01/03/2015

Noni(Morindacitrifolia)|PlantProfiler|SigmaAldrich

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Noni(Morindacitrifolia)
Synonyms / Common Names / Related Terms

ADME/Tox

Al,alizarin,alkaloids,americaninA,aminoacids,anthraquinone,anthraquinoneglycoside,asperuloside,asperulosidicacid,atchy(Hindi),
sitosterol,borreriagenin,cadapilva(Malay),caproicacid,caprylicacid,carotene,citrifolininBepimera,citrifolininBepimerb,citrifolinoside,
cytidine,deacetylasperuloside,dehydromethoxygaertneroside,dglucose,dilo'k(Pijin),dmannitol,epidihydrocornin,flavoneglycosides,
Indianmulberry,iridoidglycoside,kura(Fijian),kuti,ladda(Chamorro),Lasperuloside,linoleicacid,maddichettoo(Telugu),manjapavattay,
methylalphadfructofuranoside,methylbetadfructofuranoside,molagha,Morindacitrifolia,morindacin,morindone,murierd'Inde,najalanun,
nakura,narcissoside,nen(Chamorro),nicotifloroside,nolom,nono(CookIslandsMaori),nonu(Tongan,Wallisian,Futunian,Niuean,
Tokelauan,Tuvaluan),nonutogi(Samoan),noona(Tamil),nordamnacanthal,nowoi(Bislama),octanoicacid,potassium,riro(TokPisin),
proxeronine,Rubiaceae(family),rubiadin,rubiadin1methylether,rutin,scopoletin,tenon(Gilbertese),terpenoids,TNJ,ursolicacid,
vitaminA,vitaminC,yelotri.

CellBiology
CellsandCellBasedAssays
CellCulture
CoreBioreagents

Combinationproductexamples:TahitianNonijuice(nonifruitjuicefromjuicepuree,grapejuiceconcentrate,blueberryjuiceconcentrate,naturalflavors).

CustomOligos
Epigenetics
FunctionalGenomics&RNAi
GeneSearch

Mechanism of Action
Pharmacology:
Constituents:Variouscomponentshavebeenidentifiedinthenoniplant,suchasscopoletin,octanoicacid,potassium,vitaminC,
terpenoids,alkaloids,anthraquinones(suchasnordamnacanthal,morindone,rubiadin,rubiadin1methylether,anthraquinoneglycoside),
sitosterol,carotene,vitaminA,flavoneglycosides,linoleicacid,alizarin,aminoacids,Lasperuloside,caproicacid,caprylicacid,ursolic

Metabolomics

acid,rutin,andaputativeproxeronine.49,50,51,8,52,53,54,55,56,57,58,59,20,60Severalflavonolglycosideshavealsobeenidentified,including
aniridoidglycosidefromthenonileaves,atrisaccharidefattyacidester,rutin,twonovelglycosides,citrifolinoside,andanasperulosidicacid

MolecularBiology

fromthefruit.61,45,34,62,63,33,36Sixanthraquinones,including5,15Odimethylmorindol,andthreeiridoids,includingmorindacin,havealso

NutritionResearch
NutritionResearchProducts
LearningCenter

beenisolatedfromMorindacitrifoliafruits.1
ThemethanolextractofMorindacitrifoliafruitscontains6alphahydroxyadoxoside,6beta,7betaepoxy8episplendoside,americaninA,
narcissoside,asperuloside,asperulosidicacid,borreriagenin,citrifolininBepimersaandb,cytidine,deacetylasperuloside,
dehydromethoxygaertneroside,epidihydrocornin,dglucose,dmannitol,methylalphadfructofuranoside,methylbetadfructofuranoside,

FAQCategories

nicotifloroside,2methoxy1,3,6trihydroxyanthraquinone,andbetasitosterol3Obetadglucopyranoside.64,2
Analgesiceffects:AMorindacitrifoliaextractshowedasignificant,doserelated,centralanalgesiceffectinmice,whichwas75%asstrong

Metabolomics

asmorphine,yetnonaddictiveandsideeffectfree.12Inasimilarstudy,TahitianNonijuice(TNJ)hadadosedependentanalgesiceffect

PlantProfiler

onantimonypotassiumtartrateinducedpaininmiceandrats.11Inanaceticacidinducedwrithingtestinmice,thealcoholicextractof
Morindacitrifoliafruitshadadosedependentinhibitoryeffect,startingat4g/kg,whichwassimilartothatproducedbymorphineinadoseof

Proteomics
StemCellBiology
SyntheticBiology
TranslationalResearch
Solutions

1.5mg/kg.65Theantinociceptiveeffectinthewrithingtestwasstatisticallysignificant(p<0.001)for15minutesuntilfivehoursafter
administration.InaPhaseItrialincancerpatients,therewasastatisticallysignificant(t(35)=2.84,p=0.006)decreaseinpaininterference
afteraweekofnoniindosesof2,4,6,8,or10g.3
Anthelminticeffects:Inaninvitrostudy,anonileafethanolextractinducedparalysisanddeathofthehumanparasiticnematodeworm
Ascarislumbricoideswithin24hours.13
Antiangiogeniceffects:Noniatconcentrationsof>5%byvolumewashighlyeffectiveininhibitingtheinitiationofnewvesselsproutsfrom

ZincFingerNuclease(ZFN)

placentalveinexplants,and10%nonijuiceinmediawasaneffectiveinhibitorofcapillaryinitiationinexplantsfromhumanbreasttumors.14
Cardiovasculareffects:Theoxidativemodificationoflowdensitylipoprotein(LDL)playsanimportantroleinthegenesisofarteriosclerosis.

LearningCenter

AstudybyKamiyaetal.focusedontheeffectsofthefruitsofMorindacitrifoliaonpreventingarteriosclerosis.25TheMeOHextractand
CHCl3,EtOAc,nBuOH,andH2OsolublephasesderivedfromthefruitsofMorindacitrifoliawereevaluatedfortheirinhibitoryactivityon

Labware

copperinducedLDLoxidationbythethiobarbituricacidreactivesubstances(TBARS)method.TheMeOHextractandEtOAcsolublephase
showed88%and96%inhibitionrespectively.SixlignanswereisolatedbyrepeatedcolumnchromatographyfromtheEtOAcsolublephase:
3,3'bisdemethylpinoresinol,americanolA,americaninA,americanoicacidA,morindolinandisoprincepin.Thesecompoundsinhibited
copperinducedLDLoxidationinadosedependentmanner.1,2,5,and6exhibitedremarkablystrongactivities,whichwerethesameor
betterthanthatoftheknownantioxidant2,6ditertbutylpcresol.TheIC50valuesfor1,2,5,and6were1.057,2.447,2.020and1.362mcM,
respectively.Theactivityofthesecompoundsismainlyduetotheirnumberofphenolichydroxylgroups.Whennoni'spotentialtoinhibit
oxidationoflowdensitylipoprotein(LDL)invitroandtomodulateLDLreceptor(LDLr)activityinculturedHepG2cellswastested,LDLrwas
significantlyupregulated(p<0.05)bynoni(49%).66Inasimilarstudy,nonicausedinhibitionof14CincorporationinHepG2cells,(77%
comparedtocontrol).67However,thisdecreaseinincorporationcannotbeaccountedforbytheinhibitionofcholesterolsynthesisalone.The
proportionofcholesterolinthesampledecreasedfrom38%inthecontrolto28%inthepresenceofnoni:evidencethatsynthesisof
cholesterolwasinhibited.Aftertakingintoaccounttherelativedifferencesintotal14Cincorporation,nonicauseda26%inhibitionin
cholesterolsynthesis,comparedto55%inhibitionbythepositivecontrollovastatinhydroxyacid.Itcouldnotbeestablishedwhatcausedthe
overalldecreasein14Cincorporationinthepresenceofnoni,butitsmodeofactionwouldappeartobedifferenttothatoflovastatinhydroxy
acid.
Inanimalstudies,thetotalextractofthenonirootsandvariousnonirootextractshaveshownahypotensiveeffect,althoughthemechanism
forthiseffectisnotclear.5,6,7,8,9,10
Antibacterialeffects:Specificcompoundsfromvariouspartsofthenoniplanthavebeeneffectiveinlaboratorystudiesasantibacterial
agents,supportingthePolynesiantraditionalmedicinaluseforinfectiousdiseases.18,19Inaninvitrostudy,extractsfromtheripenonifruit,
includingLasperulosideandalizarin,exhibitedmoderateantibacterialpropertiesagainstPseudomonasaeruginosa,Micrococcus
pyrogenes,Escherichiacoli,Pseudomonasaeruginosa,Proteusmorgaii,Staphylococcusaureus,Bacillissubtilis,Salmonella,and
Shigela.16SomeanthraquinonecompoundsfromnonirootswerealsoeffectiveagainststrainsofPseudomonasaeruginosa,Proteus
morgaii,Staphylococcusaureus,Bacillissubtilis,Escherichiacoli,Salmonella,andShigela.15Specifically,thecompoundscopoletinfrom
noniinhibitstheactivityofEscherichiacoliandH.pylori.17Also,aconcentratednonileafextractkilled89%ofMycobacteriumtuberculosisin
atesttube,comparedtorifampin,aleadingantituberculosisdrug,whichhasaninhibitionrateof97%atthesameconcentration.20
Antiinflammatoryeffects:Invariousanimalandinvitrostudies,nonishowspromiseasanantiinflammatoryagent.Inaninvitrostudies,
TahitianNoniJuicehadcomparableselectivityofCOX2inhibitionascelecoxib(0.34)21andMorindacitrifoliafruitpowderexhibited
inhibitionofCOX1withtheIC50of163mc/mL,comparedtoaspirin(IC50=241mc/mL)andindomethacin(IC50=1.2mc/mL)22.Inanimal
studies,TahitianNonijuicedecreasedinflammatoryfociinanacuteliverinjuryratmodel23,andorallyandintraperitoneallyadministered
nonifruitjuiceextractreducedinflammationinbradykinininducedinflammationandcarrageenaninducedpawedema24.
Antioxidanteffects:InvitroTahitianNonijuice(TNJ)showedadosedependentinhibitionofbothlipidperoxidesandsuperoxideanion
radicalscomparabletograpeseedpowder.45,46,47Thisresultwassupportedbyaratliverinjurymodel,where10%TNJinthedrinking

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Noni(Morindacitrifolia)|PlantProfiler|SigmaAldrich
waterreducedlipidperoxidesandsuperoxideanionradicalsafterliverinjuryinduction.23Intermsofboth1,1diphenyl2picrylhydrazyl
(DPPH)andperoxynitrite(ONOO())bioassays,thenonineolignanamericaninAwasfoundtobeapotentantioxidantintheseassays.64
Varioustreatmentsofnonijuicemayaffectitsantioxidantproperties.Forexample,Yangetal.reportthetotalantioxidantcapacity(TAC)in
freshnonijuicetobeequivalentto127mgascorbicacidper100mLinascavengerassayof1,1diphenyl2picrylhydrazyl(DPPH).48After
twomonthstraditionalfermentation,TACdecreasedby70%.Storageoffreshnonijuiceat24CfortwomonthsdecreasedTACby80%,
whilestorageat18CexhibitednosignificantchangeinTAC.HotairandfreezedriednonipowdersexhibitedreductioninTACby45%and
20%,respectively.Thepasteurizationofnonijuiceseemstohavenoeffectonitschemistryandperformanceinoxygenradicalabsorbance
capacity(ORAC)assays,butenzymetreatmentseemstohaveanegativeeffectonantioxidantcapacity.40
Antitumoreffects:Variousextractsandconstituentsfromallpartsofthenoniplanthavebeentestedfortheireffectonanimalcancer
modelsandcelllines.Inseveralstudies,thenoniextractsuppressedtumorgrowththroughactivationofthehostimmune
system26,27,28,29,30,whichissupportedbyanothernonistudyshowinggeneralimmunostimulationeffects11.Nonihasalsoshowngeneral
cytotoxicityeffects31,whichmaybedosedependent11.However,theseeffectsarenotuniversalacrossallcancerlines.31Noniextracts
haveexhibitedspecificinhibitoryeffectsonRasoncogenefunction32,celltransformationinducedby12Otetradecanoylphorbol13acetate
(TPA)orepidermalgrowthfactor(EGF)33,34,thetumorpromotingeffectoftumornecrosisfactora(TNFa)35,andactivatorprotein1
transactivation36.Whenadministeredbeforetheinductionofacancer,noniextracthasshownpreventativeeffects.23,37,38,39Specifically,
theanthraquinone2methoxy1,3,6trihydroxyanthraquinonemaybeapotentquininereducataseinducerthatisnearly40timesmorepotent
thanthepositivecontrollsulforaphane.2Onasidenote,thepasteurizationofnonijuiceseemstohavenoeffectonitschemistryand
performanceinNFkappaBactivity.40
Antiviraleffects:Onespecificcompoundisolatedfromnoniroots,1methoxy2formyl3hydroxyanthraquinone,suppressedcytopathic
effectofHIVinfectedMT4cellsinvitro,withoutinhibitingcellgrowth.41However,theaqueousanddichloromethaneextractofnonifruits
showedpracticallynoactivityagainstHIV1invitro.42
Gastrointestinaleffects:Puetal.studiedtheeffectsofMorindacitrifoliajuiceongastricemptying,gastrointestinaltransit,andplasmalevel
ofcholecystokinininrats.4Maleratsweregivennonibygavageatlevelsof0.25,1,or4mL/kgonceperdayforoneorsevendays.Therats
inthecontrolgroupweregivenwater,whiletheratsintheexperimentalgroupwerefastedovernightbeforemeasurementofgastrointestinal
motility.Gastrointestinalmotilitywasassessedinrats15minutesafterintragastricinstillationofatestmealcontainingcharcoal(10%)and
Na251CrO4(0.5mcCi/mL)asamarker.Gastricemptyingwasdeterminedbymeasuringtheamountofradiolabeledchromiumcontainedin
thesmallintestineasapercentageoftheinitialamountreceived.Then,gastrointestinaltransitwasevaluatedbycalculatingthegeometric
centerofdistributionoftheradiolabeledmarker.Finally,bloodsampleswerecollectedformeasurementofcholecystokininby
radioimmunoassay.Theadministrationofnoniat0.25mL/kg,butnotat1mL/kgand4mL/kg,foronedaysignificantlyinhibitedgastric
emptying.Incontrast,gastricemptyingwassignificantlyinhibitedbyoraladministrationofnoni(0.25,1,or4mL/kg)forsevendays.
Intraperitonealinjectionoflorglumide(5or10mg/kg),aselectivecholecystokinin1receptorantagonist,effectivelyattenuatedthenoni
inducedinhibitionofgastricemptying.Intestinaltransitandbodyweight,foodintake,waterintake,urinevolume,andfecesweightwerenot
alteredbytheadministrationofnoniacutelyorchronically,buttheadministrationoforalnoni(1mL/kg)forsevendaysincreasedthelevelof
plasmacholecystokinininmalerats.Theseresultssuggestthatoralnoniinhibitsgastricemptyinginmaleratsviaamechanisminvolving
stimulationofcholecystokininsecretionandcholecystokinin1receptoractivation.
Immunesystemeffects:ThethymuswetweightinanimalstreatedwithTahitianNonijuice(TNJ)wasabout1.7timesthatofcontrol
animalsaftersevendaysadministrationof10%TNJindrinkingwater.11ThisincreaseinweightmayindicatethatTNJenhancesimmune
functionbystimulatingthymusgrowth,andthusaffectingantiagingandanticanceractivities.
Metaboliceffects:Nonifruitcontainsanaturalprecursorforxeronine,calledproxeronine,whichishypotheticallyconvertedinthebodyto
thealkaloidxeronine.Ithasbeenhypothesizedthatxeronineisabletomodifythemolecularstructureofproteinsandisacriticalnormal
metaboliccoregulator.43,44

Pharmacodynamics/Kinetics:
ThepharmacokineticsofnoniwasstudiedinfemaleSpragueDawleyratsafteroraladministrationatadoseof1mLnonipureeper100g
bodyweightwithscopoletinasamarker.11Theplasmaconcentrationofscopoletinreachedapeaktwohoursafteroraladministration.The
peakleveldecreasedto50%infourhours.Only12%and2%,respectively,wasleftintheplasmaat12and24hours.Absorptionwasrapid,
with50%peakconcentrationreachedinonly30minutes.Theconcentrationofscopoletininvariousorgansindicatesthatitisabsorbedinto
differenttissuesapproximatelyonehourafteradministration.Thepeakconcentrationindifferenttissuesoccurredafteraboutthreehours,
witharapiddecline.Thescopoletinlevelinbreasttissuewashigherrelativetootherextragastrointestinaltracttissue.Thisisnotadefinite
descriptionofnonipharmacokineticsasnoniisanextractcomposedofnumerouscomponents.Themeasurementofscopoletinasamarker
ofthenonicompoundcannotbeassumedtorepresenttherest,oreventhemajorityofnonicompounds.

References
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