POMEGRANATE JUICE GROW IN SPAINAntioxidant punicalagin in pomegranate juice and pome-granate extract, for the functional diet of the future.

Ángel Calín Sánchez (Engineer)Dr. Ángel A. Carbonell BarrachinaMIGUEL HERNANDEZ UNIVERSITY, Food Technology Department

Discover the worlds of goodness within me

1. Introduction 1.1. The origins of the pomegranate 1.2. Economic importance in Spain 1.3. The Mollar de Elche pomegranate 2. Functionalproductsderivedfromthepomegranateandintegraluseofthefruit 2.1. Chemicalcompositionofthepomegranate 2.2. Phenolic compounds 2.2.1. Low molecular weight phenolic compounds 2.2.2. High molecular weight phenolic compounds 2.3. Thepomegranateasafunctionalfood 2.4. Oxidationversusantioxidation 3. The pomegranate and health 3.1. Anti-cancerandanti-tumourproperties 3.2. Preventionofcardiovasculardisease 3.3. Anti-inflammatoryproperties 3.4. Theanti-diabeticpropertiesofthepomegranate 3.5. Preventionofoxidativedeterioration 3.6. Preventionofskindamage 3.7. Antimicrobialpropertiesofthepomegranateandderivedproducts 3.8. Effectsofthepomegranateonoralhealth 3.9. Otherhealth-relatedpropertiesofthepomegranate 3.9.1. Effectsofthepomegranateondiarrhoea 3.9.2. Effectsofthepomegranateonspermqualityanderectiledysfunction 4. Bibliography

Research results

TheresultsobtainedfollowingananalysisofcommercialpomegranatejuicesinSpainin2010indicatethatproductsfromtheGranatumPlusrangecontainedahigherconcentrationofpolyphenols, thepomegranate’snatural antioxidant, thananyof theotherproducts ana-lysed.Furthermore,ananalysisofthepricesofthedifferentpomegranateproductsonthemarketalsoestablishedthatofalltheproductsanalysed,GranatumPlusproductspresentedthebestvalueformoney.

TheFoodQualityandSafetyGroup(FQS)researchteamattheMiguelHernándezUniversityofElcheDepartmentofFoodTechnologyhasconductedseveralstudiesontheorganolepticqualityandfunctionalpropertiesofpomegranatejuiceandpomegranate-derivedproducts(peelextract,dehydratedpomegranate,etc.).

The Food quality and safety group and the pomegranate

Oneof the researchprojectsundertakenwas fundedby the companyAntioxidantesNat-uralesdelMediterráneoS.L. (NaturalMediterraneanAntioxidantsL.L.C.),andresearchfo-cusedoncomparingthefunctionalpropertiesandacceptancebySpanishconsumersofcom-mercialpomegranatejuicesavailableonthedomesticmarket.Moreover,inconjunctionwiththeUniversityofKansas(UnitedStatesofAmerica),theFQSresearchteamhasconductedastudyontheworldwideacceptanceofdifferenttypesofpomegranatejuice.Withinthisstudy,GranatumPlusjuicewasselectedasabenchmarkfor100%naturaljuice.

Grownin

Spain

The indicationgivenontheproduct labelofthegeographicoriginofthepomegranatesandthevarietyusedwasconsid-eredhighlycommendable.GranatumPlusproductsexcelledinthelistofnationalproductsanalysed,GranatumPlusistheonly commercialbrand that informs consumersof thegeo-graphic origin of the pomegranates (Spain) and the variety

Furthermore,thisproductalsocontainsabout84%pomegranateextract.Takinga“Grana-tumPlus”capsuleistheequivalentofdrinkingabout250mlofjuicesqueezedfromarilsofthesamevariety.Thisstudy,togetherwithothersconductedinrecentyearsbyprestigiousuniversitiesworldwide,hasdemonstratedthattheantioxidantpowerofpomegranatepeelis10timesstrongerthantheedibleparts.

ThesamestudyshowedthatGranatumPluscapsulescontainsaround30%punicalaginsandatotalpercentageofpolyphenolsofnearly50%.

GranatumPlusjuicesobtainedthelowestscoresinundesirableattributesandhighscoresinattributessuchassweetness,pomegranatearomaandcolour.

1. Introduction

Inordertomoveforwardstowardsthefuture,weoftenneedtolookfirstatourpast.Aclearexampleofthisisoneofthefirstcropstobedomesticatedbyhumans,thepomegran-ate.ThepresenceofthisfruitinSpanishcultureandhistoryissoubiquitousthatitevenap-pearsincoatsofarmssuchasthatoftheKingdomofGranadaduringthetimeoftheCatholicKings.

Another example highlighting the relationship between the pomegranate, Spain and re-searchistheemblemoftheSpanishNationalResearchCouncil(CSIC),whichincorporatesapomegranatetree(Figure 1).

Figure 1.ApomegranateorchardandtheemblemoftheSpanishNationalResearchCouncil.

TheaimofthepresentdocumentistohighlighttheimportanceofthiscropinSpain,whichisduebothtothehighvolumeofproductionandthebenefitsforhumannutritionprovidedbythisfruitanditsderivedproducts.

1.1. The origins of the pomegranate

Thepomegranate(PunicagranatumL.)hasbeencultivatedsinceantiquity.Itisoneofthebiblicalcrops,togetherwithgrapes,olivesanddates.AccordingtoNikolaiVavilov,thepome-granateevolvedinthe4thCentreofOrigin,theMiddleEast(AsiaMinor,Transcaucasia,IranandthehighlandsofTurkmenistan).

Thepomegranate(PunicagranatumL.)isasmalldeciduoustreethatgrowstoamaximumof8metreshighinthewild.Itisaveryvaluablefruittreeinmanyregionsoftheworld,es-peciallythosewhicharearidandsemiarid,sinceitiscapableofadaptingtodifferentareaswhereother,currentlymorewidelygrownfruittreeswouldnotyieldaprofitablecrop(MelgarejoandSalazar,2003).

Itssystematicclassificationisasfollows:

Division:MagnoliophytaClass: Magnoliopsida.Subclass:Rosidae.Order:Myrtales.Family:LythraceaeGenus: Punica.Specie: P. granatum.

1.2. The Economic Importance of the pomegranate

Thepomegranateiscurrentlycultivatedinavarietyofcountries,includingSpain,theUnitedStates,Iran,Turkey,India,Israel,ChinaandcountriesalongthenorthcoastofAfrica,amongothers.SpainranksasthelargestproducerinEurope,withanannualproductionof22,311tons(SpanishMinistryoftheEnvironmentandRuralandMarineAffairs,2010).

ProductioniscentredinValencia,AndalusiaandMurcia(Figure 1),although90%ofthisisintheprovinceofAlicante.Inturn,productioninAlicanteismainlyconcentratedinthreemunicipalities,Elche,AlbateraandCrevillente,inorderofimportance.Thishighlevelofcon-centrationclearlyindicatestheenormoussocio-economicimportanceofthepomegranateforthesethreemunicipalitiesandtheirsurroundings.

Graph 1. PomegranateproducingcommunitiesinSpain.

1.3. The Mollar de Elche pomegranate

Thepomegranatehastraditionallybeenahighlyprizedandesteemedfruitinmanyciviliza-tions.Togetherwiththepalmtree,thepomegranatetreeisthemostcharacteristictreeinCampodeElche,andhasbeenknownfromtimeimmemorial.InSpain,theMollardeElchepomegranate(Figure2) isbyfarthemostpopularvarietyandisunquestionablythemostwidelygrowninthiscountry.

-Largeorverylargesizedfruit.-Vigorous,fastgrowingtree.-Large,darkredseedcasings(arils)withverysmallandsoftseeds.-MaturingbetweenOctoberandNovember.-ItismoreproductiveandofbetterqualityandhighercalibrethantheValen-ciangrouppomegranates,whichranksecondinSpanishproduction.

The most important characteristics of the Mollar de Elche pomegranate are as follows:

Figure 2

Thestudyofthepomegranate’sbio-activecomponentsandtheirbenefitsforhumanhealthisahighlytopicalandimportantfieldofresearch.Numerousscientificstudieshaveshownthatboth thepomegranateand itsderivedproductscontainmanycomponents thatcon-tributetopreventingdiseaseandmaintaininghealth(Larrosaetal.,2006;Sartippouretal.,2008;Koyamaetal.,2010).

Thepomegranateisusuallyconsumedfresh.However,alargeproportionofthecropdoesnotpresentsufficientvisualqualitytobedestinedforfreshconsumption,sinceitsaccept-ancebyconsumersisverylow.However,thequalityoftheediblepart,thearils,issimilartothatofthosespecimenswithgoodacceptanceforfreshconsumption.Itisthereforeneces-sarytofindanalternativecommercialuseforthisproportionofthecropunsuitableforfreshconsumption,basedonindustrialprocessing.

The most important industrial products derived from the pomegranate are:

-Pomegranatejuice:widelymarketedintheUSA,andwithgreatpotentialinSpain-Readytoeatarils-Jams.-Wines,vinegarsandliqueurs.-Dehydratedarils-Nutraceuticalsmadefrompeelextract-Foodcondiments.

-Cosmetics:creams,oils,gels,etc.

2. Functional products derived from the pomegranate and integral use of the fruit.

2.1. Chemical composition of the pomegranates

Thepeel,whitepulpmembrane,arilsandseedsofthepomegranateallcontainmanychemi-calcompoundsofhighbiologicalvalue(Figure3).Themostimportantproductderivedfromthepomegranateisitsjuice,whichisunquestionablythemostresearchelement,withmanyarticlespublishedinboththeSpanishandinternationalscientificliterature.

About50%ofthetotalweightofthepomegranatecorrespondstothepeelandwhitepulpmembranes,whichareamajorsourceofbio-activecompoundssuchaspolyphenols,flavo-noids,ellagitannins,proanthocyanidinsandminerals,mainlypotassium,nitrogen,calcium,phosphorus, magnesium and sodium. Consequently, if processed correctly, nutraceuticalproductsandfoodcondimentsmadefrompeelandmembraneextractsmayprovideanim-portant source of these compounds.

Figure 3. Thedifferentpartsofthepomegranate.

Pomegranatearilsarealsoamajorsourceoflipids,sincefattyacidscomprisebetween12%and20%ofthetotaldryweightoftheseeds.

Thefattyacidprofileischaracterisedbyahighcontentinunsaturatedfattyacids,includinglinolenic,linoleic,punicic,oleic,stearicandpalmiticacids.

Theediblepartofthepomegranaterepresentsabout50%ofthetotalweightofthefruit,ofwhichthefleshypulpofthe arils accounts for 80% and the woody seeds contain20%.

Pomegranatearilsarecomposedof85%water,10%sugar(mainlyfructoseandglucose),1.5%organicacids(principal-lyascorbic,citricandmalicacids)andbioactivecompoundssuchaspolyphenolsandflavonoids(mainlyanthocyanins).

Table 1. Nutritionalcompositionoftheediblepart(USDA,2007).

Thebeneficialeffectsoffruitandvegetablesarisingfromtheirhighcontentinbioactivecom-poundsarenowwidelyaccepted.Thepresenceof thecompounds listedabove (Table 2)indicatestheimportantnutritionalvalueofthepomegranate.

Table 2.Mineralcontentoftheediblepart(USDA,2007)andinpomegranatejuicewithpulp(Andreu-Sevillaetal.,2008).

2.2. Phenolic compounds

2.2.1. Low molecular weight phenolic compounds

Phenolic compounds canbedivided into simplemolecules andpolymersof thesewith ahighermolecularweight.Theflavonoidsarethemostnumerouscompoundsinthefirstsub-group,mainlyrepresentedbyanthocyanins,whichareresponsibleforthecharacteristiccol-our of the pomegranate. The principal low molecular weight phenolic compounds are the phenolicacids,whichincludegallicacidandellagicacid(Figure 4).

Figura 4. Low molecular weight phenolic compounds

2.2.2. High molecular weight phenolic compounds

Tanninsarethemostcharacteristichighmolecularweightpolyphenols.Pomegranatepeelisrichinhydrolysabletannins,mainlypunicalin,pedunculaginandpunicalagin(Figure 5).

Figure 5. Molecular structure of punicalagin

Functionalfoodsinclude:(i)thosecontainingcertainminerals,vitamins,fattyacidsordietaryfibre,(ii)foodstowhichbiologicallyactivesubstances,suchasphytochemicalsorotheran-tioxidants,havebeenadded,and(iii)probioticfoodscontainingbeneficiallivemicroorgan-isms.

Thus,giventheresultsofvariousstudiesonthechemicalcompositionofthepomegranateandmorerecentlyonitshealthbenefits,thepomegranatecanbeconsideredafunctionalfood(Melgarejo,2010).

Anthocyaninsarethecompoundsconsideredresponsiblefortheredcolourofpomegranatearils.The importanceof thesephenolic compounds lies in theirantioxidantaction,whichprotects against free radicals and retards the cell aging process.

The freeradical scavengingactivityof theseflavonoidshasbeendemonstrated invariousstudies,suchasthatconductedbyEspínetal.(2000).Anestimated10%oftheantioxidantactionofpomegranatejuiceisduetothepresenceofthesepolyphenols,theanthocyanins(Giletal.,2000).

The concept of functional food is complex and can refer towhetherornotthecomponentsarenutrients,whethertheyhaveapositiveeffectonthebody,orwhethertheyhaveaphy-siologicalorpsychologicaleffectbeyondthepurelynutritional(Viuda-Martosetal.,2011a).

2.3. The pomegranate as a functional food

Itscontentinessentialfattyacids(linoleic,linolenicandarachidonicacids)isofgreatimportance,par-ticularlyduetothecontentinpolyunsaturatedfattyacids.Theseplayanimportantrole inthepreven-tionofcardiovasculardiseaseandsomeotherheartproblems,becausethistypeoffattyacidsignificant-lyreducesHDL-cholesterollevels(badcholesterol).Punicicacidhasanti-atherogeniceffects.

Theellagitanninscanbetransformedintourolithins;urolithinAmaybethemostactiveanti-inflammatory compound related to consumption of the pomegranate. Anti-inflammatoryprocessesinthecolonmaybeduetotheunmetabolisedfractionofellagitannins(Larrosaetal.,2010).

Punicalagin, thepolyphenolwith thehighest knownmolecularweight, is hydrolysed intoellagicacidandmetabolisedintheintestinaltracttogenerateurolithins.Punicalagincom-poundspresentveryhighantioxidantorfreeradicalscavengercapacityandareresponsibleforapproximately50%ofthisactivityinpomegranatejuice,followedbyotherhydrolysabletannins(33%oftotalactivity)and,toalesserextent,ellagicacid(3%)(Giletal.,2000;García-Vigueraetal.,2004).

The antioxidant capacity of pomegranate juice is three times that of red wine or green tea (Gil et al., 2000).

-Powerfullantioxidanteffect.-Anticanceraction.-Protectiveeffectonthecardiovascularsystem.

The main functional properties of the punicalagins are: (Sánchez et al. , 2009)

2.4. Oxidation versus Antioxidation

Livingorganismsneedenergy, and this isprovidedby thebasicfoodsubstances(carbohydrates,lipidsandproteins).

This energy is obtained through chemical reactionswhichmay ormay not involve oxygen. Thus,we distinguish be-tweenanaerobicandaerobicmetabolism.

Cellsobtainmoreenergyfromaerobicmetabolism.Withox-ygen,cellsobtainmoreATPfromthebasicnutrients(carbo-hydrates,lipidsandproteins).Withoutoxygen,theyobtain20%lessATP(energy).

C6H12O6 + 6 O2 ====> 6 CO2 + 6 H2O + 38 ATP

Theseoxidationreactions takeplace in themitochondria, structureswhicharepresent inthecellcytoplasm.Basically,theglucosemolecule(6carbonatoms)splitsintotwopyruvicacidmolecules(3carbonatoms)whichoxidiseandreleaseelectronsandprotons.Theseareeventuallyabsorbedbytheoxygen,convertingitintowaterandcarbondioxideandstoringenergyintheformoftri-phosphatebonds(ATP).

O2+4H+4e-====>2H2O

Themoleculesderived fromtheoxidationof glucose continue to be oxidised andoxygen is reduced as it absorbs the elec-trons and protons; each oxygenmoleculeabsorbs four electrons and four protons,therebyformingtwowatermolecules.Thisiswhatisknownastetra-reduction. However,thereactiondoesnotalwaysoc-curinexactlythisway,andithasbeencal-culated that an estimated five percent ofreactionsaremono-andbi-reductionsthat

insteadofgeneratingwaterandCO2,whichareeasilyandnaturallyeliminatedbytheexcre-toryorgans (kidneys, lungs, skin), generateharmful reactive speciesderived fromoxygen(ReactiveOxygenSspecies,ROS)thataredetrimentaltoourhealthbecausetheyperpetuatetheoxidationofhealthytissue,leadingtopathologies.

This5%couldbelikenedtothe“soot”froma“metabolicchimney”;ifitisnoteliminatedorneutralised,overtimewebecomeilloragefaster.Thosebodysystemsmostvulnerabletoattackarethecirculatory,nervousandimmune,ordefensive,systems.

Thereactiveoxygenspeciesproducedincellsincludehydrogenperoxide(H2O2),hydroxylradical(-OH)andsuperoxide(O2•−).

WiththeemergenceofoxygenontheEarth,thosespeciesthatwerenotequippedforoxida-tiondisappeared,whilstthosethatcouldwithstandtheimpactofoxygensurvived,becausetheymanagedtodevelopasystemthatwouldprotectthem:theantioxidantsystem.

Oxidationisdefinedasthe“theft”ofelectronsfromtheouterelectronlayersofatomsormolecules,convertingthemintochargedions.Thesubstancesthatremovetheseelectronsarecalledoxidisingagents,andwhenoxidised,theyarereduced.Ifthese“oxidised”ionsarenotneutralisedbyanotherelement(areducingagent)thatoffersitsownelectronsorpro-tons(H+),theyareconvertedintofreeradicalsandcontinuemovingthroughthebodyuntiltheycanreplacetheseelectronsbyremovingthemfromotherelements,themostvulner-ableofwhicharethemembranesthatmakeupcells.

“Uncontrolled”oxidationinourbodytissuesisresponsibleforaging,degenerationand,ofcourse,disease.Wemustfightagainstitifwewanttosurvive.

-Superoxidodismutasa(SOD)-Catalasa(CAT)-Glutathioneperoxides…andothers

Thenormalfunctionofourcellularantioxidantenzymesystemistocontrolthisexcessoffreeradicalsorreactiveoxygenspeciesproducedbyourownbodies:

Thesethreeenzymesformourstrongestanti-radicaldefenceincells.Weshouldbearinmindthattheconsequenceofanexcessoffreeradicals(oxidisingagents)ortheinabilityonthepartofourenzymaticdefencestocountersuchanexcess,istheriskofdevelopingamulti-tudeofpathologicalprocesses,andinparticular,ofdegenerativediseases,suchasAlzhei-mer’s,Parkinson’s,arthritis,etc.

CO2+ NH3+ light ====> Carbohydrates

Aging is no more than an imbalance in favour of oxidation mechanisms due to weak or inefficient antioxidant defence systems.

However,duetothepaceofmodernlife,wemustaddmanymore“oxidative”attacksfromourenvironment,whichoverwhelmour aforementioned innateantioxidativeenzymede-fencesystem:pollution,tobacco,radiation,countlesspreservativesinourfoodetc.Butwecanprotectourselveswithsubstancesthathelpusfightagainstoxidation:hydro-solublevi-tamins(vitaminsB1,B6,B12andC),fat-solublevitamins(VitaminsEandA),bio-carotenoidsandpolyphenols.Reactiveoxygenspeciesarealsoproducedinplantsduringphotosynthesis,theprocesswherebyplantsobtainenergyfromthesun.

Likeus,plantsalsoneedtodefendthemselvesinordertobeabletosurvivetheintenselightwhichproducesoxidation.Thisisthefunctionofcarotenoids,bioflavonoidsandothersub-stancesthatprotectplantsfromtheoxidationgenerated.

Everyoneknows that if tomatoes,broccoli, orangesorapplesdidnot containantioxidantsubstances,theywouldnotkeep,theywouldsimplyrot.Ifweincludethesenutrientsinourdiet,theystimulateourantioxidantsystemandreducewhatisknownasoxidativestress.

Anti-oxidanthelpisalwaysnecessary,especiallywhenourmetabolismhasbeenweakened,for example, by physical over-exertion (pregnancy, growth, sports competitions, etc.), orwhenourbodiesaretryingtorecoverfromaninfectionoranoperation,orwhenwearesimplyenteringatransitionalstage(andro-andmenopause).

This search forantioxidativenutrientsmaybewhy those fruits andvegetableswhicharemostresistanttotheimpactoflightenergyfromtheSunarealsothosetowhichwearemostattracted.

The concentrationof antioxidants provided by a fruit or vegetable is highest atmaturity,whichiswhenweshouldconsumethem.Theirattractivecoloursareaclearsignofthehighconcentrationofsubstancestheycontainwithstrongantioxidantpropertiessuchascarot-enoids,polyphenols,resveratrols,etc.

Here,specialmentionshouldbemadeofthepomegranate,becauseitcontainsmoreanti-oxidantsthatnotherfruitswhicharethoughttobeantioxidant-rich,suchascitrusfruitsorbilberries,andmoreeventhangreenteaorredwine.

Dr.JoséFausVitoria(CollegeInscriptionNumber:9582-Valencia)ExpertinOzonetherapy,HomeopathyandManualMedicineRepublicaArgentina,52,2º,3ª.46700-GandiaTelephone:962870827http://www.doctorfaus.com

Thepomegranate (Punica granatum l.),anancient,mysticalanddistinctivefruit,waspraisedinantiquityinvariousworks,suchastheBible,theJewishTorahandtheBabylonianTalmud,asasacredfruitwhichpromotedfertility,abundanceandgood luck. It also appeared in EgyptianandGreekceremonies,artandmythol-ogy, and was the personal emblem oftheRomanEmperorMaximus.

Inadditiontothesehistoricalantecedents,thepome-granate is used by several types ofmedicine for thetreatment of a variety of diseases. In Ayurvedic (tra-ditional Indian)medicine,thepomegranateisusedtotreatparasites,diarrhoeaandulcersandisconsideredtohavedepurativeproperties. ThepomegranatealsoservesasaremedyfordiabetesinUnanimedicine(alsopracticedinIndia).

The great interest shown nowadays in themedicinalandnutritionalbenefitsof thepomegranatebegan in2000,andsincethen,morethan200articleshavebeenwritten describing the beneficial health properties ofthepomegranateanditsderivedproducts.Incontrast,in theperiodbetween1950and1999,onlyabout25scientificpaperswerepublishedonthistopic.

3. Pomegranate and health

Thepomegranatehasabroadrangeofpotentiallythera-peuticuses,includingtreatmentandpreventionofcancer,cardiovasculardisease,Alzheimer’sdisease,inflammatorydisease,oralandskindisease,obesity,erectiledysfunctionand diarrhoea.

Below,detailsaregivenofthemainresultsofareviewofthescientificliteratureuntiltheyear2011,describingthevarioustherapeuticapplicationsofthepomegranatemen-tionedabove.

3.1. Anti-cancer and anti-tumour properties

Numerousstudieshavebeenconductedtoassesstheefficacyofthepomegranateanditsderivedproducts,whichhavebeenshowntohaveapotentantioxidantactionasananti-pro-liferative,anti-invasiveandpro-apoptoticagentindiseasedcellsandinanimalmodels(Lan-skyandNewman,2007;Syedetal.,2007;Hongetal.,2008;HamadandAl-Momene2009).

Hongetal.(2008)demonstratedthatpomegranatejuiceandextractsarepotentinhibitorsofcellgrowth,evenmorepotentthansomepolyphenolswhenconsideredinisolation,suggest-ingtheexistenceofasynergisticeffectwiththephytochemicalspresentinthepomegranateand its extracts.

Apomegranateextractappliedasatopicalpre-treatmentreducedtheincidenceoftumoursinmicefrom100%to30%,andalsoincreasedthelatencyintumourdevelopmentfrom9to14weeks(Afaqetal.,2005).Albretchetal.(2004)studiedtheeffectsofpomegranateoil,thepolyphenolsinthepeelandmembranesandthepolyphenolsfromfermentedjuice,onprostatecancer. Alloftheseagents individuallyprohibitedtheproliferationinvitrooftu-mourcellsinhumanLNCaP,PC-3andDU145cells,demonstratingthatpomegranate-derivedproductshaveaclearanti-tumouractioninthecaseofprostatecancer.

Kohnoetal.(2004)demonstratedthattheadministrationofpomegranateseedoilinthedietinhibitedtheincidenceandproliferationofcolonadenocarcinomasinrats.

Theinhibitionofcolontumoursbytheseedoilisassociatedwithan increase inconjugated linoleicacid inthecolonicmucosaandliver.ThereisscientificevidenceshowingthatpomegranatejuicesuppressestheexpressionofCOX-2in-ducedbyTNF- ,theNF-kBpathwayandactivationofAkt.Certain bioactive components present in pomegranatejuice,suchasanthocyaninsandflavonols,mayberespon-sibleforreducingtheproliferationofcancercells(Adamsetal.,2006).Seerametal.(2005b)describedthepowerfulanti-proliferativeactionofpomegranatejuiceagainstvari-oustumourcell lines,witha large inhibitioneffectofbe-tween30%and100%.

Pomegranatejuice,ellagicacidandpunicalagininducedapoptosis(geneticallyregulatedcelldeath)ofHT-29coloncells,butinHCT116coloncells,onlyellagicacidandpunicalaginscon-tributedtoapoptosiswhereaspomegranatejuicedidnot(Seerametal.,2005b).

Therefore,pomegranatepeelextract,which is rich in thesecompounds (punicalaginsandellagicacid)mayhavepotentialforthetreatmentofcoloncancerinthefuture.Lanskyetal.(2005b)reportedthatcertaincomponentspresentinthepomegranatesignificantlyinhibitedcancercellinvasionoftheprostateinvitro(PC-3cells).

Source: Dr.GilbertoE.ChéchileToniolo(2011).IISymposiumInternacionalsobreelGranado,Madrid,España.

Table 4.Mainantitumoraleffectsofpomegranatefruit.

- Antiproliferative: Stopping tumor growth. - Induces apoptosis: induced cell death (suicide). - Inhibits kB nuclear factor (NF-kB): regulates expression of more than 200 genes (immune system, cell proliferation, tumor invasion, metastasis). - Anti-angiogenesis: new blood vessel formation. - Inhibits tumor invasion (metalloproteinases).

FjaeraaandNanberg(2009)showedthatellagicacidinducedapoptosisbymeasuringDNAbreakageandalterationinthecellcycle.González-Sarríasetal.(2009)suggestedthatellagicacidanditsmetabolites,suchasurolithinsAandB,maycontributetothepreventionofco-loncancer.Hongetal.(2008)showedthatpomegranatejuiceanditsextractshaveapotentabilitytostopproliferationandstimulateapoptosisinprostatecancercells.Morerecently,Koyamaetal.(2010)demonstratedthattheuseofpomegranateextractswithstabilisedel-lagitannincontent(punicalagin)totreatLAPC4prostatecellsinhibitedproliferationby37%and led toapoptosis.Fromthe foregoing,wecanconcludethat thepomegranateand itsderivedproductshaveabeneficialeffectagainstcancerandtumoursduetothehighcontentofcompoundssuchasanthocyanins,ellagicacidandpunicalagins.Furthermore,thecasesstudiedhavedemonstratedthatpomegranateproductsandextractshavedifferenteffects,ashasadministrationofthecompoundsresponsibleindividuallyorinisolation.Therefore,theuseofpomegranateanditsderivedproductsishighlydependentonthetypeofclinicalcondition.Itisimportanttoemphasisethatallthecasesmentionedaboverefertothepre-ventionandtreatmentofcancer,andnevertoacureforcancerortumours.Duetotheirphy-tochemicalcomposition,thepomegranateanditsderivedproductsarehighlyrecommendedforthepreventionandtreatmentofcancer.Asummaryisgivenbelowofthemainactionsoranti-tumoureffectsofthepomegranateanditsproductsagainstdifferentcancers(breast,colon,prostate,etc.).

3.2. Prevention of cardiovascular disease

Oneofthemajorriskfactorsfordevelopingcoronaryheartdiseaseisdyslipidemia,whichischaracterisedbyelevatedlevelsoflow-densitycholesterol(LDL)and/orlowlevelsofhighdensitycholesterol(HDL)(Esmaillza-dehandAzadbakht,2008).Cholesterolisdividedintotwotypes:lowdensitycholesterol(LDL),orbadcholes-terol,andhighdensitylipoprotein(HDL),orgoodcho-lesterol. Good cholesterol (HDL) is so called becauseit is thought to help reduce cholesterol levels in theblood; highdensity cholesterol is producednaturallyby thebody itself and removes cholesterol from thearterywalls, returning it to the liver.Bad cholesterol(LDL)accumulatesonthearterywalls,formingplaqueswhichhindertheflowofbloodtotheheart.Therefore,excessivelyhighlevelsofLDLcholesterolwillincreasetheriskofcardiovasculardisease.ItisthoughtthatLDLoxidationcontributestoatherosclerosisandcardiovas-culardiseases(Heinecke,2006).

Severalinvitrostudieshavebeenconductedwithanimalsandhumanstoanalysetheeffectof variouspomegranate-relatedproductson thepreventionandmitigationofatheroscle-rosisandLDLoxidation(Avirametal.,2000;Sezeretal.,2007;BasuandPenugonda2009;Davidsonetal.,2009;Fuhrmanetal.,2010).Avirametal.(2000)analysedtheeffectofpome-granatejuiceconsumptioninhealthymenonLDLoxidationandfoundthatLDLlevelswerereducedandHDLactivitywasincreasedbyaround20%.Seezeretal.(2007)comparedthetotalpolyphenolcontentandantioxidantactionofpomegranatewineandredwine.

Bothpolyphenol content and antioxidant actionwerehigher in pomegranatewines thaninredwines.Bothwinesproducedareduction inLDL;however,dueto itshigherantioxi-dantability, thedecrease inducedbypomegranatewinewasgreater thanthatcausedbyredwine,namelyby24%forpomegranatewineand14%forredwine.Esmaillzadehetal.(2006)administered40gofconcentratedpomegranatejuicetodiabeticandhyperlipidemic(elevatedcholesterolandtriglyceridelevels)patientsfor8weeks.Bytheendofthestudy,triglycerideandHDLlevelshadnotchanged.However,totalcholesterollevelwasreducedby5.43%,LDLby9.24%,totalcholesterol/HDLratioby7.27%andtheLDL/HDLratioby11.76%.

BasuandPenugonda (2009)summarisedthemainantiatherogenicmechanismsofpome-granatejuiceasfollows:

Thus,pomegranatejuiceintakehasabeneficialeffectontheprogressionofatherosclerosisandconsequentlyontheriskofdevelopingcoronaryheartdisease.

Dr. Aviram conducted numerous experimentswith healthy and hypertensive patients, towhomheadministeredpomegranatejuicefordifferentperiodsoftime.Asaresultofthesestudies,itwasconcludedthatbloodpressurewasreducedbyupto36%aftertwoweeksoftreatmentwithpomegranatejuice.Thisreductionhasbeenattributedtothehighantioxi-dantpowerofpomegranatepolyphenols(AviramandDornfeld,2001;Avirametal.2004).

- It increases the antioxidant action of blood serum, reducing

plasma lipids and lipid peroxidation

- It reduces LDL oxidation

- It reduces the size of atherosclerosis lesions

- It reduces systolic blood pressure

3.3. Inflammatory properties

Inflammation, the human body’s first physiological defence, can protect us from lesionscausedbywoundsandpoisoning.Thisdefencesystemcaneliminateinfectiousmicroorgan-isms, eradicate irritations andmaintain normal physiological functions. However, overex-posure to inflammation can cause physiologicaldysfunctionssuchasasthmaandarthritis(Leeetal.2010).Thereisconsiderablescientificevidencedemonstrating the anti-inflammatory action ofthepomegranateanditsderivedproducts(LanskyandNewman,2007;Shuklaetal.,2008;Larrosaetal.,2010,Leeetal.,2010).Somepomegranateextracts, particularly the extract of cold-pressedseeds, inhibit the action of cyclooxygenase andlipoxygenase enzymes in vitro. Cyclooxygenaseisanimportantenzymeintheconversionofara-chidonicacidtoprostaglandins,whichareinturnimportantmediatorsofinflammation.Thislatter,therefore,issignificantlyinhibitedbytheingestionofpomegranateextracts.Lipoxygenasemediatesthetransformationofarachidonicacidintoleukotrienes,whichalsomediateinflammation,andthusinflammationisalsoinhib-itedbypomegranateseedextract(Thomas-Barberán,2010).

Boussettaetal. (2009) showed that thepunicicacidandconjugated fattyacidpresent inpomegranateseedoilhasaprovenanti-inflammatoryeffectinvivoandthereforelimitsli-pidperoxidation.Leeetal. (2010)analysedfourhydrolysabletannins,amongwhichwerepunicalaginandpunicalin,allisolatedfromthepomegranate.Eachofthesecompoundsatdifferentdosessignificantlyinhibitedtheproductionofnitrogenmonoxide(NO)invitro,pro-ducingananti-inflammatoryeffect.

DeNigrisetal.(2007)demonstratedthatadministrationofpomegranatejuiceandpome-granateextractstoobeseratssignificantlyreducedtheexpressionofcertaingeneticmarkerswhichinfluencecardiovascularinflammation.

Subsequently,Romier-Crouzet (2009)obtainedsimilarresultswithpomegranate juiceandpomegranateextracts,andobservedinflammatorypreventionduetohighellagicacidcon-tent.Lastly,Larrosaetal.(2010)foundthatadministrationofpomegranateextractsreducedprostaglandinlevelsincolonicmucosa,againduetothehighlevelsofellagicacidpresentinthe pomegranate.

3.4. The anti-diabetic properties of the pomegranate

Diabetes is themost commonmetabolicdis-easeintheworld,affectingmillionsofpeople.AccordingtotheInternationalDiabetesFeder-ation,theestimatefor2025isthatthisdiseasewillaffectabout333millionpeople.Diabetesranks third inprevalenceaftercardiovasculardisease and cancer.

Thisiswherethepomegranateanditsderivedproductscanplayakeyrole,andthereisasig-nificantbodyofscientificevidencesupporting

theanti-diabeticpropertiesofthisfruit(Huangetal.,2005;Lietal.,2005;Katzetal.,2007;ParmarandKar,2007;Lietal.,2008;Bagrietal.,2009).

Diabetesisassociatedwithhighlevelsofoxidativestressandthedevelopmentofatheroscle-rosis.Itseemsclearthattheantioxidantcompoundspresentinthepomegranatecanexertasignificanteffectondiabetes.

Forexample,Katzetal.(2007)demonstratedthehypoglycemicactionofpomegranateflow-ers,seedsandjuice.Themechanismsbywhichthepomegranateanditsderivedproductsexertthiseffectremainunknown.However,althoughtherearenumeroushypothesesaboutthesemechanisms,allseemtosuggesttheinhibitionofcertaingeneticmarkersandcertaincompoundsthatinduceoxidativestress.Forexample,Lietal.(2005)suggestedthattheanti-diabetesmechanismofpomegranateflowerextractwasinhibitionofthe -glucosidaseen-zyme.PamarandKar(2007)demonstratedthatadministrationofpomegranatepeelextractnormalisedtheadverseeffectsofacompoundthatinducesdiabetesinmice.

Mcfarlin et al. (2009) studied the effect ofpomegranateseedoilonfataccumulationinmiceandobservedanimprovementininsu-linsensitivity.

All these findings, together with those re-latedtocardiovasculardisease,suggestthatthe pomegranate and its derived productshaveabeneficialeffectondiabetesandoncardiovascular disease in diabetic patients,sincetheireffectsonheartdiseasehavealsobeenestablished.

The main components with anti-diabeticpropertiesarethepolyphenols;thesecom-poundsaffectbloodglucosethroughnumer-ousmechanisms,includingtheinhibitionofglucose absorption through the gut or viaperipheraltissues.

Themostprobableanti-diabeticmechanismisinhibitionofthe-glucosidaseenzyme.Othermechanismsmayincludethereductionofbloodsugarlevelduetoabsorptionbyperipheraltissuesratherthanthroughtheintestine(Scalbertetal.,2005).

3.5. Prevention of oxidative deterioration

Oxidativedeteriorationisaverytopicalissueandaclearexampleofthisisthattheactionoffruitandvegetablesagainstoxidativedeterioration(highcontentofantioxidantcompounds)isoneofthepropertiesorcharacteristicsmosthighlyvaluedbyconsumers.Generally,anantioxidantcanbedefinedasanaturalorartificialsubstancewiththeabilitytoprotectabio-logicalsystembyneutralisingfreeradicalssuchasoxygen,nitrogenandlipidradicals(CanoandArnao,2004).

Theseantioxidantpropertiesendowfruitandvegetableswithbeneficialhealthproperties,protectingagainstorreducingtheriskofcertaindegenerativediseases(Brandtetal.,2004,Chenetal.,2007).Consequently,antioxidantcontenthasbecomeanimportantqualitypa-rameteroffruitandvegetablesinrecentyears.

Compoundswithantioxidantproperties includeanthocyaninsandotherphenols(Espinetal.,2007;Doraisetal.,2008),carotenoids(PereraandYen,2007)andvitaminsA,CandE(Hoursomeetal.,2008).

Thecompoundsresponsible forthepotentantioxidantactionofthepomegranateand itsderivedproductshavebeen studiedbymany researchers,usingboth in vitroand in vivomodels.Theantioxidantactioninvitroofthepomegranateanditsderivedproductshasbeenassessedinseveralstudies(Naveenaetal.,2008;Cametal.,2009;Mousavinejadetal.,2009;Tezcanetal.,2009).

Tzulkeretal.(2007)determinedthatthehighantioxidantcapacityofthepomegranateanditsderivedproductsisduetothepresenceofpunicalagins,andnotofanthocyaninsasprevi-ouslythought.

Themechanismsofantioxidantactioninvivoremainunclear,althoughitisknownthatthesemechanismsactonbiologicalmatricesinaverycomplexway.Madrigal-Carballoetal.(2009)suggestedthatthepomegranate’sphenoliccompoundsundergoaredoxreaction,sincethehydroxylgroupsofthephenolicmoleculesdonateahydrogenmoleculetoreducingagents.Otherresearchers(Amarrowiczetal.,2004)havereportedthattheantioxidantactionofphe-noliccompoundsisduetotheirabilitytocapturefreeradicalsandchelatingmetalcations.

3.6. Prevention of skin damage

Theprocessofphotoageingincludesmolecularandstructuraldamageoftheskin,suchasinflammation,decreasedcollagensynthesis,thickeningorproliferationoftheepidermis(sur-faceoftheskin),incompletedegradationofcollagenfragmentsandproteinoxidation.

Allthesechangestranslateclinicallyintoathinskinwithwrinkles,yellowishdiscolouration,roundorovalwhitespotsorirregulardarkspotsandtelangiectasia(visiblebloodvessels),among others.

Thesearealsoaccompaniedbytheappearanceofbenign lesionssuchasseborrheickera-tosesorlentigines(coffee-colouredlumpsorspots),sebaceoushyperplasiaandpremalignantlesionssuchasactinickeratoses.

Skindamageoccursasaresultofnaturalaging.However,exposuretothesunalsoinducesmajordamagetotheskin.Prolongedexposuretoultravioletrayscancausenumerousprob-lems,suchasskincancer.

Studies conducted with different pomegranate extracts (Aslam et al., 2006) suggest thatpomegranatepeelextractspromoteregenerationofthedermis,whileseedoilextractsre-generate the epidermis.

Pacheco-Palenciaetal.(2008)describedtheprotectivepropertiesofpomegranateextractsagainstUVAandUVBradiationduetoareduc-tion in the generationof reactiveoxygen species (ROS). Afaq et al.(2009)suggestedthatUVBradiation-inducedskindamagecanbere-ducedbytheintakeofproductsderivedfrompomegranatepeelandseeds.

Allthesescientificresultsdemonstratetheexcellentabilityofpome-granatepeelandseedextractstoprotecttheskin.

3.7. Antimicrobial properties of the pomegranate and its derived products

Manyfoodpreservationtechnologies,someofwhichhavebeeninuseforalongtime,pro-tectfoodfromalterationbymicroorganisms.Thus,microorganismscanbeinhibitedbyre-frigeration, reducedwateractivity, acidification,modifiedatmospherepackaging,bynon-thermaltreatmentsorbyadditionofantimicrobialcompounds.

Antimicrobialproductsforfooduseconsistofchemicalcompoundswhichareaddedoral-readypresentinfoodthatkillorretardthegrowthofmicroorganisms,thusincreasingre-sistancetoalterationsinqualityorsafety.Themaintargetsofantimicrobialagentsarethemicroorganismsthatcause foodpoisoning (infectiousagentsandtoxinproducers)or thatalterfoodsandwhosemetabolicendproducts(catabolites)orenzymescausebadodours,unpleasantflavours,textureproblems,changesincolourand/orhealthrisks(DavidsonandZivanovic,2003).

Theuseof syntheticandchemicalagentswithconsiderableantimicrobialpropertiesasmicrobialgrowthinhibitorsisoneoftheoldesttechniquesonearthforthecontrolofmicrobialgrowth, and is therefore a suitable preservation technique(Viuda-Martosetal.,2008).

At present, there is a tendency to replace these chemicalswithpossiblenatural treatmentsbyusingagentspresent infruits,vegetablesandherbs.Theprincipalnaturalantimicro-bialagentsaretheessentialoilsobtainedfromherbsandspic-es.Essentialoilsderivedfromplantsareknownfortheirhighantimicrobial action against a broad range of bacteria andfungi.Inaddition,theycanenhancetheantioxidantactionofthetreatedproductsthemselves(Ayala-Zavalaetal.,2005).

Theantimicrobialactionofthepomegranateanditsderivedproductshasbeendemonstrat-edinnumerousstudieswhichhavereportedtheinhibitionoftheactivityofnumerousmi-croorganisms(Reddyetal.,2007;McCarrell,2008;Al-Zoreky2009;Choioetal.,2009;Gouldetal.,2009).

Reddyetal.(2007)foundthatdifferentpomegranateextracts indifferentsolvents(water,ethanol,etc.)presentedasignificantantimicrobialactionagainstE.coli,Pseudomonasaer-uginosa,Candidaalbicans,CryptococcusneoformansandS.aureus.Al-Zoreky(2009)showedthatthegrowthofListeriamonocytogenes,S.aureus,E.coliandYersiniaenterocoliticaissig-nificantlyinhibitedbypomegranatepeelextract.Choietal.(2009)investigatedtheinvivoandinvitroeffectoftheapplicationofdifferentconcentrationsofpomegranatepeelextractonskintoinhibitthegrowthofSalmonella,andfoundthattheminimumdosewas62.5mg/L.

Ingeneral,thepotentinhibitoryactionofthepomegranateanditsderivedproductsisat-tributedtothehighconcentrationofcompoundssuchaspolyphenols,tanninsandantho-cyanins.Veryrecentstudieshavefoundthattheuseofderivativesandby-productsasfoodadditivesnotonlyimprovesantioxidantcapacitybutalsoensurestotalsafetyduetothecon-siderableabilityofthepomegranateanditsextractstoinhibittheactivityofmicroorganismsthatcausefooddeterioration(Navarroetal.,2011;Viuda-Martosetal.,2011b).

3.8. Effects of the pomegranate on oral health

Maintainingoptimal dental health is not only important topreserve the appearance andfunctionofteeth,butalsotoprotectagainstcardiovasculardisease.Sciencenowrecognisesthatchronicinflammatoryperiodontaldiseaseiscloselyrelatedtotheworseningofcardio-vasculardisease(Dumitrescu,2005).

DiSilvestroetal. (2009)showedthatamouthwashbasedonpomegranateextractseffec-tivelyreducedtheamountofdentalplaquemicroorganisms.Thisbeneficialeffectismainlyattributed to the clear actionof polyphenol andflavonoid compounds against thedevel-opmentofgingivitis.Gingivitisisabacterialoraldiseasethatproducesinflammationandbleedingofthegums,andiscausedbyfooddebriscaughtbetweentheteeth.

Menezesetal.(2006)studiedtheeffectofapomegranateextractondentalplaquemicro-organisms.Theyfoundthatitwashighlyeffective,reducingthenumberofmicroorganismsby84%.

Sastravahaetal.(2005)demonstratedtheeffectivenessofagelcontainingpomegranateex-tractsasanadditional,complementarytreatmentforstandardperiodontaltherapy.Badriaand Zidan (2004) showed that pomegranate flavonoids possess an antibacterial action invitroagainstthemicroorganismsresponsibleforgingivitis.

Fewerstudieshavebeenconductedontheeffectofthepomegranateanditsderivedprod-uctsonoraldiseasecomparedtoresearchondiseasessuchascancerorcardiovasculardis-ease.Thecasescitedabovearethemostrecentexamplesofresearchonthisquestion.

Consumption of pomegranates, either as fresh fruit, derived products or even in extractform,isalsoenjoyablebecauseofthedeliciousflavour,makingthepomegranateaperfectsolutionforproperoralhealth.

Table 5 summarisessomeofthemostrelevantstudies.

Table 5. invivostudiesconductedtoevaluatethebeneficialeffectsofthepomegranateonlaboratoryanimal and human health.

3.9. Other health-related properties of the pomegranate

3.9.1. Effects of the pomegranate against diarrhoea

Onlytwostudieshavebeenconductedrecentlythatdemonstratedtheeffectofpomegranatepeelextractinthepreventionofdiarrhoea.Bothexperimentswereconductedonlaboratoryrats;aftertheadministrationofapomegranatepeelextract,itwasobservedthatboththenumberofbowelmovementsandthemassofthesamewerereduced.Thestudieswerecon-ductedbyQnaisetal.(2007)andOlapouretal.(2009).Thedoseproposedbythelatterforthetreatmentofthisconditionwas400mgperkgofbodyweight.

3.9.2. Effects of the pomegranate on sperm quality and erectile dysfunction

Thebasicpurposeofsemenisreproduction,sinceitactsasa“vehicle”fortransportingspermtothefemalereproductivetract.Althoughorgasmandsexualpleasureaccompanytheejacu-lationofsemen,erectionandorgasmarecontrolledbyindependentmechanisms,thustheemissionofsemenisnotessentialfortheenjoymentofsex.

Türk et al. (2008) found that consumptionof pomegranate juice produced an increase intheconcentrationofspermintheepididymis,anincreaseinmobilityandagreaterdensityofspermatogeniccells;italsoreducedtheamountofpoorqualitysemencomparedtothereference or control group.

Inamorerecentstudy,thissameresearchgroupsuggestedthatellagicacidhasaprotectiveeffectontesticlesandsperm.Thiseffectmayberelatedtothepotentactionofellagicacidagainstoxidativestress(Türketal.,2010).

Erectiledysfunctionistherepeatedinabilitytodevelopormaintainanerectionwhichisfirmenoughforsuccessfulsexualintercourse.InastudycarriedoutbyForestetal.(2007),itwasfoundthatafterfourweeksofconsumptionofpomegranatejuice,patientsshowedbettererectilefunctionthanotherpatientswhohadbeengivenaplacebo.

3.9.3 Effects of the pomegranate on obesity

Obesityisachronicdiseaseofmultifactorialoriginthatischaracterisedbytheexcessiveac-cumulationoffatorgeneralhypertrophyofadiposetissueinthebody.Obesity,therefore,referstoasituationwherethenaturalenergyreserveofhumansandothermammals,storedasbodyfat,increasestoapointwhereitisassociatedwithmultiplecomplications,suchascertainhealthconditionsordiseasesandincreasedmortality.

TheWorldHealthOrganisation’s(WHO)definitionofobesityiswhentheBodyMassIndex(BMI),whichisacalculationbasedonanindividual’sheightandweight,isequaltoorgreaterthan30kg/m2.Anothersignofobesityisanabdominalperimetergreaterthanorequalto102cminmenand88cminwomen.

Obesityformspartofthemetabolicsyndrome,andisaknownriskfactor.Inotherwords,itincreasestheriskofdevelopingvariousdiseases,particularlycardiovasculardisease,type2diabetesmellitus,sleepapnoea,stroke,osteoarthritis,andsomeformsofcancerandderma-tologicalandgastrointestinalailments.

Althoughobesityisanindividualclinicalcondition,ithasbecomeanincreasinglyseriouspub-lichealthproblem,andtheWHObelievesthat“obesityhasreachedepidemicproportionsworldwide,andatleast2.6millionpeopledieeachyearbecauseofobesityoroverweight.Althoughpreviouslyconsideredaproblemconfinedtohighincomecountries,obesityisnowalsoprevalentinlowandmiddleincomecountries”.

Table 6. Studiestoassesstheeffectinvivoofthepomegranateoritsextractsonobesity.

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