ReviewArticle

MAYTENUSEMARGINATA(WILLD.):APROMISINGDRUGFORCANCERTHERAPY

*SAVITASAGWAN,D.V.RAO,R.A.SHARMA

Biotechnologylab,DepartmentofBotany,UniversityofRajasthan,Jaipur,IndiaEmail:savita.sagwan@gmail.com

ABSTRACT

Therearehundredsofmedicinalplantsthathavealonghistoryofcurativepropertiesagainstvariousdiseasesandaliments.Maytenusemarginata(Willd.)(Family:Celastraceae) isanevergreentree thatholdsaplaceofexceptionalarroganceamong thevariousplantsbecauseof its immensemedicinalusesofgreatsignificance.PlantextractsofthecelastraceaehavebeenusedforcenturiesthroughoutSouthAmericaandChinaasinsectrepellentsandinsecticidesintraditionalagriculture,andalsoforthetreatmentofaplethoraofmedicalailmentsfromstomachcomplaintsandfevertorheumatoidarthritisandcancer.PhytochemicalinvestigationofMaytenusemarginata(Willd.)hasbeencompiledforthestudyofclinicaluseofthisplant.Theactivecompoundsincludeemarginatine[A],[B],[E],[F],[G]andemarginatininearediscussedbrieflywiththerecentadvancesandmechanismoftheiraction.Thisarticlebrieflyreviewsthebotany,distribution,ecology,usesoftheplantandasadrugforcancertherapy.ThisisanattempttocompileanddocumentinformationondifferentaspectofMaytenusemarginataanditspotentialuseasadrugsourcefordifferenttumorcells.

Keywords:Maytenusemarginata(Willd.),Emarginatine,Emarginatinine,Cancertherapy,Tumorcells.

INTRODUCTION

Chemotherapy is a kind of treatment that uses drugs to attackcancer cells. It is called a "systemic treatment" since the drug,enteringthroughthebloodstream,travelsthroughoutthebodyandkillscancercellsattheirsites.Thedrugsmayrarelybeintendedtohave a local effect, but in most cases, the intention is to destroycancercellswherevertheymayexistinthebody.Chemotherapeuticdrugs are chemically designed to target cells that aredividing andgrowingrapidly.

Once they reach the cancer cells, they act to retard their growth,eventually resulting in their destruction. Chemotherapy works bystopping or slowing the growth of cancer cells, which grow anddividequickly.Theeraofcancerchemotherapybeganinthe1940swith the first use of nitrogen mustards and folic acid antagonistdrugs. Cancer drug development has exploded since then into amultibillion dollar industry. The celastraceae family, commonlyknown as bittersweet family, is indigenous to tropical and subtropicalregionsoftheworld,includingNorthAfrica,SouthAmerica,andmanypartsofEastAsia,ParticularlyChina[1,2].

Plantsofthis familygenerallygrowassmalltrees,bushesor lianasand have resinous stems and leaves. They have been valued sinceantiquitybecausetheirextractshaveusefulmedicinalproperties[3].Thecrudeplantextractsofthecelastraceae intraditionalmedicineand agriculture is astonishing, and includes stimulant, restorative,male contraceptive, antitumor, antileukemic, antibacterial,insecticidalandinsectrepellentactivities[4].

Maytenus emarginata (Willd.) belongs to family celastraceae, is anevergreentreethattoleratesvarioustypesofstressesofthedesert,locallyknownas Kankero inHindi, Thornystaff tree inEnglish.TraditionallyspeciesofMaytenushasbeenusedforfever,asthama,rheumatismandgastrointestinaldisordersworldwide.

Recently some biomolecules from Maytenus species has beenreported to be active against HIVProtease [5] Carcinoma andleukemia [6].Ulcers [7]andMDR(MultiDrugResistance) [8].Variouspartsofthisplantcontainimmensemedicinalpropertieswhicharementionedunder:

RootUsedingastrointestinaltroubles,especiallydysentery[9]. StemTendershootsoftheplanthelpformouthulcer.Thebark

isgroundtoapasteandappliedwithmustardoil tokill lice inthehair.

Leaf Pulverized leaves of Maytenus emarginata are given inmilktochildrenasavermifuge[10].Adecoctionoftheleafytwigsisusedasamouthwashtorelievetoothache.Ashofleavesused

tohealupsoresandwoundgivescoolingeffect.Theleavesareburnt and mixed with ghee to form an ointment used to healsores[11].Thetenderleavesarechewedrawinthetreatmentofjaundice.

FruitThefruitsareusedinmedicinestopurifyblood[12].BOTANICALCLASSIFICATION:

Kingdom : Plantae

Phylum : Magnoliophyta

Class : Magnoliopsida

Order : Celastrales

Family : Celastraceae

Genus : Maytenus

BOTANICALNAME:Maytenusemarginata(Willd.)DingHou

SYNONYMS:

CelastrusemarginatusWilld. Gymnosporiaemarginata(Willd.)Thw. GymnosporiaMontana(Roth)Benth.COMMONNAMES:

Hindi : Vinger,Kankero,Baikal,Malkangni

English : Thornystafftree

Sanskrit : Vikankata,Sudhavridsha

Bengali : Bakundri,Vaichigacha

Kannada : Tandrasi,Tandraja,Haalumanike,Malega,Malkaamguni

Malayalam : Katoupatsjotti,Kanguni

Marathi : Baefal,Baekar,Bhaaroolee,Bharatti,Bharuli,Harmocha,Vekal,Vekar,Yekkadi

Tamil : Kattangi,Nandunarani,ValuluVai

Telugu : Chinni,Danthi,Sinni,Danti,Chinnituppa,ChinnichettuGoddalicippa

Gujarati : Vickado

Asian Journal of Pharmaceutical and Clinical Research Vol. 4, Issue 3, 2011 ISSN - 0974-2441

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BOTANICALDISCRIPTION

ThemembersofCelastraceaefamilygenerallyaretreesandshrubscomprising about 55 genera and 850 species that are sometimesclimbingorvining[13].Maytenusemarginataisasmall,compacttree,35meterhigh;youngbranchespurple,oftenspiny,withleavesandflowersonthespines.AllthebotanicaldescriptivecharactersofthisplantarelistedinTable1.

Table1:BotanicalDescriptionofMaytenusemarginata(Willd)

Planttype Evergreen, Dioecious tree, Very hardyplant.(Figure.A)Habit:ScandentshruborsmalltreeNamecode:202785

Growingrequirements

Lightrequirement:FullsunwithmiddayshadeSoiltolerances:Sandysoil,limestoneBestseason:MonsoonDroughttolerance:Varioustypesofstressesofthedesert

(a) Bark Palebrown,smooth,cracked(Figure.B)

(b) Leaf Thick, coriaceous and usually longer than40mm, apex rounded, alternate on youngbranchlets,fasciculateonolderones(Figure.C)

(c) Flower Bisexual or sometimes functionally unisexual,actinomorphic, white or cream colored 57mmindiameter(Figure.D)Male flower: Stamens slightly shorter thanpetals,stigmasabsent,discgreen,5lobedFemale flower: Staminodes shorter thanstamens ofmale flower, ovary 3locular, green,styleaslongasovary.

(d) Fruit Capsule, berry, 612mm long, green becomingred(Figure.E)

(e) Root Taproot,Creamyellowincolor(Figure.F)

Pest anddiseases

Troublefree

FigureA.Maytenusemarginata(Willd.)Plant

FigureB.Bark

FigureC.Leaf

FigureD.Flower

FigureE.Fruit

FigureF.Root

DISTRIBUTION:

ThespeciesisgloballydistributedinPaleotropics.WithinIndia,itiscommonindryscrubforests throughout,particularlyonpoorsoilsin Central and Western peninsular India. The genus Maytenusdistributed in drier parts of Central, SouthWestern and NorthWesternIndia.

It is found throught in India (Madhya Pradesh, Uttar Pradesh,Punjab, Maharashtra, Gujarat, Delhi, Bihar, Tamilnadu, andRajasthan).

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In Rajasthan its found in Ajmer: AjmerUdaipur road, kota:Shahabad, Pali: Gurupratap singh village, Sirohi: Vadakhoda, Tonk:Rajmahal,DoogorBeed(Nagaur),FahelpurBeed(Sikar),SikerBeed(Siker),Nokha(Bikaner),KarniMataOran,Deshnoke(Bikaner),ShriBalaji (Nagaur), Chohta (Barmer), Shri MukamNokha (Bikaner),Khejarali(Jodhpur),NurseryofRajasthanUniversity,JhalanaDungri(Jaipur).

ECOLOGY:

Growingat elevations fromnear sea level and locally abundant onthecoastonsandattheedgeofmangroveforestorsecondaryforest,at forestmargins, in thicketsonbranchesandhillsides andon seacliffs, often on limestone. Long, hot summers are needed forproductionofflowersandfruits.

PROPAGATION:

Maytenus emarginata is an out breeding tree therefore it showsgreatvariability.Sowseedunderglassinseasonofautumn.Removesuckers,whichmayappearatsomedistance fromtheparentplantin spring season. Root semiripe cuttings with bottom heat insummer.

GROWTHPATTERNS:

Maytenusemarginata(Willd.)growinmoderately fertile,moistbutwelldrained soil in full sun with midday shade. Fruit appears inJanuary to February and fruit ripens start from March to April.Flowers appears in October to January. Develops new leaves fromJunetoAugustasshowninTable2.Thebestseasonforcollectingofthisplantformedicinalusesismonsoon.

Table 2: General growth pattern of Maytenus emarginata(Willd)

Months

PlantParts

Jan

Feb

Mar

Apr

May

Jun

Jul

Aug

Sep

Oct

Nov

Dec

Newleaf

Flower

Fruit

Fruitripen

MAYTENUSEMARGINATA:PROMISINGDRUGFORANTICANCER:

The majority of chemotherapeutic drugs can be divided intoalkylating agents, antimetabolites, anthracyclines, plant alkaloids,topoisomeraseinhibitorsandotherantitumoragents[14].

Over the last 30 years or so, a large number of secondarymetabolites exhibiting a wide range of bioactivity have beenextracted from the Celastraceae. The bioactive metabolites of thegenusMaytenusinplantsbelongstofamilyCelastraceae,whicharewidelyusedasfolkmedicinesinSouthAmerica[15].

Manycharacteristicbioactivecompounds,suchasmaytansinoids[16]with antitumor activity, quinoid triterpenes [17, 18] and triterpenedimmers [19, 20] with cytotoxic activity, sesquiterpene pyridinealkaloids [21, 22]with insect antifeedant [23] and immunosuppressiveactivites [24] and sesquiterpene polyesters [25] with antitumorpromoting activity [26] are reported from genus Maytenus or thefamilyCelastraceae.

In the search for potential antitumor agents from the plant familyCelastraceae, several cytotoxic sesquiterpene pyridine pyridinealkaloidsarepresent[27,28]whichareasmentionedunder:

Emarginatine A (Fig.1a) [Molecular formula: C43H50N2O19 .Molecular weight: 898.859g/mol] which were isolated fromthe stems and branches ofMaytenus emarginata, is based onthe euonyminol skeleton and contains a C3 C13 evononicacid dilactone bridge, was slightly less active thasnemarginatinine,whichdiffers onlyby containing aC3C13hydroxywilfordic acid dilactone bridge (ED50 = 4.0 vs. 2.1 gmL1, respectively) [27]. Its structurewas determinedwithMS,UV, IR and one and two dimensional 1H and 13C NMR, andconfirmedbyXrayanalysis[29].

Emarginatine B (Fig.1b) [Molecular formula: C48H52N2O19,Molecular weight: 960.929g/mol] has been isolated fromMaytenus emarginata and its structure determined EIMS, UV,IR and 1H and 13C NMR comparison with (Fig. 1a).Emarginatine B was found to be significantly more cytotoxicthan Figure 1a against human KB cells, with an ED 50 =0.4g/ml[30].

EmarginatineE(Fig.1c)exhibitedcytotoxicityagainstKB(ED50=1.7g/ml)andCOLO205(ED50=4.1g/ml)cancercells[31].

Emarginatine F (Fig.1d) [Molecular formula: C46H50N2O18,Molecular weight: 918.891g/mol] were showed bestcytotoxicities against the human melanoma cell line RPMI7951 (ED50

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Emarginatinine (Fig. 2) were isolated from the stems andbranchesofMaytenusemarginataanditsstructureestablishedusingoneandtwodimensional1HNMR.Emarginatininewascytotoxic against KB cells with ED50 = 2.1g/ml (Kuo et al.,1994).

Figure2:ChemicalstructureofEmarginatinine

CONCLUSION:

The present study revealed that Maytenus emarginata showssignificantantitumorpropertiesthatsupporttouseinthetreatmentofcancer. These new leads could be further modified through analogstudies to yielduseful compounds or to be subjected tobiochemicaland pharmacological investigation to increase the understanding ofcancer cell biology. The sesquiterpene pyridine alkaloids reviewedabove are only one division of antitumor agents from Maytenusemarginata plant. The number of the alkaloids and their analogsdiscussed above has already been inpreclinical or clinical trials andsomeofthemarenowusedinclinics.Thispropertycouldbeexploitedfor theadvantageofcancerpatients.Continuinginvestigationonthisplantderivedalkaloidswillundoubtedlyresultinthedevelopmentofmoreselectiveandeffectivenovalanticancerdrugs.

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S.No Compound R1 R2 R3 R4 R5 R6 R7 R8Fig.1a EmarginatineA OAc OAc OAc OAc OPy CH3 OH OAcFig.1b EmarginatineB OAc OBz OAc OAc OPy CH3 OH OAcFig.1c EmarginatineE OAc OH OAc OH OPy CH3 OH OAcFig.1d EmarginatineF OH OAc OAc OBz OPy CH3 OH OAcFig.1e EmarginatineG OAc OAc OAc OMbu OPy CH3 OH OAc