufacturingadvancednutritionalproductswhobuyfromlostcost,lowqualitybrokersandwhoseproductsconsistentlyfailindependentevaluation.Thesecompaniesusuallyemployhighlyunethicalbusinesspracticesorcompeteentirelyonthebasisofprice.Moreoftenthannottheirproductsarevirtuallyworthless,theircustomerserviceisnonex-istentandtheirlifespanismeasuredinmonthsifnotweeks.

Thegoldstandardisacceptancebythemedicalandresearchcommunities

TheresveratrolbrandusedinhumantrialsatinstitutionssuchastheAlbertEinsteinMedicalSchool,OttawaHospital,Harvard,theUniversityofFerrara,UniversityofQueenslandinAustraliaandtheNIHisbyne-cessity thepurestandmost thoroughly testedsupplementsavailabletothegeneralpublic.Theseinstitutionsmustputanyproductusedinhumantrialsthrougharigorousandextensiveseriesoftestsforpurity,potencyandtoxicity.Theirendorsementisfarmorevaluablethananytestdonebythemanufacturersthemselvesorbytheso-calledindepen-dentlabs.

Onecompanywhoseproducts satisfyall of these criteria, andwhichhave been used in National Institutes of Health, Health Canada andother healthministry-funded studies isBiotivia,who introduced theoriginalresveratrolsupplementoversixyearsago.ThecompanyhasbeeninoperationintheUSandEuropeforover20years.

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Ontheoppositeendofthescalearethecompanieswhohavesprungintoexistencetotakeadvantageofthehundredsofnewsarticlesaboutresveratrol’s potential health benefits. In mid-2010 Oprah WinfreyhostedDr.MehmetOzonherprogram to talkaboutextreme lifeex-tension.Heextolledthevirtuesofresveratrolinhispresentationandshortlythereafterliterallydozensofnewsuppliersmaterializedoffer-ingfreebottlesofresveratrolandclaiminganendorsementbyDr.Oz.Notonlywere theydeceiving customerswith their sleazymarketingschemes,theirproductswerefound,inmanycases,nottocontainres-veratrolatall.ThelawyersforDr.OzandOprah’sproductioncompanyfiled suit against most of these companies, and the states’ attorneygeneralinseveralstateslaunchedcriminalinvestigations.Ifyouarein-terestedinwhichbrandwasactuallyusedbyDr.OzinhispresentationontheOprah’sshowyoucansearchforthetermresveratrolonDr.Oz’orOprah’swebsite.

FutureProspects

My prediction is that ‘resveratrol will become both a stand-alonepreventativeagentandaneffective treatment foravarietyofhumanhealthconditionswithin fiveyears.Perhapsmore importantly, itwillgainwidespreadacceptanceasaco-treatmenttobeusedtoenhancetheefficacyofexistingdrugsandnon-drugtreatmentsforawiderangeofconditions.Finally,resveratrolwill,withinthenextyear,becomeapopularsupplementandcomponentinfunctionalfoodsforitsabilitytoimprovetheoverallhealthandqualityoflifeofthosewhochoosetotakeadvantageofit.

Thepreponderanceofpeer-reviewedpublisheddatanowinthepublicdomainelucidatingthevariousbenefitsofresveratrolisverycompel-lingevidenceofresveratrol’simportancetomedicalscienceandtocon-

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sumersconcernedaboutimprovingandextendinghealthandlongev-ity.Duringthisyearandthenext,alargenumberofhumanclinicaltrialresultswillbepublishedbysomeoftheworld’smostrespectedscien-tificinstitutions.Ibelievethatvirtuallyallofthesestudieswillconfirmtheresultsandconclusionssetforthinearlierinvitroandsmall-scalehumanclinicaltrials.Ifthisturnsouttobetrueitwillbeirresponsibleofthemedicalcommunitytofailtoincorporateresveratrolintotheirrecommendedtreatmentmodalities.

Medicalethicistssetaveryhighstandardforadoptionofanewdrug,treatmentortechnology.Thisstandardiscalledtheprecautionaryprin-cipal.Onedefinitionofthisprincipleissetforthinapapertitled“ThePrecautionaryPrinciple”authoredbyUNESCO’sWorldCommissionontheEthicsofScientificKnowledgeandTechnology.

“Whenhumanactivitiesmayleadtomorallyunacceptableharmthatisscientificallyplausiblebutuncertain,actionsshallbetakentoavoidordiminishthatharm.”

So how does resveratrol stack up against this rigid standard? Givenwhatwenowknowaboutresveratrol’sabilitytobeneficiallymodulatesomanybiologicalprocesses,anditsabsenceofanysignificanttoxicityoradverseeffectsinthethousandsofstudiesdonetodate,itisfairandreasonabletocontendthatresveratrolhasmetthefirstcriterionofthisstandard.However this isonly the firstof twoprerequisiteswhichanewdrugortreatmentmustsatisfytojustifyitsadoption.

Itisequallyimperativethatthetreatment,drugortechnologyoffersalegitimatebenefittoitsusersorconsumersthatoutweighstheforesee-ablerisks.Somelevelofriskisacceptableandinevitable.Everyactionwechoosetotakeortoavoidentailsrisk.Theprecautionaryprinciplesimplystatesthatrisksmustbereasonablewhenconsideredin lightofthebenefits.Resveratrol’sbenefits,ifonlyjudgedintermsofitsan-

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tioxidantpropertiesandthefewhumanclinicaltrialstodate,satisfiesthissecondcriterionaswell. If Iamcorrect,andtheongoinghumanclinicaltrialsconfirmresveratrol’ssafetyandefficacy,notonlywill ithavejustifieditsadoptionbythemedicalcommunity, itwillhavees-tablisheditselfasacompoundwhosesafetyandimportancetohumanhealthexceeds thatofmanyof thepharmaceuticalscommonlybeingusedtodaytotreatdisease.

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Scientificstudiesconfirmingstatementsandclaimsmadeinthispublication.

Anti-inflammatoryeffectsofresveratrol1. HuangZ,WangC,WeiL,WangJ,FanY,WangL,WangY,ChenT.,Resveratrol

inhibitsEMMPRINexpressionviaP38andERK1/2pathwaysinPMA-inducedTHP-1cells.,BiochemBiophysResCommun.2008Sep26;374(3):517-21.

2. LuKT,KoMC,ChenBY,HuangJC,HsiehCW,LeeMC,ChiouRY,WungBS,PengCH,YangYL.,NeuroprotectiveEffectsofResveratrolonMPTP-InducedNeuronLossMediatedbyFreeRadicalScavenging.,JAgricFoodChem.2008Jul11.

3. DoGM,KwonEY,KimHJ,JeonSM,HaTY,ParkT,ChoiMS.,Long-termeffectsofresveratrolsupplementationonsuppressionofatherogeniclesionforma-tionandcholesterolsynthesisinapoE-deficientmice.,BiochemBiophysResCommun.2008Sep12;374(1):55-9.

4. HouX,XuS,Maitland-ToolanKA,SatoK,JiangB,IdoY,LanF,WalshK,WierzbickiM,VerbeurenTJ,CohenRA,ZangM.,SIRT1regulateshepatocytelipidmetabolismthroughactivatingAMP-activatedproteinkinase.,JBiolChem.2008Jul18;283(29):20015-26.

5. ReiterE,AzziA,ZinggJM.,Enhancedanti-proliferativeeffectsofcombinato-rialtreatmentofdelta-tocopherolandresveratrolinhumanHMC-1cells.,Biofactors.2007;30(2):67-77.

6. DasS,DasDK.,Resveratrol:atherapeuticpromiseforcardiovasculardiseases.RecentPatentsCardiovascDrugDiscov.2007Jun;2(2):133-8.

7. MagroneT,TafaroA,JirilloF,PanaroMA,CuzzuolP,CuzzuolAC,PuglieseV,AmatiL,JirilloE,CovelliV.,Redwineconsumptionandpreventionofathero-sclerosis:aninvitromodelusinghumanperipheralbloodmononuclearcells.,CurrPharmDes.2007;13(36):3718-25.

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8. VivancosM,MorenoJJ.,Effectofresveratrol,tyrosolandbeta-sitosterolonoxidisedlow-densitylipoprotein-stimulatedoxidativestress,arachidonicacidreleaseandprostaglandinE2synthesisbyRAW264.7macrophages.,BrJNutr.2008Jun;99(6):1199-207.

9. AhnJ,LeeH,KimS,HaT.,ResveratrolinhibitsTNF-alpha-inducedchangesofadipokinesin3T3-L1adipocytes.,BiochemBiophysResCommun.2007Dec28;364(4):972-7.

10. TsouprasAB,FragopoulouE,NomikosT,IatrouC,AntonopoulouS,DemopoulosCA.,Characterizationofthedenovobiosyntheticenzymeofplateletactivatingfactor,DDT-insensitivecholinephosphotransferase,ofhumanmesangialcells.,MediatorsInflamm.2007;2007:27683.

11. EkshyyanVP,HebertVY,KhandelwalA,DugasTR.,Resveratrolinhibitsrataorticvascularsmoothmusclecellproliferationviaestrogenreceptordepen-dentnitricoxideproduction.,JCardiovascPharmacol.2007Jul;50(1):83-93.

12. BertelliAA.,Wine,researchandcardiovasculardisease:instructionsforuse.Atherosclerosis.2007Dec;195(2):242-7.

13. CullenJP,MorrowD,JinY,vonOffenbergSweeneyN,SitzmannJV,CahillPA,RedmondEM.,Resveratrolinhibitsexpressionandbindingactivityofthemonocytechemotacticprotein-1receptor,CCR2,onTHP-1monocytes.,Atherosclerosis.2007Nov;195(1):e125-33.

14. SchmittCA,HandlerN,HeissEH,ErkerT,DirschVM.,Noevidenceformodula-tionofendothelialnitricoxidesynthasebytheoliveoilpolyphenolhydroxyty-rosolinhumanendothelialcells.,Atherosclerosis.2007Nov;195(1):e58-64.

15. CruzMN,AgewallS,Schenck-GustafssonK,KublickieneK.,Acutedilata-tiontophytoestrogensandestrogenreceptorsubtypesexpressioninsmallarteriesfromwomenwithcoronaryheartdisease.,Atherosclerosis.2008Jan;196(1):49-58.

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16. FragopoulouE,NomikosT,KarantonisHC,ApostolakisC,PliakisE,SamiotakiM,PanayotouG,AntonopoulouS.,Biologicalactivityofacetylatedphenoliccompounds.,JAgricFoodChem.2007Jan10;55(1):80-9.

17. ChowSE,HshuYC,WangJS,ChenJK.,ResveratrolattenuatesoxLDL-stimu-latedNADPHoxidaseactivityandprotectsendothelialcellsfromoxidativefunctionaldamages.,JApplPhysiol.2007Apr;102(4):1520-7.

18. BritoPM,MarianoA,AlmeidaLM,DinisTC.,Resveratrolaffordsprotectionagainstperoxynitrite-mediatedendothelialcelldeath:Aroleforintracellularglutathione.ChemBiolInteract.2006Dec15;164(3):157-66.

19. JunHJ,ChungMJ,KimSY,LeeHJ,LeeSJ.,Non-radioactiveandcolorimetricquantificationofmonocyteadhesiontoendothelialcellsinearlyatherogen-esis.BiotechnolLett.2006Nov;28(22):1805-10.

20. SevovM,ElfinehL,CavelierLB.,ResveratrolregulatestheexpressionofLXR-alphainhumanmacrophages.,BiochemBiophysResCommun.2006Sep29;348(3):1047-54.

21. ZangM,XuS,Maitland-ToolanKA,ZuccolloA,HouX,JiangB,WierzbickiM,VerbeurenTJ,CohenRA.,PolyphenolsstimulateAMP-activatedproteinkinase,lowerlipids,andinhibitacceleratedatherosclerosisindiabeticLDLreceptor-deficientmice.Diabetes.2006Aug;55(8):2180-91.

22. LeeKW,LeeHJ.,Therolesofpolyphenolsincancerchemoprevention.,Biofactors.2006;26(2):105-21.

23. NorataGD,MarchesiP,PassamontiS,PirilloA,VioliF,CatapanoAL.,Anti-inflammatoryandanti-atherogeniceffectsofcathechin,caffeicacidandtrans-resveratrolinapolipoproteinEdeficientmice.,Atherosclerosis.2007Apr;191(2):265-71.

24. LuKT,ChiouRY,ChenLG,ChenMH,TsengWT,HsiehHT,YangYL.,Neuroprotectiveeffectsofresveratroloncerebralischemia-inducedneuronlossmediatedbyfreeradicalscavengingandcerebralbloodflowelevation.,JAgricFoodChem.2006Apr19;54(8):3126-31.

25. DasDK,MaulikN.,Resveratrolincardioprotection:atherapeuticpromiseofalternativemedicine.,MolInterv.2006Feb;6(1):36-47.

26. KaurG,RobertiM,RaulF,PendurthiUR.,Suppressionofhumanmonocytetissuefactorinductionbyredwinephenolicsandsyntheticderivativesofresveratrol.,ThrombRes.2007;119(2):247-56.

27. WungBS,HsuMC,WuCC,HsiehCW.,ResveratrolsuppressesIL-6-inducedICAM-1geneexpressioninendothelialcells:effectsontheinhibitionofSTAT3phosphorylation.,LifeSci.2005Dec12;78(4):389-97.

28. WangZ,ZouJ,CaoK,HsiehTC,HuangY,WuJM.,Dealcoholizedredwinecon-tainingknownamountsofresveratrolsuppressesatherosclerosisinhyper-cholesterolemicrabbitswithoutaffectingplasmalipidlevels.,IntJMolMed.2005Oct;16(4):533-40.

29. SbarraV,RistorcelliE,Petit-ThéveninJL,TeissedrePL,LombardoD,VérineA.,Invitropolyphenoleffectsonactivity,expressionandsecretionofpancreaticbilesalt-dependentlipase.,BiochimBiophysActa.2005Sep5;1736(1):67-76.

30. VitracX,BornetA,VanderlindeR,VallsJ,RichardT,DelaunayJC,MérillonJM,TeissédrePL.,Determinationofstilbenes(delta-viniferin,trans-astringin,trans-piceid,cis-andtrans-resveratrol,epsilon-viniferin)inBrazilianwines.,JAgricFoodChem.2005Jul13;53(14):5664-9.

31. MorrisBJ.,Aforkheadintheroadtolongevity:themolecularbasisoflifespanbecomesclearer.,JHypertens.2005Jul;23(7):1285-309.

32. Deby-DupontG,Mouithys-MickaladA,SerteynD,LamyM,DebyC.,ResveratrolandcurcuminreducetherespiratoryburstofChlamydia-primedTHP-1cells.,BiochemBiophysResCommun.2005Jul22;333(1):21-7.

33. DelmasD,JanninB,LatruffeN.,Resveratrol:preventingpropertiesagainstvascularalterationsandageing.,MolNutrFoodRes.2005May;49(5):377-95.

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34. AronisA,MadarZ,TiroshO.,Mechanismunderlyingoxidativestress-medi-atedlipotoxicity:exposureofJ774.2macrophagestotriacylglycerolsfacilitatesmitochondrialreactiveoxygenspeciesproductionandcellularnecrosis.,FreeRadicBiolMed.2005May1;38(9):1221-30.

35. DulakJ.,Nutraceuticalsasanti-angiogenicagents:hopesandreality.,JPhysiolPharmacol.2005Mar;56Suppl1:51-67.

36. LocatelliGA,SavioM,FortiL,ShevelevI,RamadanK,StivalaLA,VanniniV,HübscherU,SpadariS,MagaG.,InhibitionofmammalianDNApolymerasesbyresveratrol:mechanismandstructuraldeterminants.,BiochemJ.2005Jul15;389(Pt2):259-68.

37. AugerC,TeissedrePL,GérainP,LequeuxN,BornetA,SerisierS,BesançonP,CaporiccioB,CristolJP,RouanetJM.,Dietarywinephenolicscatechin,quercetin,andresveratrolefficientlyprotecthypercholesterolemicham-stersagainstaorticfattystreakaccumulation.,JAgricFoodChem.2005Mar23;53(6):2015-21.

38.OakMH,ElBedouiJ,Schini-KerthVB.,Antiangiogenicpropertiesofnaturalpoly-phenolsfromredwineandgreentea.,JNutrBiochem.2005Jan;16(1):1-8.

39. CaimiG,CarolloC,LoPrestiR.,Chronicrenalfailure:oxidativestress,endo-thelialdysfunctionandwine.,ClinNephrol.2004Nov;62(5):331-5.

40. FukaoH,IjiriY,MiuraM,HashimotoM,YamashitaT,FukunagaC,OiwaK,KawaiY,SuwaM,YamamotoJ.,Effectoftrans-resveratrolonthethrombo-genicityandatherogenicityinapolipoproteinE-deficientandlow-densitylipoproteinreceptor-deficientmice.,BloodCoagulFibrinolysis.2004Sep;15(6):441-6.

41. KollárP,HotolováH.,[Biologicaleffectsofresveratrolandotherconstituentsofwine]CeskaSlovFarm.2003Nov;52(6):272-81.[Czech.]

42. SchrieverC,PendlandSL,MahadyGB.,Redwine,resveratrol,Chlamydiapneu-moniaeandtheFrenchconnection.,Atherosclerosis.2003Dec;171(2):379-80.

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43. BhavnaniBR.,Estrogensandmenopause:pharmacologyofconjugatedequineestrogensandtheirpotentialroleinthepreventionofneurode-generativediseasessuchasAlzheimer’s.,JSteroidBiochemMolBiol.2003Jun;85(2-5):473-82.

44. DeLorgerilM,SalenP,GuiraudA,BoucherF,deLeirisJ.,Resveratrolandnon-ethanoliccomponentsofwineinexperimentalcardiology.,NutrMetabCardiovascDis.2003Apr;13(2):100-3.

45. DiSantoA,MezzettiA,NapoleoneE,DiTommasoR,DonatiMB,DeGaetanoG,LorenzetR.,Resveratrolandquercetindown-regulatetissuefactorex-pressionbyhumanstimulatedvascularcells.,JThrombHaemost.2003May;1(5):1089-95.

46. ZernTL,WestKL,FernandezML.,Grapepolyphenolsdecreaseplasmatriglyc-eridesandcholesterolaccumulationintheaortaofovariectomizedguineapigs.,JNutr.2003Jul;133(7):2268-72.

47. SovakM.,GrapeExtract,Resveratrol,andItsAnalogs:AReview.,JMedFood.2001Summer;4(2):93-105.

48. GoldbergDM,YanJ,SoleasGJ.,Absorptionofthreewine-relatedpolyphe-nolsinthreedifferentmatricesbyhealthysubjects.,ClinBiochem.2003Feb;36(1):79-87.

49. SlaterSJ,SeizJL,CookAC,StaglianoBA,BuzasCJ.,InhibitionofproteinkinaseCbyresveratrol.,BiochimBiophysActa.2003Jan20;1637(1):59-69.

50. BritoP,AlmeidaLM,DinisTC.,Theinteractionofresveratrolwithferrylmyo-globinandperoxynitrite;protectionagainstLDLoxidation.,FreeRadicRes.2002Jun;36(6):621-31.

51. IgnatowiczE,Baer-DubowskaW.,Resveratrol,anaturalchemopro-tectiveagentagainstdegenerativediseases.,PolJPharmacol.2001Nov-Dec;53(6):557-69.

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52. SoleasGJ,GrassL,JosephyPD,GoldbergDM,DiamandisEP.,Acomparisonoftheanticarcinogenicpropertiesoffourredwinepolyphenols.,ClinBiochem.2002Mar;35(2):119-24.

53. WangZ,ZouJ,HuangY,CaoK,XuY,WuJM.,Effectofresveratrolonplateletaggregationinvivoandinvitro.,ChinMedJ(Engl).2002Mar;115(3):378-80.

54. LandraultN,LarrondeF,DelaunayJC,CastagninoC,VercauterenJ,MerillonJM,GascF,CrosG,TeissedrePL.,LevelsofstilbeneoligomersandastilbininFrenchvarietalwinesandingrapesduringnoblerotdevelopment.,JAgricFoodChem.2002Mar27;50(7):2046-52.

55. RatnaWN,SimonelliJA.,Theactionofdietaryphytochemicalsquercetin,cat-echin,resveratrolandnaringeninonestrogen-mediatedgeneexpression.,LifeSci.2002Feb15;70(13):1577-89.

56. PendurthiUR,MengF,MackmanN,RaoLV.,Mechanismofresveratrol-medi-atedsuppressionoftissuefactorgeneexpression.,ThrombHaemost.2002Jan;87(1):155-62.

57. RuefJ,MoserM,KüblerW,BodeC.,Inductionofendothelin-1expressionbyoxidativestressinvascularsmoothmusclecells.,CardiovascPathol.2001Nov-Dec;10(6):311-5.

58. WangZ,HuangY,ZouJ,CaoK,XuY,WuJM.,Effectsofredwineandwinepoly-phenolresveratrolonplateletaggregationinvivoandinvitro.,IntJMolMed.2002Jan;9(1):77-9.

59. BhavnaniBR,CecuttiA,GerulathA,WooleverAC,BercoM.,Comparisonoftheantioxidanteffectsofequineestrogens,redwinecomponents,vitaminE,andprobucolonlow-densitylipoproteinoxidationinpostmenopausalwomen.,Menopause.2001Nov-Dec;8(6):408-19.

60. WuJM,WangZR,HsiehTC,BruderJL,ZouJG,HuangYZ.,Mechanismofcardio-protectionbyresveratrol,aphenolicantioxidantpresentinredwine.,IntJMolMed.2001Jul;8(1):3-17.

��

61. RussoP,TedescoI,RussoM,RussoGL,VeneziaA,CicalaC.,Effectsofde-al-coholatedredwineanditsphenolicfractionsonplateletaggregation.,NutrMetabCardiovascDis.2001Feb;11(1):25-9.

62. BruderJL,HsiehT,LereaKM,OlsonSC,WuJM.,Inducedcytoskeletalchangesinbovinepulmonaryarteryendothelialcellsbyresveratrolandtheaccompa-nyingmodifiedresponsestoarterialshearstress.,BMCCellBiol.2001;2:1.

63. HerediaA,DavisC,RedfieldR.,SynergisticinhibitionofHIV-1inactivatedandrestingperipheralbloodmononuclearcells,monocyte-derivedmacrophages,andselecteddrug-resistantisolateswithnucleosideanaloguescombinedwithanaturalproduct,resveratrol.,JAcquirImmuneDeficSyndr.2000Nov1;25(3):246-55.

64. ChanMM,MattiacciJA,HwangHS,ShahA,FongD.,Synergybetweenethanolandgrapepolyphenols,quercetin,andresveratrol,intheinhibitionoftheinduciblenitricoxidesynthasepathway.,BiochemPharmacol.2000Nov15;60(10):1539-48.

65. MizutaniK,IkedaK,YamoriY.,ResveratrolinhibitsAGEs-inducedproliferationandcollagensynthesisactivityinvascularsmoothmusclecellsfromstroke-pronespontaneouslyhypertensiverats.,BiochemBiophysResCommun.2000Jul21;274(1):61-7.

66. FragopoulouE,NomikosT,AntonopoulouS,MitsopoulouCA,DemopoulosCA.,Separationofbiologicallyactivelipidsfromredwine.,JAgricFoodChem.2000Apr;48(4):1234-8.

67. HsiehTC,JuanG,DarzynkiewiczZ,WuJM.,Resveratrolincreasesnitricoxidesynthase,inducesaccumulationofp53andp21(WAF1/CIP1),andsuppressesculturedbovinepulmonaryarteryendothelialcellproliferationbyperturbingprogressionthroughSandG2.,CancerRes.1999Jun1;59(11):2596-601.

68. BelguendouzL,FrémontL,GozzelinoMT.,Interactionoftransresveratrolwithplasmalipoproteins.,BiochemPharmacol.1998Mar15;55(6):811-6.

��

69. SoleasGJ,DiamandisEP,GoldbergDM.,Resveratrol:amoleculewhosetimehascome?Andgone?,ClinBiochem.1997Mar;30(2):91-113.

70. Pace-AsciakCR,RounovaO,HahnSE,DiamandisEP,GoldbergDM.,Winesandgrapejuicesasmodulatorsofplateletaggregationinhealthyhumansubjects.,ClinChimActa.1996Mar15;246(1-2):163-82.

71. WilsonT,KnightTJ,BeitzDC,LewisDS,EngenRL.,Resveratrolpromotesath-erosclerosisinhypercholesterolemicrabbits.,LifeSci.1996;59(1):PL15-21.

72. Pace-AsciakCR,HahnS,DiamandisEP,SoleasG,GoldbergDM.,Theredwinephenolicstrans-resveratrolandquercetinblockhumanplateletaggregationandeicosanoidsynthesis:implicationsforprotectionagainstcoronaryheartdisease.,ClinChimActa.1995Mar31;235(2):207-19.

BreastCancerandResveratrol1. SchlachtermanA,ValleF,WallKM,AziosNG,CastilloL,MorellL,Washington

AV,CubanoLA,DharmawardhaneSF.,Combinedresveratrol,quercetin,andcatechintreatmentreducesbreasttumorgrowthinanudemousemodel.,TranslOncol.2008Mar;1(1):19-27.

2. NguyenTH,MustafaFB,PervaizS,NgFS,LimLH.,ERK1/2activationisre-quiredforresveratrol-inducedapoptosisinMDA-MB-231cells.,IntJOncol.2008Jul;33(1):81-92.

3. WangY,YeL,LeungLK.,Apositivefeedbackpathwayofestrogenbiosynthe-sisinbreastcancercellsiscontainedbyresveratrol.,Toxicology.2008Jun27;248(2-3):130-5.

4. SnyderRM,YuW,JiaL,SandersBG,KlineK.,VitaminEanalogalpha-TEA,methylseleninicacid,andtrans-resveratrolincombinationsyner-gisticallyinhibithumanbreastcancercellgrowth.,NutrCancer.2008May-Jun;60(3):401-11.

��

5. MuriasM,LuczakMW,NiepsujA,Krajka-KuzniakV,Zielinska-PrzyjemskaM,JagodzinskiPP,JägerW,SzekeresT,Jodynis-LiebertJ.,Cytotoxicactivityof3,3’,4,4’,5,5’-hexahydroxystilbeneagainstbreastcancercellsismediatedbyinductionofp53anddownregulationofmitochondrialsuperoxidedismutase.,ToxicolInVitro.2008Aug;22(5):1361-70.

6. SinghSK,MorettaD,AlmaguelF,DeLeónM,DeLeónDD.,PrecursorIGF-II(proIGF-II)andmatureIGF-II(mIGF-II)induceBcl-2AndBcl-XLexpressionthroughdifferentsignalingpathwaysinbreastcancercells.,GrowthFactors.2008Apr;26(2):92-103.

7. ZahidM,GaikwadNW,AliMF,LuF,SaeedM,YangL,RoganEG,CavalieriEL.,Preventionofestrogen-DNAadductformationinMCF-10Fcellsbyresvera-trol.,FreeRadicBiolMed.2008Jul15;45(2):136-45.

8. ScarlattiF,MaffeiR,BeauI,CodognoP,GhidoniR.,Roleofnon-canonicalBeclin1-independentautophagyincelldeathinducedbyresveratrolinhumanbreastcancercells.,CellDeathDiffer.2008Aug;15(8):1318-1329.

9. WuF,KhanS,WuQ,BarhoumiR,BurghardtR,SafeS.,Ligandstructure-de-pendentactivationofestrogenreceptoralpha/Spbyestrogensandxenoestro-gens.,JSteroidBiochemMolBiol.2008May;110(1-2):104-15.

10. TangFY,SuYC,ChenNC,HsiehHS,ChenKS.,Resveratrolinhibitsmigra-tionandinvasionofhumanbreast-cancercells.,MolNutrFoodRes.2008Jun;52(6):683-91.

11. SinghSK,MorettaD,AlmaguelF,WallNR,DeLeónM,DeLeónD.,DifferentialeffectofproIGF-IIandIGF-IIonresveratrolinducedcelldeathbyregulat-ingsurvivincellularlocalizationandmitochondrialdepolarizationinbreastcancercells.,GrowthFactors.2007Dec;25(6):363-72.

12. DipR,LenzS,AntignacJP,LeBizecB,GmuenderH,NaegeliH.,Globalgeneexpressionprofilesinducedbyphytoestrogensinhumanbreastcancercells.,EndocrRelatCancer.2008Mar;15(1):161-73.

��

13. BaderY,MadlenerS,StrasserS,MaierS,SaikoP,StarkN,PopescuR,HuberD,GollingerM,ErkerT,HandlerN,SzakmaryA,JägerW,KoppB,TentesI,Fritzer-SzekeresM,KrupitzaG,SzekeresT.,StilbeneanaloguesaffectcellcycleprogressionandapoptosisindependentlyofeachotherinanMCF-7arrayofcloneswithdistinctgeneticandchemoresistantbackgrounds.,OncolRep.2008Mar;19(3):801-10.

14. MaZ,MolaviO,HaddadiA,LaiR,GossageRA,LavasanifarA.,Resveratrolanalogtrans3,4,5,4’-tetramethoxystilbene(DMU-212)mediatesanti-tumoreffectsviamechanismdifferentfromthatofresveratrol.,CancerChemotherPharmacol.2008Feb20.

15. HuangTC,ChangHY,HsuCH,KuoWH,ChangKJ,JuanHF.,TargetingtherapyforbreastcarcinomabyATPsynthaseinhibitoraurovertinB.,JProteomeRes.2008Apr;7(4):1433-44.

16. AlkhalafM,El-MowafyA,RennoW,RachidO,AliA,Al-AttyiahR.,Resveratrol-inducedapoptosisinhumanbreastcancercellsismediatedprimarilythroughthecaspase-3-dependentpathway.,ArchMedRes.2008Feb;39(2):162-8.

17. KhanN,AfaqF,MukhtarH.,Cancerchemopreventionthroughdietaryantioxi-dants:progressandpromise.,AntioxidRedoxSignal.2008Mar;10(3):475-510.

18. MuriasM,MiksitsM,AustS,SpatzeneggerM,ThalhammerT,SzekeresT,JaegerW.,Metabolismofresveratrolinbreastcancercelllines:impactofsul-fotransferase1A1expressiononcellgrowthinhibition.,CancerLett.2008Mar18;261(2):172-82.

19. ZahidM,GaikwadNW,RoganEG,CavalieriEL.,Inhibitionofdepurinatinges-trogen-DNAadductformationbynaturalcompounds.,ChemResToxicol.2007Dec;20(12):1947-53.

20. DegnerSC,KempMQ,HockingsJK,RomagnoloDF.,Cyclooxygenase-2pro-moteractivationbythearomatichydrocarbonreceptorinbreastcancermcf-7cells:repressiveeffectsofconjugatedlinoleicacid.,NutrCancer.2007;59(2):248-57.

��

21. PearceVP,SherrellJ,LouZ,KopelovichL,WrightWE,ShayJW.,Immortalizationofepithelialprogenitorcellsmediatedbyresveratrol.,Oncogene.2008Apr10;27(17):2365-74.

22. Wesierska-GadekJ,KramerMP,MaurerM.,Resveratrolmodulatesroscovitine-mediatedcellcyclearrestofhumanMCF-7breastcancercells.,FoodChemToxicol.2008Apr;46(4):1327-33.,

23. NevesMA,DinisTC,ColomboG,SáeMeloML.,Combiningcomputationalandbiochemicalstudiesforarationaleontheanti-aromataseactivityofnaturalpolyphenols.,ChemMedChem.2007Dec;2(12):1750-62.

24. SareenD,DarjatmokoSR,AlbertDM,PolansAS.,Mitochondria,calcium,andcalpainarekeymediatorsofresveratrol-inducedapoptosisinbreastcancer.,MolPharmacol.2007Dec;72(6):1466-75.

25. KoohiMK,WaltherN,IvellR.,Anovelmolecularassaytodiscriminatetran-scriptionaleffectscausedbyxenoestrogens.,MolCellEndocrinol.2007Sep30;276(1-2):45-54.

26. VetvickaV,VolnyT,Saraswat-OhriS,VashishtaA,VancikovaZ,VetvickovaJ.,Glucanandresveratrolcomplex--possiblesynergisticeffectsonimmunesystem.,BiomedPapMedFacUnivPalackyOlomoucCzech.2007Jun;151(1):41-6.

27. TangFY,ChiangEP,SunYC.,Resveratrolinhibitsheregulin-beta1-mediatedmatrixmetalloproteinase-9expressionandcellinvasioninhumanbreastcancercells.JNutrBiochem.2008May;19(5):287-94.

28. AlkhalafM.,Resveratrol-inducedgrowthinhibitioninMDA-MB-231breastcancercellsisassociatedwithmitogen-activatedproteinkinasesignalingandproteintranslation.EurJCancerPrev.2007Aug;16(4):334-41.

29. AlkhalafM.,Resveratrol-inducedapoptosisisassociatedwithactivationofp53andinhibitionofproteintranslationinT47Dhumanbreastcancercells.,Pharmacology.2007;80(2-3):134-43.

��

30. MarcsekZL,KocsisZ,SzendeB,TompaA.,Effectofformaldehydeandres-veratrolontheviabilityofVero,HepG2andMCF-7cells.,CellBiolInt.2007Oct;31(10):1214-9.

31. SuJL,YangCY,ZhaoM,KuoML,YenML.,Forkheadproteinsarecriticalforbonemorphogeneticprotein-2regulationandanti-tumoractivityofresvera-trol.,JBiolChem.2007Jul6;282(27):19385-98.

32. BenitezDA,Pozo-GuisadoE,ClementiM,CastellónE,Fernandez-SalgueroPM.,Non-genomicactionofresveratrolonandrogenandoestrogenreceptorsinprostatecancer:modulationofthephosphoinositide3-kinasepathway.,BrJCancer.2007May21;96(10):1595-604.

33. LeCorreL,ChalabiN,DelortL,BignonYJ,Bernard-GallonDJ.,Differentialexpressionofgenesinducedbyresveratrolinhumanbreastcancercelllines.,NutrCancer.2006;56(2):193-203.

34. LaVecchiaC,BosettiC.,DietandcancerriskinMediterraneancountries:openissues.,PublicHealthNutr.2006Dec;9(8A):1077-82.

35. AziosNG,KrishnamoorthyL,HarrisM,CubanoLA,CammerM,DharmawardhaneSF.,EstrogenandresveratrolregulateRacandCdc42signal-ingtotheactincytoskeletonofmetastaticbreastcancercells.,Neoplasia.2007Feb;9(2):147-58.

36. LiY,LiuJ,LiuX,XingK,WangY,LiF,YaoL.,Resveratrol-inducedcellinhibi-tionofgrowthandapoptosisinMCF7humanbreastcancercellsareassoci-atedwithmodulationofphosphorylatedAktandcaspase-9.,ApplBiochemBiotechnol.2006Dec;135(3):181-92.

37. ShibataMA,AkaoY,ShibataE,NozawaY,ItoT,MishimaS,MorimotoJ,OtsukiY.,VaticanolC,anovelresveratroltetramer,reduceslymphnodeandlungmetastasesofmousemammarycarcinomacarryingp53mutation.,CancerChemotherPharmacol.2007Oct;60(5):681-91.

38. BaderY,GetoffN.,EffectofresveratrolandmixturesofresveratrolandmitomycinConcancercellsunderirradiation.,AnticancerRes.2006Nov-Dec;26(6B):4403-8.

39. Landis-PiwowarKR,MilacicV,ChenD,YangH,ZhaoY,ChanTH,YanB,DouQP.,Theproteasomeasapotentialtargetfornovelanticancerdrugsandche-mosensitizers.DrugResistUpdat.2006Dec;9(6):263-73.

40. WhitsettTGJr,LamartiniereCA.,Genisteinandresveratrol:mammarycancerchemopreventionandmechanismsofactionintherat.,ExpertRevAnticancerTher.2006Dec;6(12):1699-706.

41. NarayananBA.,Chemoprotectiveagentsaltersglobalgeneexpressionpattern:predictingtheirmodeofactionandtargets.,CurrCancerDrugTargets.2006Dec;6(8):711-27.

42. WuF,SafeS.,Differentialactivationofwild-typeestrogenreceptoralphaandC-terminaldeletionmutantsbyestrogens,antiestrogensandxenoestrogensinbreastcancercells.,JSteroidBiochemMolBiol.2007Jan;103(1):1-9.

43. EbertB,SeidelA,LampenA.,PhytochemicalsinducebreastcancerresistanceproteininCaco-2cellsandenhancethetransportofbenzo[a]pyrene-3-sulfate.ToxicolSci.2007Apr;96(2):227-36.

44. FengL,ZhangLF,YanT,JinJ,TaoWY.,[Studiesonactivesubstanceofantican-cereffectinPolygonumcuspidatum],ZhongYaoCai.2006Jul;29(7):689-91.[Chinese]

45. BreedveldP,PluimD,CiprianiG,DahlhausF,vanEijndhovenMA,deWolfCJ,KuilA,BeijnenJH,SchefferGL,JansenG,BorstP,SchellensJH.,TheeffectoflowpHonbreastcancerresistanceprotein(ABCG2)-mediatedtransportofmethotrexate,7-hydroxymethotrexate,methotrexatediglutamate,folicacid,mitoxantrone,topotecan,andresveratrolininvitrodrugtransportmodels.,MolPharmacol.2007Jan;71(1):240-9.

��

46. GeH,ZhangJF,GuoBS,HeB,WangBY,WangCQ.,[Resveratrolinhibitsexpres-sionofEMMPRINfrommacrophages],YaoXueXueBao.2006Jul;41(7):625-30.[Chinese]

47. DolfiniE,RoncoroniL,DogliottiE,SalaG,ErbaE,SacchiN,GhidoniR.,ResveratrolimpairstheformationofMDA-MB-231multicellulartumorspheroidsconcomitantwithceramideaccumulation.,CancerLett.2007May8;249(2):143-7.

48. TangHY,ShihA,CaoHJ,DavisFB,DavisPJ,LinHY.,Resveratrol-inducedcyclo-oxygenase-2facilitatesp53-dependentapoptosisinhumanbreastcancercells.MolCancerTher.2006Aug;5(8):2034-42.

49. LinHY,LansingL,MerillonJM,DavisFB,TangHY,ShihA,VitracX,KrisaS,KeatingT,CaoHJ,BerghJ,QuackenbushS,DavisPJ.,IntegrinalphaVbeta3containsareceptorsiteforresveratrol.,FASEBJ.2006Aug;20(10):1742-4.

50. WhitsettT,CarpenterM,LamartiniereCA.,Resveratrol,butnotEGCG,inthedietsuppressesDMBA-inducedmammarycancerinrats.,JCarcinog.2006May15;5:15.

51. FengL,JinJ,ZhangLF,YanT,TaoWY.,Analysisoftheresveratrol-bindingproteinusingphage-displayedrandompeptidelibrary.,ActaBiochimBiophysSin(Shanghai).2006May;38(5):342-8.

52. SevergniniM,BicciatoS,ManganoE,ScarlattiF,MezzelaniA,MattioliM,GhidoniR,PeanoC,BonnalR,VitiF,MilanesiL,DeBellisG,BattagliaC.,Strategiesforcomparinggeneexpressionprofilesfromdifferentmicroarrayplatforms:applicationtoacase-controlexperiment.,AnalBiochem.2006Jun1;353(1):43-56.

53. WangY,LeeKW,ChanFL,ChenS,LeungLK.,Theredwinepolyphenolresve-ratroldisplaysbilevelinhibitiononaromataseinbreastcancercells.,ToxicolSci.2006Jul;92(1):71-7.

��

54. KothaA,SekharamM,CilentiL,SiddiqueeK,KhaledA,ZervosAS,CarterB,TurksonJ,JoveR.,ResveratrolinhibitsSrcandStat3signalingandinducestheapoptosisofmalignantcellscontainingactivatedStat3protein.,MolCancerTher.2006Mar;5(3):621-9.

55. LarrosaM,González-SarríasA,García-ConesaMT,Tomás-BarberánFA,EspínJC.,Urolithins,ellagicacid-derivedmetabolitesproducedbyhumancolonicmicroflora,exhibitestrogenicandantiestrogenicactivities.,JAgricFoodChem.2006Mar8;54(5):1611-20.

56. ChoiHK,YangJW,KangKW.,Bifunctionaleffectofresveratrolontheex-pressionofErbB2inhumanbreastcancercell.,CancerLett.2006Oct28;242(2):198-206.

57. LanzilliG,FuggettaMP,TricaricoM,CottarelliA,SerafinoA,FalchettiR,RavagnanG,TurrizianiM,AdamoR,FranzeseO,BonmassarE.,Resveratroldown-regulatesthegrowthandtelomeraseactivityofbreastcancercellsinvitro.,IntJOncol.2006Mar;28(3):641-8.

58. VyasS,AsmeromY,DeLeónDD.,Insulin-likegrowthfactorIImediatesresve-ratrolstimulatoryeffectoncathepsinDinbreastcancercells.,GrowthFactors.2006Mar;24(1):79-87.

59. GarvinS,OllingerK,DabrosinC.,Resveratrolinducesapoptosisandinhibitsangiogenesisinhumanbreastcancerxenograftsinvivo.,CancerLett.2006Jan8;231(1):113-22.

60. MinutoloF,SalaG,BagnacaniA,BertiniS,CarboniI,PlacanicaG,ProtaG,RapposelliS,SacchiN,MacchiaM,GhidoniR.,Synthesisofaresveratrolana-loguewithhighceramide-mediatedproapoptoticactivityonhumanbreastcancercells.,JMedChem.2005Nov3;48(22):6783-6.

61. NifliAP,KampaM,AlexakiVI,NotasG,CastanasE.,Polyphenolinterac-tionwiththeT47Dhumanbreastcancercellline.,JDairyRes.2005;72SpecNo:44-50.

��

62. HarrisDM,BesselinkE,HenningSM,GoVL,HeberD.,Phytoestrogensinducedifferentialestrogenreceptoralpha-orBeta-mediatedresponsesintransfect-edbreastcancercells.,ExpBiolMed(Maywood).2005Sep;230(8):558-68.

63. MillerME,HollowayAC,FosterWG.,Benzo-[a]-pyreneincreasesinvasioninMDA-MB-231breastcancercellsviaincreasedCOX-IIexpressionandprosta-glandinE2(PGE2)output.,ClinExpMetastasis.2005;22(2):149-56.

64. BlumensteinI,KeserüB,WolterF,SteinJ.,Thechemoprotectiveagentresvera-trolstimulatescyclicAMP-dependentchloridesecretioninvitro.,ClinCancerRes.2005Aug1;11(15):551-6.

65. VyasS,AsmeromY,DeLeónDD.,Resveratrolregulatesinsulin-likegrowthfactor-IIinbreastcancercells.,Endocrinology.2005Oct;146(10):4224-33.

66. GuastallaJP,BachelotT,Ray-CoquardI.,[Cyclooxygenase2andbreastcancer.Frombiologicalconceptstoclinicaltrials],BullCancer.2004May1;91Suppl2:S99-108.Review.[French]

67. MatsumuraA,GhoshA,PopeGS,DarbrePD.,Comparativestudyofoestro-genicpropertiesofeightphytoestrogensinMCF7humanbreastcancercells.JSteroidBiochemMolBiol.2005Apr;94(5):431-43.

68. WaiteKA,SindenMR,EngC.,PhytoestrogenexposureelevatesPTENlevels.,HumMolGenet.2005Jun1;14(11):1457-63.

69. AziosNG,DharmawardhaneSF.,Resveratrolandestradiolexertdisparateeffectsoncellmigration,cellsurfaceactinstructures,andfocaladhesionassemblyinMDA-MB-231humanbreastcancercells.,Neoplasia.2005Feb;7(2):128-40.

70. MonthakantiratO,De-EknamkulW,UmeharaK,YoshinagaY,MiyaseT,WarashinaT,NoguchiH.,PhenolicconstituentsoftherhizomesoftheThaimedicinalplantBelamcandachinensiswithproliferativeactivityfortwobreastcancercelllines.,JNatProd.2005Mar;68(3):361-4.

��

71. LeCorreL,ChalabiN,DelortL,BignonYJ,Bernard-GallonDJ.,Resveratrolandbreastcancerchemoprevention:molecularmechanisms.,MolNutrFoodRes.2005May;49(5):462-71.

72. LeviF,PascheC,LucchiniF,GhidoniR,FerraroniM,LaVecchiaC.,Resveratrolandbreastcancerrisk.,EurJCancerPrev.2005Apr;14(2):139-42.

73. RodrigueCM,PorteuF,NavarroN,BruyneelE,BrackeM,RomeoPH,GespachC,GarelMC.,Thecancerchemoprotectiveagentresveratrolinducestensin,acell-matrixadhesionproteinwithsignalingandantitumoractivities.,Oncogene.2005May5;24(20):3274-84.

74. Pozo-GuisadoE,MerinoJM,Mulero-NavarroS,Lorenzo-BenayasMJ,CentenoF,Alvarez-BarrientosA,Fernandez-SalgueroPM.,Resveratrol-inducedapop-tosisinMCF-7humanbreastcancercellsinvolvesacaspase-independentmechanismwithdownregulationofBcl-2andNF-kappaB.,IntJCancer.2005May20;115(1):74-84.Erratumin:IntJCancer.2005Oct10;116(6):1004.Salguero,PedroMFernandez[correctedtoFernandez-Salguero,PedroM].

75. WietzkeJA,WardEC,SchneiderJ,WelshJ.,RegulationofthehumanvitaminD3receptorpromoterinbreastcancercellsismediatedthroughSp1sites.,MolCellEndocrinol.2005Jan31;230(1-2):59-68.

76. MansonMM,FarmerPB,GescherA,StewardWP.,Innovativeagentsincancerprevention.,RecentResultsCancerRes.2005;166:257-75.

77. KimH,HallP,SmithM,KirkM,PrasainJK,BarnesS,GrubbsC.,Chemopreventionbygrapeseedextractandgenisteinincarcinogen-inducedmammarycancerinratsisdietdependent.,JNutr.2004Dec;134(12Suppl):3445S-3452S.

78. AggarwalBB,BhardwajA,AggarwalRS,SeeramNP,ShishodiaS,TakadaY.,Roleofresveratrolinpreventionandtherapyofcancer:preclinicalandclinicalstudies.AnticancerRes.2004Sep-Oct;24(5A):2783-840.

��

79. BiancoNR,ChaplinLJ,MontanoMM.,Differentialinductionofquinonere-ductasebyphytoestrogensandprotectionagainstoestrogen-inducedDNAdamage.BiochemJ.2005Jan1;385(Pt1):279-87.

80. ZhangS,CaoHJ,DavisFB,TangHY,DavisPJ,LinHY.,Oestrogeninhibitsresve-ratrol-inducedpost-translationalmodificationofp53andapoptosisinbreastcancercells.BrJCancer.2004Jul5;91(1):178-85.

81. SimopoulosAP.,ThetraditionaldietofGreeceandcancer.,EurJCancerPrev.2004Jun;13(3):219-30.LauxMT,AregullinM,BerryJP,FlandersJA,RodriguezE.,Identificationofap53-dependentpathwayintheinductionofapoptosisofhumanbreastcancercellsbythenaturalproduct,resveratrol.,JAlternComplementMed.2004Apr;10(2):235-9.

82. LeCorreL,FustierP,ChalabiN,BignonYJ,Bernard-GallonD.,EffectsofresveratrolontheexpressionofapanelofgenesinteractingwiththeBRCA1oncosuppressorinhumanbreastcelllines.,ClinChimActa.2004Jun;344(1-2):115-21.

83. SalaG,MinutoloF,MacchiaM,SacchiN,GhidoniR.,Resveratrolstructureandceramide-associatedgrowthinhibitioninprostatecancercells.,DrugsExpClinRes.2003;29(5-6):263-9.

84. GehmBD,LevensonAS,LiuH,LeeEJ,AmundsenBM,CushmanM,JordanVC,JamesonJL.,Estrogeniceffectsofresveratrolinbreastcancercellsexpress-ingmutantandwild-typeestrogenreceptors:roleofAF-1andAF-2.,JSteroidBiochemMolBiol.2004Mar;88(3):223-34.

85. CoorayHC,JanvilisriT,vanVeenHW,HladkySB,BarrandMA.,Interactionofthebreastcancerresistanceproteinwithplantpolyphenols.,BiochemBiophysResCommun.2004Apr23;317(1):269-75.

86. JoEH,HongHD,AhnNC,JungJW,YangSR,ParkJS,KimSH,LeeYS,KangKS.,ModulationsoftheBcl-2/Baxfamilywereinvolvedinthechemoprotectiveeffectsoflicoriceroot(GlycyrrhizauralensisFisch)inMCF-7humanbreastcancercell.,JAgricFoodChem.2004Mar24;52(6):1715-9.

��

87. CheungCY,ChenJ,ChangTK.,Evaluationofareal-timepolymerasechainreactionmethodforthequantificationofCYP1B1geneexpressioninMCF-7humanbreastcarcinomacells.,JPharmacolToxicolMethods.2004Mar-Apr;49(2):97-104.

88. Pozo-GuisadoE,Lorenzo-BenayasMJ,Fernández-SalgueroPM.,Resveratrolmodulatesthephosphoinositide3-kinasepathwaythroughanestrogenrecep-toralpha-dependentmechanism:relevanceincellproliferation.,IntJCancer.2004Mar20;109(2):167-73.

89. FuldaS,DebatinKM.,Sensitizationfortumornecrosisfactor-relatedapopto-sis-inducingligand-inducedapoptosisbythechemoprotectiveagentresvera-trol.CancerRes.2004Jan1;64(1):337-46.

90. KimYA,ChoiBT,LeeYT,ParkDI,RheeSH,ParkKY,ChoiYH.,ResveratrolinhibitscellproliferationandinducesapoptosisofhumanbreastcarcinomaMCF-7cells.,OncolRep.2004Feb;11(2):441-6.

91. HoseCD,HollingsheadM,SausvilleEA,MonksA.,InductionofCYP1A1intumorcellsbytheantitumoragent2-[4-amino-3-methylphenyl]-5-fluoro-ben-zothiazole:apotentialsurrogatemarkerforpatientsensitivity.,MolCancerTher.2003Dec;2(12):1265-72.

92. ScarlattiF,SalaG,SomenziG,SignorelliP,SacchiN,GhidoniR.,Resveratrolinducesgrowthinhibitionandapoptosisinmetastaticbreastcancercellsviadenovoceramidesignaling.,FASEBJ.2003Dec;17(15):2339-41.

93. FustierP,LeCorreL,ChalabiN,Vissac-SabatierC,CommunalY,BignonYJ,Bernard-GallonDJ.,ResveratrolincreasesBRCA1andBRCA2mRNAexpres-sioninbreasttumourcelllines.,BrJCancer.2003Jul7;89(1):168-72.

94. AzizMH,KumarR,AhmadN.,Cancerchemopreventionbyresveratrol:invitroandinvivostudiesandtheunderlyingmechanisms(review).,IntJOncol.2003Jul;23(1):17-28.

��

95. El-MowafyAM,AlkhalafM.,Resveratrolactivatesadenylyl-cyclaseinhumanbreastcancercells:anovel,estrogenreceptor-independentcytostaticmecha-nism.Carcinogenesis.2003May;24(5):869-73.

96. RoyM,ChakrabortyS,SiddiqiM,BhattacharyaRK.,InductionofApoptosisinTumorCellsbyNaturalPhenolicCompounds.,AsianPacJCancerPrev.2002;3(1):61-67.

97. WietzkeJA,WelshJ.,PhytoestrogenregulationofaVitaminD3receptorpro-moterand1,25-dihydroxyvitaminD3actionsinhumanbreastcancercells.,JSteroidBiochemMolBiol.2003Feb;84(2-3):149-57.

98. KlingeCM,RisingerKE,WattsMB,BeckV,EderR,JungbauerA.,Estrogenicactivityinwhiteandredwineextracts.,JAgricFoodChem.2003Mar26;51(7):1850-7.

99. LevensonAS,GehmBD,PearceST,HoriguchiJ,SimonsLA,WardJE3rd,JamesonJL,JordanVC.,Resveratrolactsasanestrogenreceptor(ER)agonistinbreastcancercellsstablytransfectedwithERalpha.,IntJCancer.2003May1;104(5):587-96.

100. SchmittE,LehmannL,MetzlerM,StopperH.,Hormonalandgenotoxicactivityofresveratrol.,ToxicolLett.2002Dec15;136(2):133-42.

101. BrownsonDM,AziosNG,FuquaBK,DharmawardhaneSF,MabryTJ.,Flavonoideffectsrelevanttocancer.,JNutr.2002Nov;132(11Suppl):3482S-3489S.

102. DingXZ,AdrianTE.,Resveratrolinhibitsproliferationandinducesapoptosisinhumanpancreaticcancercells.,Pancreas.2002Nov;25(4):e71-6.

103. Pozo-GuisadoE,Alvarez-BarrientosA,Mulero-NavarroS,Santiago-JosefatB,Fernandez-SalgueroPM.,TheantiproliferativeactivityofresveratrolresultsinapoptosisinMCF-7butnotinMDA-MB-231humanbreastcancercells:cell-specificalterationofthecellcycle.,BiochemPharmacol.2002Nov1;64(9):1375-86.

��

104. BanerjeeS,Bueso-RamosC,AggarwalBB.,Suppressionof7,12-dimethylbenz(a)anthracene-inducedmammarycarcinogenesisinratsbyresveratrol:roleofnuclearfactor-kappaB,cyclooxygenase2,andmatrixmetalloprotease9.CancerRes.2002Sep1;62(17):4945-54.

105. LevensonAS,KliakhandlerIL,SvobodaKM,PeaseKM,KaiserSA,WardJE3rd,JordanVC.,Molecularclassificationofselectiveoestrogenreceptormodula-torsonthebasisofgeneexpressionprofilesofbreastcancercellsexpressingoestrogenreceptoralpha.,BrJCancer.2002Aug12;87(4):449-56.

106. DubuissonJG,DyessDL,GaubatzJW.,ResveratrolmodulateshumanmammaryepithelialcellO-acetyltransferase,sulfotransferase,andkinaseactivationoftheheterocyclicaminecarcinogenN-hydroxy-PhIP.,CancerLett.2002Aug8;182(1):27-32.

107. LevensonAS,SvobodaKM,PeaseKM,KaiserSA,ChenB,SimonsLA,JovanovicBD,DyckPA,JordanVC.,Geneexpressionprofileswithactivationoftheestro-genreceptoralpha-selectiveestrogenreceptormodulatorcomplexinbreastcancercellsexpressingwild-typeestrogenreceptor.,CancerRes.2002Aug1;62(15):4419-26.

108. KimHJ,ChangEJ,BaeSJ,ShimSM,ParkHD,RheeCH,ParkJH,ChoiSW.,CytotoxicandantimutagenicstilbenesfromseedsofPaeonialactiflora.,ArchPharmRes.2002Jun;25(3):293-9.

109. EngET,WilliamsD,MandavaU,KirmaN,TekmalRR,ChenS.,Anti-aromatasechemicalsinredwine.,AnnNYAcadSci.2002Jun;963:239-46.

110. BruggisserR,vonDaenikenK,JundtG,SchaffnerW,Tullberg-ReinertH.,Interferenceofplantextracts,phytoestrogensandantioxidantswiththeMTTtetrazoliumassay.PlantaMed.2002May;68(5):445-8.

111. BoveK,LincolnDW,TsanMF.,Effectofresveratrolongrowthof4T1breastcancercellsinvitroandinvivo.,BiochemBiophysResCommun.2002Mar8;291(4):1001-5.

��

112. SerreroG,LuR.,Effectofresveratrolontheexpressionofautocrinegrowthmodulatorsinhumanbreastcancercells.,AntioxidRedoxSignal.2001Dec;3(6):969-79.,

113. SimopoulosAP.,TheMediterraneandiets:WhatissospecialaboutthedietofGreece?Thescientificevidence.,JNutr.2001Nov;131(11Suppl):3065S-73S.

114. BhatKP,LantvitD,ChristovK,MehtaRG,MoonRC,PezzutoJM.,Estrogenicandantiestrogenicpropertiesofresveratrolinmammarytumormodels.,CancerRes.2001Oct15;61(20):7456-63.

115. LeeJE,SafeS.,Involvementofapost-transcriptionalmechanismintheinhibi-tionofCYP1A1expressionbyresveratrolinbreastcancercells.,BiochemPharmacol.2001Oct15;62(8):1113-24.

116. SgambatoA,ArditoR,FaragliaB,BoninsegnaA,WolfFI,CittadiniA.,Resveratrol,anaturalphenoliccompound,inhibitscellproliferationandpre-ventsoxidativeDNAdamage.,MutatRes.2001Sep20;496(1-2):171-80.

117. SoleasGJ,GoldbergDM,GrassL,LevesqueM,DiamandisEP.,Dowinepolyphe-nolsmodulatep53geneexpressioninhumancancercelllines?,ClinBiochem.2001Jul;34(5):415-20.

118. PervaizS.,Resveratrol--fromthebottletothebedside?,LeukLymphoma.2001Feb;40(5-6):491-8.

119. NakagawaH,KiyozukaY,UemuraY,SenzakiH,ShikataN,HiokiK,TsuburaA.,Resveratrolinhibitshumanbreastcancercellgrowthandmaymitigatetheeffectoflinoleicacid,apotentbreastcancercellstimulator.,JCancerResClinOncol.2001Apr;127(4):258-64.

120. CuendetM,PezzutoJM.,Theroleofcyclooxygenaseandlipoxygenaseincancerchemoprevention.,DrugMetabolDrugInteract.2000;17(1-4):109-57.

121. HuberJ.,[PhytoestrogensandSERMS,alternativestoclassicalhormonetherapy?]TherUmsch.2000Oct;57(10):651-4.[German]

122. DamianakiA,BakogeorgouE,KampaM,NotasG,HatzoglouA,PanagiotouS,GemetziC,KouroumalisE,MartinPM,CastanasE.,Potentinhibitoryactionofredwinepolyphenolsonhumanbreastcancercells.,JCellBiochem.2000Jun6;78(3):429-41.

123. BaslyJP,Marre-FournierF,LeBailJC,HabriouxG,ChuliaAJ.,Estrogenic/an-tiestrogenicandscavengingpropertiesof(E)-and(Z)-resveratrol.,LifeSci.2000Jan21;66(9):769-77.

124. SubbaramaiahK,MichaluartP,ChungWJ,TanabeT,TelangN,DannenbergAJ.,Resveratrolinhibitscyclooxygenase-2transcriptioninhumanmammaryepithelialcells.,AnnNYAcadSci.1999;889:214-23.

125. WeisburgerJH.,Mechanismsofactionofantioxidantsasexemplifiedinveg-etables,tomatoesandtea.,FoodChemToxicol.1999Sep-Oct;37(9-10):943-8.

126. UlspergerE,HamiltonG,RadererM,BaumgartnerG,HejnaM,HoffmannO,MallingerR.,ResveratrolpretreatmentdesensitizesAHTO-7humanosteo-blaststogrowthstimulationinresponsetocarcinomacellsupernatants.,IntJOncol.1999Nov;15(5):955-9.

127. GottliebN.,“Soybean”inaHaystack?pinpointingananti-cancereffect.,JNatlCancerInst.1999Oct6;91(19):1610-2.

128. HsiehTC,BurfeindP,LaudK,BackerJM,TraganosF,DarzynkiewiczZ,WuJM.,Cellcycleeffectsandcontrolofgeneexpressionbyresveratrolinhumanbreastcarcinomacelllineswithdifferentmetastaticpotentials.,IntJOncol.1999Aug;15(2):245-52.

129. LuR,SerreroG.,Resveratrol,anaturalproductderivedfromgrape,exhibitsantiestrogenicactivityandinhibitsthegrowthofhumanbreastcancercells.JCellPhysiol.1999Jun;179(3):297-304.

130. SubbaramaiahK,ChungWJ,MichaluartP,TelangN,TanabeT,InoueH,JangM,PezzutoJM,DannenbergAJ.,Resveratrolinhibitscyclooxygenase-2transcrip-tionandactivityinphorbolester-treatedhumanmammaryepithelialcells.,JBiolChem.1998Aug21;273(34):21875-82.

��

131. ClémentMV,HirparaJL,ChawdhurySH,PervaizS.,Chemoprotectiveagentres-veratrol,anaturalproductderivedfromgrapes,triggersCD95signaling-de-pendentapoptosisinhumantumorcells.,Blood.1998Aug1;92(3):996-1002.

132. KoppP.,Resveratrol,aphytoestrogenfoundinredwine.Apossibleexpla-nationfortheconundrumofthe‘Frenchparadox’?,EurJEndocrinol.1998Jun;138(6):619-20.

133. FangN,CasidaJE.,Anticanceractionofcubéinsecticide:correlationforrot-enoidconstituentsbetweeninhibitionofNADH:ubiquinoneoxidoreductaseandinducedornithinedecarboxylaseactivities.,ProcNatlAcadSciUSA.1998Mar31;95(7):3380-4.

134. MgbonyebiOP,RussoJ,RussoIH.,Antiproliferativeeffectofsyntheticresvera-trolonhumanbreastepithelialcells.,IntJOncol.1998Apr;12(4):865-9.

135. GehmBD,McAndrewsJM,ChienPY,JamesonJL.,Resveratrol,apolyphenoliccompoundfoundingrapesandwine,isanagonistfortheestrogenreceptor.,ProcNatlAcadSciUSA.1997Dec9;94(25):14138-43.

Chemoprotectiveeffectsofresveratrol1. Langcake,P.andPryce,R.J.(1976)TheproductionofresveratrolbyVitisvinif-

eraandothermembersoftheVitaceaeasaresponsetoinfectionorinjury.Physiol.PlantPathol.,9,77–86.

2. Nonomura,S.,Kanagawa,H.andMakimoto,A.(1963)Chemicalconstituentsofpolygonaceousplants.I.StudiesonthecomponentsofKo-jo-kon(PolygonumcuspidatumSIEBetZUCC).YakugakuZasshi,83,983–988.

3. Siemann,E.H.andCreasy,L.L.(1992)Concentrationofphytoalexinresveratrolinwine.Am.J.Enol.Vitic.,43,49–52.

4. Creasy,L.L.andCoffee,M.(1988)Phytoalexinproductionpotentialofgrapeberries.J.Am.Soc.Hort.Sci.,113,230–234.

��

5. Foroozesh,M.,Primrose,G.,Guo,Z.,Bell,L.C.,Alworth,W.L.andGuengerich,F.P.(1997)Arylacetylenesasmechanism-basedinhibitorsofcytochromeP450-dependentmonooxygenaseenzymes.Chem.Res.Toxicol.,10,91–102.

6. Chanvitayapongs,S.,Draczynska-Lusiak,B.andSun,A.Y.(1997)AmeliorationofoxidativestressbyantioxidantsandresveratrolinPC12cells.Neuroreport,8,1499–1502.

7. Belguendouz,L.,Fremont,L.andLinard,A.(1997)Resveratrolinhibitsmetalion-dependentandindependentperoxidationofporcinelow-densitylipopro-teins.Biochem.Pharmacol.,53,1347–1355.

8. Fauconneau,B.,Waffo-Teguo,P.,Huguet,F.,Barrier,L.,Decendit,A.andMerillon,J.M.(1997)ComparativestudyofradicalscavengerandantioxidantpropertiesofphenoliccompoundsfromVitisviniferacellculturesusinginvitrotests.LifeSci.,61,2103–2110.

9. Frankel,E.N.,Waterhouse,A.L.andKinsella,J.E.(1993)InhibitionofhumanLDLoxidationbyresveratrol(letter).Lancet,341,1103–1104.

10. Pace-Asciak,C.R.,Hahn,S.,Diamandis,E.P.,Soleas,G.andGoldberg,D.M.(1995)Theredwinephenolicstrans-resveratrolandquercetinblockhumanplate-letaggregationandeicosanoidsynthesis:implicationsforprotectionagainstcoronaryheartdisease.Clin.Chim.Acta,235,207–219.

11. Kimura,Y.,Okuda,H.andArichi,S.(1985)Effectsofstilbenesonarachidonatemetabolisminleukocytes.Biochim.Biophys.Acta,834,275–278.

12. Bertelli,A.A.,Giovannini,L.,Giannessi,D.,Migliori,M.,Bernini,W.,Fregoni,M.andBertelli,A.(1995)Antiplateletactivityofsyntheticandnaturalresveratrolinredwine.Int.J.TissueReact.,17,1–3.

13. Chung,M.I.,Teng,C.M.,Cheng,K.L.,Ko,F.N.andLin,C.N.(1992)AnantiplateletprincipleofVeratrumformosanum.PlantaMed.,58,274–276.

14. Belguendouz,L.,Fremont,L.andGozzelino,M.T.(1998)Interactionoftransres-veratrolwithplasmalipoproteins.Biochem.Pharmacol.,55,811–816.

��

15. Jang,M.,Cai,L.,Udeani,G.O.,Slowing,K.V.,Thomas,C.F.,Beecher,C.W.,Fong,H.H.,Farnsworth,N.R.,Kinghorn,A.D.,Mehta,R.G.,Moon,R.C.andPezzuto,J.M.(1997)Cancerchemoprotectiveactivityofresveratrol,anaturalproductderivedfromgrapes.Science,275,218–220.

16. Johnson,J.L.andMaddipati,K.R.(1998)ParadoxicaleffectsofresveratrolonthetwoprostaglandinHsynthases.ProstaglandinsOtherLipidMediat.,56,131–143.

17. Rotondo,S.,Rajtar,G.,Manarini,S.,Celardo,A.,Rotillo,D.,deGaetano,G.,Evangelista,V.andCerletti,C.(1998)Effectoftrans-resveratrol,anaturalpoly-phenoliccompound,onhumanpolymorphonuclearleukocytefunction.Br.J.Pharmacol.,123,1691–1699.

18. Chen,C.K.andPace-Asciak,C.R.(1996)Vasorelaxingactivityofresveratrolandquercetininisolatedrataorta.Gen.Pharmacol.,27,363–366.

19. Celotti,E.,Ferrarini,R.,Zironi,R.andConte,L.S.(1996)ResveratrolcontentofsomewinesobtainedfromdriedValpolicellagrapes:ReciotoandAmarone.J.Chromatogr.A,730,47–52.

20. Gehm,B.D.,McAndrews,J.M.,Chien,P.Y.andJameson,J.L.(1997)Resveratrol,apolyphenoliccompoundfoundingrapesandwine,isanagonistfortheestro-genreceptor.Proc.NatlAcad.Sci.USA,94,14138–14143.

21. Mizutani,K.,Ikeda,K.,Kawai,Y.andYamori,Y.(1998)ResveratrolstimulatestheproliferationanddifferentiationofosteoblasticMC3T3-E1cells.Biochem.Biophys.Res.Commun.,253,859–863.

22. Ragazzi,E.,Froldi,G.andFassina,G.(1988)Resveratrolactivityonguineapigisolatedtracheafromnormalandalbumin-sensitizedanimals.Pharmacol.Res.Commun.,20(suppl.5),79–82.

23. Han,Y.N.,Ryn,S.Y.andHan,B.H.(1990)Antioxidantactivityofresveratrolcloselycorrelateswithitsmonoamineoxidase-Ainhibitoryactivity.Arch.Pharmacol.Res.,13,132.

��

24. Murakami,S.,Arai,I.,Muramatsu,M.,Otomo,S.,Baba,K.,Kido,T.andKozawa,M.(1992)EffectofstilbenederivativesongastricH+,K(+)-ATPase.Biochem.Pharmacol.,44,1947–1951.

25. Jayatilake,G.S.,Jayasuriya,H.,Lee,E.S.,Koonchanok,N.M.,Geahlen,R.L.,Ashendel,C.L.,McLaughlin,J.L.andChang,C.J.(1993)KinaseinhibitorsfromPolygonumcuspidatum.J.Nat.Prod.,56,1805–1810.

26. BenAv,P.,Crofford,L.J.,Wilder,R.L.andHla,T.(1995)InductionofvascularendothelialgrowthfactorexpressioninsynovialfibroblastsbyprostaglandinEandinterleukin-1:apotentialmechanismforinflammatoryangiogenesis.FEBSLett.,372,83–87.

27. Goodwin,J.S.andCeuppens,J.(1983)Regulationoftheimmuneresponsebyprostaglandins.J.Clin.Immunol.,3,295–315.

28. Sheng,H.,Shao,J.,Morrow,J.D.,Beauchamp,R.D.andDuBois,R.N.(1998)ModulationofapoptosisandBcl-2expressionbyprostaglandinE2inhumancoloncancercells.CancerRes.,58,362–366.

29. Shin,N.H.,Ryu,S.Y.,Lee,H.,Min,K.R.andKim,Y.(1998)Inhibitoryeffectsofhydroxystilbenesoncyclooxygenasefromsheepseminalvesicles.PlantaMed.,64,283–284.

30. Jang,M.andPezzuto,J.M.(1998)Effectsofresveratrolon12-O-tetradec-anoylphorbol-13-acetate-inducedoxidativeeventsandgeneexpressioninmouseskin.CancerLett.,134,81–89.

31. Subbaramaiah,K.,Chung,W.J.,Michaluart,P.,Telang,N.,Tanabe,T.,Inoue,H.,Jang,M.,Pezzuto,J.M.andDannenberg,A.J.(1998)Resveratrolinhibitscyclooxy-genase-2transcriptionandactivityinphorbolester-treatedhumanmammaryepithelialcells.J.Biol.Chem.,273,21875–21882.

32. Martinez,J.andMoreno,J.J.(2000)Effectofresveratrol,anaturalpolyphe-noliccompound,onreactiveoxygenspeciesandprostaglandinproduction.Biochem.Pharmacol.,59,865–870.

��

33. Stewart,J.R.,Christman,K.L.andO’Brian,C.A.(2000)Effectsofresveratrolontheautophosphorylationofphorbolester-responsiveproteinkinases.Inhibitionofproteinkinasedbutnotproteinkinasecisozymeautophosphor-ylation.Biochem.Pharmacol.,60,1355–1359.

34. Jang,M.andPezzuto,J.M.(1999)Cancerchemoprotectiveactivityofresvera-trol.DrugsExp.Clin.Res.,25,65–77.

35. Prochaska,H.J.andSantamaria,A.B.(1988)DirectmeasurementofNAD(P)H:quinonereductasefromcellsculturedinmicrotiterwells:ascreeningassayforanticarcinogenicenzymeinducers.Anal.Biochem.,169,328–336.

36. Nielsen,M.,Ruch,R.J.andVang,O.(2000)Resveratrolreversestumor-promot-er-inducedinhibitionofgap-junctionalintercellularcommunication.Biochem.Biophys.Res.Commun.,275,804–809.

37. Trosko,J.E.andRuch,R.J.(1998)Cell–cellcommunicationincarcinogenesis.Front.Biosci.,3,D208–D236.

38. Jadeski,L.C.,Hum,K.O.,Chakraborty,C.andLala,P.K.(2000)Nitricoxidepro-motesmurinemammarytumourgrowthandmetastasisbystimulatingtumourcellmigration,invasivenessandangiogenesis.Int.J.Cancer,86,30–39.

39. Yagihashi,N.,Kasajima,H.,Sugai,S.,Matsumoto,K.,Ebina,Y.,Morita,T.,Murakami,T.andYagihashi,S.(2000)Increasedinsituexpressionofnitricoxidesynthaseinhumancolorectalcancer.VirchowsArch.,436,109–114.

40. Thomsen,L.L.,Lawton,F.G.,Knowles,R.G.,Beesley,J.E.,Riveros-Moreno,V.andMoncada,S.(1994)Nitricoxidesynthaseactivityinhumangynecologicalcancer.CancerRes.,54,1352–1354.

41. Tsai,S.H.,Lin-Shiau,S.Y.andLin,J.K.(1999)Suppressionofnitricoxidesynthaseandthedown-regulationoftheactivationofNFBinmacrophagesbyresvera-trol.Br.J.Pharmacol.,126,673–680.

��

42. Huang,S.,DeGuzman,A.,Bucana,C.D.andFidler,I.J.(2000)Nuclearfactor-Bactivitycorrelateswithgrowth,angiogenesis,andmetastasisofhumanmela-nomacellsinnudemice.Clin.CancerRes.,6,2573–2581.

43. Manna,S.K.,Mukhopadhyay,A.andAggarwal,B.B.(2000)Resveratrolsuppress-esTNF-inducedactivationofnucleartranscriptionfactorsNF-B,activatorprotein-1,andapoptosis:potentialroleofreactiveoxygenintermediatesandlipidperoxidation.J.Immunol.,164,6509–6519.

44. Wadsworth,T.L.andKoop,D.R.(1999)Effectsofthewinepolyphenolicsquer-cetinandresveratrolonpro-inflammatorycytokineexpressioninRAW264.7macrophages.Biochem.Pharmacol.,57,941–949.

45. Kawada,N.,Seki,S.,Inoue,M.andKuroki,T.(1998)Effectofantioxidants,resve-ratrol,quercetin,andN-acetylcysteine,onthefunctionsofculturedrathepaticstellatecellsandKupffercells.Hepatology,27,1265–1274.

46. Matsuda,H.,Kageura,T.,Morikawa,T.,Toguchida,I.,Harima,S.andYoshikawa,M.(2000)Effectsofstilbeneconstituentsfromrhubarbonnitricoxideproduc-tioninlipopolysaccharide-activatedmacrophages.Bioorg.Med.Chem.Lett.,10,323–327.

47. Shamon,L.A.,Chen,C.,Mehta,R.G.,Steele,V.,Moon,R.C.andPezzuto,J.M.(1994)Acorrelativeapproachfortheidentificationofantimutagensthatdemon-stratechemoprotectiveactivity.AnticancerRes.,14,1775–1778.

48. Mehta,R.G.andMoon,R.C.(1991)Characterizationofeffectivechemoprotec-tiveagentsinmammaryglandinvitrousinganinitiation-promotionprotocol.AnticancerRes.,11,593–596.

49. Lee,S.K.,Mbwambo,Z.H.,Chung,H.,Luyengi,L.,Gamez,E.J.,Mehta,R.G.,Kinghorn,A.D.andPezzuto,J.M.(1998)Evaluationoftheantioxidantpotentialofnaturalproducts.Comb.Chem.HighThroughput.Screen.,1,35–46.

50. Ciolino,H.P.,Daschner,P.J.andYeh,G.C.(1998)Resveratrolinhibitstranscrip-tionofCYP1A1invitrobypreventingactivationofthearylhydrocarbonreceptor.CancerRes.,58,5707–5712.

��

51. Ciolino,H.P.andYeh,G.C.(1999)Inhibitionofarylhydrocarbon-inducedcy-tochromeP-4501A1enzymeactivityandCYP1A1expressionbyresveratrol.Mol.Pharmacol.,56,760–767.

52. Casper,R.F.,Quesne,M.,Rogers,I.M.,Shirota,T.,Jolivet,A.,Milgrom,E.andSavouret,J.F.(1999)Resveratrolhasantagonistactivityonthearylhydrocar-bonreceptor:implicationsforpreventionofdioxintoxicity.Mol.Pharmacol.,56,784–790.

53. Singh,S.U.,Casper,R.F.,Fritz,P.C.,Sukhu,B.,Ganss,B.,Girard,J.B.,Savouret,J.F.andTenenbaum,H.C.(2000)Inhibitionofdioxineffectsonboneformationinvitrobyanewlydescribedarylhydrocarbonreceptorantagonist,resveratrol.J.Endocrinol.,167,183–195.[Abstract]

54. Chun,Y.J.,Kim,M.Y.andGuengerich,F.P.(1999)ResveratrolisaselectivehumancytochromeP4501A1inhibitor.Biochem.Biophys.Res.Commun.,262,20–24.

55. Hecht,S.S.,Kenney,P.M.,Wang,M.,Trushin,N.,Agarwal,S.,Rao,A.V.andUpadhyaya,P.(1999)Evaluationofbutylatedhydroxyanisole,myo-inositol,curcumin,esculetin,resveratrolandlycopeneasinhibitorsofbenzo(a)pyreneplus4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-inducedlungtumori-genesisinA/Jmice.CancerLett.,137,123–130.

56. Sharma,S.,Stutzman,J.D.,Kelloff,G.J.andSteele,V.E.(1994)Screeningofpo-tentialchemoprotectiveagentsusingbiochemicalmarkersofcarcinogenesis.CancerRes.,54,5848–5855.

57. Damianaki,A.,Bakogeorgou,E.,Kampa,M.,Notas,G.,Hatzoglou,A.,Panagiotou,S.,Gemetzi,C.,Kouroumalis,E.,Martin,P.M.andCastanas,E.(2000)Potentinhibitoryactionofredwinepolyphenolsonhumanbreastcancercells.J.CellBiochem.,78,429–441.

58. Huang,C.,Ma,W.Y.,Goranson,A.andDong,Z.(1999)Resveratrolsuppressescelltransformationandinducesapoptosisthroughap53-dependentpathway.Carcinogenesis,20,237–242.

��

59. Waffo,T.P.,Fauconneau,B.,Deffieux,G.,Huguet,F.,Vercauteren,J.andMerillon,J.M.(1998)Isolation,identification,andantioxidantactivityofthreestilbeneglucosidesnewlyextractedfromVitisviniferacellcultures.J.Nat.Prod.,61,655–657.

60. Zini,R.,Morin,C.,Bertelli,A.,Bertelli,A.A.andTillement,J.P.(1999)Effectsofresveratrolontheratbrainrespiratorychain.DrugsExp.Clin.Res.,25,87–97.

61. Zou,J.G.,Huang,Y.Z.,Chen,Q.,Wei,E.H.,Hsieh,T.C.andWu,J.M.(1999)Resveratrolinhibitscopperion-inducedandazocompound-initiatedoxidativemodificationofhumanlowdensitylipoprotein.Biochem.Mol.Biol.Int.,47,1089–1096.

62. Fukuhara,K.andMiyata,N.(1998)ResveratrolasanewtypeofDNA-cleavingagent.Bioorg.Med.Chem.Lett.,8,3187–3192.

63. Ahmad,A.,Farhan,A.S.,Singh,S.andHadi,S.M.(2000)DNAbreakagebyresve-ratrolandCu(II):reactionmechanismandbacteriophageinactivation.CancerLett.,154,29–37.

64. Miura,T.,Muraoka,S.,Ikeda,N.,Watanabe,M.andFujimoto,Y.(2000)Antioxidativeandprooxidativeactionofstilbenederivatives(InProcessCitation).Pharmacol.Toxicol.,86,203–208.

65. Cadenas,S.andBarja,G.(1999)Resveratrol,melatonin,vitaminE,andPBNprotectagainstrenaloxidativeDNAdamageinducedbythekidneycarcinogenKBrO3.FreeRadic.Biol.Med.,26,1531–1537.

66. Fontecave,M.,Lepoivre,M.,Elleingand,E.,Gerez,C.andGuittet,O.(1998)Resveratrol,aremarkableinhibitorofribonucleotidereductase.FEBSLett.,421,277–279.

67. Sun,N.J.,Woo,S.H.,Cassady,J.M.andSnapka,R.M.(1998)DNApolymeraseandtopoisomeraseIIinhibitorsfromPsoraleacorylifolia.J.Nat.Prod.,61,362–366.

��

68. Schneider,Y.,Vincent,F.,Duranton,B.,Badolo,L.,Gosse,F.,Bergmann,C.,Seiler,N.andRaul,F.(2000)Anti-proliferativeeffectofresveratrol,anaturalcomponentofgrapesandwine,onhumancoloniccancercells.CancerLett.,158,85–91.

69. Elattar,T.M.andVirji,A.S.(1999)Theeffectofredwineanditscomponentsongrowthandproliferationofhumanoralsquamouscarcinomacells.AnticancerRes.,19,5407–5414.

70. Surh,Y.J.,Hurh,Y.J.,Kang,J.Y.,Lee,E.,Kong,G.andLee,S.J.(1999)Resveratrol,anantioxidantpresentinredwine,inducesapoptosisinhumanpromyelocyticleukemia(HL-60)cells.CancerLett.,140,1–10.

71. Babich,H.,Reisbaum,A.G.andZuckerbraun,H.L.(2000)InvitroresponseofhumangingivalepithelialS-Gcellstoresveratrol.Toxicol.Lett.,114,143–153.

72. Moreno,J.J.(2000)Resveratrolmodulatesarachidonicacidrelease,prosta-glandinsynthesis,and3T6fibroblastgrowth.J.Pharmacol.Exp.Ther.,294,333–338.

73. Clement,M.V.,Hirpara,J.L.,Chawdhury,S.H.andPervaiz,S.(1998)Chemoprotectiveagentresveratrol,anaturalproductderivedfromgrapes,triggersCD95signaling-dependentapoptosisinhumantumorcells.Blood,92,996–1002.

74. Holmes-McNary,M.andBaldwin,A.S.,Jr(2000)Chemoprotectivepropertiesoftrans-resveratrolareassociatedwithinhibitionofactivationoftheIBkinase.CancerRes.,60,3477–3483.

75. Ragione,F.D.,Cucciolla,V.,Borriello,A.,Pietra,V.D.,Racioppi,L.,Soldati,G.,Manna,C.,Galletti,P.andZappia,V.(1998)ResveratrolarreststhecelldivisioncycleatS/G2phasetransition.Biochem.Biophys.Res.Commun.,250,53–58.

76. Suh,N.,Luyengi,L.,Fong,H.H.,Kinghorn,A.D.andPezzuto,J.M.(1995)DiscoveryofnaturalproductchemoprotectiveagentsutilizingHL-60celldifferentiationasamodel.AnticancerRes.,15,233–239.

77. Hsieh,T.C.,Juan,G.,Darzynkiewicz,Z.andWu,J.M.(1999)Resveratrolincreasesnitricoxidesynthase,inducesaccumulationofp53andp21(WAF1/CIP1),andsuppressesculturedbovinepulmonaryarteryendothelialcellproliferationbyperturbingprogressionthroughSandG2.CancerRes.,59,2596–2601.

78. Tsan,M.F.,White,J.E.,Maheshwari,J.G.,Bremner,T.A.andSacco,J.(2000)ResveratrolinducesFassignalling-independentapoptosisinTHP-1humanmonocyticleukaemiacells.Br.J.Haematol.,109,405–412.

79. Carbo,N.,Costelli,P.,Baccino,F.M.,Lopez-Soriano,F.J.andArgiles,J.M.(1999)Resveratrol,anaturalproductpresentinwine,decreasestumourgrowthinarattumourmodel.Biochem.Biophys.Res.Commun.,254,739–743.

80. Tessitore,L.,Davit,A.,Sarotto,I.andCaderni,G.(2000)Resveratroldepressesthegrowthofcolorectalaberrantcryptfocibyaffectingbaxandp21CIPex-pression.Carcinogenesis,21,1619–1622.

81. Gautam,S.C.,Xu,Y.X.,Dumaguin,M.,Janakiraman,N.andChapman,R.A.(2000)Resveratrolselectivelyinhibitsleukemiacells:aprospectiveagentforexvivobonemarrowpurging.BoneMarrowTransplant.,25,639–645.

82. Hsieh,T.C.,Burfeind,P.,Laud,K.,Backer,J.M.,Traganos,F.,Darzynkiewicz,Z.andWu,J.M.(1999)Cellcycleeffectsandcontrolofgeneexpressionbyresveratrolinhumanbreastcarcinomacelllineswithdifferentmetastaticpotentials.Int.J.Oncol.,15,245–252.

83. MacCarrone,M.,Lorenzon,T.,Guerrieri,P.andAgro,A.F.(1999)Resveratrolpre-ventsapoptosisinK562cellsbyinhibitinglipoxygenaseandcyclooxygenaseactivity.Eur.J.Biochem.,265,27–34.

84. MacCarrone,M.,Nieuwenhuizen,W.E.,Dullens,H.F.,Catani,M.V.,Melino,G.,Veldink,G.A.,Vliegenthart,J.F.andFinazzo,A.A.(1996)Membranemodifica-tionsinhumanerythroleukemiaK562cellsduringinductionofprogrammedcelldeathbytransforminggrowthfactorß1orcisplatin.Eur.J.Biochem.,241,297–302.

��

85. Lu,R.andSerrero,G.(1999)Resveratrol,anaturalproductderivedfromgrape,exhibitsantiestrogenicactivityandinhibitsthegrowthofhumanbreastcancercells.J.CellPhysiol.,179,297–304.

86. Basly,J.P.,Marre-Fournier,F.,LeBail,J.C.,Habrioux,G.andChulia,A.J.(2000)Estrogenic/antiestrogenicandscavengingpropertiesof(E)-and(Z)-resvera-trol.LifeSci.,66,769–777.

87. Mgbonyebi,O.P.,Russo,J.andRusso,I.H.(1998)Antiproliferativeeffectofsyn-theticresveratrolonhumanbreastepithelialcells.Int.J.Oncol.,12,865–869.

88. Ashby,J.,Tinwell,H.,Pennie,W.,Brooks,A.N.,Lefevre,P.A.,Beresford,N.andSumpter,J.P.(1999)Partialandweakoestrogenicityoftheredwineconstitu-entresveratrol:considerationofitssuperagonistactivityinMCF-7cellsanditssuggestedcardiovascularprotectiveeffects.J.Appl.Toxicol.,19,39–45.

89. Slater,I.,Odum,J.andAshby,J.(1999)Resveratrolandredwineconsump-tion.Hum.Exp.Toxicol.,18,625–626.[FreeFullText]Turner,R.T.,Evans,G.L.,Zhang,M.,Maran,A.andSibonga,J.D.(1999)Isresveratrolanestrogenagonistingrowingrats?Endocrinology,140,50–54.

90. Mizutani,K.,Ikeda,K.,Kawai,Y.andYamori,Y.(2000)Resveratrolattenuatesovariectomy-inducedhypertensionandbonelossinstroke-pronespontane-ouslyhypertensiverats.J.Nutr.Sci.Vitaminol.(Tokyo),46,78–83.

91. Hsieh,T.C.andWu,J.M.(1999)Differentialeffectsongrowth,cellcyclearrest,andinductionofapoptosisbyresveratrolinhumanprostatecancercelllines.Exp.CellRes.,249,109–115.

92. Mitchell,S.H.,Zhu,W.andYoung,C.Y.(1999)ResveratrolinhibitstheexpressionandfunctionoftheandrogenreceptorinLNCaPprostatecancercells.CancerRes.,59,5892–5895.

93. Hsieh,T.C.andWu,J.M.(2000)Grape-derivedchemoprotectiveagentresve-ratroldecreasesprostate-specificantigen(PSA)expressioninLNCaPcellsbyanandrogenreceptor(AR)-independentmechanism.AnticancerRes.,20,225–228.

��

94. Ulsperger,E.,Hamilton,G.,Raderer,M.,Baumgartner,G.,Hejna,M.,Hoffmann,O.andMallinger,R.(1999)ResveratrolpretreatmentdesensitizesAHTO-7humanosteoblaststogrowthstimulationinresponsetocarcinomacellsupernatants.Int.J.Oncol.,15,955–959.

95. McMurtey,K.D.(1996)Resveratrolinwine.InWatkins,T.R.(ed.)Wine:NutritionalandTherapeuticBenefits.Am.Chem.Soc.

96. Bertelli,A.A.,Giovannini,L.,Stradi,R.,Urien,S.,Tillement,J.P.andBertelli,A.(1998)Evaluationofkineticparametersofnaturalphytoalexininresveratrolorallyadministeredinwinetorats.DrugsExp.Clin.Res.,24,51–55.

97. Bertelli,A.A.,Giovannini,L.,Stradi,R.,Bertelli,A.andTillement,J.P.(1996)Plasma,urineandtissuelevelsoftrans-andcis-resveratrol(3,4’,5-trihydroxys-tilbene)aftershort-termorprolongedadministrationofredwinetorats.Int.J.TissueReact.,18,67–71.

98. Bertelli,A.,Bertelli,A.A.,Gozzini,A.andGiovannini,L.(1998)Plasmaandtissueresveratrolconcentrationsandpharmacologicalactivity.DrugsExp.Clin.Res.,24,133–138.

99. Kuhnle,G.,Spencer,J.P.,Chowrimootoo,G.,Schroeter,H.,Debnam,E.S.,Srai,S.K.,Rice-Evans,C.andHahn,U.(2000)Resveratrolisabsorbedinthesmallintestineasresveratrolglucuronide.Biochem.Biophys.Res.Commun.,272,212–217.

100. Andlauer,W.,Kolb,J.,Siebert,K.andFurst,P.(2000)Assessmentofresveratrolbioavailabilityintheperfusedsmallintestineoftherat.DrugsExp.Clin.Res.,26,47–55.

101. Teel,R.W.andHuynh,H.(1998)ModulationbyphytochemicalsofcytochromeP450-linkedenzymeactivity.CancerLett.,133,135–141.

��

Decreasedplateletaggregationandresveratrol1. YangYM,WangXX,ChenJZ,WangSJ,HuH,WangHQ.,Resveratrolattenuates

adenosinediphosphate-inducedplateletactivationbyreducingproteinkinaseCactivity.,AmJChinMed.2008;36(3):603-13.

2. YangYM,ChenJZ,WangXX,WangSJ,HuH,WangHQ.,ResveratrolattenuatesthromboxaneA2receptoragonist-inducedplateletactivationbyreducingphospholipaseCactivity.,EurJPharmacol.2008Mar31;583(1):148-55.

3. YangYM,WangXX,WangSJ,WangHQ,ChenJZ.,[SuppressiveeffectinvitroofresveratrolonADPinducedhumanplateletaggregationanditsactivemecha-nism]YaoXueXueBao.2008Apr;43(4):356-60.[Chinese]

4. OlasB,WachowiczB,TomczakA,ErlerJ,StochmalA,OleszekW.,Comparativeanti-plateletandantioxidantpropertiesofpolyphenol-richextractsfrom:berriesofAroniamelanocarpa,seedsofgrapeandbarkofYuccaschidigerainvitro.,Platelets.2008Feb;19(1):70-7.

5. KoutsasC,SarigiannisY,StavropoulosG,Liakopoulou-KyriakidesM.,ConjugationofresveratrolwithRGDandKGDderivatives.,ProteinPeptLett.2007;14(10):1014-20.

6. delaLastraCA,VillegasI.,Resveratrolasanantioxidantandpro-oxidantagent:mechanismsandclinicalimplications.,BiochemSocTrans.2007Nov;35(Pt5):1156-60.

7. SaikoP,SzakmaryA,JaegerW,SzekeresT.,Resveratrolanditsanalogs:defenseagainstcancer,coronarydiseaseandneurodegenerativemaladiesorjustafad?,MutatRes.2008Jan-Feb;658(1-2):68-94.Epub2007Aug17.

8. ShenMY,HsiaoG,LiuCL,FongTH,LinKH,ChouDS,SheuJR.,Inhibitorymechanismsofresveratrolinplateletactivation:pivotalrolesofp38MAPKandNO/cyclicGMP.BrJHaematol.2007Nov;139(3):475-85.

9. OlasB,Saluk-JuszczakJ,WachowiczB.,D-glucaro1,4-lactoneandresveratrolasantioxidantsinbloodplatelets.,CellBiolToxicol.2008Apr;24(2):189-99.

��

10. ChenYJ,WangJS,ChowSE.,Resveratrolprotectsvascularendothelialcellfromox-LDL-inducedreductioninantithrombogenicactivity.,ChinJPhysiol.2007Feb28;50(1):22-8.Erratumin:ChinJPhysiol.2007Apr30;50(2):98.

11. WuCC,WuCI,WangWY,WuYC.,Lowconcentrationsofresveratrolpotentiatetheantiplateleteffectofprostaglandins.,PlantaMed.2007May;73(5):439-43.

12. OpieLH,LecourS.,Theredwinehypothesis:fromconceptstoprotectivesig-nallingmolecules.,EurHeartJ.2007Jul;28(14):1683-93.

13. deLangeDW,VerhoefS,GorterG,KraaijenhagenRJ,vandeWielA,AkkermanJW.,PolyphenolicgrapeextractinhibitsplateletactivationthroughPECAM-1:anexplanationfortheFrenchparadox.,AlcoholClinExpRes.2007Aug;31(8):1308-14.

14. SaeedSA,ConnorJD,Imran,QuadriJ,TasneemS,AhmedS,MesaikMA,ChoudharyMI.,Inhibitorsofphosphatidylinositide3-kinase:effectsonreactiveoxygenspeciesandplateletaggregation.,PharmacolRep.2007Mar-Apr;59(2):238-43.

15. AtharM,BackJH,TangX,KimKH,KopelovichL,BickersDR,KimAL.,Resveratrol:areviewofpreclinicalstudiesforhumancancerprevention.,ToxicolApplPharmacol.2007Nov1;224(3):274-83.

16. ProvidênciaR.,Cardiovascularprotectionfromalcoholicdrinks:scientificbasisoftheFrenchParadox.,RevPortCardiol.2006Nov;25(11):1043-58.

17. FragopoulouE,NomikosT,KarantonisHC,ApostolakisC,PliakisE,SamiotakiM,PanayotouG,AntonopoulouS.,Biologicalactivityofacetylatedphenoliccompounds.,JAgricFoodChem.2007Jan10;55(1):80-9.

18. CsiszarA,SmithK,LabinskyyN,OroszZ,RiveraA,UngvariZ.,ResveratrolattenuatesTNF-alpha-inducedactivationofcoronaryarterialendothelialcells:roleofNF-kappaBinhibition.,AmJPhysiolHeartCircPhysiol.2006Oct;291(4):H1694-9.

��

19. StefG,CsiszarA,LereaK,UngvariZ,VeressG.,Resveratrolinhibitsaggrega-tionofplateletsfromhigh-riskcardiacpatientswithaspirinresistance.,JCardiovascPharmacol.2006Aug;48(2):1-5.

20. OlasB,NowakP,PonczekM,WachowiczB.,Resveratrol,anaturalphenoliccompoundmayreducecarbonylationproteinsinducedbyperoxynitriteinbloodplatelets.,GenPhysiolBiophys.2006Jun;25(2):215-22.

21. ZbikowskaHM,OlasB,WachowiczB,KrajewskiT.,Responseofbloodplateletstoresveratrol.,Platelets.1999Jul;10(4):247-52.

22. FengL,JinJ,ZhangLF,YanT,TaoWY.,Analysisoftheresveratrol-bindingproteinusingphage-displayedrandompeptidelibrary.,ActaBiochimBiophysSin(Shanghai).2006May;38(5):342-8.

23. VilarS,QuezadaE,SantanaL,UriarteE,YánezM,FraizN,AlcaideC,CanoE,OralloF.,Design,synthesis,andvasorelaxantandplateletantiaggregatoryactivitiesofcoumarin-resveratrolhybrids.,BioorgMedChemLett.2006Jan15;16(2):257-61.

24. WirleitnerB,SchroecksnadelK,WinklerC,SchennachH,FuchsD.,Resveratrolsuppressesinterferon-gamma-inducedbiochemicalpathwaysinhumanperipheralbloodmononuclearcellsinvitro.,ImmunolLett.2005Sep15;100(2):159-63.

25. MousaSS,MousaSS,MousaSA.,Effectofresveratrolonangiogenesisandplatelet/fibrin-acceleratedtumorgrowthinthechickchorioallantoicmem-branemodel.,NutrCancer.2005;52(1):59-65.

26. OlasB,WachowiczB,HolmsenH,FukamiMH.,Resveratrolinhibitspolyphos-phoinositidemetabolisminactivatedplatelets.,BiochimBiophysActa.2005Aug15;1714(2):125-33.

27. OlasB,WachowiczB.,Resveratrol,aphenolicantioxidantwitheffectsonbloodplateletfunctions.,Platelets.2005Aug;16(5):251-60.

��

29. UlrichS,WolterF,SteinJM.,Molecularmechanismsofthechemoprotectiveeffectsofresveratrolanditsanalogsincarcinogenesis.,MolNutrFoodRes.2005May;49(5):452-61.

30. HuangYL,TsaiWJ,ShenCC,ChenCC.,ResveratrolderivativesfromtherootsofVitisthunbergii.,JNatProd.2005Feb;68(2):217-20.

31. OlasB,WachowiczB,StochmalA,OleszekW.,Inhibitionofbloodplateletad-hesionandsecretionbydifferentphenolicsfromYuccaschidigeraRoezl.bark.,Nutrition.2005Feb;21(2):199-206.

32. WolterF,UlrichS,SteinJ.,Molecularmechanismsofthechemoprotectiveeffectsofresveratrolanditsanalogsincolorectalcancer:keyroleofpoly-amines?,JNutr.2004Dec;134(12):3219-22.

33. SzewczukLM,PenningTM.,Mechanism-basedinactivationofCOX-1byredwinem-hydroquinones:astructure-activityrelationshipstudy.,JNatProd.2004Nov;67(11):1777-82.

34. DongHH,RenHL.,Newprogressioninthestudyofprotectiveprop-ertiesofresveratrolinanticardiovasculardisease.,BratislLekListy.2004;105(5-6):225-9.

35. BradamanteS,BarenghiL,VillaA.,Cardiovascularprotectiveeffectsofresve-ratrol.CardiovascDrugRev.2004Fall;22(3):169-88.

36. HaoHD,HeLR.,Mechanismsofcardiovascularprotectionbyresveratrol.,JMedFood.2004Fall;7(3):290-8.

37. KaneiderNC,MosheimerB,ReinischN,PatschJR,WiedermannCJ.,Inhibitionofthrombin-inducedsignalingbyresveratrolandquercetin:effectsonad-enosinenucleotidemetabolisminendothelialcellsandplatelet-neutrophilinteractions.,ThrombRes.2004;114(3):185-94.

��

38. FukaoH,IjiriY,MiuraM,HashimotoM,YamashitaT,FukunagaC,OiwaK,KawaiY,SuwaM,YamamotoJ.,Effectoftrans-resveratrolonthethrombo-genicityandatherogenicityinapolipoproteinE-deficientandlow-densitylipoproteinreceptor-deficientmice.,BloodCoagulFibrinolysis.2004Sep;15(6):441-6.

40. SchrieverC,PendlandSL,MahadyGB.,Redwine,resveratrol,Chlamydiapneu-moniaeandtheFrenchconnection.,Atherosclerosis.2003Dec;171(2):379-80.

41. ChenLN,ZangWJ,TangYH.,[Progressincardiovascularprotectiveeffectsofresveratrol],ShengLiKeXueJinZhan.2003Jul;34(3):272-4.[Chinese]

42. Granados-SotoV.,Pleiotropiceffectsofresveratrol.,DrugNewsPerspect.2003Jun;16(5):299-307.

43. TognaGI,TognaAR,FranconiM,MarraC,GuisoM.,Oliveoilisochromansinhibithumanplateletreactivity.,JNutr.2003Aug;133(8):2532-6.

44. OlasB,WachowiczB,StochmalA,OleszekW.,InhibitionofoxidativestressinbloodplateletsbydifferentphenolicsfromYuccaschidigeraRoezl.bark.,Nutrition.2003Jul-Aug;19(7-8):633-40.

45. KaldasMI,WalleUK,WalleT.,ResveratroltransportandmetabolismbyhumanintestinalCaco-2cells.,JPharmPharmacol.2003Mar;55(3):307-12.

46. OlasB,WachowiczB,Saluk-JuszczakJ,ZielinskiT.,Effectofresveratrol,anaturalpolyphenoliccompound,onplateletactivationinducedbyendotoxinorthrombin.,ThrombRes.2002Aug15;107(3-4):141-5.SuttnarJ,MásováL,ScheinerT,SorelováV,DyrJE.,[Roleoffreeradicalsinbloodplateletactiva-tion],CasLekCesk.2002Sep22;141Suppl:47-9.[Czech]

47. OlasB,WachowiczB,StochmalA,OleszekW.,Anti-plateleteffectsofdiffer-entphenoliccompoundsfromYuccaschidigeraRoezl.bark.,Platelets.2002May;13(3):167-73.

��

48. SinhaK,ChaudharyG,GuptaYK.,Protectiveeffectofresveratrolagainstoxida-tivestressinmiddlecerebralarteryocclusionmodelofstrokeinrats.,LifeSci.2002Jun28;71(6):655-65.

49. IgnatowiczE,Baer-DubowskaW.,Resveratrol,anaturalchemo-protectiveagentagainstdegenerativediseases.,PolJPharmacol.2001Nov-Dec;53(6):557-69.

50. WangZ,ZouJ,HuangY,CaoK,XuY,WuJM.,Effectofresveratrolonplateletaggregationinvivoandinvitro.,ChinMedJ(Engl).2002Mar;115(3):378-80.

51. El-MowafyAM.,Resveratrolactivatesmembrane-boundguanylylcyclaseincoronaryarterialsmoothmuscle:anovelsignalingmechanisminsupportofcoronaryprotection.,BiochemBiophysResCommun.2002Mar15;291(5):1218-24.

52. BhatKPL,KosmederJW2nd,PezzutoJM.,Biologicaleffectsofresveratrol.AntioxidRedoxSignal.2001Dec;3(6):1041-64.

53. WangZ,HuangY,ZouJ,CaoK,XuY,WuJM.,Effectsofredwineandwinepoly-phenolresveratrolonplateletaggregationinvivoandinvitro.,IntJMolMed.2002Jan;9(1):77-9.

54. HuangSS,TsaiMC,ChihCL,HungLM,TsaiSK.,ResveratrolreductionofinfarctsizeinLong-Evansratssubjectedtofocalcerebralischemia.,LifeSci.2001Jul20;69(9):1057-65.

55. PervaizS.,Resveratrol--fromthebottletothebedside?,LeukLymphoma.2001Feb;40(5-6):491-8.

56. StojanovicS,SprinzH,BredeO.,Efficiencyandmechanismoftheantioxidantactionoftrans-resveratrolanditsanaloguesintheradicalliposomeoxida-tion.,ArchBiochemBiophys.2001Jul1;391(1):79-89.

57. WuJM,WangZR,HsiehTC,BruderJL,ZouJG,HuangYZ.,Mechanismofcardio-protectionbyresveratrol,aphenolicantioxidantpresentinredwine.,IntJMolMed.2001Jul;8(1):3-17.

��

59. OlasB,WachowiczB,SzewczukJ,Saluk-JuszczakJ,KacaW.,Theeffectofres-veratrolontheplateletsecretoryprocessinducedbyendotoxinandthrom-bin.,Microbios.2001;105(410):7-13.

60. Ibern-GómezM,Roig-PérezS,Lamuela-RaventósRM,delaTorre-BoronatMC.,Resveratrolandpiceidlevelsinnaturalandblendedpeanutbutters.,JAgricFoodChem.2000Dec;48(12):6352-4.

61. JonssonKO,HedinHL,FowlerCJ.,Investigationintotherapideffectsof17beta-estradiolandneuroactivesteroidsuponbeta-amyloid(25-35)-inducedactivationofphosphoinositide-specificphospholipaseCinhumanplatelets.,MethodsFindExpClinPharmacol.2000Oct;22(8):615-20.

62. Romero-PérezAI,Lamuela-RaventósRM,Andrés-LacuevaC,deLaTorre-BoronatMC.,Methodforthequantitativeextractionofresveratrolandpiceidisomersingrapeberryskins.Effectofpowderymildewonthestilbenecontent.,JAgricFoodChem.2001Jan;49(1):210-5.

63. AburjaiTA.,Anti-plateletstilbenesfromaerialpartsofRheumpalaestinum.,Phytochemistry.2000Nov;55(5):407-10.

64. KirkRI,DeitchJA,WuJM,LereaKM.,Resveratroldecreasesearlysignalingeventsinwashedplateletsbuthaslittleeffectonplateletinwholeblood.,BloodCellsMolDis.2000Apr;26(2):144-50.

65. OlasB,ZbikowskaHM,WachowiczB,KrajewskiT,BuczynskiA,MagnuszewskaA.,Inhibitoryeffectofresveratrolonfreeradicalgenerationinbloodplatelets.,ActaBiochimPol.1999;46(4):961-6.

66. ZhuY,HuangT,CregorM,LongH,KissingerCB,KissingerPT.,Liquidchro-matographywithmultichannelelectrochemicaldetectionforthedetermina-tionoftrans-resveratrolinratbloodutilizinganautomatedbloodsamplingdevice.,JChromatogrBBiomedSciAppl.2000Mar31;740(1):129-33.

67. NaderaliEK,DoylePJ,WilliamsG.,Resveratrolinducesvasorelaxationofmes-entericanduterinearteriesfromfemaleguinea-pigs.,ClinSci(Lond).2000May;98(5):537-43.

68. SandersTH,McMichaelRWJr,HendrixKW.,Occurrenceofresveratrolinediblepeanuts.,JAgricFoodChem.2000Apr;48(4):1243-6.

69. FragopoulouE,NomikosT,AntonopoulouS,MitsopoulouCA,DemopoulosCA.,Separationofbiologicallyactivelipidsfromredwine.,JAgricFoodChem.2000Apr;48(4):1234-8.

70. PaulB,MasihI,DeopujariJ,CharpentierC.,Occurrenceofresveratrolandpterostilbeneinage-olddarakchasava,anayurvedicmedicinefromIndia.,JEthnopharmacol.1999Dec15;68(1-3):71-6.

71. Romero-PérezAI,Ibern-GómezM,Lamuela-RaventósRM,deLaTorre-BoronatMC.,Piceid,themajorresveratrolderivativeingrapejuices.,JAgricFoodChem.1999Apr;47(4):1533-6.

72. DobrydnevaY,WilliamsRL,BlackmorePF.,Trans-Resveratrolinhibitscalciuminfluxinthrombin-stimulatedhumanplatelets.,BrJPharmacol.1999Sep;128(1):149-57.

73. DasDK,SatoM,RayPS,MaulikG,EngelmanRM,BertelliAA,BertelliA.,Cardioprotectionofredwine:roleofpolyphenolicantioxidants.,DrugsExpClinRes.1999;25(2-3):115-20.

74. BlardiP,DeLallaA,VolpiL,DiPerriT.,Stimulationofendogenousadenosinereleasebyoraladministrationofquercetinandresveratrolinman.,DrugsExpClinRes.1999;25(2-3):105-10.

75. BavarescoL,FregoniC,CantùE,TrevisanM.,Stilbenecompounds:fromthegrapevinetowine.,DrugsExpClinRes.1999;25(2-3):57-63.

76. BertelliAA.,Recentprogressinresearchonwineanditscomponentsandtheirfavorableeffectsonhealth.,DrugsExpClinRes.1999;25(2-3):51-2.

��

77. FerreroME,BertelliAA,PellegattaF,FulgenziA,CorsiMM,BertelliA.,Phytoalexinresveratrol(3-4’-5-trihydroxystilbene)modulatesgranulocyteandmonocyteendothelialadhesion.,TransplantProc.1998Dec;30(8):4191-3.

78. BertelliA,BertelliAA,GozziniA,GiovanniniL.,Plasmaandtissueresve-ratrolconcentrationsandpharmacologicalactivity.,DrugsExpClinRes.1998;24(3):133-8.

79. CichewiczRH,KouziSA.,BiotransformationofresveratroltopiceidbyBacilluscereus.,JNatProd.1998Oct;61(10):1313-4.

80. KoppP.,Resveratrol,aphytoestrogenfoundinredwine.Apossibleexpla-nationfortheconundrumofthe‘Frenchparadox’?,EurJEndocrinol.1998Jun;138(6):619-20.

81. ConstantJ.,Alcohol,ischemicheartdisease,andtheFrenchparadox.,CoronArteryDis.1997Oct;8(10):645-9.

82. BlacheD,RustanI,DurandP,LesgardsG,LoreauN.,Gaschromatographicanalysisofresveratrolinplasma,lipoproteinsandcellsafterinvitroincuba-tions.,JChromatogrBBiomedSciAppl.1997Nov21;702(1-2):103-10.

83. OrsiniF,PelizzoniF,VerottaL,AburjaiT,RogersCB.,Isolation,synthesis,andantiplateletaggregationactivityofresveratrol3-O-beta-D-glucopyranosideandrelatedcompounds.,JNatProd.1997Nov;60(11):1082-7.

84. OrsiniF,PelizzoniF,BelliniB,MiglieriniG.,Synthesisofbiologicallyactivepolyphenolicglycosides(combretastatinandresveratrolseries).,CarbohydrRes.1997Jun20;301(3-4):95-109.

85. SoleasGJ,DiamandisEP,GoldbergDM.,Resveratrol:amoleculewhosetimehascome?Andgone?,ClinBiochem.1997Mar;30(2):91-113.

86. SoleasGJ,DiamandisEP,GoldbergDM.,Wineasabiologicalfluid:history,pro-duction,androleindiseaseprevention.,JClinLabAnal.1997;11(5):287-313.

��

87. RotondoS,RotilioD,CerlettiC,deGaetanoG.,Redwine,aspirinandplateletfunction.,ThrombHaemost.1996Nov;76(5):818-9.

88. GoldbergDM,TsangE,KarumanchiriA,DiamandisE,SoleasG,NgE.,Methodtoassaytheconcentrationsofphenolicconstituentsofbiologicalinterestinwines.,AnalChem.1996May15;68(10):1688-94.

89. Pace-AsciakCR,RounovaO,HahnSE,DiamandisEP,GoldbergDM.,Winesandgrapejuicesasmodulatorsofplateletaggregationinhealthyhumansubjects.ClinChimActa.1996Mar15;246(1-2):163-82.

90. BertelliAA,GiovanniniL,StradiR,BertelliA,TillementJP.,Plasma,urineandtissuelevelsoftrans-andcis-resveratrol(3,4’,5-trihydroxystilbene)aftershort-termorprolongedadministrationofredwinetorats.,IntJTissueReact.1996;18(2-3):67-71.

91. BertelliAA,GiovanniniL,BerniniW,MiglioriM,FregoniM,BavarescoL,BertelliA.,Antiplateletactivityofcis-resveratrol.,DrugsExpClinRes.1996;22(2):61-3.

92. WilsonT,KnightTJ,BeitzDC,LewisDS,EngenRL.,Resveratrolpromotesath-erosclerosisinhypercholesterolemicrabbits.,LifeSci.1996;59(1):PL15-21.

93. GoldbergDM.,Moreonantioxidantactivityofresveratrolinredwine.,ClinChem.1996Jan;42(1):113-4.

94. Pace-AsciakCR,HahnS,DiamandisEP,SoleasG,GoldbergDM.,Theredwinephenolicstrans-resveratrolandquercetinblockhumanplateletaggregationandeicosanoidsynthesis:implicationsforprotectionagainstcoronaryheartdisease.,ClinChimActa.1995Mar31;235(2):207-19.

95. BertelliAA,GiovanniniL,GiannessiD,MiglioriM,BerniniW,FregoniM,BertelliA.,Antiplateletactivityofsyntheticandnaturalresveratrolinredwine.,IntJTissueReact.1995;17(1):1-3.

96. ChungMI,TengCM,ChengKL,KoFN,LinCN.,AnantiplateletprincipleofVeratrumformosanum.,PlantaMed.1992Jun;58(3):274-6.

��

Antiaging1. OlivaJ,FrenchBA,LiJ,Bardag-GorceF,FuP,FrenchSW.,Sirt1isinvolvedin

energymetabolism:Theroleofchronicethanolfeedingandresveratrol.,ExpMolPathol.2008Aug28.

2. OralloF.,Trans-resveratrol:amagicalelixirofeternalyouth?,CurrMedChem.2008;15(19):1887-98.

3. RayalamS,YangJY,AmbatiS,Della-FeraMA,BaileCA.,Resveratrolinducesapoptosisandinhibitsadipogenesisin3T3-L1adipocytes.,PhytotherRes.2008Aug7.

4. MarkusMA,MorrisBJ.,Resveratrolinpreventionandtreatmentofcommonclinicalconditionsofaging.,ClinIntervAging.2008;3(2):331-9.

5. CaoC,LuS,KivlinR,WallinB,CardE,BagdasarianA,TamakloeT,WangWJ,SongX,ChuWM,KouttabN,XuA,WanY.,SIRT1confersprotectionagainstUVB-andH(2)O(2)-inducedcelldeathviamodulationofp53andJNKincul-turedskinkeratinocytes.,JCellMolMed.2008Aug4.

6. López-LluchG,IrustaPM,NavasP,deCaboR.,Mitochondrialbiogenesisandhealthyaging.ExpGerontol.2008Sep;43(9):813-9.

7. BargerJL,KayoT,PughTD,ProllaTA,WeindruchR.,Short-termconsump-tionofaresveratrol-containingnutraceuticalmixturemimicsgeneexpres-sionoflong-termcaloricrestrictioninmouseheart.,ExpGerontol.2008Sep;43(9):859-66.

8. MattsonMP,SonTG,CamandolaS.,Viewpoint:mechanismsofactionandtherapeuticpotentialofneurohormeticphytochemicals.,DoseResponse.2007Aug6;5(3):174-86.

��

9. CalabreseV,CorneliusC,MancusoC,PennisiG,CalafatoS,BelliaF,BatesTE,GiuffridaStellaAM,SchapiraT,DinkovaKostovaAT,RizzarelliE.,CellularStressResponse:ANovelTargetforChemopreventionandNutritionalNeuroprotectioninAging,NeurodegenerativeDisordersandLongevity.,NeurochemRes.2008Jul16.

10. PearsonKJ,BaurJA,LewisKN,PeshkinL,PriceNL,LabinskyyN,SwindellWR,KamaraD,MinorRK,PerezE,JamiesonHA,ZhangY,DunnSR,SharmaK,PleshkoN,WoollettLA,CsiszarA,IkenoY,LeCouteurD,ElliottPJ,BeckerKG,NavasP,IngramDK,WolfNS,UngvariZ,SinclairDA,deCaboR.,Resveratroldelaysage-relateddeteriorationandmimicstranscriptionalaspectsofdietaryrestrictionwithoutextendinglifespan.,CellMetab.2008Aug;8(2):157-68.

11. BargerJL,KayoT,VannJM,AriasEB,WangJ,HackerTA,WangY,RaederstorffD,MorrowJD,LeeuwenburghC,AllisonDB,SaupeKW,CarteeGD,WeindruchR,ProllaTA.,Alowdoseofdietaryresveratrolpartiallymimicscaloricrestric-tionandretardsagingparametersinmice.,PLoSONE.2008Jun4;3(6):e2264.

12. ChenCY,BlumbergJB.,Phytochemicalcompositionofnuts.,AsiaPacJClinNutr.2008;17Suppl1:329-32.

13. DengJY,HsiehPS,HuangJP,LuLS,HungLM.,Activationofestrogenreceptoriscrucialforresveratrol-stimulatingmuscularglucoseuptakeviabothinsulin-dependentand-independentpathways.,Diabetes.2008Jul;57(7):1814-23.

14. CsiszarA,LabinskyyN,PodlutskyA,KaminskiPM,WolinMS,ZhangC,MukhopadhyayP,PacherP,HuF,deCaboR,BallabhP,UngvariZ.,VasoprotectiveeffectsofresveratrolandSIRT1:attenuationofcigarettesmoke-inducedoxidativestressandproinflammatoryphenotypicalterations.,AmJPhysiolHeartCircPhysiol.2008Jun;294(6):H2721-35.

15. GuarenteL.,Sirtuinsinaginganddisease.,ColdSpringHarbSympQuantBiol.2007;72:483-8.

16. RossiL,MazzitelliS,ArcielloM,CapoCR,RotilioG.,BenefitsfromDietaryPolyphenolsforBrainAgingandAlzheimer’sDisease.,NeurochemRes.2008Apr16.

��

17. HarikumarKB,AggarwalBB.,Resveratrol:amultitargetedagentforage-asso-ciatedchronicdiseases.,CellCycle.2008Apr;7(8):1020-35.

18. HuangJ,GanQ,HanL,LiJ,ZhangH,SunY,ZhangZ,TongT.,SIRT1overexpres-sionantagonizescellularsenescencewithactivatedERK/S6k1signalinginhumandiploidfibroblasts.,PLoSONE.2008Mar5;3(3):e1710.

19. BaxterRA.,Anti-agingpropertiesofresveratrol:reviewandreportofapotentnewantioxidantskincareformulation.,JCosmetDermatol.2008Mar;7(1):2-7.

20. PallàsM,VerdaguerE,TajesM,Gutierrez-CuestaJ,CaminsA.,Modulationofsirtuins:newtargetsforantiageing.,RecentPatentsCNSDrugDiscov.2008Jan;3(1):61-9.

21. HsuCP,OdewaleI,AlcendorRR,SadoshimaJ.,Sirt1protectstheheartfromagingandstress.BiolChem.2008Mar;389(3):221-31.

22. EngelN,MahlknechtU.,Agingandanti-aging:unexpectedsideeffectsofeverydaymedicationthroughsirtuin1modulation.,IntJMolMed.2008Feb;21(2):223-32.

23. BickenbachKA,VeerapongJ,ShaoMY,MauceriHJ,PosnerMC,KronSJ,WeichselbaumRR.,ResveratrolisaneffectiveinducerofCArG-drivenTNF-alphagenetherapy.,CancerGeneTher.2008Mar;15(3):133-9.

24. SwindellWR.,Comparativeanalysisofmicroarraydataidentifiescommonresponsestocaloricrestrictionamongmousetissues.,MechAgeingDev.2008Mar;129(3):138-53.

25. BurtonDG,SheerinAN,OstlerEL,SmithK,GilesPJ,LoweJ,Rhys-WilliamsW,KiplingDG,FaragherRG.,CyclinD1overexpressionpermitsthereproducibledetectionofsenescenthumanvascularsmoothmusclecells.,AnnNYAcadSci.2007Nov;1119:20-31.

26. BaumannLS.,Less-knownbotanicalcosmeceuticals.,DermatolTher.2007Sep-Oct;20(5):330-42.

��

27. GambutiA,StrolloD,ErbaggioA,LecceL,MoioL.,Effectofwinemakingprac-ticesoncolorindexesandselectedbioactivephenolicsofAglianicowine.,JFoodSci.2007Nov;72(9):S623-8.

28. delaLastraCA,VillegasI.,Resveratrolasanantioxidantandpro-oxidantagent:mechanismsandclinicalimplications.,BiochemSocTrans.2007Nov;35(Pt5):1156-60.

29. PuticsA,VéghEM,CsermelyP,SotiC.,Resveratrolinducestheheat-shockresponseandprotectshumancellsfromsevereheatstress.,AntioxidRedoxSignal.2008Jan;10(1):65-75.

30. RasouriS,LagougeM,AuwerxJ.,[SIRT1/PGC-1:aneuroprotectiveaxis?],MedSci(Paris).2007Oct;23(10):840-4.[French]

31. MattsonMP.,Dietaryfactors,hormesisandhealth.,AgeingResRev.2008Jan;7(1):43-8.Epub2007Sep1.

32. BassTM,WeinkoveD,HouthoofdK,GemsD,PartridgeL.,EffectsofresveratrolonlifespaninDrosophilamelanogasterandCaenorhabditiselegans.,MechAgeingDev.2007Oct;128(10):546-52.

33. HudsonTS,HartleDK,HurstingSD,NunezNP,WangTT,YoungHA,AranyP,GreenJE.,Inhibitionofprostatecancergrowthbymuscadinegrapeskinextractandresveratrolthroughdistinctmechanisms.,CancerRes.2007Sep1;67(17):8396-405.

34. StefaniM,MarkusMA,LinRC,PineseM,DawesIW,MorrisBJ.,Theeffectofresveratrolonacellmodelofhumanaging.,AnnNYAcadSci.2007Oct;1114:407-18.

35. CucciollaV,BorrielloA,OlivaA,GallettiP,ZappiaV,DellaRagioneF.,Resveratrol:frombasicsciencetotheclinic.,CellCycle.2007Oct15;6(20):2495-510.

��

36. Barrera-GarcíaVD,GougeonRD,DiMajoD,DeAguirreC,VoilleyA,ChassagneD.,Differentsorptionbehaviorsforwinepolyphenolsincontactwithoakwood.,JAgricFoodChem.2007Aug22;55(17):7021-7.

37. KaeberleinM,KennedyBK.,DoesresveratrolactivateyeastSir2invivo?,AgingCell.2007Aug;6(4):415-6.

38. HeissEH,SchilderYD,DirschVM.,Chronictreatmentwithresveratrolinducesredoxstress-andataxiatelangiectasia-mutated(ATM)-dependentsenescenceinp53-positivecancercells.,J

39. BiolChKimD,NguyenMD,DobbinMM,FischerA,SananbenesiF,RodgersJT,DelalleI,BaurJA,SuiG,ArmourSM,PuigserverP,SinclairDA,TsaiLH.,SIRT1deacetylaseprotectsagainstneurodegenerationinmodelsforAlzheimer’sdiseaseandamyotrophiclateralsclerosis.,EMBOJ.2007Jul11;26(13):3169-79.

40. FröjdöS,CozzoneD,VidalH,PirolaL.,ResveratrolisaclassIAphosphoinosit-ide3-kinaseinhibitor.,BiochemJ.2007Sep15;406(3):511-8.

41. SeddingD,HaendelerJ.,DoweageonSirt1expression?,CircRes.2007May25;100(10):1396-8.

42. GruberJ,TangSY,HalliwellB.,Evidenceforatrade-offbetweensurvivalandfitnesscausedbyresveratroltreatmentofCaenorhabditiselegans.,AnnNYAcadSci.2007Apr;1100:530-42.

43. DasguptaB,MilbrandtJ.,ResveratrolstimulatesAMPkinaseactivityinneurons.,ProcNatlAcadSciUSA.2007Apr24;104(17):7217-22.

44. UngvariZ,OroszZ,LabinskyyN,RiveraA,XiangminZ,SmithK,CsiszarA.,IncreasedmitochondrialH2O2productionpromotesendothelialNF-kappaBactivationinagedratarteries.,AmJPhysiolHeartCircPhysiol.2007Jul;293(1):H37-47.

��

45. KallithrakaS,MamalosA,MakrisDP.,Differentiationofyoungredwinesbasedonchemometricsofminorpolyphenolicconstituents.,JAgricFoodChem.2007May2;55(9):3233-9.

46. BastianettoS,BrouilletteJ,QuirionR.,Neuroprotectiveeffectsofnaturalprod-ucts:interactionwithintracellularkinases,amyloidpeptidesandapossiblerolefortransthyretin.,NeurochemRes.2007Oct;32(10):1720-5.

47. JefremovV,ZilmerM,ZilmerK,BogdanovicN,KarelsonE.,Antioxidativeeffectsofplantpolyphenols:fromprotectionofGproteinsignalingtopreven-tionofage-relatedpathologies.,AnnNYAcadSci.2007Jan;1095:449-57.

48. TangBL,ChuaCE.,SIRT1andneuronaldiseases.,MolAspectsMed.2008Jun;29(3):187-200.

49. RussoGL.,Insandoutsofdietaryphytochemicalsincancerchemoprevention.,BiochemPharmacol.2007Aug15;74(4):533-44.

50. BlagosklonnyMV.,Ananti-agingdrugtoday:fromsenescence-promotinggenestoanti-agingpill.DrugDiscovToday.2007Mar;12(5-6):218-24.

51. AustadSN.,Vertebrateagingresearch2006.,AgingCell.2007Apr;6(2):135-8.

52. StippD.,Liveforever?,Fortune.2007Feb5;155(2):68-70,72,74passim.

53. HolmeAL,PervaizS.,Resveratrolincellfatedecisions.,JBioenergBiomembr.2007Feb;39(1):59-63.

54. LabieD,FerréP.,[Cheers!],MedSci(Paris).2007Feb;23(2):122.[French]

55. UngvariZ,OroszZ,RiveraA,LabinskyyN,XiangminZ,OlsonS,PodlutskyA,CsiszarA.,Resveratrolincreasesvascularoxidativestressresistance.,AmJPhysiolHeartCircPhysiol.2007May;292(5):H2417-24.

56. ChenD,GuarenteL.,SIR2:apotentialtargetforcalorierestrictionmimetics.,TrendsMolMed.2007Feb;13(2):64-71.

��

57. SinclairD,KomaroffAL.,Canweslowaging?,Newsweek.2006Dec11;148(24):80,82,84.

58. KooSH,MontminyM.,Invinoveritas:ataleoftwosirt1s?,Cell.2006Dec15;127(6):1091-3.

59. YangH,BaurJA,ChenA,MillerC,AdamsJK,KisielewskiA,HowitzKT,ZipkinRE,SinclairDA.,Designandsynthesisofcompoundsthatextendyeastrepli-cativelifespan.,AgingCell.2007Feb;6(1):35-43.Erratumin:AgingCell.2007Aug;6(4):593.Adams,JeffreyK[added];Kisielewski,Anne[added];Howitz,KonradT[added];Zipkin,RobertE[added].

60. KaeberleinM,RabinovitchPS.,Medicine:grapesversusgluttony.,Nature.2006Nov16;444(7117):280-1.

61. BaurJA,PearsonKJ,PriceNL,JamiesonHA,LerinC,KalraA,PrabhuVV,AllardJS,Lopez-LluchG,LewisK,PistellPJ,PoosalaS,BeckerKG,BossO,GwinnD,WangM,RamaswamyS,FishbeinKW,SpencerRG,LakattaEG,LeCouteurD,ShawRJ,NavasP,PuigserverP,IngramDK,deCaboR,SinclairDA.,Resveratrolimproveshealthandsurvivalofmiceonahigh-caloriediet.,Nature.2006Nov16;444(7117):337-42.

62. TerzibasiE,ValenzanoDR,CellerinoA.,Theshort-livedfishNothobranchiusfurzeriasanewmodelsystemforagingstudies.,ExpGerontol.2007Jan-Feb;42(1-2):81-9.

63. YangSR,WrightJ,BauterM,SeweryniakK,KodeA,RahmanI.,Sirtuinregu-latescigarettesmoke-inducedproinflammatorymediatorreleaseviaRelA/p65NF-kappaBinmacrophagesinvitroandinratlungsinvivo:implicationsforchronicinflammationandaging.,AmJPhysiolLungCellMolPhysiol.2007Feb;292(2):L567-76.

64. MattsonMP,ChengA.,Neurohormeticphytochemicals:Low-dosetoxinsthatinduceadaptiveneuronalstressresponses.,TrendsNeurosci.2006Nov;29(11):632-9.

65. YaoY,TianT,NanKJ.,[Researchonresveratrol’smechanismofimmunityinanti-aging],ZhongYaoCai.2006May;29(5):464-7.[Chinese]

67. HornTL,CwikMJ,MorrisseyRL,KapetanovicI,CrowellJA,BoothTD,McCormickDL.,Oncogenicityevaluationofresveratrolinp53(+/-)(p53knockout)mice.,FoodChemToxicol.2007Jan;45(1):55-63.

68. RamassamyC.,Emergingroleofpolyphenoliccompoundsinthetreatmentofneurodegenerativediseases:areviewoftheirintracellulartargets.,EurJPharmacol.2006Sep1;545(1):51-64.

69. AfaqF,MukhtarH.,Botanicalantioxidantsinthepreventionofphotocarcino-genesisandphotoaging.,ExpDermatol.2006Sep;15(9):678-84.

70. CollinsJJ,EvasonK,KornfeldK.,PharmacologyofdelayedagingandextendedlifespanofCaenorhabditiselegans.,ExpGerontol.2006Oct;41(10):1032-9.

71. SpinneyL.,Gerontology:eatyourcakeandhaveit.,Nature.2006Jun15;441(7095):807-9.

72. AnekondaTS.,Resveratrol--aboonfortreatingAlzheimer’sdisease?,BrainResRev.2006Sep;52(2):316-26.

73. BaurJA,SinclairDA.,Therapeuticpotentialofresveratrol:theinvivoevi-dence.,NatRevDrugDiscov.2006Jun;5(6):493-506.

74. ValenzanoDR,CellerinoA.,Resveratrolandthepharmacologyofaging:anewvertebratemodeltovalidateanoldmolecule.,CellCycle.2006May;5(10):1027-32.

�0�

75. IngramDK,ZhuM,MamczarzJ,ZouS,LaneMA,RothGS,deCaboR.,Calorierestrictionmimetics:anemergingresearchfield.,AgingCell.2006Apr;5(2):97-108.

76. LabinskyyN,CsiszarA,VeressG,StefG,PacherP,OrosziG,WuJ,UngvariZ.,Vasculardysfunctioninaging:potentialeffectsofresveratrol,ananti-inflam-matoryphytoestrogen.,CurrMedChem.2006;13(9):989-96.

77. SinclairDA,GuarenteL.,Unlockingthesecretsoflongevitygenes.,SciAm.2006Mar;294(3):48-51,54-7.

78. ValenzanoDR,TerzibasiE,GenadeT,CattaneoA,DomeniciL,CellerinoA.,Resveratrolprolongslifespanandretardstheonsetofage-relatedmarkersinashort-livedvertebrate.,CurrBiol.2006Feb7;16(3):296-300.

79. OsawaT.,[Recentdevelopmentandfuturedirectionofanti-agingtherapybysupplements]NipponRonenIgakkaiZasshi.2005Nov;42(6):587-95.[Japanese]

80. TatarM.,SIR2callsupontheER.,CellMetab.2005Nov;2(5):281-2.

81. SupornsilchaiV,SvechnikovK,Seidlova-WuttkeD,WuttkeW,SöderO.,Phytoestrogenresveratrolsuppressessteroidogenesisbyratadrenocor-ticalcellsbyinhibitingcytochromeP450c21-hydroxylase.,HormRes.2005;64(6):280-6.

82. ViswanathanM,KimSK,BerdichevskyA,GuarenteL.,AroleforSIR-2.1regula-tionofERstressresponsegenesindeterminingC.eleganslifespan.,DevCell.2005Nov;9(5):605-15.

83. AnekondaTS,ReddyPH.,NeuronalprotectionbysirtuinsinAlzheimer’sdisease.,JNeurochem.2006Jan;96(2):305-13.Epub2005Oct7.

84. MorrisBJ.,Aforkheadintheroadtolongevity:themolecularbasisoflifespanbecomesclearer.JHypertens.2005Jul;23(7):1285-309.

�0�

85. SinclairDA.,Towardaunifiedtheoryofcaloricrestrictionandlongevityregu-lation.,MechAgeingDev.2005Sep;126(9):987-1002.

86. delaLastraCA,VillegasI.,Resveratrolasananti-inflammatoryandanti-agingagent:mechanismsandclinicalimplications.,MolNutrFoodRes.2005May;49(5):405-30.

88. ProvincialiM,ReF,DonniniA,OrlandoF,BartozziB,DiStasioG,SmorlesiA.,EffectofresveratrolonthedevelopmentofspontaneousmammarytumorsinHER-2/neutransgenicmice.,IntJCancer.2005May20;115(1):36-45.

89. KaeberleinM,McDonaghT,HeltwegB,HixonJ,WestmanEA,CaldwellSD,NapperA,CurtisR,DiStefanoPS,FieldsS,BedalovA,KennedyBK.,Substrate-specificactivationofsirtuinsbyresveratrol.JBiolChem.2005Apr29;280(17):17038-45.

90. BurzynskiSR.,Aging:genesilencingorgeneactivation?,MedHypotheses.2005;64(1):201-8.

91. JarolimS,MillenJ,HeerenG,LaunP,GoldfarbDS,BreitenbachM.,AnovelassayforreplicativelifespaninSaccharomycescerevisiae.,FEMSYeastRes.2004Nov;5(2):169-77.

92. BauerJH,GoupilS,GarberGB,HelfandSL.,Anacceleratedassayfortheidenti-ficationoflifespan-extendinginterventionsinDrosophilamelanogaster.,ProcNatlAcadSciUSA.2004Aug31;101(35):12980-5.

93. FlurkeyK,CurrerJM.,Pitfallsofanimalmodelsystemsinageingresearch.,BestPractResClinEndocrinolMetab.2004Sep;18(3):407-21.

94. WoodJG,RoginaB,LavuS,HowitzK,HelfandSL,TatarM,SinclairD.,Sirtuinactivatorsmimiccaloricrestrictionanddelayageinginmetazoans.,Nature.2004Aug5;430(7000):686-9.

�0�

95. LeslieM.,Resveratroltotherescue.,SciAgingKnowledgeEnviron.2004Jul14;2004(28):nf67.

96. PicardF,KurtevM,ChungN,Topark-NgarmA,SenawongT,MachadoDeOliveiraR,LeidM,McBurneyMW,GuarenteL.,Sirt1promotesfatmobili-zationinwhiteadipocytesbyrepressingPPAR-gamma.,Nature.2004Jun17;429(6993):771-6.

97. HorsemanRE.,Sayyestosirtuin;notolampshades.,JCalifDentAssoc.2004Feb;32(2):198,197.

98. CouzinJ.,Scientificcommunity.Agingresearch’sfamilyfeud.,Science.2004Feb27;303(5662):1276-9.

99. O’NeillB.,InMethuselah’sMould.,PLoSBiol.2004Jan;2(1):E12.

100. PocarP,AugustinR,FischerB.,ConstitutiveexpressionofCYP1A1inbovinecumulusoocyte-complexesinvitro:mechanismsandbiologicalimplications.,Endocrinology.2004Apr;145(4):1594-601.

101. CorderR,CrozierA,KroonPA.,Drinkingyourhealth?It’stooearlytosay.,Nature.2003Nov13;426(6963):119.

102. FinkelT.,Ageing:atoasttolonglife.,Nature.2003Sep11;425(6954):132-3.

103. HallSS.,Longevityresearch.Invinovitalis?Compoundsactivatelife-extend-inggenes.,Science.2003Aug29;301(5637):1165.

104. BhavnaniBR.,Estrogensandmenopause:pharmacologyofconjugatedequineestrogensandtheirpotentialroleinthepreventionofneurode-generativediseasessuchasAlzheimer’s.,JSteroidBiochemMolBiol.2003Jun;85(2-5):473-82.

105. HowitzKT,BittermanKJ,CohenHY,LammingDW,LavuS,WoodJG,ZipkinRE,ChungP,KisielewskiA,ZhangLL,SchererB,SinclairDA.,SmallmoleculeactivatorsofsirtuinsextendSaccharomycescerevisiaelifespan.,Nature.2003Sep11;425(6954):191-6.

�0�

106. FlaminiR.,Massspectrometryingrapeandwinechemistry.PartI:polyphe-nols.,MassSpectromRev.2003Jul-Aug;22(4):218-50.

107. BoscoloP,delSignoreA,SabbioniE,DiGioacchinoM,DiGiampaoloL,RealeM,ContiP,PaganelliR,GiaccioM.,Effectsofresveratrolonlymphocyteprolifera-tionandcytokinerelease.,AnnClinLabSci.2003Spring;33(2):226-31.

108. SchwedhelmE,MaasR,TroostR,BögerRH.,Clinicalpharmacokineticsofan-tioxidantsandtheirimpactonsystemicoxidativestress.,ClinPharmacokinet.2003;42(5):437-59.

109. López-BurilloS,TanDX,MayoJC,SainzRM,ManchesterLC,ReiterRJ.,Melatonin,xanthurenicacid,resveratrol,EGCG,vitaminCandalpha-lipoicaciddifferentiallyreduceoxidativeDNAdamageinducedbyFentonre-agents:astudyoftheirindividualandsynergisticactions.,JPinealRes.2003May;34(4):269-77.

110. SparrowJR,Vollmer-SnarrHR,ZhouJ,JangYP,JockuschS,ItagakiY,NakanishiK.,A2E-epoxidesdamageDNAinretinalpigmentepithelialcells.VitaminEandotherantioxidantsinhibitA2E-epoxideformation.,JBiolChem.2003May16;278(20):18207-13.

111. Pozo-BayónMA,HernándezMT,Martín-AlvarezPJ,PoloMC.,Studyoflowmolecularweightphenoliccompoundsduringtheagingofsparklingwinesmanufacturedwithredandwhitegrapevarieties.,JAgricFoodChem.2003Mar26;51(7):2089-95.

112. LiuC,RussellRM,WangXD.,Exposingferretstocigarettesmokeandaphar-macologicaldoseofbeta-carotenesupplementationenhanceinvitroretinoicacidcatabolisminlungsviainductionofcytochromeP450enzymes.,JNutr.2003Jan;133(1):173-9.

113. BastianettoS,QuirionR.,Naturalextractsaspossibleprotectiveagentsofbrainaging.,NeurobiolAging.2002Sep-Oct;23(5):891-97.

114. SunAY,SimonyiA,SunGY.,The“FrenchParadox”andbeyond:neuroprotectiveeffectsofpolyphenols.,FreeRadicBiolMed.2002Feb15;32(4):314-8.

�0�

115. IguraK,OhtaT,KurodaY,KajiK.,Resveratrolandquercetininhibitangiogen-esisinvitro.CancerLett.2001Sep28;171(1):11-6.

116. FrankelD,SchipperHM.,Cysteaminepretreatmentoftheastroglialsubstra-tum(mitochondrialironsequestration)enhancesPC12cellvulnerabilitytooxidativeinjury.,ExpNeurol.1999Dec;160(2):376-85.

117. SunAY,ChenYM,James-KrackeM,WixomP,ChengY.,Ethanol-inducedcelldeathbylipidperoxidationinPC12cells.,NeurochemRes.1997Oct;22(10):1187-92.

118. PezzutoJM.,Grapesandhumanhealth:aperspective.,JAgricFoodChem.2008Aug27;56(16):6777-84.

Immuneboostingeffectofresveratrol1. UdenigweCC,RamprasathVR,AlukoRE,JonesPJ.,Potentialofresveratrolin

anticancerandanti-inflammatorytherapy.,NutrRev.2008Aug;66(8):445-54.

2. BargerJL,KayoT,PughTD,ProllaTA,WeindruchR.,Short-termconsump-tionofaresveratrol-containingnutraceuticalmixturemimicsgeneexpres-sionoflong-termcaloricrestrictioninmouseheart.,ExpGerontol.2008Sep;43(9):859-66.

3. YangY,PaikJH,ChoD,ChoJA,KimCW.,Resveratrolinducesthesuppressionoftumor-derivedCD4+CD25+regulatoryTcells.,IntImmunopharmacol.2008Apr;8(4):542-7.

4. ClarkeJO,MullinGE.,Areviewofcomplementaryandalternativeapproachestoimmunomodulation.,NutrClinPract.2008Feb;23(1):49-62.

5. PanMH,GaoJH,LaiCS,WangYJ,ChenWM,LoCY,WangM,DushenkovS,HoCT.,Antitumoractivityof3,5,4’-trimethoxystilbeneinCOLO205cellsandxenograftsinSCIDmice.,MolCarcinog.2008Mar;47(3):184-96.

�0�

6. BanerjeeT,DuhadawayJB,GaspariP,Sutanto-WardE,MunnDH,MellorAL,MalachowskiWP,PrendergastGC,MullerAJ.,Akeyinvivoantitumormecha-nismofactionofnaturalproduct-basedbrassininsisinhibitionofindole-amine2,3-dioxygenase.,Oncogene.2008May1;27(20):2851-7.

7. BlockG,JensenCD,NorkusEP,DalviTB,WongLG,McManusJF,HudesML.,Usagepatterns,health,andnutritionalstatusoflong-termmultipledietarysupplementusers:across-sectionalstudy.,NutrJ.2007Oct24;6:30.

8. HsiehSC,LuCC,HorngYT,SooPC,ChangYL,TsaiYH,LinCS,LaiHC.,Thebacterialmetabolite2,3-butanediolamelioratesendotoxin-inducedacutelunginjuryinrats.,MicrobesInfect.2007Oct;9(12-13):1402-9.

9. DasS,DasDK.,Anti-inflammatoryresponsesofresveratrol.,InflammAllergyDrugTargets.2007Sep;6(3):168-73.

10. VetvickaV,VolnyT,Saraswat-OhriS,VashishtaA,VancikovaZ,VetvickovaJ.,Glucanandresveratrolcomplex--possiblesynergisticeffectsonimmunesystem.,BiomedPapMedFacUnivPalackyOlomoucCzechRepub.2007Jun;151(1):41-6.

11. LiT,FanGX,WangW,LiT,YuanYK.,Resveratrolinducesapoptosis,influencesIL-6andexertsimmunomodulatoryeffectonmouselymphocyticleukemiabothinvitroandinvivo.,IntImmunopharmacol.2007Sep;7(9):1221-31.

12. SalinasI,RodríguezA,MeseguerJ,EstebanMA.,Adenosinearrestsapoptosisinlymphocytesbutnotinphagocytesfromprimaryleucocyteculturesoftheteleostfish,SparusaurataL.,DevCompImmunol.2007;31(12):1233-41.

13. PenberthyWT.,PharmacologicaltargetingofIDO-mediatedtolerancefortreatingautoimmunedisease.,CurrDrugMetab.2007Apr;8(3):245-66.

14. SharmaS,ChopraK,KulkarniSK,AgrewalaJN.,ResveratrolandcurcuminsuppressimmuneresponsethroughCD28/CTLA-4andCD80co-stimulatorypathway.,ClinExpImmunol.2007Jan;147(1):155-63.

�0�

15. NamNH.,NaturallyoccurringNF-kappaBinhibitors.,MiniRevMedChem.2006Aug;6(8):945-51.

16.RachonD,RimoldiG,WuttkeW.,Invitroeffectsofgenisteinandresveratrolontheproductionofinterferon-gamma(IFNgamma)andinterleukin-10(IL-10)bystimulatedmurinesplenocytes.,Phytomedicine.2006Jun;13(6):419-24.

17. BártaI,SmerákP,PolívkováZ,SestákováH,LangováM,TurekB,BártováJ.,Currenttrendsandperspectivesinnutritionandcancerprevention.,Neoplasma.2006;53(1):19-25.

18. TaoHY,WuCF,ZhouY,GongWH,ZhangX,IribarrenP,ZhaoYQ,LeYY,WangJM.,Thegrapecomponentresveratrolinterfereswiththefunctionofche-moattractantreceptorsonphagocyticleukocytes.,CellMolImmunol.2004Feb;1(1):50-6.

19. SchroecksnadelK,WinklerC,WirleitnerB,SchennachH,WeissG,FuchsD.,Anti-inflammatorycompoundresveratrolsuppresseshomocysteineformationinstimulatedhumanperipheralbloodmononuclearcellsinvitro.,ClinChemLabMed.2005;43(10):1084-8.

20. WirleitnerB,SchroecksnadelK,WinklerC,SchennachH,FuchsD.,Resveratrolsuppressesinterferon-gamma-inducedbiochemicalpathwaysinhumanperipheralbloodmononuclearcellsinvitro.,ImmunolLett.2005Sep15;100(2):159-63.

21. LiT,ShengL,FanGX,YuanYK,LiT.,[Preliminarystudyonanti-tumorfunctionofresveratrolanditsimmunologicalmechanism],XiBaoYuFenZiMianYiXueZaZhi.2005Sep;21(5):575-9.[Chinese]

22. MarierJF,ChenK,PrinceP,ScottG,delCastilloJR,VachonP.,Productionofexvivolipopolysaccharide-inducedtumornecrosisfactor-alpha,interleukin-1beta,andinterleukin-6issuppressedbytrans-resveratrolinaconcentration-dependentmanner.,CanJVetRes.2005Apr;69(2):151-4.

�0�

23. delaLastraCA,VillegasI.,Resveratrolasananti-inflammatoryandanti-agingagent:mechanismsandclinicalimplications.,MolNutrFoodRes.2005May;49(5):405-30.

24. KimuraY.,Newanticanceragents:invitroandinvivoevaluationoftheantitu-morandantimetastaticactionsofvariouscompoundsisolatedfrommedicinalplants.,InVivo.2005Jan-Feb;19(1):37-60.

26. WangLX,HerediaA,SongH,ZhangZ,YuB,DavisC,RedfieldR.,Resveratrolglucuronidesasthemetabolitesofresveratrolinhumans:characterization,synthesis,andanti-HIVactivity.,JPharmSci.2004Oct;93(10):2448-57.

27. KhandujaKL,BhardwajA,KaushikG.,ResveratrolinhibitsN-nitrosodiethyl-amine-inducedornithinedecarboxylaseandcyclooxygenaseinmice.,JNutrSciVitaminol(Tokyo).2004Feb;50(1):61-5.

28. YuL,WuSL,ZhangM,PanCE.,[Effectofresveratrolaloneanditscombina-tionwithcyclosporinAontheimmunefunctionofhumanperipheralbloodTlymphocytes],XiBaoYuFenZiMianYiXueZaZhi.2003Nov;19(6):549-51.[Chinese]

29. KimGY,ChoH,AhnSC,OhYH,LeeCM,ParkYM.,Resveratrolinhibitspheno-typicandfunctionalmaturationofmurinebonemarrow-deriveddendriticcells.,IntImmunopharmacol.2004Feb;4(2):245-53.

30. GaoX,DeebD,MediaJ,DivineG,JiangH,ChapmanRA,GautamSC.,Immunomodulatoryactivityofresveratrol:discrepantinvitroandinvivoim-munologicaleffects.,BiochemPharmacol.2003Dec15;66(12):2427-35.

31. LosaGA.,Resveratrolmodulatesapoptosisandoxidationinhumanbloodmononuclearcells.,EurJClinInvest.2003Sep;33(9):818-23.

�0�

32. BoscoloP,delSignoreA,SabbioniE,DiGioacchinoM,DiGiampaoloL,RealeM,ContiP,PaganelliR,GiaccioM.,Effectsofresveratrolonlymphocyteprolifera-tionandcytokinerelease.,AnnClinLabSci.2003Spring;33(2):226-31.

33. DallalO,RavindranathTM,ChoudhryMA,KohnA,MuraskasJK,NamakSY,AlattarMH,SayeedMM.,T-cellproliferativeresponsesfollowingsepsisinneonatalrats.,BiolNeonate.2003;83(3):201-7.

34. FengYH,ZhouWL,WuQL,LiXY,ZhaoWM,ZouJP.,Lowdoseofresve-ratrolenhancedimmuneresponseofmice.,ActaPharmacolSin.2002Oct;23(10):893-7.

35. BhatKP,PezzutoJM.,Cancerchemoprotectiveactivityofresveratrol.,AnnNYAcadSci.2002May;957:210-29.

36. IgnatowiczE,Baer-DubowskaW.,Resveratrol,anaturalchemo-protectiveagentagainstdegenerativediseases.,PolJPharmacol.2001Nov-Dec;53(6):557-69.

37. FalchettiR,FuggettaMP,LanzilliG,TricaricoM,RavagnanG.,Effectsofresve-ratrolonhumanimmunecellfunction.,LifeSci.2001Nov21;70(1):81-96.

38. GaoX,XuYX,JanakiramanN,ChapmanRA,GautamSC.,Immunomodulatoryactivityofresveratrol:suppressionoflymphocyteproliferation,developmentofcell-mediatedcytotoxicity,andcytokineproduction.,BiochemPharmacol.2001Nov1;62(9):1299-308.

39. SchneiderY,DurantonB,GosséF,SchleifferR,SeilerN,RaulF.,Resveratrolinhibitsintestinaltumorigenesisandmodulateshost-defense-relatedgeneex-pressioninananimalmodelofhumanfamilialadenomatouspolyposis.,NutrCancer.2001;39(1):102-7.

40. BertelliAA,FerraraF,DianaG,FulgenziA,CorsiM,PontiW,FerreroME,BertelliA.,Resveratrol,anaturalstilbeneingrapesandwine,enhancesintra-phagocytosisinhumanpromonocytes:aco-factorinantiinflammatoryandanticancerchemoprotectiveactivity.,IntJTissueReact.1999;21(4):93-104.

��0

41. WadsworthTL,KoopDR.,Effectsofthewinepolyphenolicsquercetinandresveratrolonpro-inflammatorycytokineexpressioninRAW264.7macro-phages.,BiochemPharmacol.1999Apr15;57(8):941-9.

42. TanY,LimLH.,trans-Resveratrol,anextractofredwine,inhibitshumaneo-sinophilactivationanddegranulation.,BrJPharmacol.2008Sep8.

43. DaveM,AtturM,PalmerG,Al-MussawirHE,KennishL,PatelJ,AbramsonSB.,TheantioxidantresveratrolprotectsagainstchondrocyteapoptosisviaeffectsonmitochondrialpolarizationandATPproduction.,ArthritisRheum.2008Sep;58(9):2786-97.

44. KhannaD,SethiG,AhnKS,PandeyMK,KunnumakkaraAB,SungB,AggarwalA,AggarwalBB.,Naturalproductsasagoldmineforarthritistreatment.,CurrOpinPharmacol.2007Jun;7(3):344-51.Epub2007May1.

45. InoueH.,[EndogenousligandsforPPARs],NipponRinsho.2005Apr;63(4):578-83.[Japanese]

46. AdamsM,PacherT,GregerH,BauerR.,InhibitionofleukotrienebiosynthesisbystilbenoidsfromStemonaspecies.,JNatProd.2005Jan;68(1):83-5.

47. BaolinL,InamiY,TanakaH,InagakiN,IinumaM,NagaiH.,Resveratrolinhibitsthereleaseofmediatorsfrombonemarrow-derivedmousemastcellsinvitro.,PlantaMed.2004Apr;70(4):305-9.

48. ShigematsuS,IshidaS,HaraM,TakahashiN,YoshimatsuH,SakataT,KorthuisRJ.,Resveratrol,aredwineconstituentpolyphenol,preventssuperoxide-de-pendentinflammatoryresponsesinducedbyischemia/reperfusion,platelet-activatingfactor,oroxidants.,FreeRadicBiolMed.2003Apr1;34(7):810-7.

49. HuangKS,LinM,ChengGF.,Anti-inflammatorytetramersofresveratrolfromtherootsofVitisamurensisandtheconformationsoftheseven-memberedringinsomeoligostilbenes.,Phytochemistry.2001Sep;58(2):357-62.

��

50. SchwartzZ,SylviaVL,DelToroF,HardinRR,DeanDD,BoyanBD.,24R,25-(OH)(2)D(3)mediatesitsmembranereceptor-dependenteffectsonproteinkinaseCandalkalinephosphataseviaphospholipaseA(2)andcyclooxygen-ase-1butnotcyclooxygenase-2ingrowthplatechondrocytes.,JCellPhysiol.2000Mar;182(3):390-401.

51. MacCarroneM,LorenzonT,GuerrieriP,AgròAF.,Resveratrolpreventsapopto-sisinK562cellsbyinhibitinglipoxygenaseandcyclooxygenaseactivity.,EurJBiochem.1999Oct1;265(1):27-34.

52. KnightJ,TaylorGW,WrightP,ClareAS,RowleyAF.,Eicosanoidbiosynthesisinanadvanceddeuterostomateinvertebrate,theseasquirt(Cionaintestinalis).,BiochimBiophysActa.1999Jan4;1436(3):467-78.

53. HallLM,MurphyRC.,Electrospraymassspectrometricanalysisof5-hydro-peroxyand5-hydroxyeicosatetraenoicacidsgeneratedbylipidperoxida-tionofredbloodcellghostphospholipids.,JAmSocMassSpectrom.1998May;9(5):527-32.

54. RotondoS,RajtarG,ManariniS,CelardoA,RotilloD,deGaetanoG,EvangelistaV,CerlettiC.,Effectoftrans-resveratrol,anaturalpolyphenoliccompound,onhumanpolymorphonuclearleukocytefunction.,BrJPharmacol.1998Apr;123(8):1691-9.

55. SoleasGJ,DiamandisEP,GoldbergDM.,Wineasabiologicalfluid:history,pro-duction,androleindiseaseprevention.,JClinLabAnal.1997;11(5):287-313.

56. KimuraY,OkudaH,KuboM.,Effectsofstilbenesisolatedfrommedicinalplantsonarachidonatemetabolismanddegranulationinhumanpolymorpho-nuclearleukocytes.,JEthnopharmacol.1995Feb;45(2):131-9.

57. PendurthiUR,RaoLV.,Resveratrolsuppressesagonist-inducedmonocyteadhesiontoculturedhumanendothelialcells.,ThrombRes.2002May15;106(4-5):243-8.

��

58. DoGM,KwonEY,KimHJ,JeonSM,HaTY,ParkT,ChoiMS.,Long-termeffectsofresveratrolsupplementationonsuppressionofatherogeniclesionforma-tionandcholesterolsynthesisinapoE-deficientmice.,BiochemBiophysResCommun.2008Sep12;374(1):55-9.

59. ZhouM,HeJL,YuSQ,ZhuRF,LuJ,DingFY,XuGL.,[Effectofresveratrolonchronicobstructivepulmonarydiseaseinratsanditsmechanism],YaoXueXueBao.2008Feb;43(2):128-32.[Chinese]

60. CsiszarA,LabinskyyN,PodlutskyA,KaminskiPM,WolinMS,ZhangC,MukhopadhyayP,PacherP,HuF,deCaboR,BallabhP,UngvariZ.,VasoprotectiveeffectsofresveratrolandSIRT1:attenuationofcigarettesmoke-inducedoxidativestressandproinflammatoryphenotypicalterations.,AmJPhysiolHeartCircPhysiol.2008Jun;294(6):H2721-35.

61. HarikumarKB,AggarwalBB.,Resveratrol:amultitargetedagentforage-asso-ciatedchronicdiseases.,CellCycle.2008Apr;7(8):1020-35.

62. NamaziH.,Anovelmolecularmechanismtoaccountfortheactionofresvera-trolagainstreperfusioninjury.,AnnVascSurg.2008May-Jun;22(3):492.

63. BukowskaA,SchildL,KeilhoffG,HirteD,NeumannM,GardemannA,NeumannKH,RöhlFW,HuthC,GoetteA,LendeckelU.,Mitochondrialdysfunc-tionandredoxsignalinginatrialtachyarrhythmia.,ExpBiolMed(Maywood).2008May;233(5):558-74.

64. YuHP,HsuJC,HwangTL,YenCH,LauYT.,Resveratrolattenuateshepaticinjuryaftertrauma-hemorrhageviaestrogenreceptor-relatedpathway.,Shock.2008Sep;30(3):324-8.

��

66. WungBS,HsuMC,WuCC,HsiehCW.,Piceatannolupregulatesendothelialhemeoxygenase-1expressionvianovelproteinkinaseCandtyrosinekinasepathways.,PharmacolRes.2006Feb;53(2):113-22.

67. KaplanS,MorganJA,BisleriG,CheemaFH,AkmanHO,TopkaraVK,OzMC.,Effectsofresveratrolinstoragesolutiononadhesionmoleculeexpressionandnitricoxidesynthesisinveingrafts.,AnnThoracSurg.2005Nov;80(5):1773-8.

68. UchidaY,YamazakiH,WatanabeS,HayakawaK,MengY,HiramatsuN,KasaiA,YamauchiK,YaoJ,KitamuraM.,EnhancementofNF-kappaBactivitybyresveratrolincytokine-exposedmesangialcells.,ClinExpImmunol.2005Oct;142(1):76-83.

69. WungBS,HsuMC,WuCC,HsiehCW.,ResveratrolsuppressesIL-6-inducedICAM-1geneexpressioninendothelialcells:effectsontheinhibitionofSTAT3phosphorylation.,LifeSci.2005Dec12;78(4):389-97.

70. LeiroJ,ArranzJA,FraizN,SanmartínML,QuezadaE,OralloF.,Effectofcis-resveratrolongenesinvolvedinnuclearfactorkappaBsignaling.,IntImmunopharmacol.2005Feb;5(2):393-406.

71. MengY,ZhangM,XuJ,LiuXM,MaQY.,Effectofresveratrolonmicrocirculationdisorderandlunginjuryfollowingsevereacutepancreatitisinrats.,WorldJGastroenterol.2005Jan21;11(3):433-5.

72. AhnKS,KimJH,OhSR,RyuSY,LeeHK.,InhibitoryactivityofstilbenesfrommedicinalplantsontheexpressionofcelladhesionmoleculesonTHP1cells.,PlantaMed.2000Oct;66(7):641-4.

73. FerreroME,BertelliAE,FulgenziA,PellegattaF,CorsiMM,BonfrateM,FerraraF,DeCaterinaR,GiovanniniL,BertelliA.,Activityinvitroofresveratrolongranulocyteandmonocyteadhesiontoendothelium.,AmJClinNutr.1998Dec;68(6):1208-14.

��

InhibitLDLoxidation1. DongHH,RenHL.,Newprogressioninthestudyofprotectiveprop-

ertiesofresveratrolinanticardiovasculardisease.,BratislLekListy.2004;105(5-6):225-9.

2. BradamanteS,BarenghiL,VillaA.,Cardiovascularprotectiveeffectsofresve-ratrol.CardiovascDrugRev.2004Fall;22(3):169-88.

4. BritoP,AlmeidaLM,DinisTC.,Theinteractionofresveratrolwithferrylmyo-globinandperoxynitrite;protectionagainstLDLoxidation.,FreeRadicRes.2002Jun;36(6):621-31.

5. ZouJG,HuangYZ,ChenQ,WeiEH,HsiehTC,WuJM.,Resveratrolinhib-itscopperion-inducedandazocompound-initiatedoxidativemodifi-cationofhumanlowdensitylipoprotein.,BiochemMolBiolInt.1999Jun;47(6):1089-96.

6. BelguendouzL,FremontL,LinardA.,Resveratrolinhibitsmetalion-depen-dentandindependentperoxidationofporcinelow-densitylipoproteins.,BiochemPharmacol.1997May9;53(9):1347-55.

CancerandResveratrol1. VidavalurR,OtaniH,SingalPK,MaulikN.,Significanceofwineandresveratrol

incardiovasculardisease:Frenchparadoxrevisited.,ExpClinCardol.2006Fall;11(3):217-25.

2. WangTT,HudsonTS,WangTC,RemsbergCM,DaviesNM,TakahashiY,KimYS,SeifriedH,VinyardBT,PerkinsSN,HurstingSD.,DifferentialEffectsofResveratrolonAndrogen-responsiveLNCaPHumanProstateCancerCellsInVitroandInVivo.,Carcinogenesis.2008Jun26.

��

3. SnyderRM,YuW,JiaL,SandersBG,KlineK.,VitaminEanalogalpha-TEA,methylseleninicacid,andtrans-resveratrolincombinationsyner-gisticallyinhibithumanbreastcancercellgrowth.,NutrCancer.2008May-Jun;60(3):401-11.

4. SeeniA,TakahashiS,TakeshitaK,TangM,SugiuraS,SatoSY,ShiraiT.,SuppressionofProstateCancerGrowthbyResveratrolinTheTransgenicRatforAdenocarcinomaofProstate(TRAP)Model.,AsianPacJCancerPrev.2008Jan-Mar;9(1):7-14.

5. HsiehTC,WangZ,DengH,WuJM.,Identificationofglutathionesulfotrans-ferase-pi(GSTP1)asanewresveratroltargetingprotein(RTP)andstudiesofresveratrol-responsiveproteinchangesbyresveratrolaffinitychromatogra-phy.,AnticancerRes.2008Jan-Feb;28(1A):29-36.

6. HaradaN,MurataY,YamajiR,MiuraT,InuiH,NakanoY.,Resveratroldown-regulatestheandrogenreceptoratthepost-translationallevelinprostatecancercells.JNutrSciVitaminol(Tokyo).2007Dec;53(6):556-60.

7. KhanN,AfaqF,MukhtarH.,Cancerchemopreventionthroughdietaryantioxi-dants:progressandpromise.,AntioxidRedoxSignal.2008Mar;10(3):475-510.

8. ZahidM,GaikwadNW,RoganEG,CavalieriEL.,Inhibitionofdepurinatinges-trogen-DNAadductformationbynaturalcompounds.,ChemResToxicol.2007Dec;20(12):1947-53.

9. SallmanDA,ChenX,ZhongB,GilvaryDL,ZhouJ,WeiS,DjeuJY.,ClusterinmediatesTRAILresistanceinprostatetumorcells.,MolCancerTher.2007Nov;6(11):2938-47.

10. HorvathZ,Marihart-FazekasS,SaikoP,GruschM,OzsüyM,HarikM,HandlerN,ErkerT,JaegerW,Fritzer-SzekeresM,DjavanB,SzekeresT.,Novelresvera-trolderivativesinduceapoptosisandcausecellcyclearrestinprostatecancercelllines.,AnticancerRes.2007Sep-Oct;27(5A):3459-64.

��

11. GillC,WalshSE,MorrisseyC,FitzpatrickJM,WatsonRW.,Resveratrolsensitizesandrogenindependentprostatecancercellstodeath-recep-tormediatedapoptosisthroughmultiplemechanisms.,Prostate.2007Nov1;67(15):1641-53.

12. HudsonTS,HartleDK,HurstingSD,NunezNP,WangTT,YoungHA,AranyP,GreenJE.,Inhibitionofprostatecancergrowthbymuscadinegrapeskinextractandresveratrolthroughdistinctmechanisms.,CancerRes.2007Sep1;67(17):8396-405.

13. ShankarS,ChenQ,SiddiquiI,SarvaK,SrivastavaRK.,SensitizationofTRAIL-resistantLNCaPcellsbyresveratrol(3,4’,5tri-hydroxystilbene):molecularmechanismsandtherapeuticpotential.JMolSignal.2007Aug24;2:7.

14. DjavanB,MarihartS,KuehhasF,RomM,PartinA,SchalkenJ,SekeresT.,[Resveratrolandnewlysynthetizedresveratrolanalogsintherapyofprostatecarcinoma],UrologeA.2007Sep;46(9):1101-3.[German]

15. HarperCE,PatelBB,WangJ,ArabshahiA,EltoumIA,LamartiniereCA.,Resveratrolsuppressesprostatecancerprogressionintransgenicmice.,Carcinogenesis.2007Sep;28(9):1946-53.

16. ShankarS,SiddiquiI,SrivastavaRK.,Molecularmechanismsofresveratrol(3,4,5-trihydroxy-trans-stilbene)anditsinteractionwithTNF-relatedapopto-sisinducingligand(TRAIL)inandrogen-insensitiveprostatecancercells.,MolCellBiochem.2007Oct;304(1-2):273-85.Epub2007Jul17.

17. CardileV,ChillemiR,LombardoL,SciutoS,SpataforaC,TringaliC.,AntiproliferativeactivityofmethylatedanaloguesofE-andZ-resveratrol.,ZNaturforsch[C].2007Mar-Apr;62(3-4):189-95.

18. WietrzykJ.,[TheinfluenceofisoflavonoidsontheantitumoractivityofvitaminD3]PostepyHigMedDosw(Online).2007;61:253-60.[Polish]

��

19. BenitezDA,Pozo-GuisadoE,ClementiM,CastellónE,Fernandez-SalgueroPM.,Non-genomicactionofresveratrolonandrogenandoestrogenreceptorsinprostatecancer:modulationofthephosphoinositide3-kinasepathway.,BrJCancer.2007May21;96(10):1595-604.

20. VonLöwEC,PeraboFG,SienerR,MüllerSC.,Review.Factsandfictionofphy-totherapyforprostatecancer:acriticalassessmentofpreclinicalandclinicaldata.,InVivo.2007Mar-Apr;21(2):189-204.

21. AhmadKA,HarrisNH,JohnsonAD,LindvallHC,WangG,AhmedK.,ProteinkinaseCK2modulatesapoptosisinducedbyresveratrolandepigallocatechin-3-gallateinprostatecancercells.,MolCancerTher.2007Mar;6(3):1006-12.

22. ScarlattiF,SalaG,RicciC,MaioliC,MilaniF,MinellaM,BotturiM,GhidoniR.,ResveratrolsensitizationofDU145prostatecancercellstoionizingradiationisassociatedtoceramideincrease.,CancerLett.2007Aug8;253(1):124-30.Epub2007Feb26.

23. Landis-PiwowarKR,MilacicV,ChenD,YangH,ZhaoY,ChanTH,YanB,DouQP.,Theproteasomeasapotentialtargetfornovelanticancerdrugsandche-mosensitizers.DrugResistUpdat.2006Dec;9(6):263-73.

24. NarayananBA.,Chemoprotectiveagentsaltersglobalgeneexpressionpattern:predictingtheirmodeofactionandtargets.,CurrCancerDrugTargets.2006Dec;6(8):711-27.

25. NonnL,DuongD,PeehlDM.,Chemoprotectiveanti-inflammatoryactivitiesofcurcuminandotherphytochemicalsmediatedbyMAPkinasephosphatase-5inprostatecells.,Carcinogenesis.2007Jun;28(6):1188-96.

26. BenitezDA,Pozo-GuisadoE,Alvarez-BarrientosA,Fernandez-SalgueroPM,CastellónEA.,Mechanismsinvolvedinresveratrol-inducedapoptosisandcellcyclearrestinprostatecancer-derivedcelllines.,JAndrol.2007Mar-Apr;28(2):282-93.

��

27. BemisDL,KatzAE,ButtyanR.,Clinicaltrialsofnaturalproductsasche-moprotectiveagentsforprostatecancer.,ExpertOpinInvestigDrugs.2006Oct;15(10):1191-200.

28. AzizMH,NihalM,FuVX,JarrardDF,AhmadN.,Resveratrol-causedapoptosisofhumanprostatecarcinomaLNCaPcellsismediatedviamodulationofphos-phatidylinositol3’-kinase/AktpathwayandBcl-2familyproteins.,MolCancerTher.2006May;5(5):1335-41.

29. YooKM,KimS,MoonBK,KimSS,KimKT,KimSY,ChoiSY.,Potentinhibitoryeffectsofresveratrolderivativesonprogressionofprostatecancercells.,ArchPharm(Weinheim).2006May;339(5):238-41.

30. ScifoC,MilasiA,GuarneraA,SinatraF,RenisM.,Resveratrolandpropolisextract:aninsightintothemorphologicalandmolecularchangesinducedinDU145cells.,OncolRes.2006;15(9):409-21.

32. JonesSB,DePrimoSE,WhitfieldML,BrooksJD.,Resveratrol-inducedgeneexpressionprofilesinhumanprostatecancercells.,CancerEpidemiolBiomarkersPrev.2005Mar;14(3):596-604.

33. CardileV,LombardoL,SpataforaC,TringaliC.,Chemo-enzymaticsynthesisandcell-growthinhibitionactivityofresveratrolanalogues.,BioorgChem.2005Feb;33(1):22-33.

34. AwadAB,BurrAT,FinkCS.,Effectofresveratrolandbeta-sitosterolincom-binationonreactiveoxygenspeciesandprostaglandinreleasebyPC-3cells.,ProstaglandinsLeukotEssentFattyAcids.2005Mar;72(3):219-26.

35. MansonMM,FarmerPB,GescherA,StewardWP.,Innovativeagentsincancerprevention.,RecentResultsCancerRes.2005;166:257-75.

��

36. NarayananNK,NarayananBA,NixonDW.,Resveratrol-inducedcellgrowthinhibitionandapoptosisisassociatedwithmodulationofphosphoglyceratemutaseBinhumanprostatecancercells:two-dimensionalsodiumdodecylsulfate-polyacrylamidegelelectrophoresisandmassspectrometryevalua-tion.,CancerDetectPrev.2004;28(6):443-52.

37. ShihA,ZhangS,CaoHJ,BoswellS,WuYH,TangHY,LennartzMR,DavisFB,DavisPJ,LinHY.,Inhibitoryeffectofepidermalgrowthfactoronresvera-trol-inducedapoptosisinprostatecancercellsismediatedbyproteinkinaseC-alpha.,MolCancerTher.2004Nov;3(11):1355-64.

38. AggarwalBB,BhardwajA,AggarwalRS,SeeramNP,ShishodiaS,TakadaY.,Roleofresveratrolinpreventionandtherapyofcancer:preclinicalandclinicalstudies.AnticancerRes.2004Sep-Oct;24(5A):2783-840.

39. ScifoC,CardileV,RussoA,ConsoliR,VancheriC,CapassoF,VanellaA,RenisM.,Resveratrolandpropolisasnecrosisorapoptosisinducersinhumanpros-tatecarcinomacells.,OncolRes.2004;14(9):415-26.

40. ShenoudaNS,ZhouC,BrowningJD,AnsellPJ,SaklaMS,LubahnDB,MacdonaldRS.,Phytoestrogensincommonherbsregulateprostatecancercellgrowthinvitro.,NutrCancer.2004;49(2):200-8.

41. WangZ,HsiehTC,ZhangZ,MaY,WuJM.,Identificationandpurificationofresveratroltargetingproteinsusingimmobilizedresveratrolaffinitychroma-tography.,BiochemBiophysResCommun.2004Oct22;323(3):743-9.

42. YuanH,PanY,YoungCY.,Overexpressionofc-Juninducedbyquercetinandresverolinhibitstheexpressionandfunctionoftheandrogenreceptorinhumanprostatecancercells.,CancerLett.2004Sep30;213(2):155-63.

43. SimopoulosAP.,ThetraditionaldietofGreeceandcancer.,EurJCancerPrev.2004Jun;13(3):219-30.

44. SalaG,MinutoloF,MacchiaM,SacchiN,GhidoniR.,Resveratrolstructureandceramide-associatedgrowthinhibitioninprostatecancercells.,DrugsExpClinRes.2003;29(5-6):263-9.

��0

45. GaoS,LiuGZ,WangZ.,Modulationofandrogenreceptor-dependenttranscrip-tionbyresveratrolandgenisteininprostatecancercells.,Prostate.2004May1;59(2):214-25.

46. CardileV,ScifoC,RussoA,FalsaperlaM,MorgiaG,MottaM,RenisM,ImbrianiE,SilvestreG.,InvolvementofHSP70inresveratrol-inducedapoptosisofhumanprostatecancer.,AnticancerRes.2003Nov-Dec;23(6C):4921-6.

47. KimYA,RheeSH,ParkKY,ChoiYH.,Antiproliferativeeffectofresveratrolinhumanprostatecarcinomacells.,JMedFood.2003Winter;6(4):273-80.

48. HoSM.,Estrogensandanti-estrogens:keymediatorsofprostatecarci-nogenesisandnewtherapeuticcandidates.,JCellBiochem.2004Feb15;91(3):491-503.

49. StewartJR,O’BrianCA.,ResveratrolantagonizesEGFR-dependentErk1/2activationinhumanandrogen-independentprostatecancercellswithas-sociatedisozyme-selectivePKCalphainhibition.,InvestNewDrugs.2004Apr;22(2):107-17.

50. FuldaS,DebatinKM.,Sensitizationfortumornecrosisfactor-relatedapopto-sis-inducingligand-inducedapoptosisbythechemoprotectiveagentresvera-trol.,CancerRes.2004Jan1;64(1):337-46.

51. CarrawayRE,HassanS,CochraneDE.,Polyphenolicantioxidantsmimictheeffectsof1,4-dihydropyridinesonneurotensinreceptorfunctioninPC3cells.,JPharmacolExpTher.2004Apr;309(1):92-101.

52. StewartJR,ArtimeMC,O’BrianCA.,Resveratrol:acandidatenutri-tionalsubstanceforprostatecancerprevention.,JNutr.2003Jul;133(7Suppl):2440S-2443S.

53. AzizMH,KumarR,AhmadN.,Cancerchemopreventionbyresveratrol:invitroandinvivostudiesandtheunderlyingmechanisms(review).,IntJOncol.2003Jul;23(1):17-28.PeterGuengerichF,ChunYJ,KimD,GillamEM,ShimadaT.,CytochromeP4501B1:atargetforinhibitioninanticarcinogenesisstrategies.,MutatRes.2003Feb-Mar;523-524:173-82.

��

54. NarayananBA,NarayananNK,ReGG,NixonDW.,DifferentialexpressionofgenesinducedbyresveratrolinLNCaPcells:P53-mediatedmoleculartargets.,IntJCancer.2003Mar20;104(2):204-12.

55. Kris-EthertonPM,HeckerKD,BonanomeA,CovalSM,BinkoskiAE,HilpertKF,GrielAE,EthertonTD.,Bioactivecompoundsinfoods:theirroleinthepreven-tionofcardiovasculardiseaseandcancer.,AmJMed.2002Dec30;113Suppl9B:71S-88S.

56. DeebD,XuYX,JiangH,GaoX,JanakiramanN,ChapmanRA,GautamSC.,Curcumin(diferuloyl-methane)enhancestumornecrosisfactor-relatedapop-tosis-inducingligand-inducedapoptosisinLNCaPprostatecancercells.,MolCancerTher.2003Jan;2(1):95-103.

57. RatanHL,StewardWP,GescherAJ,MellonJK.,Resveratrol--aprostatecancerchemoprotectiveagent?,UrolOncol.2002Nov-Dec;7(6):223-7.

58. DingXZ,AdrianTE.,Resveratrolinhibitsproliferationandinducesapoptosisinhumanpancreaticcancercells.,Pancreas.2002Nov;25(4):e71-6.

59. CuligZ,KlockerH,BartschG,HobischA.,Androgenreceptorsinprostatecancer.EndocrRelatCancer.2002Sep;9(3):155-70.

60. MorrisGZ,WilliamsRL,ElliottMS,BeebeSJ.,ResveratrolinducesapoptosisinLNCaPcellsandrequireshydroxylgroupstodecreaseviabilityinLNCaPandDU145cells.,Prostate.2002Sep1;52(4):319-29.

61. LinHY,ShihA,DavisFB,TangHY,MartinoLJ,BennettJA,DavisPJ.,Resveratrolinducedserinephosphorylationofp53causesapoptosisinamutantp53pros-tatecancercellline.,JUrol.2002Aug;168(2):748-55.

62. NarayananBA,NarayananNK,StonerGD,BullockBP.,Interactivegeneexpres-sionpatterninprostatecancercellsexposedtophenolicantioxidants.,LifeSci.2002Mar1;70(15):1821-39.

��

63. KuwajerwalaN,CifuentesE,GautamS,MenonM,BarrackER,ReddyGP.,ResveratrolinducesprostatecancercellentryintosphaseandinhibitsDNAsynthesis.,CancerRes.2002May1;62(9):2488-92.

64. SgambatoA,ArditoR,FaragliaB,BoninsegnaA,WolfFI,CittadiniA.,Resveratrol,anaturalphenoliccompound,inhibitscellproliferationandpre-ventsoxidativeDNAdamage.,MutatRes.2001Sep20;496(1-2):171-80.

65. CuendetM,PezzutoJM.,Theroleofcyclooxygenaseandlipoxygenaseincancerchemoprevention.,DrugMetabolDrugInteract.2000;17(1-4):109-57.

66. KampaM,HatzoglouA,NotasG,DamianakiA,BakogeorgouE,GemetziC,KouroumalisE,MartinPM,CastanasE.,Wineantioxidantpolyphenolsinhibittheproliferationofhumanprostatecancercelllines.,NutrCancer.2000;37(2):223-33.

67. DamianakiA,BakogeorgouE,KampaM,NotasG,HatzoglouA,PanagiotouS,GemetziC,KouroumalisE,MartinPM,CastanasE.,Potentinhibitoryactionofredwinepolyphenolsonhumanbreastcancercells.,JCellBiochem.2000Jun6;78(3):429-41.

68. HsiehTC,WuJM.,Grape-derivedchemoprotectiveagentresveratrolde-creasesprostate-specificantigen(PSA)expressioninLNCaPcellsbyanandrogenreceptor(AR)-independentmechanism.,AnticancerRes.2000Jan-Feb;20(1A):225-8.

69. MitchellSH,ZhuW,YoungCY.,ResveratrolinhibitstheexpressionandfunctionoftheandrogenreceptorinLNCaPprostatecancercells.,CancerRes.1999Dec1;59(23):5892-5.WeisburgerJH.,Mechanismsofactionofantioxidantsasexemplifiedinvegetables,tomatoesandtea.,FoodChemToxicol.1999Sep-Oct;37(9-10):943-8.

70. UlspergerE,HamiltonG,RadererM,BaumgartnerG,HejnaM,HoffmannO,MallingerR.,ResveratrolpretreatmentdesensitizesAHTO-7humanosteo-blaststogrowthstimulationinresponsetocarcinomacellsupernatants.,IntJOncol.1999Nov;15(5):955-9.

��

71. HsiehTC,WuJM.,Differentialeffectsongrowth,cellcyclearrest,andinduc-tionofapoptosisbyresveratrolinhumanprostatecancercelllines.,ExpCellRes.1999May25;249(1):109-15.

ProteinActivation1. MaHJ,CaoYK,LiuYX,WangR,WuYM.,Microinjectionofresveratrolinto

rostralventrolateralmedulladecreasessympatheticvasomotortonethroughnitricoxideandintracellularCa2+inanesthetizedmalerats.,ActaPharmacolSin.2008Aug;29(8):906-12.

2. VenkatesanB,Ghosh-ChoudhuryN,DasF,MahimainathanL,KamatA,KasinathBS,AbboudHE,ChoudhuryGG.,ResveratrolinhibitsPDGFreceptormitogenicsignalinginmesangialcells:roleofPTP1B.,FASEBJ.2008Jun20.

3. ChakrabortyPK,MustafiSB,GangulyS,ChatterjeeM,RahaS.,ResveratrolinducesapoptosisinK562(chronicmyelogenousleukemia)cellsbytar-getingakeysurvivalprotein,heatshockprotein70.,CancerSci.2008Jun;99(6):1109-16.

4. KlingeCM,WickramasingheNS,IvanovaMM,DoughertySM.,Resveratrolstimulatesnitricoxideproductionbyincreasingestrogenreceptoralpha-Src-caveolin-1interactionandphosphorylationinhumanumbilicalveinendothe-lialcells.,FASEBJ.2008Jul;22(7):2185-97.

5. LeeKW,KangNJ,HeoYS,RogozinEA,PuglieseA,HwangMK,BowdenGT,BodeAM,LeeHJ,DongZ.,RafandMEKproteinkinasesaredirectmoleculartargetsforthechemoprotectiveeffectofquercetin,amajorflavonolinredwine.,CancerRes.2008Feb1;68(3):946-55.

6. SallmanDA,ChenX,ZhongB,GilvaryDL,ZhouJ,WeiS,DjeuJY.,ClusterinmediatesTRAILresistanceinprostatetumorcells.,MolCancerTher.2007Nov;6(11):2938-47.

7. OhshiroK,RayalaSK,El-NaggarAK,KumarR.,Deliveryofcytoplasmicpro-teinstoautophagosomes.,Autophagy.2008Jan-Feb;4(1):104-6.

��

8. OhshiroK,RayalaSK,KondoS,GaurA,VadlamudiRK,El-NaggarAK,KumarR.,IdentifyingtheestrogenreceptorcoactivatorPELP1inautophagosomes.,CancerRes.2007Sep1;67(17):8164-71.

9. LeeKW,KangNJ,RogozinEA,KimHG,ChoYY,BodeAM,LeeHJ,SurhYJ,BowdenGT,DongZ.,MyricetinisanovelnaturalinhibitorofneoplasticcelltransformationandMEK1.,Carcinogenesis.2007Sep;28(9):1918-27.

10. WuCC,WuCI,WangWY,WuYC.,Lowconcentrationsofresveratrolpotentiatetheantiplateleteffectofprostaglandins.,PlantaMed.2007May;73(5):439-43.

11. SuJL,YangCY,ZhaoM,KuoML,YenML.,Forkheadproteinsarecriticalforbonemorphogeneticprotein-2regulationandanti-tumoractivityofresvera-trol.,JBiolChem.2007Jul6;282(27):19385-98.

12. KutukO,BasagaH.,Apoptosissignallingby4-hydroxynonenal:aroleforJNK-c-Jun/AP-1pathway.,RedoxRep.2007;12(1):30-4.

13. FaberAC,ChilesTC.,ResveratrolinducesapoptosisintransformedfollicularlymphomaOCI-LY8cells:evidenceforanovelmechanisminvolvinginhibitionofBCL6signaling.,IntJOncol.2006Dec;29(6):1561-6.

14. FuldaS,DebatinKM.,Resveratrolmodulationofsignaltransductioninapop-tosisandcellsurvival:amini-review.,CancerDetectPrev.2006;30(3):217-23.

15. OvesnáZ,KozicsK,BaderY,SaikoP,HandlerN,ErkerT,SzekeresT.,Antioxidantactivityofresveratrol,piceatannoland3,3’,4,4’,5,5’-hexahydroxy-trans-stilbeneinthreeleukemiacelllines.,OncolRep.2006Sep;16(3):617-24.

16. KimAL,ZhuY,ZhuH,HanL,KopelovichL,BickersDR,AtharM.,ResveratrolinhibitsproliferationofhumanepidermoidcarcinomaA431cellsbymodulat-ingMEK1andAP-1signallingpathways.,ExpDermatol.2006Jul;15(7):538-46.

17. KooN,ChoD,KimY,ChoiHJ,KimKM.,Effectsofresveratrolonmastcellde-granulationandtyrosinephosphorylationofthesignalingcomponentsoftheIgEreceptor.,PlantaMed.2006Jun;72(7):659-61.

��

19. ChoiHK,YangJW,KangKW.,Bifunctionaleffectofresveratrolontheex-pressionofErbB2inhumanbreastcancercell.,CancerLett.2006Oct28;242(2):198-206.

20. FukudaS,KagaS,ZhanL,BagchiD,DasDK,BertelliA,MaulikN.,Resveratrolamelioratesmyocardialdamagebyinducingvascularendothelialgrowthfactor-angiogenesisandtyrosinekinasereceptorFlk-1.,CellBiochemBiophys.2006;44(1):43-9.

21. LiX,ZhangS,SafeS.,ActivationofkinasepathwaysinMCF-7cellsby17beta-estradiolandstructurallydiverseestrogeniccompounds.,JSteroidBiochemMolBiol.2006Feb;98(2-3):122-32.

22. ZhangLP,YinJX,LiuZ,ZhangY,WangQS,ZhaoJ.,EffectofresveratrolonL-typecalciumcurrentinratventricularmyocytes.,ActaPharmacolSin.2006Feb;27(2):179-83.

23. JuanSH,LeeJL,HoPY,LeeYH,LeeWS.,Antiproliferativeandantiangiogeniceffectsof3-methylcholanthrene,anaryl-hydrocarbonreceptoragonist,inhumanumbilicalvascularendothelialcells.,EurJPharmacol.2006Jan13;530(1-2):1-8.

24. KutukO,PoliG,BasagaH.,Resveratrolprotectsagainst4-hydroxynonenal-inducedapoptosisbyblockingJNKandc-JUN/AP-1signaling.,ToxicolSci.2006Mar;90(1):120-32.

25. WungBS,HsuMC,WuCC,HsiehCW.,Piceatannolupregulatesendothelialhemeoxygenase-1expressionvianovelproteinkinaseCandtyrosinekinasepathways.,PharmacolRes.2006Feb;53(2):113-22.

��

26. LiuZ,ZhangLP,MaHJ,WangC,LiM,WangQS.,Resveratrolreducesintracellu-larfreecalciumconcentrationinratventricularmyocytes.,ShengLiXueBao.2005Oct25;57(5):599-604.

27. ChanWH,ChangYJ.,Dosageeffectsofresveratrolonethanol-inducedcelldeathinthehumanK562cellline.,ToxicolLett.2006Feb8;161(1):1-9.

28. TyagiA,SinghRP,AgarwalC,SiriwardanaS,SclafaniRA,AgarwalR.,ResveratrolcausesCdc2-tyr15phosphorylationviaATM/ATR-Chk1/2-Cdc25CpathwayasacentralmechanismforSphasearrestinhumanovariancarci-nomaOvcar-3cells.,Carcinogenesis.2005Nov;26(11):1978-87.

29. MorrisBJ.,Aforkheadintheroadtolongevity:themolecularbasisoflifespanbecomesclearer.,JHypertens.2005Jul;23(7):1285-309.

30. DasS,AlagappanVK,BagchiD,SharmaHS,MaulikN,DasDK.,CoordinatedinductionofiNOS-VEGF-KDR-eNOSafterresveratrolconsumption:apotentialmechanismforresveratrolpreconditioningoftheheart.,VasculPharmacol.2005Apr-May;42(5-6):281-9.

31. HaiderUG,RoosTU,KontaridisMI,NeelBG,SorescuD,GriendlingKK,VollmarAM,DirschVM.,ResveratrolinhibitsangiotensinII-andepidermalgrowthfactor-mediatedAktactivation:roleofGab1andShp2.,MolPharmacol.2005Jul;68(1):41-8.

32. AziosNG,DharmawardhaneSF.,Resveratrolandestradiolexertdisparateeffectsoncellmigration,cellsurfaceactinstructures,andfocaladhesionassemblyinMDA-MB-231humanbreastcancercells.,Neoplasia.2005Feb;7(2):128-40.

33. ChanWH.,Effectofresveratrolonhighglucose-inducedstressinhumanleu-kemiaK562cells.,JCellBiochem.2005Apr15;94(6):1267-79.

��

35. KlingeCM,BlankenshipKA,RisingerKE,BhatnagarS,NoisinEL,SumanasekeraWK,ZhaoL,BreyDM,KeyntonRS.,ResveratrolandestradiolrapidlyactivateMAPKsignalingthroughestrogenreceptorsalphaandbetainendothelialcells.,JBiolChem.2005Mar4;280(9):7460-8.

36. EversDL,WangX,HuongSM,HuangDY,HuangES.,3,4’,5-Trihydroxy-trans-stilbene(resveratrol)inhibitshumancytomegalovirusreplicationandvirus-inducedcellularsignaling.,AntiviralRes.2004Aug;63(2):85-95.

37. GuastallaJP,BachelotT,Ray-CoquardI.,[Cyclooxygenase2andbreastcancer.Frombiologicalconceptstotherapeutictrials],BullCancer.2004May;91SpecNo:S99-108.[French]

38. StorzP,DöpplerH,TokerA.,ActivationloopphosphorylationcontrolsproteinkinaseD-dependentactivationofnuclearfactorkappaB.,MolPharmacol.2004Oct;66(4):870-9.Epub2004Jun29.

39. ConteA,PellegriniS,TagliazucchiD.,EffectofresveratrolandcatechinonPC12tyrosinekinaseactivitiesandtheirsynergisticprotectionfrombeta-amyloidtoxicity.,DrugsExpClinRes.2003;29(5-6):243-55.

40. Reagan-ShawS,AfaqF,AzizMH,AhmadN.,ModulationsofcriticalcellcycleregulatoryeventsduringchemopreventionofultravioletB-mediatedre-sponsesbyresveratrolinSKH-1hairlessmouseskin.,Oncogene.2004Jul1;23(30):5151-60.

41. AndrieuxL,LangouëtS,FautrelA,EzanF,KrauserJA,SavouretJF,GuengerichFP,BaffetG,GuillouzoA.,Arylhydrocarbonreceptoractivationandcyto-chromeP4501Ainductionbythemitogen-activatedproteinkinaseinhibitorU0126inhepatocytes.,MolPharmacol.2004Apr;65(4):934-43.

42. StewartJR,O’BrianCA.,ResveratrolantagonizesEGFR-dependentErk1/2activationinhumanandrogen-independentprostatecancercellswithas-sociatedisozyme-selectivePKCalphainhibition.,InvestNewDrugs.2004Apr;22(2):107-17.

��

43. KubotaT,UemuraY,KobayashiM,TaguchiH.,Combinedeffectsofres-veratrolandpaclitaxelonlungcancercells.,AnticancerRes.2003Sep-Oct;23(5A):4039-46.

44. WooJH,LimJH,KimYH,SuhSI,MinDS,ChangJS,LeeYH,ParkJW,KwonTK.,Resveratrolinhibitsphorbolmyristateacetate-inducedmatrixmetallopro-teinase-9expressionbyinhibitingJNKandPKCdeltasignaltransduction.,Oncogene.2004Mar11;23(10):1845-53.

45. ArakakiN,NagaoT,NikiR,ToyofukuA,TanakaH,KuramotoY,EmotoY,ShibataH,MagotaK,HigutiT.,PossibleroleofcellsurfaceH+-ATPsynthaseintheextracellularATPsynthesisandproliferationofhumanumbilicalveinendothelialcells.,MolCancerRes.2003Nov;1(13):931-9.

46. LinMT,YenML,LinCY,KuoML.,Inhibitionofvascularendothelialgrowthfactor-inducedangiogenesisbyresveratrolthroughinterruptionofSrc-depen-dentvascularendothelialcadherintyrosinephosphorylation.,MolPharmacol.2003Nov;64(5):1029-36.

47. StewartJR,ArtimeMC,O’BrianCA.,Resveratrol:acandidatenutri-tionalsubstanceforprostatecancerprevention.,JNutr.2003Jul;133(7Suppl):2440S-2443S.

48. MaccagliaA,MallozziC,MinettiM.,DifferentialeffectsofquercetinandresveratrolonBand3tyrosinephosphorylationsignallingofredbloodcells.,BiochemBiophysResCommun.2003Jun6;305(3):541-7.

49. LiangYC,TsaiSH,ChenL,Lin-ShiauSY,LinJK.,Resveratrol-inducedG2arrestthroughtheinhibitionofCDK7andp34CDC2kinasesincoloncarcinomaHT29cells.,BiochemPharmacol.2003Apr1;65(7):1053-60.

50. DellaRagioneF,CucciollaV,CrinitiV,IndacoS,BorrielloA,ZappiaV.,Antioxidantsinducedifferentphenotypesbyadistinctmodulationofsignaltransduction.,FEBSLett.2002Dec18;532(3):289-94.

��

51. AshikawaK,MajumdarS,BanerjeeS,BhartiAC,ShishodiaS,AggarwalBB.,PiceatannolinhibitsTNF-inducedNF-kappaBactivationandNF-kappaB-medi-atedgeneexpressionthroughsuppressionofIkappaBalphakinaseandp65phosphorylation.,JImmunol.2002Dec1;169(11):6490-7.

52. BrownsonDM,AziosNG,FuquaBK,DharmawardhaneSF,MabryTJ.,Flavonoideffectsrelevanttocancer.,JNutr.2002Nov;132(11Suppl):3482S-3489S.

53. TouJS.,Differentialregulationofneutrophilphospholipasedactivityanddegranulation.,BiochemBiophysResCommun.2002Apr12;292(4):951-6.

54. SekharKR,SpitzDR,HarrisS,NguyenTT,MeredithMJ,HoltJT,GiusD,MarnettLJ,SummarML,FreemanML.,Redox-sensitiveinteractionbetweenKIAA0132andNrf2mediatesindomethacin-inducedexpressionofgamma-glutamyl-cysteinesynthetase.,FreeRadicBiolMed.2002Apr1;32(7):650-62.Erratumin:FreeRadicBiolMed2002Jul31;33(1):149.GuisDavid[correctedtoGiusDavid].

55. KongAN,YuR,HebbarV,ChenC,OwuorE,HuR,EeR,MandlekarS.,Signaltransductioneventselicitedbycancerpreventioncompounds.,MutatRes.2001Sep1;480-481:231-41.

56. DeLédinghenV,MonvoisinA,NeaudV,KrisaS,PayrastreB,BedinC,DesmoulièreA,Bioulac-SageP,RosenbaumJ.,Trans-resveratrol,agrapevine-derivedpolyphenol,blockshepatocytegrowthfactor-inducedinvasionofhepatocellularcarcinomacells.,IntJOncol.2001Jul;19(1):83-8.

57. YuR,HebbarV,KimDW,MandlekarS,PezzutoJM,KongAN.,Resveratrolin-hibitsphorbolesterandUV-inducedactivatorprotein1activationbyinterfer-ingwithmitogen-activatedproteinkinasepathways.,MolPharmacol.2001Jul;60(1):217-24.

58. ShihA,LinHY,DavisFB,DavisPJ.,Thyroidhormonepromotesserinephos-phorylationofp53bymitogen-activatedproteinkinase.,Biochemistry.2001Mar6;40(9):2870-8.

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59. SheQB,BodeAM,MaWY,ChenNY,DongZ.,Resveratrol-inducedactivationofp53andapoptosisismediatedbyextracellular-signal-regulatedproteinkinasesandp38kinase.,CancerRes.2001Feb15;61(4):1604-10.

60. BruderJL,HsiehT,LereaKM,OlsonSC,WuJM.,Inducedcytoskeletalchangesinbovinepulmonaryarteryendothelialcellsbyresveratrolandtheaccompa-nyingmodifiedresponsestoarterialshearstress.,BMCCellBiol.2001;2:1.

61. SaijonmaaO,NymanT,KosonenR,FyhrquistF.,Upregulationofangiotensin-convertingenzymebyvascularendothelialgrowthfactor.,AmJPhysiolHeartCircPhysiol.2001Feb;280(2):H885-91.

62. LinJK,TsaiSH.,Chemopreventionofcancerandcardiovasculardiseasebyresveratrol.,ProcNatlSciCouncRepubChinaB.1999Jul;23(3):99-106.

63. PalmieriL,MameliM,RoncaG.,Effectofresveratrolandsomeothernaturalcompoundsontyrosinekinaseactivityandoncytolysis.,DrugsExpClinRes.1999;25(2-3):79-85.

64. El-MowafyAM,WhiteRE.,ResveratrolinhibitsMAPKactivityandnucleartranslocationincoronaryarterysmoothmuscle:reversalofendothelin-1stimulatoryeffects.,FEBSLett.1999May14;451(1):63-7.

65. LuR,SerreroG.,Resveratrol,anaturalproductderivedfromgrape,exhibitsantiestrogenicactivityandinhibitsthegrowthofhumanbreastcancercells.,JCellPhysiol.1999Jun;179(3):297-304.

66. FerreroME,BertelliAE,FulgenziA,PellegattaF,CorsiMM,BonfrateM,FerraraF,DeCaterinaR,GiovanniniL,BertelliA.,Activityinvitroofresveratrolongranulocyteandmonocyteadhesiontoendothelium.,AmJClinNutr.1998Dec;68(6):1208-14.

67. KawadaN,SekiS,InoueM,KurokiT.,Effectofantioxidants,resveratrol,quer-cetin,andN-acetylcysteine,onthefunctionsofculturedrathepaticstellatecellsandKupffercells.,Hepatology.1998May;27(5):1265-74.

��

68. JayatilakeGS,JayasuriyaH,LeeES,KoonchanokNM,GeahlenRL,AshendelCL,McLaughlinJL,ChangCJ.,KinaseinhibitorsfromPolygonumcuspidatum.,JNatProd.1993Oct;56(10):1805-10.

Reducingheartattackandstrokeinjury1. PenumathsaSV,KoneruS,SamuelSM,MaulikG,BagchiD,YetSF,MenonVP,

MaulikN.,Strategictargetstoinduceneovascularizationbyresveratrolinhypercholesterolemicratmyocardium:Roleofcaveolin-1,endothelialnitricoxidesynthase,hemeoxygenase-1,andvascularendothelialgrowthfactor.,FreeRadicBiolMed.2008Jul27.

2. LinJF,LinSM,ChihCL,NienMW,SuHH,HuBR,HuangSS,TsaiSK.,Resveratrolreducesinfarctsizeandimprovesventricularfunctionaftermyocardialisch-emiainrats.,LifeSci.2008Jun27.

3. LekliI,SzaboG,JuhaszB,DasS,DasM,VargaE,SzendreiL,GesztelyiR,VaradiJ,BakI,DasDK,TosakiA.,Protectivemechanismsofresveratrolagainstischemia-reperfusion-induceddamageinheartsobtainedfromZuckerobeserats:theroleofGLUT-4andendothelin.,AmJPhysiolHeartCircPhysiol.2008Feb;294(2):H859-66.

4. BursteinB,MaguyA,ClémentR,GosselinH,PoulinF,EthierN,TardifJC,HébertTE,CalderoneA,NattelS.,Effectsofresveratrol(trans-3,5,4’-trihy-droxystilbene)treatmentoncardiacremodelingfollowingmyocardialinfarc-tion.,JPharmacolExpTher.2007Dec;323(3):916-23.

5. CruzMN,AgewallS,Schenck-GustafssonK,KublickieneK.,Acutedilata-tiontophytoestrogensandestrogenreceptorsubtypesexpressioninsmallarteriesfromwomenwithcoronaryheartdisease.,Atherosclerosis.2008Jan;196(1):49-58.Epub2007Mar23.

6. DasS,FalchiM,BertelliA,MaulikN,DasDK.,Attenuationofischemia/re-perfusioninjuryinratsbytheanti-inflammatoryactionofresveratrol.,Arzneimittelforschung.2006;56(10):700-6.

��

7. PenumathsaSV,ThirunavukkarasuM,KoneruS,JuhaszB,ZhanL,PantR,MenonVP,OtaniH,MaulikN.,Statinandresveratrolincombinationinducescardioprotectionagainstmyocardialinfarctioninhypercholesterolemicrat.,JMolCellCardiol.2007Mar;42(3):508-16.

8. VigneP,FrelinC.,AlowproteindietincreasesthehypoxictoleranceinDrosophila.,PLoSONE.2006Dec20;1:e56.,

9. BezstarostiK,DasS,LamersJM,DasDK.,Differentialproteomicprofilingtostudythemechanismofcardiacpharmacologicalpreconditioningbyresvera-trol.,JCellMolMed.2006Oct-Dec;10(4):896-907.

10. MaulikN.,Reactiveoxygenspeciesdrivesmyocardialangiogenesis?,AntioxidRedoxSignal.2006Nov-Dec;8(11-12):2161-8.

11. DasS,FragaCG,DasDK.,CardioprotectiveeffectofresveratrolviaHO-1expressioninvolvesp38mapkinaseandPI-3-kinasesignaling,butdoesnotinvolveNFkappaB.,FreeRadicRes.2006Oct;40(10):1066-75.

12. BaurJA,SinclairDA.,Therapeuticpotentialofresveratrol:theinvivoevi-dence.,NatRevDrugDiscov.2006Jun;5(6):493-506.Epub2006May26.

13. BakI,LekliI,JuhaszB,NagyN,VargaE,VaradiJ,GesztelyiR,SzaboG,SzendreiL,BacskayI,VecsernyesM,AntalM,FesusL,BoucherF,deLeirisJ,TosakiA.,CardioprotectivemechanismsofPrunuscerasus(sourcherry)seedextractagainstischemia-reperfusion-induceddamageinisolatedrathearts.,AmJPhysiolHeartCircPhysiol.2006Sep;291(3):H1329-36.DasS,TosakiA,BagchiD,MaulikN,DasDK.,Potentiationofasurvivalsignalintheischemicheartbyresveratrolthroughp38mitogen-activatedproteinkinase/mitogen-andstress-activatedproteinkinase1/cAMPresponseelement-bindingproteinsignaling.,JPharmacolExpTher.2006Jun;317(3):980-8.

14. FukudaS,KagaS,ZhanL,BagchiD,DasDK,BertelliA,MaulikN.,Resveratrolamelioratesmyocardialdamagebyinducingvascularendothelialgrowthfactor-angiogenesisandtyrosinekinasereceptorFlk-1.,CellBiochemBiophys.2006;44(1):43-9.

��

15. CruzMN,LukshaL,LogmanH,PostonL,AgewallS,KublickieneK.,Acuteresponsestophytoestrogensinsmallarteriesfrommenwithcoronaryheartdisease.,AmJPhysiolHeartCircPhysiol.2006May;290(5):H1969-75.

16. MorelliR,DasS,BertelliA,BolliniR,LoScalzoR,DasDK,FalchiM.,Theintro-ductionofthestilbenesynthasegeneenhancesthenaturalantiradicalactivityofLycopersiconesculentummill.,MolCellBiochem.2006Jan;282(1-2):65-73.

17. KagaS,ZhanL,MatsumotoM,MaulikN.,Resveratrolenhancesneovascu-larizationintheinfarctedratmyocardiumthroughtheinductionofthiore-doxin-1,hemeoxygenase-1andvascularendothelialgrowthfactor.,JMolCellCardiol.2005Nov;39(5):813-22.

18. DasS,AlagappanVK,BagchiD,SharmaHS,MaulikN,DasDK.,CoordinatedinductionofiNOS-VEGF-KDR-eNOSafterresveratrolconsumption:apotentialmechanismforresveratrolpreconditioningoftheheart.,VasculPharmacol.2005Apr-May;42(5-6):281-9.

19. DasS,TosakiA,BagchiD,MaulikN,DasDK.,Resveratrol-mediatedactivationofcAMPresponseelement-bindingproteinthroughadenosineA3receptorbyAkt-dependentand-independentpathways.,JPharmacolExpTher.2005Aug;314(2):762-9.

20. SzmitkoPE,VermaS.,Cardiologypatientpages.Redwineandyourheart.,Circulation.2005Jan18;111(2):e10-1.

21. DasS,CordisGA,MaulikN,DasDK.,Pharmacologicalpreconditioningwithresveratrol:roleofCREB-dependentBcl-2signalingviaadenosineA3receptoractivation.,AmJPhysiolHeartCircPhysiol.2005Jan;288(1):H328-35.

22. HungLM,SuMJ,ChenJK.,Resveratrolprotectsmyocardialischemia-reperfu-sioninjurythroughbothNO-dependentandNO-independentmechanisms.,FreeRadicBiolMed.2004Mar15;36(6):774-81.

23. SatoM,MaulikN,DasDK.,Cardioprotectionwithalcohol:roleofbothalcoholandpolyphenolicantioxidants.,AnnNYAcadSci.2002May;957:122-35.

��

24. CuiJ,TosakiA,BertelliAA,BertelliA,MaulikN,DasDK.,Cardioprotectionwithwhitewine.,DrugsExpClinRes.2002;28(1):1-10.

25. ImamuraG,BertelliAA,BertelliA,OtaniH,MaulikN,DasDK.,Pharmacologicalpreconditioningwithresveratrol:aninsightwithiNOSknockoutmice.,AmJPhysiolHeartCircPhysiol.2002Jun;282(6):H1996-2003.

26. HattoriR,OtaniH,MaulikN,DasDK.,Pharmacologicalpreconditioningwithresveratrol:roleofnitricoxide.,AmJPhysiolHeartCircPhysiol.2002Jun;282(6):H1988-95.

27. HaleSL,KlonerRA.,Effectsofresveratrol,aflavinoidfoundinredwine,oninfarctsizeinanexperimentalmodelofischemia/reperfusion.,JStudAlcohol.2001Nov;62(6):730-5.

29. HungLM,ChenJK,LeeRS,LiangHC,SuMJ.,Beneficialeffectsofastringinin,aresveratrolanalogue,ontheischemiaandreperfusiondamageinratheart.,FreeRadicBiolMed.2001Apr15;30(8):877-83.

30. BradamanteS,PiccininiF,BarenghiL,BertelliAA,DeJongeR,BeemsterP,DeJongJW.,Doesresveratrolinducepharmacologicalpreconditioning?,IntJTissueReact.2000;22(1):1-4.

31. BallmerPE.,[TheMediterraneandiet--healthybutandstilldelicious],TherUmsch.2000Mar;57(3):167-72.[German]

32. SatoM,RayPS,MaulikG,MaulikN,EngelmanRM,BertelliAA,BertelliA,DasDK.,Myocardialprotectionwithredwineextract.,JCardiovascPharmacol.2000Feb;35(2):263-8.

33. SatoM,MaulikG,BagchiD,DasDK.,Myocardialprotectionbyprotykin,anovelextractoftrans-resveratrolandemodin.,FreeRadicRes.2000Feb;32(2):135-44.

��

34. RayPS,MaulikG,CordisGA,BertelliAA,BertelliA,DasDK.,Theredwineantioxidantresveratrolprotectsisolatedratheartsfromischemiareperfusioninjury.,FreeRadicBiolMed.1999Jul;27(1-2):160-9.

35. ConstantJ.,Alcohol,ischemicheartdisease,andtheFrenchparadox.,CoronArteryDis.1997Oct;8(10):645-9.

36. DongW,LiN,GaoD,ZhenH,ZhangX,LiF.,ResveratrolattenuatesischemicbraindamageinthedelayedphaseafterstrokeandinducesmessengerRNAandproteinexpressforangiogenicfactors.,JVascSurg.2008Jun21.

37. BanJY,ChoSO,ChoiSH,JuHS,KimJY,BaeK,SongKS,SeongYH.,NeuroprotectiveeffectofSmilacischinaerhizomeonNMDA-inducedneu-rotoxicityinvitroandfocalcerebralischemiainvivo.,JPharmacolSci.2008Jan;106(1):68-77.

38. DongW,GaoD,LinH,ZhangX,LiN,LiF.,Newinsightsintomechanismfortheeffectofresveratrolpreconditioningagainstcerebralischemicstroke:Possibleroleofmatrixmetalloprotease-9.,MedHypotheses.2008;70(1):52-5.

39. TsaiSK,HungLM,FuYT,ChengH,NienMW,LiuHY,ZhangFB,HuangSS.,Resveratrolneuroprotectiveeffectsduringfocalcerebralischemiainjuryvianitricoxidemechanisminrats.,JVascSurg.2007Aug;46(2):346-53.

40. DongW,GaoD,ZhangX.,Mitochondriabiogenesisinducedbyresveratrolagainstbrainischemicstroke.,MedHypotheses.2007;69(3):700-1.

41. MokniM,LimamF,ElkahouiS,AmriM,AouaniE.,Strongcardioprotectiveeffectofresveratrol,aredwinepolyphenol,onisolatedratheartsafterisch-emia/reperfusioninjury.,ArchBiochemBiophys.2007Jan1;457(1):1-6.

42. GaoD,ZhangX,JiangX,PengY,HuangW,ChengG,SongL.,ResveratrolreducestheelevatedlevelofMMP-9inducedbycerebralischemia-reperfusioninmice.,LifeSci.2006Apr25;78(22):2564-70.

��

43. ZhuangH,KimYS,KoehlerRC,DoréS.,Potentialmechanismbywhichres-veratrol,aredwineconstituent,protectsneurons.,AnnNYAcadSci.2003May;993:276-86;discussion287-8.

44. ìkedaK,NegishiH,YamoriY.,Antioxidantnutrientsandhypoxia/ischemiabraininjuryinrodents.,Toxicology.2003Jul15;189(1-2):55-61.

45. SinhaK,ChaudharyG,GuptaYK.,Protectiveeffectofresveratrolagainstoxida-tivestressinmiddlecerebralarteryocclusionmodelofstrokeinrats.,LifeSci.2002Jun28;71(6):655-65.

46. agchiD,DasDK,TosakiA,BagchiM,KothariSC.,Benefitsofresveratrolinwomen’shealth.,DrugsExpClinRes.2001;27(5-6):233-48.

47. HuangSS,TsaiMC,ChihCL,HungLM,TsaiSK.,ResveratrolreductionofinfarctsizeinLong-Evansratssubjectedtofocalcerebralischemia.,LifeSci.2001Jul20;69(9):1057-65.

48. WangMJ,HuangHM,HsiehSJ,JengKC,KuoJS.,Resveratrolinhibitsinterleu-kin-6productionincorticalmixedglialcellsunderhypoxia/hypoglycemiafollowedbyreoxygenation.,JNeuroimmunol.2001Jan1;112(1-2):28-34.

ReducingLDLlevels1. DoGM,KwonEY,KimHJ,JeonSM,HaTY,ParkT,ChoiMS.,Long-termeffects

ofresveratrolsupplementationonsuppressionofatherogeniclesionforma-tionandcholesterolsynthesisinapoE-deficientmice.,BiochemBiophysResCommun.2008Sep12;374(1):55-9.

2. ZangM,XuS,Maitland-ToolanKA,ZuccolloA,HouX,JiangB,WierzbickiM,VerbeurenTJ,CohenRA.,PolyphenolsstimulateAMP-activatedproteinkinase,lowerlipids,andinhibitacceleratedatherosclerosisindiabeticLDLreceptor-deficientmice.Diabetes.2006Aug;55(8):2180-91.

��

3. ZernTL,WoodRJ,GreeneC,WestKL,LiuY,AggarwalD,ShachterNS,FernandezML.,Grapepolyphenolsexertacardioprotectiveeffectinpre-andpostmenopausalwomenbyloweringplasmalipidsandreducingoxidativestress.,JNutr.2005Aug;135(8):1911-7.

4. RimandoAM,NagmaniR,FellerDR,YokoyamaW.,Pterostilbene,anewagonistfortheperoxisomeproliferator-activatedreceptoralpha-isoform,lowersplasmalipoproteinsandcholesterolinhypercholesterolemicham-sters.,JAgricFoodChem.2005May4;53(9):3403-7.

5. ZernTL,WestKL,FernandezML.,Grapepolyphenolsdecreaseplasmatriglyc-eridesandcholesterolaccumulationintheaortaofovariectomizedguineapigs.,JNutr.2003Jul;133(7):2268-72.

6. PalS,HoN,SantosC,DuboisP,MamoJ,CroftK,AllisterE.,Redwinepolyphe-nolicsincreaseLDLreceptorexpressionandactivityandsuppressthesecre-tionofApoB100fromhumanHepG2cells.,JNutr.2003Mar;133(3):700-6.

7. WeisburgerJH.,Mechanismsofactionofantioxidantsasexemplifiedinveg-etables,tomatoesandtea.,FoodChemToxicol.1999Sep-Oct;37(9-10):943-8.

8. FrémontL,BelguendouzL,DelpalS.,Antioxidantactivityofresveratrolandalcohol-freewinepolyphenolsrelatedtoLDLoxidationandpolyunsaturatedfattyacids.LifeSci.1999;64(26):2511-21.

Triglyceridelevelsandresveratrol1. ShanT,WangY,WuT,GuoJ,LiuJ,FengJ,XuZ.,Porcineadiposetriglyceride

lipasecomplementarydeoxyribonucleicacidclone,expressionpattern,andregulationbyresveratrol.,JAnimSci.2008Aug;86(8):1781-8.

2. ChoIJ,AhnJY,KimS,ChoiMS,HaTY.,ResveratrolattenuatestheexpressionofHMG-CoAreductasemRNAinhamsters.,BiochemBiophysResCommun.2008Feb29;367(1):190-4.

��

3. WangZ,ZouJ,CaoK,HsiehTC,HuangY,WuJM.,Dealcoholizedredwinecon-tainingknownamountsofresveratrolsuppressesatherosclerosisinhyper-cholesterolemicrabbitswithoutaffectingplasmalipidlevels.,IntJMolMed.2005Oct;16(4):533-40.

4. IlanE,TiroshO,MadarZ.,Triacylglycerol-mediatedoxidativestressin-hibitsnitricoxideproductioninratisolatedhepatocytes.,JNutr.2005Sep;135(9):2090-5.

5. ZernTL,WoodRJ,GreeneC,WestKL,LiuY,AggarwalD,ShachterNS,FernandezML.,Grapepolyphenolsexertacardioprotectiveeffectinpre-andpostmenopausalwomenbyloweringplasmalipidsandreducingoxidativestress.,JNutr.2005Aug;135(8):1911-7.

6. AronisA,MadarZ,TiroshO.,Mechanismunderlyingoxidativestress-medi-atedlipotoxicity:exposureofJ774.2macrophagestotriacylglycerolsfacilitatesmitochondrialreactiveoxygenspeciesproductionandcellularnecrosis.,FreeRadicBiolMed.2005May1;38(9):1221-30.

7. MiuraD,MiuraY,YagasakiK.,Hypolipidemicactionofdietaryresveratrol,aphytoalexiningrapesandredwine,inhepatoma-bearingrats.,LifeSci.2003Aug1;73(11):1393-400.

Vasodilationandloweringheartdisease1. SoylemezS,GurdalH,SepiciA,AkarF.,Theeffectoflong-termresveratrol

treatmentonrelaxationtoestrogeninaortaefrommaleandfemalerats:Roleofnitricoxideandsuperoxide.,VasculPharmacol.2008Jul4.

2. ZambléA,Martin-NizardF,SahpazS,HennebelleT,StaelsB,BordetR,DuriezP,BrunetC,BailleulF.,Vasoactivity,antioxidantandaphrodisiacpropertiesofCaesalpiniabenthamianaroots.,JEthnopharmacol.2008Feb28;116(1):112-9.

��

3. CalderoneV,MartelliA,TestaiL,MartinottiE,BreschiMC.,Functionalcontri-butionoftheendothelialcomponenttothevasorelaxingeffectofresveratrolandNS1619,activatorsofthelarge-conductancecalcium-activatedpotassiumchannels.,NaunynSchmiedebergsArchPharmacol.2007Mar;375(1):73-80.

4. YooMY,OhKS,LeeJW,SeoHW,YonGH,KwonDY,KimYS,RyuSY,LeeBH.,Vasorelaxanteffectofstilbenesfromrhizomeextractofrhubarb(Rheumundulatum)onthecontractilityofrataorta.,PhytotherRes.2007Feb;21(2):186-9.

5. Granados-SotoV.,Pleiotropiceffectsofresveratrol.,DrugNewsPerspect.2003Jun;16(5):299-307.

6. OralloF,AlvarezE,CamiñaM,LeiroJM,GómezE,FernándezP.,Thepossibleimplicationoftrans-Resveratrolinthecardioprotectiveeffectsoflong-termmoderatewineconsumption.,MolPharmacol.2002Feb;61(2):294-302.

7. MizutaniK,IkedaK,KawaiY,YamoriY.,Extractofwinephenolicsimprovesaorticbiomechanicalpropertiesinstroke-pronespontaneouslyhypertensiverats(SHRSP).,JNutrSciVitaminol(Tokyo).1999Jan;45(1):95-106.

8. ChenCK,Pace-AsciakCR.,Vasorelaxingactivityofresveratrolandquercetininisolatedrataorta.,GenPharmacol.1996Mar;27(2):363-6.

9. FitzpatrickDF,HirschfieldSL,CoffeyRG.,Endothelium-dependentvasorelax-ingactivityofwineandothergrapeproducts.,AmJPhysiol.1993Aug;265(2Pt2):H774-8.

UseinaCosmetictopreventphotoagingandrepairDNA

1. Mizutani,K.,Ikeda,K.,Kawai,Y.,andYamori,Y.,ResveratrolStimulatestheProliferationandDifferentiationofOsteoblasticMC3T3Cells.,BiochemBiophysResCommun253(1998):859—863.

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2. RucinskiM,ZiolkowskaA,HocholA,PucherA,MacchiC,BelloniAS,NussdorferGG,MalendowiczLK.,Estradiolandresveratrolstimulatingeffectonosteocalcin,butnotosteonectinandcollagen-1alphageneexpressioninprimarycultureofratcalvarialosteoblast-likecells.,IntJMolMed.2006Oct;18(4):565-70.

3. ZiolkowskaA,RucinskiM,PucherA,TortorellaC,NussdorferGG,MalendowiczLK.,Expressionofosteoblastmarkergenesinratcalvarialosteoblast-likecells,andeffectsoftheendocrinedisruptersdiphenylolpropane,benzophenone-3,resveratrolandsilymarin.,ChemBiolInteract.2006Dec15;164(3):147-56.

4. Chanvitayapongs,S.,Draczynska-Lusiak,B.,andSun,A.Y.,AmeliorationofOxidativeStressbyAntioxidantsandResveratrolinPCI2Cells.,Neuroreport8(1997):1499—1502.

5. Leung,A.,andMo,Z.,ProtectiveEffectsofPolydatin,anActiveCompoundfromPolygonumcuspidatum,onCerebralIschemiaDamageinRats.,ChinPharmBull12(1996):128-129.

6. Nigdikar,S.V.,Williams,N.R.,Griffin,B.A.,andHoward,A.N.,ConsumptionofRedWinePolyphenolsReducestheSusceptibilityofLow-DensityLipoproteinstoOxidationinVivo.,AmerIClinNutr68(1998):258—265.

7. Sato,M.,Maulik,C.,Bagchi,D.,andDas,D.K.,MyocardialProtectionbyProtykin,aNovelExtractoftrans-ResveratrolandEmodin.,FreeRadicalResearch32(2000):135—144.

8. Frankel,F.,Waterhouse,A.L.,andKinsella,J.F.,InhibitionofHumanLDLOxidationbyResveratrol.,TheLancet341(1993):1103—1104.

9. Han,Y.N.,Ryu,S.Y.,andHan,B.H.,AntioxidantActivityofResveratrolCloselyCorrelateswithitsMonoamineOxidase-AInhibitoryActivity.,ArchPharmRes13(1990):132—135.

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CerebralbloodflowandcognitionDavidOKennedy,EmmaLWightman,JonathonLReay,GeorgLietz,EdwardJOkello,AntheaWildeandCrystalFHaskell

FromtheBrainPerformanceNutritionResearchCentreNorthumbriaUniversityNewcastleuponTyneUnitedKingdom(DOKELWJLRAWCFH)theSchoolofAgricultureFoodRuralDevelopmentNewcastleUniversityNewcastleuponTyneUnitedKingdom(GLEJO).

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