Phyto-Pharmacology of Ziziphus jujuba Mill- A plant review

Abstract

Herbs have always been the natural form of medicine in India. Medicinal plants have curative properties due to presence of various complex chemical substances of different composition which contain secondary metabolites such as alkaloids, flavonoids, terpenoids, saponin and phenolic compounds distributed in different parts of the plants. Ziziphus jujuba Mill, a member of the family Rhamnaceae, commonly known as Bor, is used traditionally as tonic and aphrodisiac and sometimes as Hypnotic-sedative and Anxiolytic, anticancer (Melanoma cells), Antifungal, Antibacterial, Antiulcer, Anti-inflammatory, Cognitive, Antispastic, Antifertility/contraception, Hypotensive and Antinephritic, Cardiotonic, Antioxidant, Immunostimulant, and Wound healing properties. It possesses allied compounds viz. Ascorbic acid, thiamine, riboflavin-bioflavonoids and Pectin A and various chemical substances like Mauritine-A; Amphibine-H; Jubanine-A; Jubanine-B; Mucronine-D and Nummularine-B. Sativanine-E. Frangufoline, Ziziphine-A to Q, betulinic acid colubrinic acid, alphitolic acid, 3-O-cis-p-coumaroylalphitolic acid, 3-O- transpcoumaroylalphitolic acid, 3-O-cis-p-coumaroylmaslinic acid, 3-O-trans-pcoumaroylmaslinic acid, oleanolic acid, betulonic acid, oleanonic acid, zizyberenalic acid and betulinic acid, jujubosides A, B, A1 B1 and C and acetyljujuboside B and the protojujubosides A, B and B1, saponin, ziziphin, from the dried leaves of Z. jujube - 3-O-a-L-rhamnopyranosyl (1-2)- aarabinopyranosyl-20-O- (2,3)-di-O-acetyl-a-L-rhamnopyranosyl jujubogenin. Saponin from leaves and stem are 3-O- ((2-O- alpha - D - furopyranosyl - 3-O- beta - D -glucopyranosyl) - alpha - L - arabinopyranosyl) jujubogenin and (6‴-sinapoylspinosin, ‴-feruloylspinosin and 6‴-p- coumaroylspinosin. The present review discusses photo-chemistry, pharmacology, medicinal properties and biological activities of Z. jujuba and its usage in different ailments.

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4/25/2016 PhytoPharmacologyof<i>Ziziphusjujuba</i>Mill Aplantreview:RTMahajan,MZChopda,PharmacognosyReviews
http://www.phcogrev.com/printarticle.asp?issn=09737847;year=2009;volume=3;issue=6;spage=320;epage=329;aulast=M ahajan 1/5
REVIEWARTICLE
Year:2009|Volume:3|Issue:6|Page:32032 9
PhytoPharmacologyofZiziphusjujubaMillAplantreview
RTMahajan1,MZChopda2,
1DepartmentofBiotechnology,MooljiJaithaCollege,Jalgaon,425001,M.S,India
2DepartmentofZoology,MooljiJaithaCollege,Jalgaon,425001,M.S,India
CorrespondenceAddress:
MZChopda
DepartmentofZoology,MooljiJaithaCollege,Jalgaon,425001,M.S
India
Abstract
Herbs ha ve alwa ys been the n atural form of medi cine in Ind ia. Medicin al plan tsh ave curative  properties d ue to presen ce of various co mplex chemi cal substan ces of different
compositio n whi ch contain  second ary metabol ites such as a lkalo ids, flavono ids, terpen oids, sapo nin and phe noli cco mpoun ds distributed in d ifferent parts of the pla nts.Zizip hus
jujubaM ill, a member o fthe  family Rhamn aceae, common ly known as Bo r, is use d traditiona lly as tonic a nd aphrod isiac and  sometimes as Hyp noticsedative  and Anxiolytic,
anticance r (Melan oma cel ls), Antifungal, Antibacteria l, Antiulcer, Antiinflammatory, Cognitive , Antispastic, Antifertility/contraception , Hypotensive  and Antine phritic, Ca rdiotoni c,
Antioxida nt,Immunostimul ant,and Woundh ealingpro perties.Itposse ssesal liedcompou ndsviz.Ascorbicacid ,thiamine ,ribofla vinbioflavono idsa ndPectin Aandvario usche mical
substances l ike Mauri tineA;Amphibin eH; JubanineA; Jub anine B;Mu cronineD and N ummula rineB. Sativan ineE. Frangu foline ,Zizi phine Ato Q,b etulin ic acid colubrin ic acid,
alphi tolicaci d,3Ocispcou maroyla lphi tolicaci d,3Otranspcoumaroylalphitol icacid ,3Ocispcouma roylmasl inica cid,3Otranspco umaroylmaslini cacid,oleano licaci d,betulo nic
acid,o lean onic acid ,zizyberenali caci da nd betulin ica cid,j ujub osidesA,B,A1B1 and C and ace tyljuju boside B and the protoju jubosi desA,B and B1, sapon in,ziziphin ,fromthe
driedle avesofZ.jujube 3OaLrha mnopyran osyl(12 )aarabinop yranosyl20O(2,3)diOace tylaLrha mnopyra nosylj ujubo geni n.Sapon infromle avesand stemare3O((2O
alpha Dfuropyranosyl3ObetaDgluco pyranosyl)alphaLarabi nopyra nosyl)ju jubog enin and(6«SQ»«SQ»«SQ»sinap oylspi nosin ,6«SQ»«SQ»«SQ»ferulo ylspin osinand
6«SQ»«SQ»«SQ»p coumaro ylspino sin. The presen trevi ew discu sses photoche mistry,pharma cology, medicin al prop erties and b iolog ical activi ties of Zajujub a and i tsu sage in
differentailme nts.
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Mahaja nRT,Chopd aMZ.PhytoPharmacolog yofZiziphusjuju baMill Aplantreview.PhcogRev2009;3:32 0329
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Mahaja nRT,Chopd aMZ.PhytoPharmacolog yofZiziphusjuju baMill Aplantreview.PhcogRev[serialonli ne]2009 [cited2016Apr25];3:320329
Availablefrom:http://www.phco grev.com/text.asp?2009/3/6/32 0/59530
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Introduction
Traditional medici nesareused bynearabo ut60percentofthe world 'spopul ation.These aren otonlyusedforp rimaryh ealthca rein rurala reasbu talsoi ndeve lopi ngcou ntries.In
develo pedco untriesmo dernme dicin esarep redomin antlyuse d.Whilethe tradition almed icine sarede rivedfromme dicinalpla nts,mineral s,andorg anicma tter,theh erbal drugsa re
prepare dfrommedi cinalplantson ly.Useofplantsasaso urceofmedi cineh asbeeninhe ritedan disani mportantcomponentoftheh ealthcare systeminIndia.IntheIndian systems
of medicin e, most practition ers formulate a nd disp ense the ir own re cipes; hen ce this req uires pro per docu mentation  and rese arch. Publi c,a cademi c and Govern ment interest in
traditiona lmedi cinesi sgrowi ngexp onen tiallyd uetothei ncrease dinci dence oftheadve rsedrug reaction sande conomi cburde nofthemod ernsystemo fmedicin e.Therearea bout
45,000pl antspecie sinIndia.Indiaisthelarge stproducerofmedi cinal herbsand isapprop riatelycal ledthe"Botani calgard enoftheworld ".InruralIndia,70percen tofthepopulatio n
isdepend ento nthe tradi tional system ofmed icine[1]. Seven membersof thefami lyR hamnace ae occurred in Kha ndeshregion i.e.NorthMah arashtra Reg ion. Outofthe sethre e
membersarena tivesofthesame.Variousgenera andspeci esofthefamilyRhamna ceaeare givenbe low.
Rhamnaceae
Distributio nofSpecies
Ziziphusju juba Mill.
Kingdo m:Plantae
Divisio n:Magnol ioph yta
Class:Magno liop sida
Order:Rosales
Family:Rhamna ceae
Genus:Ziziphus
Species:juj uba

4/25/2016 PhytoPharmacologyof<i>Ziziphusjujuba</i>Mill Aplantreview:RTMahajan,MZChopda,PharmacognosyReviews
http://www.phcogrev.com/printarticle.asp?issn=09737847;year=2009;volume=3;issue=6;spage=320;epage=329;aulast=M ahajan 2/5
Taxono micDescrip tion
Jujube sarespe ciesoftheg enusZizi phusTourn.exL.Zijihu sbelo ngstothefami lyRhamn aceae named afterthegen usRhamn us.TheRhamnaceae havefrui tswhicha redrup esor
are dry and a re closel yre lated to ano ther family,Vitaceae, whichi nclude s major eco nomic species whose fruitsa re berrie s.The na me Ziziphu si sre lated to an Arabi cw ord and
ancien tGreeksu sedthe word zizip hon forthejujub e.There aretwo majo rdome sticatedjujub es,Z.mauri tiana Lam.the Indian juj ube orbe r,andZ.ju juba Mill .thecommo nju jube .
Thesetwospe cieshave been cultivatedo vervastareaso ftheworld.Thespe cieshasa wide rangeo fmorpholo giesfromshrubstosmall ormediu msizedtreesw hichmightbeere ct,
semierectorspreadi ng.Hei ghtcanva ryfrom34to1016mormorealthoughtree sof20ma rerare.Treesarese mideci duousandmuchbranch ed.Theba rkhasde eplongitudi nal
furrowsan disgra yishbro wnorreddish incolor.Usuall ytheshrub ortreei sspino us,butoccasi onal lyuna rmed.Branch letsared ensel ywhitep ubesce nt,especia llywh enyou ngan d
tendtobezig zag.Branche sspread erect,becomin gflexuou sanddu llbrow ngrey.Fruitingbran chesarenotdecidu ous.Lea flaminae areell iptictoovateornearlyorbicula r.Thea pex
isro unde d,ob tuseo rsuba cuteto emarg inated ,the base rou nded,sometime scun eate,mostlysymme trical ornearly so. Margin sare min utely seriate.There are 3 marked nerve s
almost tothe ape x,the nerves bei ng depre ssed in theupper,light ord arkg reen, glab rous surface.L ower surface is whitish du eto persistentdense hairs butmay be buffcol ored.
Occasional lythe lowe rsurface isgl abrou s.Leavesare petiola te1.15.8 mmlon gan dstipu lesa remostly spine s,ine achp aironeho oked and one straight,or bothh ooked,ormore
rarely notde velope dintoa spine.Flowers have sepal swhi chare dorsa llytome ntose,a diskabout3mmi ndi ametera nda 2cel led ovary,immersedin thedi sk.Stylesare2,1 mm
long a nd con nate for hal fthe ir len gth. Flowers tend  to have a n acrid  smell. Flowe rs are bo rne in cyme s or small  axilla ry clusters. Cymes ca n be se ssile or sh ortly ped uncula te,
pedun cles14 mmtomentose.Pedicelsare alsotome ntoseand are24 mmatfloweri ngand 36mmatfruitin g.Fruitisagla brousg lobo seoroval edib ledru pevaryin ggrea tlyinsize
from(1)1.5(2)cmdiameterbutsomeovalvari etiescanrea ch5x3cm.Thepulpisacidican dsweet,thefruitgreeni sh,yelloworsometimesreddi sh.
Indiannames
Rajab adari (Sanskrit);Beri (Punjab i);Kul (Beng ali);Bogori (Assamese );Bodori (Uriya);Bordi (Gujarati);Ber(Hindi );Bor(Marathi);Ba daram,(Ma layal am);Boga ri(Ka nnada);Vadari
(Tamil);Renu(Telu gu);Ber(Urdu);Jang ri(Sindhi)
Historical eviden ces
Berhasb eenre cogni zedasa usefuledibl efruitsincemythologyofRama ndSha barii nIndia anddepictedinR amayana.Resea rchersmen tionbo thZ.mauritiana andZ.ju jubaand
eventhewi ldZ.nummula ria[2].Deccanpl ateauare aisone wherebe risthough ttohavebeen trulywild.[3].Oncecultiva ted,berwou ldbecarri edwithhistorical migration sofpeople
andtheirtrade .
Medicin alUses
Thereare larg enumb ersoftraditional medi cinalusestha tareno tnecessa rilyba sedo nknow ledg eofthe constituen ts.AccordingtoAyurveda ,therootofZ.nummulariais bitterand
coolin g,an dcu resco ughs, bili ousness and he adach e[4] .Thebarkcu resb oils and is goo dfor the treatmento fdysen teryanddiarrhea [5]. Thel eaves are antipyre tican dre duce
obesity.Thefruitiscool ing,di gestibl e,tonic,aph rodisi ac,laxative andre movesbi liou sness,burn ingse nsation s,thirst,vomiting[1]andisal sogoo dintrea tingtube rculosi sandb lood
disease s.Theseedscureeyedisea sesand areal souseful inl eucorrhoea[6].Thetradi tional workerso fChhattisgarh,Indiausefruittotrea tcommonfevers andforvo mitingu sethe
seedswithba rsprouts(Ficusbeng halensis)andsug ar.Thetraditionalhe alersofBastarregionusethedrie dleave sandpowd eredba rktodresswound s[5].Thefreshleave sarealso
usedforthesa mepurpo se.Theaque ouspa steoftheleave sisappl iede xternallytorelieve aburningsen sation.Rootsareused totreatdysentery;theyare givenw ithcow'smil kuntil
thepatien tiscured.Senio rcitizensuse dthefreshle afjuicew ithbuffalo'smilktoreducetheintensityofsmallp ox.Simila rly,intheearlydays,theuseofseedstotreateyetrou bleswa s
common.Totreathoarsenesso fthethroat,tradition alhealersad visepa tientstokeep thefreshroo tsofthisplan tinside theirmouth.Thetraditiona lhealersusethefreshlea vesofthis
plantwithcumi ntotreaturina ryinfectio ns[6].The fruitise mploye das ana ntidotetoaconi tepoi sonin g,abd ominal pai nin preg nancy and externallyinpoul ticean dap plica tionsfor
wound s.The  kernels incre ase flesh an d strength and a re sedative i n activity [7] . Here, some al lied substan ces are descri bed such a s ascorbic acid ,thi amine, ribo flavin and
bioflavo noid sand pectinA.Zizi phusj ujub afruitsare veryrich invi taminsC (188 to544mgpe r100 gmpul p)an dB1(thi amine )and B2(ribo flavin) studied[8].Compare dwi thother
edibl efruits,onefruitofbe rperdayw ould meetthedie trequireme ntsforVitaminCan dVitaminBco mplexforan adultmanasrecommendedb yFAO/WHO.Itisalsoknown tohavea
high Vitami n P (354 to 88 8 mg pe r1 00 gm pulp) (bi oflavon oid) con tent.It enh ances the a ction of Vitamin C .Antiba cterial, anti i nflammatory an d antio xidantare  some medicinal
propertie s.Itisalsoknowntostimulatebil eprodu ction,promoteci rculatio nandpreventall ergies.PresenceofPectinAinZ.juju bafruitisalso reported[9].Chemi callyitcontains2,3,
6trioacetylDla ctoseunits.Pectinhasanu mberofpharmaceuticalpro pertiessuch asbindingbile acid,lowe ringplasmachole steroland antidiarrhoealpro perties[10].
PhytochemistryofZ.jujuba
Alkaloi ds
Alkaloi dsare distributedin all partsofp lant.Stemb arkofZizip hussp eciesco ntain alkal oids[3].Asapog enin,zizogen inh asbee niso latedfromZ.mauritian astems[11].Thecycli c
peptide a lkalo ids,mauritine A,mucro nine D,amp hibi neH, nummularine Aand B [12] ,sativa nine Aandsativa nine B,frang ulani ne, nummul arineBan d mucroni ne were iso lated
fromthe ba rkofZa juju ba by [12]. The cyclic peptid e alkalo ids sativan ineC,sativan ineG, sativanin eE,sa tivanin eH,sa tivanin eF, sativanineD and sativanine Ki solatedfrom Z.
jujub astem bark[13].Thealkaloid scocla urine ,isobo ldine,norisobold ine,a similo bine ,iusip hine and iusiri new erei solated fromZ.ju juba leave sby [14].Cyclo peptideandpeptide
alkalo idsfromZ.juju bawe refoundtosh owsed ativeeffects[15].TheseedsofZ.juju bavar.spino saalsocontaincycl icpep tideal kaloid ssanjo inen ine,frangu loin eand amphibineD
and four p eptide  alkal oids; sanj oini neBDF an d G2 [16] .The  seeds a re used i n Chi nese me dicine  as a sed ative. Chemi cal studi es of Z.ma uritian a led to the  isola tion of the
cyclopep tide alka loids, mauri tines Aan d B; CF, G and H, frang ufoline ;a mphibin es D, E, B and F; hysodri caninA, scutian inF and a ralioni nC [12] . The cyclope ptide al kaloid,
mauritine J, was isol ated fromtheroo tbark of Z.mauri tiana [17] .For thefirst time [12]re ported six Cyclopeptide alkaloi ds isolatedfrom the stembark ofZ.juju ba are Mauri tineA;
Amphibi neH; Juba nine A;Jub anin eB;Mu cronin eD and Nummula rineB. Latter [13] repo rted Sativani neE.Antib acterial p eptide a lkalo id Frangu folinefrom Zizip hus speci es was
reported [18 ]. Ha n and cow orkers repo rted Melono vineA; Frangan ine; Frangul anine; Da echuin eS3; Daechu ineS6; Nummu larineA and  Nummular ineR, all  are cyclope ptide
alkalo ids[16].Fourcyclop eptide alkaloidsfromthestembarkZ.jujuba ,whichareScutiani neC;ScutianineD ;Jubani neCan dZiziph ineAreported [19].Twore portsappe aredi nthe
literatureo nisol ateding redie ntsfromtherootbarkofZ.jujuba.Adouetin eXandFran gula ninew hicha reactive(sed ative)in gredie ntcyclope ptideal kaloi dsisolatedand characterized
[20].Someoftherep resentative alkalo idsaregive nin[Tabl e1][21],[22].
Somecyclope ptideal kaloi dsofZ.jujuba
Glycosides
(i)Flavono idglycosides/spi nosin s:Thestructureofspinosi n(2"Obetaglu cosylswe rtisin)extractedfromZ.juju bavar.spinosaseed[23 ].Theyl ateridentifiedthree acylatedfla vone
Cglycosides(6'''sinap oylspin osin,6'''feruloylsp inosi nand6'''pcoumaroylspi nosin ),pharmacological lytheyhavesed ativeactivityinrat.
(ii)Glycosid es/sapon ins:DifferentpartsofZ.juju bathatissee ds,leafand stemcontaing lycosid es.Thesaponi nsisol atedfromthesee dsofZ.jujuba includ ejuj ubosi desA,B[24],A1
B1andCandacetyljuj ubosi deB[25]andtheprotoj ujubosidesA,BandB1[26].Kuriharaetal.extractedthesapo nin,zizip hin,fromthedriedleavesofZ.jujuba[27].Ithasastructure,
3Oa L rhamnopyran osyl (12) a arab inopyranosyl20 O(2,3) diOace tyla L rhamno pyrano sylju jubo geni n.Ikrame tal.i solated a sapon infrom Z.jujuba leave sand
stem.Itw as assigned the structure 3O((2Oalpha  D  furopyran osyl  3Ob eta D g lucop yranosyl ) al pha  L arabino pyrano syl) jujubogen in [28] .They arebeing wi dely
researche dforcancerp reventionand cholesterol control as mentioned byOgi hara [29]. Same compound is also repo rtedb ySha rmaa nd Kumar [30]ina nother speciestha tis Z.
mauritian a.Sapon insshow edad juvantandhemo lytic[31],sedative[32]anxiolytica ndswee tnessinh ibitingprope rties[27].Jujubo sideA(JuA),isalsokno wntobea noncomp etitive
inhib itorofcalmodu linan disthoughttobelin kedtoitssedativepro perties[33].
Flavonoi ds
Sedative flavon oids such asSw ertisha nd spinosinw ere isolatedan dre ported byGon get al.,[34] fromfruita nd seeds ofZ.juju ba.Puerarin; 6"'feruloylsp inosi n;Apigen in6C bD
glucop yranoside; 6"'ferul oylisospino sin; Isospinosin  and Isovitexin2 "ObDglucopyran oside these fla vonoids iso lated and re ported by Gong, et al .[34 ]. Ten flavonoid s were

4/25/2016 PhytoPharmacologyof<i>Ziziphusjujuba</i>Mill Aplantreview:RTMahajan,MZChopda,PharmacognosyReviews
http://www.phcogrev.com/printarticle.asp?issn=09737847;year=2009;volume=3;issue=6;spage=320;epage=329;aulast=M ahajan 3/5
reportedb yPawlow skaetal.,[35]areQuercetine3O0robinobi oside;Querce tine3Orutino side;Quercetin e3OαLara binosyl(1→2)αLrhamnosid e;Quercetine3ObDxylosyl
(1→2)α Lrhamn oside ;Quercetine 3OβDgalactosi de;Querce tine3 OβDgluco side;3 ',5'DiCβDglucosyl phlore tin;Quercetine3 OβDxylosyl(1 →2)α Lrhamnosid e4'O
aLrhamn oside ;Kaempferol3Orobino biosi deandKaempfero l3Orutino side.Someo ftherepresentativeflavon oidsaredescrib edbyGongetal.,[34].Zengetal.,[24]discove reda
newflavon oid,name dzivulg arin,compou nd(4be taDglyco pyranosyl swetisin).
Terpenoids
Thetriterpeno icacid shavebe enisol atedfromthefruitsofZ.jujuba:someofthema recolub rinica cid,alph itolica cid,3Ocispco umaroyla lphi tolicacid,3Otranspcouma roylal phitol ic
acid,3Ocispcoumaroylma slini cacid,3Otranspcou maroylma slinicacid,oleanolicaci d,betulon icacid,ole anon icacid,zizybe renalicacidandbetulin icacid[36].Triterpenoicaci ds
haveal sobee nextractedfromroo tsofZ.mauritiana[37].Betulin;Betulin icacid ;Ursolicaci d;2αhydro xyursoli cacidandCea nothica cidaretriterp enesre portedbyShoeie tal.,[38].
Some of them ha ve antica ncer and antiHIV pro perties. San g et al., [39] demon strated three triterp ene estersviz.2Oprotocatechu oyl al phitolic acid, Ca ffeoyl alph itolic a cid and
Ceano thicacidd imethylester.
PhenolicCompounds
RecentlyPaw lowska etal.,[35]reportedphenoliccompou ndsfromthefruitofZ.juj uba,withoutcitinganybio logi calactivity.
Chemica lstructureofPhenol iccompou ndofthefruitofZ.juj uba
Betulini cacid
Betulini ca cid is wide ly distributedi n all parts of plant. Itis a natural ly occurrin gp entacycli ctriterp enoid w hich hasde monstrated selective cytotoxicity again sta nu mber ofsp ecific
tumourtypes.Ithasbee nfoun dtose lectivel ykill humanmela noma cells whil eleaving heal thycell sali ve.Inad dition,betulin icaci dha sbee nfound toha vean tiinflamma toryactivity
[40]andantiba cterialpro pertiesandinhib itsthegrowthofbothStaphyl ococcusaure usandEsche richeri acoli[41].
Pharmacol ogica lprope rtiesofZ.jujba
Hypnoticse dativean dAnxiol yticeffect
Thesee dsan dle aves ofmany Ziziphu sspeciesh aveb een found toha vean xiolytic and hypno ticsedative effects.Theyare know nto depre ssactivityofthece ntral nervous system
which redu cesa nxiety and indu cessl eep. Itwas found thatitprodu ced sleep ,but wasnotan ticonvul santo rmuscl erelaxant [42].Theinh ibitory effectofJu jubo sideA(Ju A)on rat
hippo campus is de monstrated by Feng an d Zheng, [43].An xiolytic effectsi n mice of a polyhe rbal sub stance containing see d extracto fZ.jujuba re ported by Line tal .,[44] .Both
sanjoi nine Aandn uciferin e,alka loid sobtai ned fromfruit,pro long edthe sleeping time produ cedb yhexo barbi tal.When sanjo inin ewa sheatedi twas found toprod ucea nisomero f
evengrea tersedativeeffect[15].
Sweetnessin hibi tors
Triterpenoid sweetnessin hibitorswereisola tedfromZ.jujuba.ExtractsfromtheleavesofZ.jujubaha vebeen foundtosuppresssweettastesensationinfly(Pharmaregina),ratandin
hamster.Antisweetsubstancesiso latedfromZ.juju baincl uded jujub aspon insII,III,IV,VandVIand fromtheleaves,jujubo sideBfromthele avesand seedsan dzizip hussapo ninsIIII
fromdriedfruit.Ziziphi nandju jubo sapon insIIandIII,theon lythreeoftheantisweetsaponi nsfromthisplan twithacylgroup s,wereupto4timesmore activeinsupp ressing thesweet
tasteo fsucrose than the o ther antiswe etconstituents an d thereby red ucing  obesity in d iabe tic or overwe ight peo ple [45] . The sapon in, ziziph in extractedb y Kurihara  eta l. [27]
suppresse d the swee tness indu ced by Dgl ucose, Dfructose, steviosi de, glycin e, sodium sa ccharin, asp artame and n aring in dih ydrochal cone. Ith oweve rsh owed n o suppre ssive
effecton the sour tasteo fhydro chlori cacid and the bitter tasteof qui ninein dicatingtha tzizip hin is hig hly specific to sweet taste[46 ].Zizi phinwa sfoun d toin hibi tthe sweettaste
receptorsin humans[47].Themechani smwhichzi ziphin usedwa sidentifie dastastemodificatio n.Oncompariso nwithknow ngymnemi cacids,effectssuggestthatnetdissoci ationof
ziziphi nsfromtastereceptormembran esand/orinactivationin themembrane maybemuchfasterthanwithgymne micacids.
Cancer(che motherap y)
The in vitro cytotoxicitie so fthetriterp enoic a cids extracted from Z.j ujuba were tested ag ainst tumour cel l line s. The lup anetype triterp enes sho wed hi gh cytotoxic activitie s.The
cytotoxicactivitieso f3Opcoumaroyl alph itolicacidswere foundtobe betterthanthose ofnonco umaroictriterp enen oids.Theseresultssugge stthatthecoumaroyl moietyattheC3
position ofthe lupa netype triterpen ema yp lay an importan trole ine nhancing cytotoxic activity[36 ].Thetriterpo nic acid, betuli nic acid, extracted fromZ. jujub a and Z.mauri tiana,
showed selective toxicityaga instcultured human melan omacells[40].Betulini cacidi scurrentlyundergo ingp reclin icalde velop ment[48].Itisthoughtthatbetulinica cidmaya lsobe
effective agai nst other types of cance r.Rece ntly,con siderab le in vi tro evidence  has demo nstrated that betul inic aci d is effective aga inst small a nd non smallcel l lung ,o varian,
cervical,and headan dneckcarcinomas[48].Published datasugge stthatbetulinicacid induce sapoptosi s[40],[49]insensitivecellsin ap53and CD95indepe nden tfashion[41].
Antimicrobi alactivity
Sarfarazetal.,[50]reported antifunga leffectsofZ.jujuba.Ethanol extractoftherootshowe dsignificantinh ibitoryactivi tyonfungiC andi daalb icans,C.tropica lis,Aspergill usflavus,A.
niger andMalassezia furfur(strains1 374a nd17 65).Addition ally,extractofrootbarko fZ.jujubaexhibi tedantib acterial activityaga inst20bacteria[51 ].LeafextractsofZ.mauritia na
werefoundtoshowantiba cteriale ffectsagainstEscherichiaco li,Kleb siell aspp.,Pseud omona sspp.,Proteusvul garisa ndBacillussubtiliswh enmetha nola ndace toneextractswe re
used[52].Betulinicaci disola tedfromstembarkofZ.jujubahasal sobeen foundtoretardtheprogre ssionofHIV1infection thatisantiviralactivity[53].
Antiulceractivi ty
Anantiu lcerp ropertyofZ.mauritiana lea fextracts(ZJE)wasreported byGana charia ndsh iv[54]i nrat.Thise xtractpossesses signi ficantanddose depe ndentantiulce ractivity.The
antiulce ractivityofZJEcanbeattributedtoitscytoprotectiveandantisecretoryaction[54].
Antiinflamma toryandantisp asticeffect
Thecompou ndprescriptionH uang qinTangwhichco ntainsthefrui tofZ.jujubasho wedmarkedantii nflammatoryan dsign ificantantisp asticorantispasmodi ceffect[55].Z.mauritiana
leafextractswerefound topossesssigni ficantantiin flammatoryactivityagai nstcarragee nani nduced ratpawedema [56].
Antialle rgic
Theantiallerg icactivi tyofthea queo usextractso fleave sofZ.juj uba wasstudiedb ymeasu ring itsinh ibitory effectonhya luron idase(bovin etestes)a ctivation invi tro.Z.jujub awa s
showntohave strongantial lergi cactivity[57].
Permeabi lityenha ncemen tactivity
Delive ryofce rtaincl asseso fdrugs sucha spep tidescreatesproblems in transportation across cellmembranesandsu bseque ntdimi nishe dbi oavai lability.Toovercomethis barrie r,
permeab ilitye nhance rscanb eusedtoaid thepa ssage ofdrugsacrosscel lmembra nes.Toassessthepermeabil ityenhancing activityofZ,juj uba,a naqu eouse xtractofseeds was
compared totwomembersofaknownseri esofpermeabilityenha ncemen tagentsbelonging tothealkylglycosi des[58].

4/25/2016 PhytoPharmacologyof<i>Ziziphusjujuba</i> Mill Aplantreview:RTMahajan,MZChopda,PharmacognosyReviews
http://www.phcogrev.com/printarticle.asp?issn=09737847;year=2009;volume=3;issue=6;spage=320;epage=329;aulast=M ahaj an 4/5
Cogni tiveactivities
Heo et al.[59]sug gested that olea mide, a compon ent ofZ.j ujub a extract,coul d be a useful che mopreven tative agen taga instAlzh eimer's disea se.They foun d thatmetha noli cZ.
jujub a showe d34.1 % activation effect on choli ne acetyltransferase in vitro, an enzyme that controlsthe pro duction ofacetylch olin e which ap pears to be dep leted in the bra ins of
Alzheime rpatients.Using sequen tialfractionatio ntheactiveing redientwasfoundtobecis9o ctadecen oamid e(oleami de)whi chshowe d65%activatio neffect.
Antifertility/contracep tiveprope rty
Theethyl acetate extractof Z.jujub aba rkwa sfound toe ffectantisteroidogeni cactivityand hence fertilityinadult female mice.Itwa sfound toa rrestthe normal estrus cycleo fadu lt
female mice atdi estrusstagean dre ducedthe wetw eigh tofovaries signi ficantly.Hematol ogica lpro files,b ioche mical estimation sof whol ebl ood and serumremai ned una ltered in
extracttreatedmice .Normalestruscycle and ovaria nsteroid ogen isiswe rerestore dafterwi thdrawaloftreatmen t.Antifertilityactivitieso fcrudee xtractswerefou ndtob ereve rsible in
rat[60].
Hypotensi veandAntin ephri ticeffect
Ziziphus juj uba hasb een found tostimul aten itricoxi dere lease in vitro,in cul turede ndothe lialcell sand invivo,inthe kidn eytissuesofrats[61].They bel ievedthatZa juju bama y
contributetoitshypoten sive(redu ctionofbloodpressure)an dantine phritic(reductionofinflamma tionofthekidne y)action,possibl ybyincreasi ngrena lblood flow.
Cardio vascula ractivity
Ane olign an isol ated from Z. mauritian a leave s was found  to increase  the relea se of endo genou s prostaglan din I2 (the mo stp otent natural  inhib itor of platel et aggreg ation yet
discovere dandapo werfulvaso dilator)fromtherataortabyupto25.3%at3microg/ml[62].
Immunostimula nteffects
TheleafextractofZ.juj ubawa sfoundtostimulatechemotactic,phagocyticand intracell ularkillingpo tencyofhumanne utrophils(infectionfigh tingwhi tebloodcells)at550microg/ml
[63].
Antioxida nteffects
Recently,acomp rehensi vean danexhaustive accoun ton70 antioxi dantKoreanme dicinalpl antshave been reportedbySeo ngetal.,[64]andthe yconfirme dantio xidanteffectofZ.
jujub a(invitro)asrepo rtedbyNaetal.[65].
Woundhealingactivi ty
Recently,Ansari et al.,[66] mention ed therooto fZ.jujub aa sa wound healer in their book entitle dH erbal Dru gs.The expe rimental da taon wo und hea ling activi tyof thero otof Z.
jujub ai sno tavai labl ei nl iterature in lab oratory anima ls[67 ].Veryre cently we confirmed the wou nd heal ing activity ofthe root ofZ.juju ba in experi mental ani mal,ra tmode l,in an
ointmentformatadose0.5%an d1%ontopi calappl ication [68]andthisconfirmsthevali dityofclaimmadebyAnsa rietal.,[66]
Summary
Z.j ujuba, an  indig enous p lant posse sses terrific medici nal pro perties, attributed  by a dive rse group  ofse condary me tabolites. Phytoch emicall y 64 alka loids, 16 g lycoside s and
flavonoi ds,14terpeno idsandothersarepresen tinthisplant.Eaching redien thasuniqu eandmul tifactorialprop erties.Theimportan ceofsuchconstituentsinhealthprod uctsandfood
supple mentsis igno red.Althoug hthere isa rang eofp otential lyuse fulmed icinalsubstan cesin pla nt,therese archi nthis area isscan ty.Commercial industriesneglected theuse of
suchcon stituentsinp harmace uticala ndne utraceutica lcompa nies.Thebenefitoftheh ardyna tureofZ.juju baan ditswi dege ographicaldistributio ngave ano pportunitytoagroa nd
pharmain dustries.Thus,thisarticlepro videsexcellentaccessi blesou rceofactivecompoundsfortraditiona lmedici neandallied appli cations.
Acknowledgement
TheauthorsarethankfultothePrin cipal ,A.G.Rao,Moolj iJaithaColle ge,Jalga on,notonl yforhisinspirationb utalsoforprovi ding librarya ndlab oratoryfacili tiesduri ngthecourseof
thisinvestiga tion.
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4/25/2016 PhytoPharmacologyof<i>Ziziphusjujuba</i> Mill Aplantreview:RTMahajan,MZChopda,PharmacognosyReviews
http://www.phcogrev.com/printarticle.asp?issn=09737847;year=2009;volume=3;issue=6;spage=320;epage=329;aulast=M ahaj an 5/5
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