review article ornamental exterior versus therapeutic

Review ArticleOrnamental Exterior versus Therapeutic Interior ofMadagascar Periwinkle (Catharanthus roseus) The Two Facesof a Versatile Herb

Naghmeh Nejat1 Alireza Valdiani2 David Cahill3 Yee-How Tan4

Mahmood Maziah125 and Rambod Abiri2

1 Institute of Tropical Agriculture Universiti Putra Malaysia (UPM) 43400 Serdang Selangor DE Malaysia2 Department of Biochemistry Faculty of Biotechnology and Biomolecular Sciences Universiti Putra Malaysia (UPM)43400 Serdang Selangor DE Malaysia

3 School of Life and Environmental Sciences Faculty of Science Engineering amp Built Environment Deakin UniversityMelbourne VIC 3220 Australia

4Department of Plant Protection Faculty of Agriculture Universiti Putra Malaysia (UPM) 43400 Serdang Selangor DE Malaysia5 Institute of Bioscience Universiti Putra Malaysia (UPM) 43400 Serdang Selangor DE Malaysia

Correspondence should be addressed to Naghmeh Nejat nanejatgmailcom Alireza Valdiani alirezavaldianigmailcomand Mahmood Maziah maziahmupmedumy

Received 3 July 2014 Accepted 29 September 2014

Academic Editor Da C Hao

Copyright copy 2015 Naghmeh Nejat et alThis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Catharanthus roseus (L) known as Madagascar periwinkle (MP) is a legendary medicinal plant mostly because of possessing twoinvaluable antitumor terpenoid indole alkaloids (TIAs) vincristine and vinblastine The plant has also high aesthetic value as anevergreen ornamental that yields prolific blooms of splendid colors The plant possesses yet another unique characteristic as anamiable experimental host for the maintenance of the smallest bacteria found on earth the phytoplasmas and spiroplasmas andserves as a model for their study Botanical information with respect to synonyms vernacular names cultivars floral morphologyand reproduction adds to understanding of the plant while the geography and ecology of periwinkle illustrate the organismrsquosubiquity Good agronomic practices ensure generous propagation of healthy plants that serve as a source of bioactive compoundsand multitudinous horticultural applications The correlation between genetic diversity variants and TIA production exists MPis afflicted with a whole range of diseases that have to be properly managed The ethnobotanical significance of MP is exemplifiedby its international usage as a traditional remedy for abundant ailments and not only for cancer TIAs are present only in microquantities in the plant and are highly poisonous per se rendering a challenge for researchers to increase yield and reduce toxicity

1 Introduction

The genus Catharanthus consists of eight species of whichseven are endemic to Madagascar and one C pusillus isendemic to India Catharanthus roseus Madagascar periwin-kle (hereafter MP) is an important floral species in horti-culture and is one of the few pharmacological plants thathave a long history It could be traced to Mesopotamianfolklore going as far back as 2600 BCE This plant still playsa considerable role today in herbal and traditional medicinefor treatment of various diseases The therapeutic properties

were ascribed to a number of chemicals in the alkaloid classsometime in the mid-1950s [1 2]

Medicinal plants have played a key role in world healthcare [3] MP apart from being the most important source ofnatural drugs is also one of the premier model organisms tostudy plant alkaloidmetabolites due to its ability to synthesizeawide range of terpenoid indole alkaloids (TIAs)with a broadpharmaceutical spectrum [4ndash7] However MP is potentiallypoisonous as are many plants of the dogbane family Nowa-daysMP comes inmany different varieties and colors rangingfrom white hot pink and mauve to the original pink as

Hindawi Publishing Corporatione Scientific World JournalVolume 2015 Article ID 982412 19 pageshttpdxdoiorg1011552015982412

2 The Scientific World Journal

a result of breeding experiments As previously publishedreviews onMPmostly concentrate on the pharmaceutical andchemical compounds of the herb lack of information aboutthe other features of the species is extremely tangibleThe aimof this review is to provide insights into agrotechnologicalbiological ecological and medicinal aspects (particularlyanticancer compounds) ofMP aswell as updated informationon the new cultivars that have been introduced to thehorticultural industry

2 Botany

21 Taxonomic Classification Inconsistency of nomenclaturein the literature is due to changes made in plant taxonomicclassification with continuous research [8] In the appellationof Catharanthus roseus (L) G Don Catharanthus meansclean or pure flower in Greek roseus signifies being rose-colored in Latin L is the standard abbreviation for Linnaeuswho first published the plantrsquos description and G Don refersto George Don who named the flower as such in 1837 [6]

Catharanthus roseus known as the Madagascar periwin-kle (MP) was formerly classified as the species Vinca roseaL (1759) (basionym or original name) Pervinca rosea (L)Moench (1794) Lochnera rosea (L) Rchb ex Endl (1838) andAmmocallis rosea (L) Small (1903) which are homotypic syn-onyms [9] Vinca guilelmi-waldemarii Klotzsch is recognizedas a heterotypic synonym [10]

Below describes the classification of the Catharanthusroseus species

Domain Eukarya eukaryotesKingdom Plantae plantsSubkingdom Tracheobionta vascular plantsSuperdivision Spermatophyta seed plantsDivision Magnoliophyta flowering plantsClass Magnoliopsida dicotyledonsSubclass AsteridaeSuperorder GentiananaeOrder GentianalesFamily Apocynaceae dogbaneSubfamily RauvolfioideaeTribe VinceaeGenus Catharanthus G DonSpecific epithet roseus (Linnaeus) G DonBotanical name Catharanthus roseus (Linnaeus) GDon (1837) Madagascar periwinkle [8 11ndash13]

Vernacular names of the herb in various cultures andlanguages have been listed in Table 1

22 Morphological Characteristics MP is a perennial orannual evergreen semishrub or herbaceous plant that growsup to one meter in height and secretes milky latex The rootsextend to 70 cm in depth The leaves of the plant are elliptical

Table 1 Vernacular names ofMadagascar periwinkle (Catharanthusroseus) in different languageslowast

Language Common name

Bengali NayantaraChinese Chang Chun HuaDutch Roze maagdenpalm

EnglishBright-eyes Cape periwinkle graveyard plantMadagascar periwinkle old-maidold-maid-flower rose periwinkle rosy periwinkle

Ethiopia PhloxCreole Bigalo

French Pervenche de Madagascar rose amere sorcererrsquosviolet

German ZimmerimmergrunCreole Kaka pouleHindi Sadabahar Baramassi Ainskati UshamanjairiIndonesian Tapak dara kembang sari cinaKonkani SadapushpaMalayalam Nithyakalyani Savakkottappacha UshamalariMalay Kemunting cinaMarathi Sada-phul (Sadaphuli)Myanmarese Thin-Baw-MA-HnyoPersian Gul-e-farang

PortugueseBoa-noite Boa-tarde Lavadeira Pervinca-rosaVinca-de-gatoVinca-de-madagascar Vina-rosea

Punjabi RattanjotSanskrit NityakalyaniKrio NgyangeAfrikaans Kanniedood

Spanish Chatas Chula Pervinca de Madagascar Vincapervinca Hierba doncella

Swedish RosenskonaTamil Sudukattu mallikaiTelugu BillagannerulowastReferences [9 17]

to oblong in shape 25ndash9 cm long 1ndash35 cm broad glossygreen above and pale green below with a pale midrib andopposite in orientation Petioles are green or red and 1ndash18 cmlong The inflorescence is racemose Flowers are pentamer-ous actinomorphic and colored pink rose-purple bluesalmon scarlet or white with purple red pink pale yellowor white ldquoeyerdquo in the center and a mauve throat (Figures1(a)ndash1(c)) The corolla tube is cylindrical 2-3 cm long withfive petal-like lobes Stamens are inserted 04ndash06 cm belowthe corolla mouth consisting of very short white coloredfilaments and filiform subsessile anthers Pistils range from17 to 26mm in length made up of two narrow long carpelsconsisting of a glabrous stigma style ovary and 2-seriate

The Scientific World Journal 3

(a)

(b)

(c)

(d) (e) (f)

Figure 1 (a) Artificial hybrids of MP in flower stage (b) wild types with purple flowers ldquoroseardquo (c) wild types with white flowers ldquoalbardquo(d) fruits which are composed of two free narrow cylindrical follicles (e) seeds inside the follicle (f) seeds All images represent the real sizesapproximately The artificial hybrids are clearly differentiated from those wild types due to their floral architecture and petals structure whichare wider thicker and more compressed than the wild ones


ovules Each fruit is composed of two free narrow cylindricalfollicles 2ndash45 cm long and 3mm wide which houses 10ndash20 oblong minute seeds 2-3mm in length (Figures 1(d)ndash1(f)) These seeds comprise black cotyledons which are flatand slightly shorter than the radical and a scanty endosperm[9 14ndash16]

3 Geographical Distribution and Ecology

MP is a plant species native to Western Indian Oceanrsquos largeisland ofMadagascar next to Africa It has been introduced asa popular ornamental plant in many tropical and subtropicalregions worldwide This herb is widely cultivated commer-cially in Spain United States China Africa Australia Indiaand Southern Europe for its medicinal uses The drugsderived from this plant findmajor markets in USA HungaryWest Germany Italy The Netherlands and UK [17ndash19]

MP is a tolerant plant against abiotic stresses such asdrought and salinity which can survive in a variety of habitatssuch as sandy soils shrublands grasslands inland riverbanks dunes in savannas dry wastelands houses roadsidesand even beaches and limestone rocks all due to its hardinessIt can be found proliferating at a range of altitudes from 0 to900metersMPprefers a soil pHof 55ndash65 canwithstand saltup to 2000 ppm andhas excellent heat and drought toleranceIt thrives well in dry frost-free and humid environmentswith favorable moisture conditions under full sun or partialshade and in soils that are well-drained It bears flowers andfruits the whole year in warm climates MP cannot withstandtoo much water wet soils or a cool spring Under adverseweather or in poorly drained soils MP turns yellow-greenwhile overwatering could lead to bacterial and fungal rotdiseases of stem and root [9 10 20]

4 Genetics

41 Cytology The chromosome number of all species of thegenus Catharanthus is 2119899 = 16 [9 21 22] with a genomesize of 1500Mbp (van Iren unpublished) Doubling of chro-mosome number tetraploidy has been induced by colchicinetreatment that resulted in an increase in TIAs larger stomatabranches and leaves although there was reduced pollenfertility and poor seed set compared with diploid plants [2324]

42 Reproduction MP is a unique species because of itsself-compatibility unlike most of the other species in thefamily However intraflower self-pollination does not nor-mally occur in periwinkle because of the physical sep-aration between the stigma and anthers a phenomenonknown as reverse herkogamy when the stigma is recessedbelow the level of anthers [25ndash28] Even so some periwin-kles contain elongated ovaries or styles thus allowing forintraflower self-pollination Basically MP is an allogamous(cross-pollinating) species The degree of outcrossing varieswith environmental conditions and the presence of seasonalpollinators mainly butterflies and moths whereby the floralstructure is adapted to pollination by these long-tongued

insects [29] Self-incompatible strains of MP engage in natu-ral interspecific hybridization which is found to be commonlocally in Madagascar [18 30] But in all reality both types ofpollination occur in MP

43 Genetic Diversity Although many aspects of alkaloidbiosynthesis have been investigated the genetic variationbetween accessions in relation to alkaloid content and theeffects of breeding for flower color or growth habit on thelevels of vinblastine (VBL) and vincristine (VCR) are stillpoorly understood Dissimilar cultivars accumulate TIAs invarious parts of the plant Hence efforts need to be madeto identify accessions out of the vast resources of naturallyoccurring MP germplasm for their chemotherapeutic poten-tial determine the type of plant tissues accumulating theseactive compounds and administer genetic improvements forhigher yield of alkaloids [31 32] A summary of geneticrelatedness among C roseus accessions based on differentmarkers is shown in Table 2

5 Agrotechnology

51 Cultivation Even though many investigations have beencarried out over the last few decades on the phytochemicaland therapeutic properties of MP few studies have beenconducted on the agronomic and genetic aspects of this herbMP is very easy to cultivate The seed germinates within aweek in the dark Seeds are easily sown directly or seedlingstransplanted at a seeding rate of 2-3 kgha and 05 kgharespectively [33ndash35] In a temperate climate seeding takesplace from March to April the best temperature for seedgermination being 25ndash30∘C Seeds should be planted with aspacing of 45times 30 cmor 45times 45 cm Transplanting takes placebetween June and July or September and October in the caseof 45ndash60-day-old seedlings spaced at 45 times 20 cm Softwoodstem cuttings or apical semiripe cuttings could also easily begrown in spring or summer under lighted conditions at 20∘Cand on drained compost [19 36]

Effects of different levels of nitrogen application ratesfrom 50 to 150 kgha on plant yield have been testedwith 150 kgha giving the best response [37ndash41] Root andshoot dry weights were greatest when high nitrate-N toammonium-N ratio fertilizerswere employedwith high levelsof ammonium-N having an adverse effect [20]

A planting density of 75000 plantsh and nutrient dosecomprising a mixture of 15 tha farm yard manure (FYM)plus 80 kgha N with irrigation (4-5 times) or 15 tha FYM +40 kgha N under rainfed conditions are recommendedregimes in India Dry yield (DY) was reported at 18 thafor leaves and 08 tha for roots [42] 306 tha DY could beobtained with N P (P

2O5) and K (K

2O) application at a rate

of 150 40 40 kgha [40] Mineral nutrition can increase theyield and the alkaloid content in periwinkle [43] Nitrogenfertilization has been found to increase leaf and root yieldssignificantly Alkaloids are nitrogenous compounds there-fore nitrogen may play an important role in the biosynthesisand accumulation of alkaloids in plants [40]


Table 2 Genetic diversity in Catharanthus roseus accessions using different marker systems

NUA1 Type of marker(s) Clusteringmethod

Similarityindices Ranges Genetic

variationReferences

8 RAPD2 UPGMA7 NP 86ndash100 Low-moderate [159]

8 AFLP3 UPGMA NP 85ndash100 Low-moderate [159]

8 1H NMRlowast UPGMA NP 0ndash3 Moderate [159]

8 Chemical (ion content) UPGMA Euclideandistance 32ndash100 High [160]

14 ISSR4 SAHN8 Jaccard 057ndash100 Moderate [161]

14 RAPD SAHN Jaccard 04ndash097 High [161]

32 Morphochemicalphytochemical UPGMA Neirsquos 55ndash100 Moderate [131]

50 Phytochemicalenzymatic mdash Meancomparison mdash Highmoderate [162]

72 Isozymephytochemical NP9 Meancomparison NP Moderate [30]

40 ISSR mdash Neirsquos 015ndash09 High [163]

9 RAPDISSRSSR5 UPGMA Jaccard 019ndash073025ndash064026ndash073 High [164]

32 SSRSTMS6 UPGMA Nei and Lirsquos 007ndash079 High [165]1Number of used accessions 2RAPD random amplified polymorphic DNA 3AFLP amplified fragment length polymorphism lowast1H NMR hydrogen-1 nuclearmagnetic resonance 4ISSR intersimple sequence repeat 5SSR simple sequence repeat 6STMS sequence-tagged microsatellites sites 7UPGMA unweightedpair group method with arithmetic mean 8SAHN sequential agglomerative hierarchical nonoverlapping and 9NP not presented in the related reference

Planting distance 30 times 20 cm produced the highest foliageand root yields [44] Highest foliage yield was also reported at45 times 20 cm distance with an NPK 20 30 30 kgha formula-tion [45] An early June planting spacing at 30 times 50 cm NPKapplication of 150 40 30 kgha and a late September harvestare recommended for higher yields in Iran [41] The bestsowing date under temperate climatic conditions in Polandis the second half of May an optimum planting distance is 60times 60 cm while harvesting in early September is ideal [19 46]

52 Wild Types and Breeding Synthetic Cultivars There aretwo types of MP in the wild one with pink flowers andreddish stems and the other white flowers and green stemsoften found growing sympatrically MP has been bred sincethe 1920s [47] Over the past two decades conventionalbreeding techniques conducted by horticulturists and seedcompanies entailed crossing C roseus with other speciesthat resulted in a large number of marvelous new cultivarsor varieties Breeding not only improved floral traits suchincreasing color range blooms and size enhancing plantgrowth augmenting tolerance to disease and cooler growingconditions but also boosted herbage and alkaloid yield Forexample Dhawal white flower cultivar not only produces ahigher plant and alkaloid yield but also is dieback-tolerant[48] Nirmal white flower cultivar can endure salt and fungalinfection by Pythium aphanidermatum and Phytophthoranicotianae [15] and possesses a coveted leafless inflorescence(lli) architecture that increased the flower frequency [49]

The different cultivars are usually arranged in seriesand subsequent grouping is based on corolla color [50]Periwinkle plants now are readily available for gardenersworldwide in pink deep rose red scarlet white white with ared eye lavender blue peach apricot orchid burgundy and

many other shades An international register of Catharan-thus cultivars was published in 1998 There are few reliablecompendia on this topic and reliance has to be placed oninformation from the web Series and cultivars of MP [10 4751ndash54] are presented in Tables 3 and 4 respectively Thereare also nonseries selections that include Apricot DelightBlue Pearl ParasolMorningMistMerry-Go-Round FanfareOrchid Dwarf Little Salmon [55] Pink Panther [56] Santa Fe[57] and Snow Flake

There have been numerous studies performed on twovarieties rosea and alba of MP All the results revealed thatrosea is superior to alba in the overall performance of theplant Rosea has higher alkaloid content in leaves and rootsand more antioxidant activity than alba rosea fared muchbetter under water stress [58ndash60] Triadimefon treatmentincreased the antioxidant potential and alkaloid ajmalicinecontent in rosea more than in alba [61]

53 Horticulture MP is an easy growing and spreadingper ennial herb that has multitudinous horticultural usesdecoration annual ground cover bedding edging bordercontainer gardening mass planting naturalizing hangingbasket and wall cascade Surprisingly the herb is naturalisedfor medicinal purposes in many parts of the world whileit is considered as a weed or as an ornamental plant inthe other parts This conflict is the result of the MPrsquos longhistory as a horticultural variety especially over the pasttwo centuries [62] Horticultural practices caused changesin the distribution and biology of MP and this in turngenerated changes in peoplersquos valuation of the species [62]The new lines are novel in displaying an increased number offlowers on the inflorescence unhindered by leaves In the newfloricultural lines the overflowering ldquoLLIrdquo trait was combined


Table 3 Catharanthus roseus series

Series CharacteristicsCarpet Height 3-4 inches (76ndash102 cm) width 24 in (60 cm) dwarf great for groundcovers blooms all summer

Cobra Height 6ndash12 in (15ndash30 cm) spacing 6ndash9 in (15ndash22 cm) flower size 5-6 cm compact drought-tolerant suitablefor xeriscaping and growing in container

Cooler Height 10ndash14 in (30ndash35 cm) spread 15ndash20 cm low growing compact plants more tolerant of cool wetconditions vibrant colors

CoraHeight 14ndash16 in (35ndash40 cm) width 22ndash25 in (55ndash62 cm) large bold bright flowers first series to be resistant tothe ldquosudden deathrdquo bloom early heat tolerant Disease-resistant to the fungus (Phytophthora) causing aerialblight

Heat Wave Height 14ndash20 inches remarkable tolerance to heat and drought blooms early suitable for containers or hangingbaskets

First Kiss Height 10ndash14 in (28 cm) compact large-flowered (flower size 6 cm) and very heavy bloomingJaio Compact vigorous heat and drought tolerant disease-resistantLittle Height 10 to 14 in best used in small patio planters and decorative pots

Mediterranean Grows 5-6 inches tall cascading habit fairly vigorous excellent heat and drought tolerance performs well invery warm conditions many color combinations good for use in hanging baskets or window boxes

Nirvana Upright and cascading types resistant to the fungus causing aerial blight

PacificaHeight 14ndash20 in (35ndash50 cm) spread 15ndash20 cm open-pollinated group blooms early 2-inch flowers withoverlapping petals heat and humidity tolerant more stress tolerant on the bench and in the garden veryfloriferous

Pretty Height 12 inches (305 cm) compact multiflowered plants

Solar Heat and humidity tolerant ideal for early sowings early flowering perfect for packs and pots better diseasetolerant

Stardust Height 25ndash30 cm compact many flowered blooms have a star-shaped solid white center and bright petalborder

Sunstorm Large-flowered compact and tolerant of both hot and cool growing conditions

TitanHeight up to 16 in (35ndash40 cm) spread 10ndash12 in (25ndash30 cm) bushy growing habit vigorous moredisease-resistant than other Vinca series cool and drought tolerant earlier flowering has neat moundinghabits large-flowered flowers profusely highest seed quality

Tropicana Height 14ndash20 in fast-growing blooms early large rounded flowers heat and humidity tolerantTutti Frutti Large-flowered heat and drought tolerant

Victory Height 25ndash35 cm spread 15ndash20 cm intense clear colors compact growing habit disease tolerance low andearly basal branching formed large round flowers with overlapping petals

Viper Height 20ndash50 cm F1 Viper is the king of Vinca-vigorous large mounded plant covered in massive flowersVitesse Height 32ndash35 cm compact with basal branching ideal for early planting

with variation in plant height petal and eye colors andtolerance to the common fungal diseases [60]

54 Model Plant in Phytopathology MP acts as a uniquehost for a series of microorganisms such as bacteria andfungi Hence the herb serves as a model plant for studyingthe biology of microbial pathogenesis As an invaluablemodel indicator plant for mollicutes in plant pathologyMP has no peers It is an excellent experimental host formost phytoplasmas and spiroplasmas where high titres areachieved [63] MP is highly susceptible to phytoplasmainfection from different crops and exhibits highly distinctivesymptoms such as phyllody and virescenceThis popular herbis commonly used as a source plant to maintainmollicutes bygrafting dodder or vector transmission Infecting mollicutes

induce symptoms on this experimental host similar to thoseon the original hosts [64] MP has also been used as amodel plant to study the interaction between the endophytesMethylobacterium mesophilicum and Xylella fastidiosa [65]

6 Diseases and Management

61 Diseases Periwinkle plants are known to be susceptibleto the aster yellows (16SrI) group phytoplasma in Argentina[66] Egypt [67] India [68] Malaysia [69 70] and Myanmar[71] and have also been found to be naturally infected withspirea stunt (16SrIII-E) peach yellow leaf roll (16SrIII-A)clover proliferation (16SrVI) potato witchesrsquo broom (16SrVI-A) [72] Mexican periwinkle virescence (16SrXIII) [73] andMalaysian periwinkle virescence (16SrXXXII) [74 75] MP


Table 4 Available cultivars of Catharanthus roseus

Series CultivarsCarpet Rose Carpet Pink Carpet Magic Carpet

Cobra Cobra Apricot Cobra Orchid WEye Cobra Passion Fruit Cobra Peppermint Cobra Purple Cobra PurpleWEye Cobra Red Cobra Red WEye Cobra Rose Cobra Strawberry Red Cobra White

Cooler

Cooler Apricot Cooler Blush Cooler Coconut Cooler Deep Orchid Cooler Grape Cooler Hot Rose CoolerIcy Pink Cooler Lavender Halo Cooler Mixture Cooler Orchid Cooler Orchid Deep Cooler PeppermintCooler Peppermint Improved Cooler Pink Cooler Raspberry Red Cooler Red Cooler Rose CoolerStrawberry

Cora Cora Apricot Cora Burgundy Cora Deep Lavender Cora Lavender Cora Mix Cora Pink Cora Punch CoraViolet Cora White Cora Cascade Cherry Cora Cascade Lilac Cora Cascade Polka Dot

Heat Wave

Heatwave Apricot Heatwave Blue WEye Heatwave Burgundy Heatwave Cherry Heatwave Deep RoseHeatwave Formula Mixture Heatwave Grape Heatwave Midnight Mix Heatwave Orchid Heatwave PeachHeatwave Peppermint Heatwave Pink Heatwave Raspberry Heatwave Red Heatwave Rose Heatwave SantaFe Heatwave Southwest Mix Heatwave White

First KissFirst Kiss Apricot First Kiss Blueberry First Kiss Blush First Kiss Cherry red First Kiss Coral First Kiss IcyPink First Kiss Orchid First Kiss Peach First Kiss Polka Dot First Kiss Raspberry First Kiss Rose First KissRuby First Kiss Sunrise First Kiss Think Pink First Kiss White

Jaio Jaio Dark Red Jaio Scarlet EyeLittle Little Blanche Little Bright Eye Little Delicata Little Linda Little Pinkie

Mediterranean

Mediterranean Apricot Broadeye Mediterranean Cherry Red Halo Mediterranean Dark Red MediterraneanDeep Rose Mediterranean Deep Orchid Mediterranean Halo Mix Mediterranean Lilac Mediterranean MixMediterranean Peach Improved Mediterranean Peach XP Mediterranean Pink Mediterranean Polka DotMediterranean Red Mediterranean Rose Mediterranean Rose Red Mediterranean Rose Hot MediterraneanWhite Broadeye Mediterranean White Mediterranean Strawberry

NirvanaNirvana Cascade Lavender WEye Nirvana Cascade Orchid Nirvana Cascade Pink Splash Nirvana CascadeRose Nirvana Cascade Shell Pink Nirvana Cascade White Nirvana Pink Blush Nirvana Red Nirvana DarkRed

Pacifica

Pacifica Apricot Pacifica Blush Pacifica Burgundy Pacifica Burgundy Halo Pacifica Burgundy Pacifica CherryHalo Pacifica Cherry Red Pacifica Coral Pacifica Dark Red Pacifica Deep Orchid Pacifica Icy Pink PacificaLilac Pacifica Lipstick Mix Pacifica Magenta Halo Pacifica Mix Pacifica Orchid Halo Pacifica Peach PacificaPink Pacifica Polka Dot Pacifica Punch Pacifica Punch Halo Pacifica Raspberry Pacifica Really Red PacificaRed Pacifica Rose Halo Pacifica Pure White

Pretty Aureo-variegata Bowles

SolarSolar Apple Blossom Solar Apricot Solar Blueberry Solar Blush Pink Solar Cherry with Eye Solar FormulaMixture Solar Fresh Red Solar Lilac Solar Orange with Eye Solar Orchid with Eye Solar Pink SolarRaspberry with Eye Solar Red Solar Red with Eye Solar White

Stardust Stardust Orchid Stardust Pink Stardust Mix Stardust Rose

Sunstorm Sunstorm Apricot Sunstorm Bright Red Sunstorm Blush Sunstorm Lilac Sunstorm Orchid Sunstorm PinkSunstorm Rose WEye Sunstorm Violet WEye Sunstorm White WEye

TitanTitan Apricot Titan Blush Titan Burgundy Titan Cotton Candy Mix Titan Dark Red Titan Icy Pink TitanLavender Blue Halo Titan Lilac Titan Mix Titan Polka Dot Titan Punch Titan Pure White Titan Rose TitanWhite

Tropicana Tropicana Apricot Tropicana Blush Tropicana Bright Eye Tropicana Pink Tropicana RoseTutti Frutti Agastache Rose

VictoryVictory Apricot Victory Blue Victory Bright Eye Victory Carmine Victory Carmine Rose Victory CranberryVictory Deep Apricot Victory Deep Pink Victory Grape Victory Lavender Victory Light Pink Victory PureWhite Victory Purple Victory Red

Viper Viper Apricot Viper Grape Viper Orchid Halo Viper Pink Viper Purple Viper Purple Halo Viper Red ViperRed WEye Viper Rose Viper Watermelon

Vitesse

Vitesse Apricot Vitesse Blush Vitesse Cranberry Vitesse Fuchsia Vitesse Grape Vitesse Hot Pink VitesseLavender Vitesse Orange Vitesse Orchid Vitesse Peach Vitesse Peppermint Vitesse Pink Vitesse PurpleVitesse Raspberry Vitesse Red WEye Vitesse Rose Vitesse Strawberry Red Vitesse Strawberry Twist TropicalOrange Vitesse White


was the first nonrutaceous plant found naturally infectedwithSpiroplasma citri in the United States [76] This pathogenwas subsequently discovered in Mediterranean countriesincluding Morocco Syria Cyprus and Turkey [77] and inSoutheast Asia Malaysia [78] Periwinkle is also known to besusceptible to the cucumbermosaic virus (CMV) and diseaseincidence has been reported in Australia [79] India [80] andMalaysia [81]

Bedding plants such as periwinkle are susceptible tomanydamping-off diseases MP is prone to blight canker leaf spotand root rot Pathogenic fungi include Alternaria (leaf spot)Rhizoctonia solani (stem crown and root rot) and Phy-tophthora parasitica Dast (foliars and stems) P parasiticaa soilborne fungus causes serious losses and death in theperiwinkle with reports from India and theUnited States [82ndash85] Fusarium root rot has been reported from Taiwan [86]Blight caused by P nicotianae (syn = P parasitica) is one ofthe most damaging diseases of MP in Florida [87] Otherknown blights include twig blight caused by Colletotrichumdematium [88] foliar blight brought about by P tropicalisin Virginia [89] and gray mold blight affected by Botrytiscinerea in the United States Italy and Taiwan [90ndash92] Otherfungi identified to incite disease in periwinkle seedlings inTaiwan include Botrytis cinerea Colletotrichum gloeospori-oides Fusarium oxysporum F solani P parasitica Pythiumaphanidermatum Rhizoctonia solani Sclerotinia sclerotio-rum and Sclerotium rolfsii [92] Black root rot throughThielaviopsis infection is the most serious root disease inMP because it is very difficult to control [47] Periwinklerust due to Puccinia vincae attack (httpdonsgardencouk)is another disease to be noted Fungal problems can occurunder humid or wet conditions so care has to be exercisedto prevent overwatering Insect pests are no major concernalthough aphids thrips spider mites mealy bugs and scaleinsects can infest this plant [47]

62 Disease Management Environmentally a full-sun plant-ing location reduced humidity levels and increased aircirculation around the plants should be targeted Pottingmixes have to be pathogen-free and new containers preparedfor each planting Sanitation-wise weeds should be keptdown infected soils and plants removed immediately upondetection all equipment kept clean and the planting areacleared of old potting media and plant debris In fertilizationand irrigation avoid heavy fertilization and overwatering ofplants Overhead irrigation and prolonged periods of leafwetness should be avoided with watering done only duringthe day Soil fertility has to be properly adjusted to pHmaintained at 55 Transplants need to be spaced at least10ndash12 inches apart Biocontrol of soilborne fungal pathogenscould be attempted with Trichoderma virens binucleateRhizoctonia or Burkholderia cepacia [47 87 93ndash96]

7 Phytochemistry

Two commercially and pharmacologically important cyto-toxic dimeric alkaloids of MP vinblastine and vincristinehave been widely used for cancer chemotherapy which areonly present in extremely low yields in the leaves [31]

The three-dimensional structure of these two compounds hasbeen featured in Figures 2(a)-2(b) In addition to alkaloidsand phenolics (as themost important compounds ofMP) thepresence of different chemical groups such as polyphenolsalkaloids steroids flavonoid glycosides anthocyanins andiridoid glucosides has been confirmed in different parts ofMP [97] However some evidence implicates the availabilityof similar compounds in the leaves and stems of the plantbut the same does not comply with the contents of seeds andpetals [98] Flower extract of MP has been used as a naturalacid-base indicator [99 100]

71 Major Alkaloids All parts of the plant contain severalactive alkaloids with an indole moiety More than 130 indolealkaloids collectively termed terpenoid indole alkaloids(TIAs) have been extracted from periwinkle [31 101ndash104]Some of these alkaloid compounds have distinct medicinalproperties The alkaloid content is highest at the floweringstage [50] The principal alkaloids present in the aerial(nonfloral) parts are VBL (vincaleukoblastine VLB) VCR(leurocristine vincaleurocristine) vincarodine vincolineleurocolombine viramidine vincathicine vincubine isosit-sirikine vincolidine lochrovicine catharanthine vindolineleurosine lochnerine tetrahydroalstonine and vindolinineAjmalicine (raubasine) serpentine and reserpine are themain alkaloids in the root while coronaridine 11-methoxytabersonine tetrahydroalstonine ajmalicine vindorosidineand vincristine dominate in the flower However of the overhundred alkaloids discovered only five consisting of vinblas-tine vincristine 3101584041015840-anhydrovinblastine serpentine andajmalicine are marketed [102] Other Catharanthus speciessuch as C longifolius C trichophyllus and C lanceus areknown to possess vindoline type alkaloids

72 Major Phenolics Phenolic compounds are a group ofmetabolites available in all plant species These compoundscan range from simple compounds bearing just one phenolichydroxyl to some more complex ones like flavonoids whichare often polyphenols Besides alkaloids MP produces awide spectrum of phenolic compounds with radical scav-enging ability including C6C1 compounds such as 23-dihydroxybenzoic acid as well as phenylpropanoids such ascinnamic acid derivatives flavonoids and anthocyanins [97]Mustafa and Verpoorte [97] have listed the most impor-tant phenolic compounds of MP including 23-DHBAGSA SAG benzoic acid 25-DHBA and 25-DHBAG gallicacid glucovanillin vanillic acid glucovanillic acid vanillylalcohol vanillyl alcohol-phenyl-glucoside C6C3conjugatedC6C3 trans-cinnamic acid hydroxytyrosol ferulic acidchlorogenic acid C6C3C6conjugated C6C3C6 kaempferoltrisaccharides quercetin syringetin glycosides malvidinmalvidin 3-O-glycosides malvidin 3-O-(6-O-p-coumaroyl)petunidin petunidin 3-O-glucosides and petunidin 3-O-(6-O-p-coumaroyl)

8 Phytobioactivity

81 Ethnobotanical Importance Decoctions of MP are men-tioned in folklore remedies for treatment of diabetes malaria


(a) (b)

Figure 2The three-dimensional structures of themain anticancer compounds ofMP (a) vincristine and (b) vinblastine in a ball-stickmodel(httpwwwchemspidercomImageView)

[105] dengue fever dysentery [106] insect bites [107] skininfection diarrhea leukemia eye irritation dyspepsiadysentery toothache sore throat and lung congestion [106]The root of the plant is reported to be a tonic and possesshypotensive sedative and tranquillizing properties [108]In Ayurveda it is used for treating diabetes Hypoglycemicactivity of aqueous extracts from MP has been proved inmodern studies as well [109] In Madagascar the bitter andastringent leaves have been applied as an emetic roots havebeen used as a purgative vermifuge depurative hemostaticagent and toothache remedy In the Philippines the leafdecoction is an herbal treatment for diabetes young leavesare for stomach cramps and root decoction is for intestinalparasitism Mauritians employ infusion of leaves for indiges-tion and dyspepsia In India (Orissa and Assam) juices fromthe leaves are used to treat wasp stings while roots and leavesare utilized as anticarcinogenic agents [18 110]

MP floral extracts enjoy wide usage in many countriesas a remedy for many ailments Cuba and Jamaica eyewashfor infants Bahamas asthma Bermuda high blood pres-sure Indo-China dysmenorrhea Surinam and throughoutthe Caribbean eye irritationinfections malaria menstrualpains and diaphoresis Ugandans put faith in leaf infusions totreat stomach ulcers while Batswana ground leaves inmilk formature abscesses In Togo a root decoction is taken to treatdysmenorrhoea [18 110] Even in developed countries such asEuropeMP is used as a folk remedy for diabetes for centuriesInHawaii the plant is boiled tomake a poultice stop bleedingThe Chinese have widely applied this versatile herb in thetreatment of leukemia hypertension lymphosarcoma andgiant follicular lymphoma while adapting it as an astringentdiuretic and cough remedy Similarly in central and southAmerica it is popular as a homemade cold remedy toease lung congestion inflammation and sore throat whileit is trusted as an alternative medical treatment source forleukemia inHongKong andKorea Japan has targetedMP forarresting diabetes and malignant lymphatic tumours [111] In

addition modern research has revealed a broad spectrum ofmedicinal applications for the herb (Table 5)

82 Toxicity and Side Effects MP can be dangerous if con-sumed orally It can be hallucinogenic and is cited as such(under its synonym Vinca rosea) in the Louisiana StateAct 159 TIAs have been applied clinically since the end ofthe 1950s as major drugs in the treatment of acute lym-phoblastic leukemia non-Hodgkin lymphomas myelomaandHodgkin lymphoma [112]Despite their benefits all of theMP alkaloids have neurotoxic activity especially vincristineaffecting neurotransmission [113] Vincristine and vinblastineare highly toxic antimitotics blocking mitosis in metaphaseafter binding to the microtubules [114] Moreover many sideeffects have been reported for these drugs comprising myelo-suppression alopecia abdominal cramps constipation nau-seavomiting paralytic ileus ulcerations of the mouth hep-atocellular damage kidney impairment pulmonary fibrosisurinary retention amenorrhoea azoospermia orthostatichypotension and hypertension [113 115 116] The dosage andadministration must be carefully controlled to reduce sideeffects [112]

83 Formulations and International Trade The two key phar-maceutical dimeric alkaloid compounds VBL andVCR existmainly in the aerial parts of the plant in extremely lowconcentrations the latter quantitatively much less than theformer [50 117ndash119] Vincristine sulfate originally knownas leurocristine is the only effective antileukemic drug thatreduces white blood cell count drastically since the 1950s ithas increased the survival rate of childrenwith leukemia from20 to 80 It is one of the most expensive plant products onthe market with considerable side effects Vinblastine simi-larly decreases the quantity of white blood cells in the blood[112] Vinblastine sulfate has now been marketed for morethan 40 years as an anticancer drug It has proven effectiveagainst Hodgkinrsquos disease Vincristine sulfate and vinblastine


Table 5 List of the most important studies on the medicinal effects of Catharanthus roseus

ApplicationModern researches References

In vitro In vivoAcetylcholinesterase and cholinergicantagonism inhibition Microplate assay Male Wistar ratslowast [166 167]

Alzheimerrsquos syndrome Human (clinical trial) [168]Anthelminthic activity Pheretima posthuma [169]Antiandrogenic activity Mice [170]Antiangiogenesis activity Chicken eggs [171]Antibacterial (antiseptic) activity Bacteria [106 172ndash175]Antidysenteric activity Wistar rats [176]Antifertility effect Male rat [115 177 178]

Antifungal activity Trichophyton rubrumHendersonula toruloidea

[179 180]

Antihyperglycemic activity (antidiabetic) Mice rat rabbit Wistar albino rats [109 181ndash188]Antihypercholesterolemic activity(antihyperlipidemic) Rabbit rat [184 189]

Anti-inflammatory activity Rat [189]Antimutagenic activity Micronucleated erythrocytes [190]Antineoplastic activity Mice rat Clinical use [113 191ndash198]Antioxidant activity Rat [61 184 199]Antiplasmodial activity Human erythrocytes [200 201]Antiproliferative activity Human cells [202 203]Antispermatogenic Male rat mice [204 205]Blood cleanser [206]Cytochrome P450 inhibition CYP2D6 [207]Cytotoxic activity Human cell line [208 209]Enhances kidney and liver functions Wistar rat [185 210]Epididymal dysfunction Rat [211]Generate giant spermatogonial cells Albino rat [212]Hypotensive activity Rat [108]

Larvicidal activity Anopheles stephensi (malariavector) Aedes aegypti

[213 214]

Regression of accessory reproductiveorgans Male Wistar rats [215]

Regression of entire reproductive system Male rat [216]Stomachic mdash [108 217]Tonic mdash [108 217]Tranquilizing and sedative action mdash [101 108 217]Wound healing Rat [218]lowastThe research was done ex vivo

sulfate are being sold for a total US$ 100 million per year[50 120] Developing food stuff incorporated by fresh leavesofMP gives rise to the economic importance of the herbwhilesuch products possess both pharmaceutical and nutritionalproperties simultaneously [121]

These injectable drugs and their semisynthetic analoguessuch as vinorelbine (VRLB) and vindesine (VDS) interferewith the division of cancer cells [31 122ndash126] Navelbine(51015840-noranhydrovinblastine) is a semisynthetic vinca alkaloid

with complete microtubule depolymerization ability broaderantitumor activity and a lower neurotoxicity than VBL andVCR because it selectively interferes with tubulin assembly[127] Fully synthetic vincristine is far less efficient (only20 efficiency) compared to the natural product derivedfrom MP and hence the importance of the species and itsbioactive compounds is unchallenged owing to their complexstructures [119] The other valuable therapeutic alkaloidldquoajmalicinerdquo is a constituent of hypotensive drugs employed


in the treatment of high blood pressure Two to three hundredtons of MP roots is required for 3600Kg annual worldproduction of ajmalicine [119]

9 Promising Horizons in Biosynthesis ofthe Phytochemicals

91 TIAs Pathways Studies There are two different metabolicpathways for the biosynthesis of terpenoids leading to the for-mation of the C

5central precursor isopentenyl diphosphate

(IPP) namely the classical cytosolic mevalonate pathwayand the mevalonate-independent plastidic 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway The biosynthesisof MP TIAs starts with the condensation of tryptamine(shikimate pathway) and secologanin (MEPpathway) to formthe key intermediate strictosidine the common backbonestructure of all TIAs [128] However the alkaloid pathway inMP and the involved genes remain partly unknown [128] butgene-to-metabolite networks studies for understanding thebiosynthesis of TIAs in MP using the cDNA-amplified frag-ment length polymorphism (AFLP) markers have revealedvaluable information [129] At the same time the drawnnetworks increase the practical potential of metabolic engi-neering of MP

92 Cell and Tissue Culture VBL andVCR are only producedin very low concentrations in MP The high therapeutic valueand cost of production of the minute amounts of these bis-indole alkaloids (VBL and VCR) have prompted extensiveefforts to increase their levels by cell-tissue culture andmutation induction [130ndash132] In vitro methods such as cellsuspension hairy root and callus cultures shoot culturesmetabolic engineering and regulation studies to improvethe phytochemicals production are uncontested shortcutstrategies to those time-consuming conventional breedingmethods In other words when there is a high demand forplant-based pharmaceutics and only low amounts accumu-late in plants plant cell cultures have shown to be an efficientalternative production system of valuable phytochemicals ona large scale Rapid reproduction and preservation of naturalsources are of the beneficial points of such an approach[133] Plant growth regulators (PGRs) activate plant naturaldefence mechanisms thereby leading to increase the biosyn-thesis of the secondary metabolites in plants In this regardapplication of PGRs like methyl jasmonate (MeJA) dimethylsulfoxide (DMSO) jasmonates and salicylic acid as elicitorsof secondary metabolites has led to positive results in recentexperiments [128 134 135] Isolation of VBL and VCR usingcallus culture [136] cell culture [137] shoot culture [138]semisynthetic [139] and totally synthetic approaches [140] iscurrently considered Unfortunately drug supplementationusing the aforementioned techniques is limited and cannotmeet the existing requirements Application of artemisinicacid as a useful elicitor has recently been highlighted insuspension-cultured cells of MP [141]

93 Plant-Fungal Symbiotic Fashion As mentioned despitea nonstop explorative trend the desired level of productionof the bioactive compounds such as VBL and VCR has still

not been achieved at optimum level [142] For this reasonisolation of endophytic fungi from the MP plant has beentaken into consideration as an alternative solution morerecently [143] Investigations on the pathobiology of thespecies have led to very exciting results Mechanisticallyendophytic fungi reside in a symbiotic fashion inside peri-winkle plant imitate their chemistry and produce the samenatural products as their hosts and are thus being screened forthe production of themost valuable anticancer compounds ofthe herb namely VBL and VCR In line with this researcherstook the first steps toward producing VCR using Fusariumoxysporum an endophyte of MP [144 145] Later on Guoand Kunming [146] obtained VBL by Alternaria speciesisolated from the same plant found in China and showedthe production based upon thin layer chromatography (TLC)and high performance liquid chromatography (HPLC) onlyEventually the latest innovation in this area happened byemploying the same endophytic fungus (F oxysporum strainAA-CRL-6) for isolation of both anticancer compoundsVBLand VCR in appreciable amounts successfully [147]

94 Functional Genomics and Proteomics Exploration Thebiosynthesis of VBL includesmore than 20 enzymatic phasesin which nine out of 20 are now well characterized at theenzyme and gene level and several regulatory genes of thepathway (ORCAs) have also been cloned [148] Proteomicanalysis of the plant using two-dimensional electrophoresisled to the identification of 58 proteins including two iso-forms of strictosidine synthase (EC 4332) which catalyzethe formation of strictosidine in the alkaloid biosynthesistryptophan synthase (EC 41128) which is required as asupplying source of the alkaloid precursor tryptamine 12-oxophytodienoate reductase which is indirectly involvedin the alkaloid biosynthesis as it catalyzes the last stepin the biosynthesis of the regulator jasmonic acid [149]Recently scientists have detected a higher number of proteinsusing two-dimensional differential in gel electrophoresis(2D-DIGE) technique in two different lines of the herb358 proteins in one and 1663 in another line most ofwhich corresponded to housekeeping proteins or involved inprimary metabolism [150] Of these a total of 63 enzymesonly potentially involved in secondary metabolism of which22 were related to TIAs biosynthesis and 16 were predictedtransporters putatively involved in secondary metabolitetransport As amatter of fact these results are important stepstowards elucidating the proteome of MP which are essentialto understanding the modality of TIAs biosynthesis [150]

941 Transformation of Specific Genes Quantitative analysisof metabolic pathways in MP revealed that metabolicallyengineered hairy roots can lead to overproduction of TIAs[151] Recent studies are focused on cloning characterizationand transformation of the genes involved with the relatedbiosynthetic cycles such as CrPrx1 that belongs to an evolu-tionary branch of vacuolar class III peroxidases [148]

942 Transformation of Genes Affecting the IntermediateCompounds Recent genetic engineering of MP not only islimited to the genes enhancing the VBL and VCR production


directly but also includes the genes augmenting the biosyn-thesis of the intermediate compounds such as vindoline animportant intermediate leading to VBL and VCR Genessuch as desacetoxyvindoline-4-hydroxylase-like (d4h-like)ORCA3 (octadecanoid-derivative responsive CatharanthusAP2-domain) and G10H (geraniol 10-hydroxylase) are suit-able examples of the aforementioned trend [152 153]

943 Application of Reverse Genetics for Gene IdentificationThe concept of ldquoreverse geneticsrdquo is widely used for charac-terization of plant enzymes (more precisely genes encodingenzymes involved in alkaloid metabolism) in which thepartial sequencing of proteins is carried out after purificationof the isolated enzymes from plants or plant cell culture bytraditional biochemical chromatography techniques Thesesequences are consequently used to identify the correspond-ing gene from a plant cDNA library [154] Homology-basedcloning of candidate genes and their succeeding functionaltesting in heterologous expression systems are hastening thepace at which the gene catalogues of alkaloid biosynthesisare developing For example putrescineN-methyltransferasethe first enzyme in the nicotine-specific pathway and anisoflavone reductase-like enzyme putatively involved in nico-tine biosynthesis are both expressed specifically in the cortexand endodermis of tobacco root tips However intenseexpression of these enzymes shifts to the xylem parenchymaand outer cortex cells in more differentiated parts of theroot [155] This developmentally regulated spatial expressionpattern may be complicatedly associated with nicotine dis-semination in tobacco tissues and organs Tropane alkaloidsas well as nicotine are mainly synthesized in the root andtransported to aerial parts where they accumulate in vacuolesat high levels Analysis of xylem saps taken from the stemshows that these alkaloids are transported via the xylem [156]

944 Promoter Engineering The gene transformation pro-cedure not only is limited to transferring the genes withthe ldquoconstitutiverdquo promoters but also can be implementedby fusing the ldquoregulatedrdquo promoters to the target gene Thebest example of the mentioned process is the agrobacterium-mediated transformation of the hydroxymethylbutenyl 4-diphosphate synthase gene (HDS) from the methyl erythritolphosphate (MEP) pathway by replacing an HDS-GUS fusedpromoter with the constitutive CaMV35S promoter Thefunctional characterization of the transformed cells con-firmed the induction of HDS promoter by several hormonalindicators (auxin cytokininmethyl jasmonate and ethylene)leading to the MIAs production in MP [157]

945 Gene Silencing Conceivably one of the most advancedtechnologies to scrutinize the MIAs metabolism in MP isthe virus-induced gene silencing (VIGS) strategy by estab-lishing tobacco rattle virus- (TRV-) based approach [158]Secologanin is a versatile iridoid and a precursor for theassembly of countless MIAs as well as a number of quinolinealkaloids In a very recent attempt employing the VIGS-based method led to the identification of the 7-deoxyloganicacid 7-hydroxylase (CrDL7H) gene involved in the third to

the last step of secologanin biosynthesis [121] Silencing thementioned gene reduced the level of secologanin up to at least70 and increased the level of 7-deoxyloganic acid to over4mg gminus1 fresh leaf weight compared with the control plantsin which this iridoid is not detected Functional expressionof this gene confirmed its priority as a specific substrate for7-deoxyloganic acid compared to other related substratesTherefore it seems that hydroxylation precedes carboxy-O-methylation in the secologanin pathway leading to the MIAsbiosynthesis in C roseus [121]

10 Conclusion

Nowadays the demand for natural products and plant-based medicines is growing throughout the world MP is aremarkable herb owing to its broad spectrum of applicationsApart from its natural supply of anticancer compounds formedicine on the international market it ranks highly as apopular ornamental plant in the horticultural industry andas a model plant for studies in phytopathology as well asbiotechnology The ultimate goal of current research is toproduceMP disease-resistant cultivars with a high content ofantitumor alkaloids Several cultivars have been introducedprimarily as ornamental plants with their alkaloid com-position agronomic performance and genetic affiliationsunknown As such agronomic and genetic elucidation of newcultivars with exploration of their physiology and secondarymetabolism are required for achieving a high quantity andquality output of TIAs It is unfortunate that MP anticancerdrugs have several adverse side effects This renders furtherexploration of the clinical pharmacokinetics of MP alkaloidsand drug-drug interactions indispensable

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

References

[1] M Faheem S Singh B S Tanwer M Khan and A ShahzadldquoIn vitro Regeneration of multiplication shoots in Catharanthusroseusmdashan important medicinal plantrdquo Advances in AppliedScience Research vol 2 pp 208ndash213 2011

[2] F E Koehn andG T Carter ldquoThe evolving role of natural prod-ucts in drug discoveryrdquo Nature Reviews Drug Discovery vol 4no 3 pp 206ndash220 2005

[3] A Valdiani M A Kadir S G Tan D Talei M P Abdullah andS Nikzad ldquoNain-e havandi Andrographis paniculata presentyesterday absent today a plenary review on underutilized herbof Iranrsquos pharmaceutical plantsrdquo Molecular Biology Reports vol39 no 5 pp 5409ndash5424 2012

[4] P J Facchini ldquoAlkaloid biosynthesis in plants biochemistrycell biology molecular regulation and metabolic engineeringapplicationsrdquo Annual Review of Plant Biology vol 52 pp 29ndash66 2001

[5] P J Facchini and V de Luca ldquoOpium poppy and Madagascarperiwinkle model non-model systems to investigate alkaloid


biosynthesis in plantsrdquoThePlant Journal vol 54 no 4 pp 763ndash784 2008

[6] S Kohlmuzer ldquoAlkaloids of Catharanthus roseus (L) G Don-a new group of biologically active compoundsrdquo Postepy Bio-chemii vol 14 no 2 pp 209ndash232 1968

[7] J Roepke V SalimMWu et al ldquoVinca drug components accu-mulate exclusively in leaf exudates of Madagascar periwinklerdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 107 no 34 pp 15287ndash15292 2010

[8] D Whiting A OrsquoConnor J Jones L McMulkin and L PottsldquoTaxonomic Classificationrdquo CMG GardenNotes vol 122 pp 1ndash8 2011

[9] A C Plaizier ldquoA revision of Catharanthus roseus (L) G Don(Apocynaceae)rdquoMededelingen Landbouwhogeschool vol 81 no9 pp 1ndash12 1981

[10] M A van Bergen ldquoRevision of Catharanthus roseus G Donseries of revisions of Apocynaceae XLIrdquo Agricultural Universityof Wageningen Papers vol 96 no 3 pp 9ndash46 1996

[11] IPNI (The International Plant Names Index) 2008 httpwwwipniorg

[12] Royal Botanic Gardens Kew Resource Page httpwwwkeworgdatasubjectshtml

[13] USDA Plant Data Base httpplantsusdagov[14] J Aslam S H Khan Z H Siddiqui et al ldquoCatharanthus roseus

(L) G Don an important drugs itrsquos applications and produc-tionrdquo Pharmacie Globale vol 4 no 12 pp 1ndash16 2010

[15] S Chaudhary V Sharma M Prasad et al ldquoCharacterizationand genetic linkage mapping of the horticulturally importantmutation leafless inflorescence (LLI) in periwinkle Catharan-thus roseusrdquo Scientia Horticulturae vol 129 no 1 pp 142ndash1532011

[16] Y Sreevalli R N Kulkarni and K Baskaran ldquoInheritance offlower color in periwinkle orange-red corolla and white eyerdquoJournal of Heredity vol 93 no 1 pp 55ndash57 2002

[17] P P Joy JThomas SMathew and B P SkariaMedicinal PlantsKerala Agricultural University 1998

[18] PROTA Plant Resources of Tropical Africa African Ornamen-tals Proposals and Examples PROTAFoundationWageningenThe Netherlands 2011

[19] B Łata ldquoCultivation mineral nutrition and seed production ofCatharanthus roseus (L) G Don in the temperate climate zonerdquoPhytochemistry Reviews vol 6 no 2-3 pp 403ndash411 2007

[20] P A Thomas and J G Latimer ldquoGrowth of vinca as affected byform of nitrogen presence of bark and type of micronutrientsrdquoJournal of Plant Nutrition vol 18 pp 2127ndash2134 1996

[21] G V A Balamani and R S Rao ldquoIn chromosome numberreports LXXIIIrdquo Taxon vol 30 pp 855ndash856 1981

[22] M S Mendioro M Q D Diaz M T B Alcantara O JHilario P Mateo and R D M Maghirang ldquoCytological studiesof selected medicinal plants Euphorbia pulcherrina Willd ExKlotz Moringa oleifera Lam Catharanthus roseus (L) Donand Chrysanthemum indicum Linnrdquo The Philippine Journal ofScience vol 134 pp 31ndash37 2005

[23] V R Dnyansagar and I V Sudhakaran ldquoInduced tetraploidy inVinca rosea Lrdquo Cytologia vol 35 pp 227ndash241 1970

[24] K-X Tang S-H Xing X-B Guo et al ldquoInduction andflow cytometry identification of tetraploids from seed-derivedexplants through colchicine treatments in Catharanthus roseus(L) GDonrdquo Journal of Biomedicine andBiotechnology vol 2011Article ID 793198 10 pages 2011

[25] R N Kulkarni Y Sreevalli K Baskaran and S Kumar ldquoThemechanism and inheritance of intraflower self-pollination inself-pollinating variant strains of periwinklerdquo Plant Breedingvol 120 no 3 pp 247ndash250 2001

[26] R N Kulkarni Y Sreevalli and K Baskaran ldquoAllelic differencesat two loci govern different mechanisms of intraflower self-pollination in self-pollinating strains of periwinklerdquo Journal ofHeredity vol 96 no 1 pp 71ndash77 2005

[27] R N Kulkarni and K Baskaran ldquoFrom herkogamy tocleistogamymdashdevelopment of cleistogamy in periwinklerdquo Jour-nal of Heredity vol 104 no 1 pp 140ndash148 2013

[28] Y Sreevalli K Baskaran R N Kulkarni and S Kumar ldquoFurtherevidence for the absence of automatic and intra-flower self-pollination in periwinklerdquo Current Science vol 79 no 12 pp1648ndash1649 2000

[29] P Albers and L J G van der Maesen ldquoPollination of Apocy-naceaerdquo Agricultural University Wageningen Papers vol 3 pp61ndash81 1994

[30] M Sevestre-Rigouzzo C Nef-Campa A Ghesquiere and HChrestin ldquoGenetic diversity and alkaloid production in Catha-ranthus roseus C trichophyllus and their hybridsrdquo Euphyticavol 66 no 1-2 pp 151ndash159 1992

[31] R van der Heijden D I Jacobs W Snoeijer D Hallard and RVerpoorte ldquoThe Catharanthus alkaloids pharmacognosy andbiotechnologyrdquo Current Medicinal Chemistry vol 11 no 5 pp607ndash628 2004

[32] R Zarate and R Verpoorte ldquoStrategies for the genetic modifi-cation of the medicinal plant Catharanthus roseus (L) G DonrdquoPhytochemistry Reviews vol 6 no 2-3 pp 475ndash491 2007

[33] R Gupta ldquoPeriwinkle-produces anticancer drugrdquo Indian Farm-ing vol 7 pp 11ndash13 1977

[34] S K Parrek S Singh V K Srivastava S Mandal M LMaheswari and R Gupta ldquoAdvances in periwinkle cultivationrdquoIndian Farming vol 31 pp 18ndash21 1981

[35] A Sadowska G Obidowska and M Szacho-GuchowiczldquoWpływ nawozenia NPK na masę ziela oraz zawartosc alka-loidow u Catharanthus roseus (L) G Donrdquo Biuletyn IHAR vol170 pp 55ndash63 1989

[36] M Shamim S R Voleti R LMisra and S P S Raghava ldquoInflu-ence of temperature on seed germination in three ornamentalspeciesrdquo Journal of Ornamental Horticulture vol 2 pp 89ndash911999

[37] B R Rajeswara Rao andM Singh ldquoEffect of NPK fertilizers andspacing on periwinkle (Catharanthus roseus) under irrigatedand rained conditionsrdquo Herba Hungarica vol 29 pp 1ndash2 1990

[38] M R Shylaja M A Sankar G S Nair and K A MercyldquoResponse of Catharanthus roseus L (G Don) to nitrogenphosphorus and potassium fertilizationrdquo Indian Cocoa Are-canut and Spices Journal vol 20 pp 83ndash88 1996

[39] M R Shylaja A Ashashankar and G S Nair ldquoEffect of N Pand K on the leaf alkaloid content in Catharanthus roseus L (GDon)rdquo Indian Journal of Horticulture vol 46 pp 192ndash195 1998

[40] Y Sreevalli R N Kulkarni K Baskaran and R S Chan-drashekara ldquoIncreasing the content of leaf and root alkaloids ofhigh alkaloid content mutants of periwinkle through nitrogenfertilizationrdquo Industrial Crops and Products vol 19 no 2 pp191ndash195 2004

[41] Z Gholamhosseinpour K Hemati H Dorodian and Z Bashir-Sadr ldquoEffect of nitrogen fertilizer on yield and amount ofalkaloids in periwinkle and determination of vinblastine andvincristine by HPLC and TLCrdquo Plant Sciences Research vol 3pp 4ndash9 2011


[42] S Maiti ldquoInventory documentation and status of medicinalplants research in Indiardquo in Medicinal Plants Research in AsiaVolume I The Framework and Project Workplans P A BatugalJ Kanniah S Y Lee and J T Oliver Eds p 89 InternationalGenetic Resources Institute-Regional Office for Asia the Pacificand Oceania (IPGRI-APO) Selangor Malaysia 2004

[43] B K Jana and B Varghese ldquoEffect of mineral nutrition ongrowth and alkaloid content of Catharanthus roseusrdquo IndianAgriculture vol 40 pp 93ndash99 1996

[44] B N Dahatonde ldquoEffect of non-monetary inputs on the yield-ing performance of periwinkle (Catharanthus sp)rdquo AncientScience of Life vol 5 pp 65ndash67 1985

[45] P P Khode P U Ghatol S A Bhuyar D D Deo and VM Dhumal ldquoPerformance of Vinca rosea (Catharanthus SPP)to different fertility and irrigation levelsrdquo Agricultural ScienceDigest vol 20 no 2 pp 135ndash136 2000

[46] Z Staszewski Z Bodzon and B Lata ldquoPossibilities and limi-tations of seed production of Catharanthus roseus (L) G Donunder Polish climatic conditionsrdquo Phytochemistry Reviews vol6 no 2-3 pp 397ndash402 2007

[47] P A Thomas J Woodward F E Stegelin and S V Pennisi AGuide for Commercial Production of Vinca Bulletin 1219 2009

[48] R N Kulkarni K Bhaskaran R S Chandrashekhara et alldquoDhawal-a high alkaloid producing periwinkle plantrdquo USAPatent 6548746

[49] S Kumar S P Rai S K Rai D V Singh S Srivastava and RK Mishra ldquoPlant variety of Catharanthus roseus named lsquollirsquordquoUnited States Patent PP18315 2007

[50] G H Schmelzer and A Gurib-Fakim Plant Resources of Trop-ical Africa Medicinal Plants PROTA Foundation BackhuysCTA Wageningen The Netherlands 2008

[51] T K Howe and W E Waters ldquoEvaluation of Catharanthusroseus (Vinca) cultivars for the landscaperdquo in Proceedings of theFlorida State Horticultural Society vol 107 pp 404ndash408 1994

[52] W Snoeijer ldquoCatharanthus roseus the Madagascar Periwinklea review of its cultivarsrdquo Agricultural University WageningenPapers vol 96 pp 47ndash120 1996

[53] W Snoeijer International Register of Catharanthus roseusLeidenAmsterdam Centre for Drug Research Division ofPharmacognosy Leiden The Netherlands 2001

[54] ldquoUSDA ARS National Genetic Resources Program Germ-plasm Resources Information Network-(GRIN)rdquo NationalGermplasm Resources Laboratory Beltsville Md USA httpwwwars-gringovcgi-binnpgsaccdisplaypl1548027

[55] USDA ARS andNational Genetic Resources Program ldquoGerm-plasm resources information networkmdash(GRIN)rdquo Online Data-base National Germplasm Resources Laboratory BeltsvilleMd USA 2012 httpwwwars-gringovcgi-binnpgsaccdis-playpl1157360

[56] USDA and ARS National Genetic Resources Program Germ-plasm Resources Information Networkmdash(GRIN) [Online Data-base] National Germplasm Resources Laboratory BeltsvilleMd USA 2012 httpwwwars-gringovcgi-binnpgsaccdis-playpl1161274

[57] USDA ARS and National Genetic Resources Program Germ-plasm Resources Information Networkmdash(GRIN) NationalGermplasm Resources Laboratory Beltsville Md USAMay 2012 httpwwwars-gringovcgi-binnpgsaccdisplaypl1573079

[58] M A Bhutkar and S B Bhise ldquoComparative studies on antiox-idant properties of Catharanthus rosea and Catharanthus albardquo

International Journal of PharmTech Research vol 3 no 3 pp1551ndash1556 2011

[59] M IdreesMNaeem andMMA Khan ldquoThe superiority of cvldquoroseardquo over cv ldquoalbardquo of periwinkle (Catharanthus roseus L) inalkaloid production and other physiological attributesrdquo TurkishJournal of Biology vol 34 no 1 pp 81ndash88 2010

[60] S Kumar S Chaudhary R Kumari V Sharma and A KumarldquoDevelopment of improved horticultural genotypes character-ized by novel over-flowering inflorescence trait in periwinkleCatharanthus roseusrdquo Proceedings of the National Academy ofSciences India Section B Biological Sciences vol 82 no 3 pp399ndash404 2012

[61] C A Jaleel R Gopi G M Alagu Lakshmanan and R Pan-neerselvam ldquoTriadimefon induced changes in the antioxidantmetabolism and ajmalicine production in Catharanthus roseus(L) G Donrdquo Plant Science vol 171 no 2 pp 271ndash276 2006

[62] H A Curry ldquoNaturalising the exotic and exoticising the natu-ralised horticulture natural history and the rosy periwinklerdquoEnvironment and History vol 18 no 3 pp 343ndash365 2012

[63] I-M Lee D E Gundersen-Rindal and A Bertaccini ldquoPhyto-plasma ecology and genomic diversityrdquo Phytopathology vol 88no 12 pp 1359ndash1366 1998

[64] S Jagoueix-Eveillard F Tarendeau K Guolter J-L Danet JM Bove and M Garnier ldquoCatharanthus roseus genes regulateddifferentially by mollicute infectionsrdquo Molecular Plant-MicrobeInteractions vol 14 no 2 pp 225ndash233 2001

[65] F D Andreote P T Lacava C S Gai et al ldquoModel plantsfor studying the interaction between Methylobacterium meso-philicum and Xylella fastidiosardquo Canadian Journal of Microbiol-ogy vol 52 no 5 pp 419ndash426 2006

[66] L Torres E Galdeano D Docampo and L Conci ldquoCharacter-ization of aster yellows phytoplasma associated with Catharan-thus little leaf in Argentinardquo Journal of Plant Pathology vol 86no 3 pp 209ndash214 2004

[67] O F Omar A A Emeran and J M Abass ldquoDetection ofphytoplasma associated with periwinkle virescence in EgyptrdquoPlant Pathology Journal vol 7 no 1 pp 92ndash97 2008

[68] Y Chaturvedi A K Tewari P P Upadhyaya S K Prabhuji andG P Rao ldquoAssociation of Candidatus phytoplasma asteris withlittle leaf and phyllody disease ofCatharanthus roseus in EasternUttar Pradesh Indiardquo International Journal of Phytomedicinesand Related Industries vol 1 pp 103ndash108 2009

[69] Khew KL R E Davis C A Ong I-M Lee H J Su and MC Tsai ldquoDetection of a Malaysian mycoplasmalike organism(MLO) and its differentiation from other Asian Europeanand North American MLOs by use of cloned chromosomaland extra chromosomal MLO DNA probesrdquo Journal of PlantProtection in the Tropics vol 8 pp 167ndash180 1991

[70] N Nejat K Sijam S N A Abdullah G Vadamalai andM Dickinson ldquoMolecular characterization of an aster yellowsphytoplasma associated with proliferation of periwinkle inMalaysiardquo African Journal of Biotechnology vol 9 no 15 pp2305ndash2315 2010

[71] N K KWin andH-Y Jung ldquoThe distribution of phytoplasmasin myanmarrdquo Journal of Phytopathology vol 160 no 3 pp 139ndash145 2012

[72] I-M Lee D E Gundersen-Rindal R E Davis and I M Bar-toszyk ldquoRevised classification scheme of phytoplasmas basedon RFLP analyses of 16S rRNA and ribosomal protein genesequencesrdquo International Journal of Systematic Bacteriology vol48 no 4 pp 1153ndash1169 1998


[73] D E Gundersen I-M Lee S A Rehner R E Davis and DT Kingsbury ldquoPhylogeny ofmycoplasmalike organisms (phyto-plasmas) a basis for their classificationrdquo Journal of Bacteriologyvol 176 no 17 pp 5244ndash5254 1994

[74] N Nejat K Sijam S N A Abdullah G Vadamalai and MDickinson ldquoPhytoplasmas associated with disease of coconutin Malaysia phylogenetic groups and host plant speciesrdquo PlantPathology vol 58 no 6 pp 1152ndash1160 2009

[75] N Nejat G Vadamalai and R E Davis ldquolsquoCandidatus Phyto-plasma malaysianumrsquo a novel taxon associated with virescenceand phyllody ofMadagascar periwinkle (Catharanthus roseus)rdquoInternational Journal of Systematic and Evolutionary Microbiol-ogy vol 63 no 2 pp 540ndash548 2013

[76] R M Allen ldquoSpiroplasma organism found in naturally infectedperiwinklerdquo Citrograph vol 60 pp 428ndash446 1975

[77] J M Bove ldquoStubborn and its natural transmission in theMediterranean area and the Near Eastrdquo FAO Plant ProtectionBulletin vol 34 pp 15ndash23 1986

[78] N Nejat G Vadamalai K Sijam and M Dickinson ldquoFirstreport of Spiroplasma citri (-induced) associated with periwin-kle lethal yellows in Southeast Asiardquo Plant Disease vol 95 no10 p 1312 2011

[79] D D Shukla D S Teakle and K H Gough ldquoPeriwinkle alatent host for broad bean wilt and cucumber mosaic virusesin Australiardquo Plant Disease vol 64 pp 802ndash803 1980

[80] A Samad P V Ajayakumar M K Gupta et al ldquoNaturalinfection of periwinkle (Catharanthus roseus) with Cucumbermosaic virus subgroup IBrdquo Australasian Plant Disease Notesvol 3 pp 30ndash34 2008

[81] M Mazidah K Yusoff H Habibuddin Y H Tan and WH Lau ldquoCharacterization of cucumber mosaic virus (CMV)causing mosaic symptom on Catharanthus roseus (L) G Donin Malaysiardquo Pertanika Journal of Tropical Agricultural Sciencevol 35 no 1 pp 41ndash53 2012

[82] J F Dastur ldquoPhytophthora on Vinca roseardquo in Memoirs of theDepartment of Agriculture in India vol 8 of Botanical Series pp233ndash242 1916

[83] A R Chase ldquoPhytophthora aerial blight of vinca and otherbedding plantsrdquo Western Connection Turf amp Ornamentals vol1 pp 1ndash4 1999

[84] R Keim ldquoFoliage blight of perwinkle in southern CaliforniardquoPlant Disease Report vol 61 pp 182ndash184 1977

[85] R T McMillan Jr and J F Garofalo ldquoPhytophthora parasiticawilt of new cultivars of Catharanthus roseusrdquo Proceedings of theFlorida State Horticultural Society vol 117 pp 316ndash317 2004

[86] W C Chung J W Huang and J C Sheu ldquoFusarium root rotof periwinkle in Taiwanrdquo Plant Protection Bulletin vol 40 pp177ndash183 1998

[87] R J McGovern T E Seijo and T A Davis ldquoEvaluation offungicides and a fertilizer for control of Phytophthora blightin Madagascar periwinklerdquo Fungic Nematicide Tests vol 58 pOT048 2003

[88] R T McMillan Jr and W R Graves ldquoPeriwinkle twig blightcaused by Colletotricum dematium on Catharanthus roseus LrdquoProceedings of the Florida State Horticultural Society vol 9 no109 pp 19ndash20 1996

[89] W Hao P A Richardson and C X Hong ldquoFoliar blight ofannual vinca (Catharanthus roseus) caused by Phytophthoratropicalis in Virginiardquo Plant Disease vol 94 no 2 article 2742010

[90] M L Daughtrey R L Wick and J L Peterson Compendium ofFlowering Potted Plant Diseases APS Press St Paul Minn USA1995

[91] A Garibaldi D Bertetti and M L Gullino ldquoFirst reportof botrytis blight caused by Botrytis cinerea on Periwinkle(Catharanthus roseus) in Italyrdquo Plant Disease vol 93 no 5 p554 2009

[92] W Ou-Yang and W S Wu ldquoSurvey of periwinkle diseases inTaiwanrdquo Plant Pathology Bulletin vol 7 pp 147ndash149 1998

[93] M Baligh M A Delgado and K E Conway ldquoEvaluation ofBurkholderia cepacia strains root colonization of Catharanthusroseus and in-vitro inhibition of selected soil-borne fungalpathogensrdquo Proceedings of the Oklahoma Academy of Sciencevol 79 pp 19ndash27 1999

[94] D M Benson ldquoAluminum amendment of potting mixes forcontrol of phytophthora damping-off in bedding plantsrdquoHortScience vol 30 no 7 pp 1413ndash1416 1995

[95] J R Burns and D M Benson ldquoBiocontrol of damping-offofCatharanthus roseus caused byPythiumultimumwithTricho-derma virens and binucleate Rhizoctonia fungirdquo Plant Diseasevol 84 no 6 pp 644ndash648 2000

[96] C B Yandoc E N Rosskopf D A Shah and J P AlbanoldquoEffect of fertilization and biopesticides on the infection ofCatharanthus roseus by Phytophthora nicotianaerdquo Plant Diseasevol 91 no 11 pp 1477ndash1483 2007

[97] N R Mustafa and R Verpoorte ldquoPhenolic compounds inCatharanthus roseusrdquo Phytochemistry Reviews vol 6 no 2-3pp 243ndash258 2007

[98] F Ferreres D M Pereira P Valentao P B Andrade R MSeabra and M Sottomayor ldquoNew phenolic compounds andantioxidant potential of Catharanthus roseusrdquo Journal of Agri-cultural and Food Chemistry vol 56 no 21 pp 9967ndash99742008

[99] R Candido and D M Martinez ldquoThe stability of an acid-baseindicator paper from Catharanthus roseus (Periwinkle) flowerextractrdquo WMSU Research Journal vol 28 no 1 pp 1ndash13 2009

[100] S U Kokil D G Joshi and R L Jadhav ldquoCatharanthus roseusflower extract as natural indicator in acid base titrationrdquoArticlesbase 2007 httpwwwarticlesbasecomscience-arti-clescatharanthus-roseus-flower-extract-as-natural-indicator-in-acid-base-titration-236311html

[101] M Daniel Medicinal Plants Chemistry and Properties SciencePublishers 2006

[102] S Hisiger and M Jolicoeur ldquoAnalysis of Catharanthus roseusalkaloids by HPLCrdquo Phytochemistry Reviews vol 6 no 2-3 pp207ndash234 2007

[103] J-H Renault J-M Nuzillard G Le Crouerour P ThepenierM Zeches-Hanrot and L Le Men-Olivier ldquoIsolation of indolealkaloids from Catharanthus roseus by centrifugal partitionchromatography in the pH-zone refining moderdquo Journal ofChromatography A vol 849 no 2 pp 421ndash431 1999

[104] L Wang Y Zhang H P He Q Zhang S F Li and X J HaoldquoThree new terpenoid indole alkaloids from Catharanthusroseusrdquo Planta Medica vol 77 no 7 pp 754ndash758 2011

[105] J A Duke Handbook of Medicinal Herbs Catharanthus roseusCRC Press Boca Raton Fla USA 1985

[106] O P Virmani G N Srivastava and P Singh ldquoCatharanthusroseus the tropical periwinklerdquo Indian Drugs vol 15 pp 231ndash252 1978

[107] K Sukumar and Z Osmani ldquoInsect sterilants from Catharan-thus roseusrdquo Current Science vol 50 no 12 pp 552ndash553 1981


[108] M R Narayana and B P Dimri Periwinkle and its Cultivationin India CIMAP Lucknow India 1990

[109] E Vega-Avila J L Cano-Velasco F J Alarcon-Aguilar M DC Fajardo Ortız J C Almanza-Perez and R Roman-RamosldquoHypoglycemic activity of aqueous extracts from Catharan-thus roseusrdquo Evidence-Based Complementary and AlternativeMedicine vol 2012 Article ID 934258 7 pages 2012

[110] H D Neuwinger African Traditional Medicine A Dictionaryof Plant Use and Applications Medpharm Scientific StuttgartGermany 2000

[111] J X Guo T Kimura P P H But C K Sung and B H HanInternational Collation of Traditional and Folk Medicine vol 4World Scientific Publishers 2001

[112] D Leveque and F Jehl ldquoMolecular pharmacokinetics of Catha-ranthus (Vinca) alkaloidsrdquoThe Journal of Clinical Pharmacologyvol 47 no 5 pp 579ndash588 2007

[113] S Nobili D Lippi E Witort et al ldquoNatural compounds forcancer treatment and preventionrdquo Pharmacological Researchvol 59 no 6 pp 365ndash378 2009

[114] M A Jordan and L Wilson ldquoMicrotubules as a target foranticancer drugsrdquoNature Reviews Cancer vol 4 no 4 pp 253ndash265 2004

[115] R J Sherines and S S Howard ldquoMale infertilityrdquo in CampbellsUrology J H Harrison R F Gittes A D Perlmutter T AStamey and P C Walsh Eds vol 1 p 715 WB SaundersPhiladelphia Pa USA 4th edition 1978

[116] S A James L Bilbiss and B Y Muhammad ldquoThe effects ofCatharanthus roseus (L) G Don 1838 aqueous leaf extract onsome liver enzymes serum proteins and vital organsrdquo ScienceWorld Journal vol 2 pp 5ndash9 2007

[117] J M Pezzuto ldquoPlant-derived anticancer agentsrdquo BiochemicalPharmacology vol 53 no 2 pp 121ndash133 1997

[118] V E Tyler ldquoMedicinal plant research 1953ndash1987rdquo Planta Med-ica vol 54 no 2 pp 95ndash100 1988

[119] R Verpoorte R van der Heijden J Schripsema J H C Hogeand H J G Ten Hoopen ldquoPlant cell biotechnology for theproduction of alkaloids present status and prospectsrdquo Journalof Natural Products vol 56 no 2 pp 186ndash207 1993

[120] G H Schmelzer ldquoCatharanthus roseus (L)rdquo in MedicinalplantsPlantes medicinales 1 G H Schmelzer and A Gurib-Fakim Eds PROTA Wageningen The Netherlands 2007

[121] V Salim F Yu J Altarejos and V de Luca ldquoVirus-induced genesilencing identifies Catharanthus roseus 7-deoxyloganic acid-7-hydroxylase a step in iridoid and monoterpene indole alkaloidbiosynthesisrdquoThePlant Journal vol 76 no 5 pp 754ndash765 2013

[122] M Debnath C P Malik and P S Bisen ldquoMicropropagation atool for the production of high quality plant-based medicinesrdquoCurrent Pharmaceutical Biotechnology vol 7 no 1 pp 33ndash492006

[123] S Foster ldquoFrom herbs to medicines the Madagascar periwin-klersquos impact on childhood leukemia a serendipitous discoveryfor treatmentrdquo in Alternative amp Complementary Therapies ANew Bimonthly Publication for Health Care Practitioners JSimon R Cooper and K Hughes Eds pp 347ndash350 2010

[124] M Y Khan S Aliabbas V Kumar and S Rajkumar ldquoRecentadvances in medicinal plant biotechnologyrdquo Indian Journal ofBiotechnology vol 8 no 1 pp 9ndash22 2009

[125] AMujib A Ilah N Gandotra andM Z Abdin ldquoIn vitro appli-cation to improve alkaloid yield in Catharanthus roseusrdquo inRecent Progress inMedicinal Plants Volume 4 Biotechnology andGenetic Engineering J N Govil P A Kumar and V K Singh

Eds pp 415ndash440 Sci Tech Publication Houston Tex USA2002

[126] M Sottomayor and A R Barcelo ldquoThe Vinca alkaloids frombiosynthesis and accumulation in plant cells to uptake activityand metabolism in animal cellsrdquo Studies in Natural ProductsChemistry vol 33 pp 813ndash857 2005

[127] S Binet E Chaineau A Fellous et al ldquoImmunofluorescencestudy of the action of navelbine vincristine and vinblastineon mitotic and axonal microtubulesrdquo International Journal ofCancer vol 46 no 2 pp 262ndash266 1990

[128] C Antonio N R Mustafa S Osorio et al ldquoAnalysis of theinterface between primary and secondarymetabolism inCatha-ranthus roseus cell cultures using 13C-stable isotope feeding andcoupled mass spectrometryrdquo Molecular Plant vol 6 no 2 pp581ndash584 2013

[129] H Rischer M Oresic T Seppanen-Laakso et al ldquoGene-to-metabolite networks for terpenoid indole alkaloid biosynthe-sis in Catharanthus roseus cellsrdquo Proceedings of the NationalAcademy of Sciences of the United States of America vol 103 no14 pp 5614ndash5619 2006

[130] A Dutta J Batra S Pandey-Rai D Singh S Kumar andJ Sen ldquoExpression of terpenoid indole alkaloid biosyntheticpathway genes corresponds to accumulation of related alkaloidsin Catharanthus roseus (L) G Donrdquo Planta vol 220 no 3 pp376ndash383 2005

[131] P Mishra G C Uniyal S Sharma and S Kumar ldquoPatternof diversity for morphological and alkaloid yield related traitsamong the periwinkle Catharanthus roseus accessions collectedfrom in and around Indian subcontinentrdquoGenetic Resources andCrop Evolution vol 48 no 3 pp 273ndash286 2001

[132] S P Rai R Luthra and S Kumar ldquoSalt-tolerant mutantsin glycophytic salinity response (GSR) genes in CatharanthusroseusrdquoTheoretical and Applied Genetics vol 106 no 2 pp 221ndash230 2003

[133] K-M Oksman-Caldentey and D Inze ldquoPlant cell factories inthe post-genomic era new ways to produce designer secondarymetabolitesrdquo Trends in Plant Science vol 9 no 9 pp 433ndash4402004

[134] M El-Sayed and R Verpoorte ldquoCatharanthus terpenoid indolealkaloids biosynthesis and regulationrdquo Phytochemistry Reviewsvol 6 no 2-3 pp 277ndash305 2007

[135] P Lackman M Gonzalez-Guzman S Tilleman et al ldquoJas-monate signaling involves the abscisic acid receptor PYL4to regulate metabolic reprogramming in Arabidopsis andtobaccordquo Proceedings of the National Academy of Sciences of theUnited States of America vol 108 no 14 pp 5891ndash5896 2011

[136] P R Moreno R Van Der Heijden and R Verpoorte ldquoCell andtissue cultures of Catharanthus roseus a literature surveyrdquo PlantCell Tissue and Organ Culture vol 42 no 1 pp 1ndash25 1995

[137] A Datta and P S Srivastava ldquoVariation in vinblastine pro-duction by Catharanthus roseus during in vivo and in vitrodifferentiationrdquo Phytochemistry vol 46 no 1 pp 135ndash137 1997

[138] Y Miura K Hirata N Kurano K Miyamoto and K UchidaldquoFormation of vinblastine in multiple shoot culture of Catha-ranthus roseusrdquo Planta Medica vol 54 no 1 pp 18ndash20 1988

[139] A Ataei-Azimi H B Delnavaz H Ebrahimzadeh and AMajd ldquoHigh in vitro production of ant-canceric indole alkaloidsfrom periwinkle (Catharanthus roseus) tissue culturerdquo AfricanJournal of Biotechnology vol 7 no 16 pp 2834ndash2839 2008

[140] S Yokoshima T Ueda S Kobayashi et al ldquoStereocontrolledtotal synthesis of (+)-vinblastinerdquo Journal of the AmericanChemical Society vol 124 no 10 pp 2137ndash2139 2002


[141] J Liu J Zhu L Tang W Wen S Lv and R Yu ldquoEnhancementof vindoline and vinblastine production in suspension-culturedcells of Catharanthus roseus by artemisinic acid elicitationrdquoWorld Journal of Microbiology and Biotechnology vol 30 no 1pp 175ndash180 2014

[142] M Koul N S Lakra R Chandra and S Chandra ldquoCatharan-thus roseus and prospects of its endophytes a new avenue forproduction of bioactive metabolitesrdquo International Journal ofPharmaceutical Sciences and Research vol 4 no 7 pp 2705ndash2716 2013

[143] R N Kharwar V C Verma G Strobel andD Ezra ldquoThe endo-phytic fungal complex of Catharanthus roseus (L) G DonrdquoCurrent Science vol 95 no 2 pp 228ndash233 2008

[144] L B Zhang L H Gou and S V Zeng ldquoPreliminary studyon the isolation of endophytic fungus of Catharanthus roseusand its fermentation to produce product of therapeutic valuerdquoChinese Traditional andHerbal Drugs vol 11 pp 805ndash807 2000

[145] C Y Tung D B Yang and M Gou ldquoA preliminary study onthe condition of the culture and isolate of endophytic fungusproducing Vincristinerdquo Journal of Chuxiong Normal Universityvol 6 pp 39ndash41 2002

[146] B Guo and L H Kunming ldquoA middle vinblastine fungi iso-latedrdquo Journal of Yunnan University vol 20 pp 214ndash215 1998

[147] A Kumar D Patil P R Rajamohanan and A Ahmad ldquoIsola-tion purification and characterization of vinblastine and vin-cristine from endophytic fungus Fusarium oxysporum isolatedfrom Catharanthus roseusrdquo PLoS ONE vol 8 no 9 Article IDe71805 2013

[148] M M R Costa F Hilliou P Duarte et al ldquoMolecular cloningand characterization of a vacuolar class III peroxidase involvedin the metabolism of anticancer alkaloids in Catharanthusroseusrdquo Plant Physiology vol 146 no 2 pp 403ndash417 2008

[149] D I Jacobs M Gaspari J Van Der Greef R Van Der Heijdenand R Verpoorte ldquoProteome analysis of the medicinal plantCatharanthus roseusrdquo Planta vol 221 no 5 pp 690ndash704 2005

[150] A Champagne H Rischer K M Oksman-Caldentey and MBoutry ldquoIn-depth proteome mining of cultured Catharanthusroseus cells identifies candidate proteins involved in the synthe-sis and transport of secondary metabolitesrdquo Proteomics vol 12no 23-24 pp 3536ndash3547 2012

[151] G W Sander Quantitative analysis of metabolic pathways inCatharanthus roseus hairy roots metabolically engineered forterpenoid indole alkaloid overproduction [PhD thesis] IowaState University Ames Iowa USA 2009

[152] C Zhou J Zhang S-J Zhao andZ-BHu ldquoAn activeCatharan-thus roseus desacetoxyvindoline-4-hydroxylase-like gene andits transcriptional regulatory profilerdquo Botanical Studies vol 55no 1 article 29 2014

[153] Q Pan Q Wang F Yuan et al ldquoOverexpression of ORCA3and G10H in Catharanthus roseus plants regulated alkaloidbiosynthesis andmetabolism revealed by NMR-metabolomicsrdquoPLoS ONE vol 7 no 8 Article ID e43038 2012

[154] S E OrsquoConnor and J J Maresh ldquoChemistry and biology ofmonoterpene indole alkaloid biosynthesisrdquo Natural ProductReports vol 23 no 4 pp 532ndash547 2006

[155] T Hashimoto and Y Yamada ldquoNew genes in alkaloid metab-olism and transportrdquo Current Opinion in Biotechnology vol 14no 2 pp 163ndash168 2003

[156] M Wink and M Roberts ldquoCompartmentation of alkaloid syn-thesis transport and storagerdquo in Alkaloids M Roberts and MWink Eds pp 301ndash307 Plenum Press New York NY USA1998

[157] O Ginis V Courdavault C Melin et al ldquoMolecular cloningand functional characterization of Catharanthus roseus hydrox-ymethylbutenyl 4-diphosphate synthase gene promoter fromthe methyl erythritol phosphate pathwayrdquo Molecular BiologyReports vol 39 no 5 pp 5433ndash5447 2012

[158] Y-C Sung C-P Lin and J-C Chen ldquoOptimization of virus-induced gene silencing inCatharanthus roseusrdquoPlant Pathologyvol 63 no 5 pp 1159ndash1167 2014

[159] S W Kim S H Ban S-C Jeong et al ldquoGenetic discrim-ination between Catharanthus roseus cultivars by metabolicfingerprinting using 1H NMR spectra of aromatic compoundsrdquoBiotechnology and Bioprocess Engineering vol 12 no 6 pp 646ndash652 2007

[160] S W Kim J H Kim and J R Liu ldquoGenetic discrimination ofCatharanthus roseus cultivars by pyrolysis mass spectrometryrdquoJournal of Plant Biology vol 52 no 5 pp 462ndash465 2009

[161] R K Shaw L Acharya and A K Mukherjee ldquoAssessment ofgenetic diversity in a highly valuable medicinal plant Catha-ranthus roseus using molecular markersrdquo Crop Breeding andApplied Biotechnology vol 9 no 1 pp 52ndash59 2009

[162] M Magnotta J Murata J Chen and V de Luca ldquoIdentificationof a low vindoline accumulating cultivar ofCatharanthus roseus(L) G Don by alkaloid and enzymatic profilingrdquo Phytochem-istry vol 67 no 16 pp 1758ndash1764 2006

[163] Y D Qing P BinYe R D L Kun et al ldquoISSR analysis of geneticrelationships between forty varieties of Catharanthus roseusrdquoJournal of Shanghai Jiaotong UniversitymdashAgricultural Sciencevol 27 pp 138ndash142 2011

[164] S Lal K N Mistry S D Shah R Thaker and P B VaidyaldquoGenetic diversity assessment in nine cultivars of Catharanthusroseus from Central Gujarat (India) through RAPD ISSR andSSRmarkersrdquo Journal of Biological Research vol 8 pp 667ndash6752011

[165] B Shokeen N K Sethy S Kumar and S Bhatia ldquoIsolation andcharacterization ofmicrosatellite markers for analysis of molec-ular variation in the medicinal plant Madagascar periwinkle(Catharanthus roseus (L) G Don)rdquo Plant Science vol 172 no3 pp 441ndash451 2007

[166] D M Pereira F Ferreres J Oliveira P Valentao P B Andradeand M Sottomayor ldquoTargeted metabolite analysis of Catha-ranthus roseus and its biological potentialrdquo Food and ChemicalToxicology vol 47 no 6 pp 1349ndash1354 2009

[167] D M Pereira F Ferreres J M A Oliveira et al ldquoPharmaco-logical effects of Catharanthus roseus root alkaloids in acetyl-cholinesterase inhibition and cholinergic neurotransmissionrdquoPhytomedicine vol 17 no 8-9 pp 646ndash652 2010

[168] N Singh B R Pandey and P Verma ldquoAn overview ofphytotherapeutic approach in prevention and treatment ofAlzheimerrsquos Syndrome amp Dementiardquo International Journal ofPharmaceutical Sciences and Drug Research vol 3 no 3 pp162ndash172 2011

[169] S Agarwal S Jacob N Chettri et al ldquoEvaluation of in-vitro anthelminthic activity of Catharanthus roseus extractrdquoThe International Journal of Pharmaceutical Sciences and DrugResearch vol 3 no 3 pp 211ndash213 2011

[170] T Murugavel and M A Akbarsha ldquoAnti-spermatogenic effectofVinca roseaLinnrdquo Indian Journal of Experimental Biology vol29 no 9 pp 810ndash812 1991

[171] S Wang Z Zheng Y Weng et al ldquoAngiogenesis and anti-angiogenesis activity of Chinese medicinal herbal extractsrdquo LifeSciences vol 74 no 20 pp 2467ndash2478 2004


[172] P Goyal A Khanna A Chauhan G Chauhan and P KaushikldquoIn vitro evaluation of crude extracts of Catharanthus roseus forpotential antibacterial activityrdquo International Journal of GreenPharmacy vol 2 pp 176ndash181 2008

[173] P J Patil and J S Ghosh ldquoAntimicrobial activity of Catharan-thus roseusmdasha detailed studyrdquo British Journal of Pharmacologyand Toxicology vol 1 pp 40ndash44 2010

[174] S Ramya V Govindaraji K Navaneetha and R JayakumararajldquoIn vitro evaluation of antibacterial activity using crude extractsof Catharanthus roseus L (G) Donrdquo Ethnobotanical Leafletsvol 12 pp 1067ndash1072 2008

[175] A K Verma and R R Singh ldquoInduced dwarf mutant in Catha-ranthus roseus with enhanced antibacterial activityrdquo IndianJournal of Pharmaceutical Sciences vol 72 no 5 pp 655ndash6572010

[176] K A Hassan A T Brenda V Patrick andO E Patrick ldquoIn vivoantidiarrheal activity of the ethanolic leaf extract of Catharan-thus roseus linn (Apocyanaceae) in wistar ratsrdquo African Journalof Pharmacy and Pharmacology vol 5 no 15 pp 1797ndash18002011

[177] R Mathur and S Chaudan ldquoAntifertility efficacy of Catharan-thus roseus Linn a biochemical and histological studyrdquo ActaEuropaea Fertilitatis vol 16 no 3 pp 203ndash205 1985

[178] V Prajapati A K Tripathi D C Jain S Sharma and S P SKhanuja ldquoSensitivity of Spilarctia obliqua to root extracts ofCatharanthus roseusrdquo Phytotherapy Research vol 12 no 4 pp270ndash274 1998

[179] S K Chile and K M Vyas ldquoEfficacy of Vinca rosea extractsagainst protease from human pathogenic strains of Trichophy-ton rubrum SabrdquoHindustan Antibiotics Bulletin vol 26 no 3-4pp 114ndash116 1984

[180] A K Barde and S M Singh ldquoActivity of plant extracts againstScytalidium anamorph ofHendersonula toruloidea causing skinand nail diseases in manrdquo Indian Drugs vol 20 pp 362ndash3641983

[181] B D Benjamin S M Kelkar M S Pote G S Kaklij A TSipahimalani and M R Heble ldquoCatharanthus roseus cell cul-tures growth alkaloid synthesis and antidiabetic activityrdquoPhytotherapy Research vol 8 no 3 pp 185ndash186 1994

[182] M Bnouham A Ziyyat H Mekhfi A Tahri and A LegssyerldquoMedicinal plants with potential antidiabetic activitymdasha reviewof ten years of herbal medicine research (1990ndash2000)rdquo Interna-tional Journal of Diabetes andMetabolism vol 14 no 1 pp 1ndash252006

[183] R R Chattopadhyay ldquoA comparative evaluation of some bloodsugar lowering agents of plant originrdquo Journal of Ethnopharma-cology vol 67 no 3 pp 367ndash372 1999

[184] K Chauhan S Sharma K Rohatgi and B Chauhan ldquoAntihy-perlipidemic and antioxidative efficacy of Catharanthus roseusLinn [Sadabahar] in streptozotocin induced diabetic ratsrdquoAsian Journal of Pharmaceutical and Health Sciences vol 2 no1 pp 235ndash243 2011

[185] E E J Iweala and C U Okeke ldquoComparative study of the hypo-glycemic and biochemical effects of Catharanthus roseus (Linn)G Apocynaceae (Madagascar periwinkle) and chlorpropamide(diabenese) on alloxan-induced diabetic ratsrdquo Biokemistri vol17 no 2 pp 149ndash156 2005

[186] E Jarald S B Joshi and D C Jain ldquoDiabetes and herbalmedicinesrdquo Iranian Journal of Pharmacology and Therapeuticsvol 7 no 1 pp 97ndash106 2008

[187] S Nammi M K Boini S D Lodagala and R B S BeharaldquoThe juice of fresh leaves of Catharanthus roseus Linn reduces

blood glucose in normal and alloxan diabetic rabbitsrdquo BMCComplementary and Alternative Medicine vol 3 no 1 article4 2003

[188] S N Singh P Vats S Suri et al ldquoEffect of an antidiabetic extractof Catharanthus roseus on enzymic activities in streptozotocininduced diabetic ratsrdquo Journal of Ethnopharmacology vol 76no 3 pp 269ndash277 2001

[189] R R Chattopadhyay R N Banerjee S K Sarkar S Gangulyand T K Basu ldquoAntiinflammatory and acute toxicity studieswith the leaves of Vinca rosea linn in experimental animalsrdquoIndian Journal of Physiology and Pharmacology vol 36 no 4pp 291ndash292 1992

[190] C Y Lim-Sylianco and F Blanco ldquoAntimutagenic effects ofsome anti-cancer agentsrdquo Bulletin of the Philippine Society forBiochemistry and Molecular Biology vol 4 pp 1ndash7 1981

[191] G M Cragg and D J Newman ldquoPlants as a source of anti-cancer agentsrdquo Journal of Ethnopharmacology vol 100 no 1-2pp 72ndash79 2005

[192] J-G DongW Bornmann K Nakanishi andN Berova ldquoStruc-tural studies of vinblastine alkaloids by exciton coupled circulardichroismrdquo Phytochemistry vol 40 no 6 pp 1821ndash1824 1995

[193] M M El-Merzabani A A El-Aaser M A Attia A K El-Duweini and A M Ghazal ldquoScreening system for Egyptianplants with potential anti-tumour activityrdquo Planta Medica vol36 no 2 pp 150ndash155 1979

[194] A El-Sayed andGA Cordell ldquoCatharanthus alkaloids XXXIVCatharanthamine a new antitumor bisindole alkaloid fromCatharanthus roseusrdquo Journal of Natural Products vol 44 no3 pp 289ndash293 1981

[195] A El-Sayed G A Handy and G A Cordell ldquoCatharanthusalkaloids XXXVIII Confirming structural evidence and anti-neoplastic activity of the bisindole alkaloids Leurosine-N1015840

119887-

oxide (pleurosine) roseadine and vindolicine from Catharan-thus roseusrdquo Journal of Natural Products vol 46 no 4 pp 517ndash527 1983

[196] I S Johnson H F Wright G H Svoboda and J VlantisldquoAntitumor principles derived from Vinca rosea Linn I Vin-caleukoblastine and leurosinerdquo Cancer Research vol 20 pp1016ndash1022 1960

[197] A KMukherjee S BasuN Sarkar andA CGhosh ldquoAdvancesin cancer therapy with plant based natural productsrdquo CurrentMedicinal Chemistry vol 8 no 12 pp 1467ndash1486 2001

[198] R L Noble ldquoThe discovery of the vinca alkaloids-chemothera-peutic agents against cancerrdquo Biochemistry and Cell Biology vol68 no 12 pp 1344ndash1351 1990

[199] W Zheng and S Y Wang ldquoAntioxidant activity and phenoliccompounds in selected herbsrdquo Journal of Agricultural and FoodChemistry vol 49 no 11 pp 5165ndash5170 2001

[200] J W Gathirwa G M Rukunga E N M Njagi et al ldquoIn vitroanti-plasmodial and in vivo anti-malarial activity of some plantstraditionally used for the treatment of malaria by the Merucommunity in Kenyardquo Journal of Natural Medicines vol 61 no3 pp 261ndash268 2007

[201] S Ponarulselvam C Panneerselvam KMurugan N Aarthi KKalimuthu and S Thangamani ldquoSynthesis of silver nanopar-ticles using leaves of Catharanthus roseus Linn G Don andtheir antiplasmodial activitiesrdquo Asian Pacific Journal of TropicalBiomedicine vol 2 no 7 pp 574ndash580 2012

[202] D R A Mans A B da Rocha and G Schwartsmann ldquoAnti-cancer drug discovery and development in Brazil targeted plantcollection as a rational strategy to acquire candidate anti-cancercompoundsrdquo Oncologist vol 5 no 3 pp 185ndash198 2000


[203] J Y Ueda Y Tezuka A H Banskota et al ldquoAntiproliferativeactivity of Vietnamese medicinal plantsrdquo Biological and Phar-maceutical Bulletin vol 25 no 6 pp 753ndash760 2002

[204] R S Gupta and R Sharma ldquoA review on medicinal plantsexhibiting antifertility activity in malesrdquo Natural Product Radi-ance vol 5 pp 389ndash410 2006

[205] M S Joshi and R Y Ambaye ldquoEffect of alkaloids from Vincarosea L on spermatogenesis in male ratsrdquo Indian Journal ofExperimental Biology vol 6 no 4 pp 256ndash257 1968

[206] D E Moerman Native American Medicinal Plants An Ethnob-otanical Dictionary Timber Press Portland Ore USA 2009

[207] T Usia TWatabe S Kadota and Y Tezuka ldquoCytochrome P4502D6 (CYP2D6) inhibitory constituents ofCatharanthus roseusrdquoBiological and Pharmaceutical Bulletin vol 28 no 6 pp 1021ndash1024 2005

[208] K Hostettmann A Marston K Ndjoko and J-L WolfenderldquoThe potential of African plants as a source of drugsrdquo CurrentOrganic Chemistry vol 4 no 10 pp 973ndash1010 2000

[209] M J Siddiqui Z Ismail A F A Aisha and A M S AbdulMajid ldquoCytotoxic activity of Catharanthus roseus (Apocy-naceae) crude extracts and pure compounds against humancolorectal carcinoma cell linerdquo International Journal of Pharma-cology vol 6 no 1 pp 43ndash47 2010

[210] D A Adekomi ldquoMadagascar periwinkle (Catharanthus roseus)enhances kidney and liver functions in Wistar ratsrdquo EuropeanJournal of Anatomy vol 14 no 3 pp 111ndash119 2010

[211] H I Averal A Stanley PMurugaianM Palanisamy andM AAkbarsha ldquoSpecific effect of vincristine on epididymisrdquo IndianJournal of Experimental Biology vol 34 no 1 pp 53ndash56 1996

[212] A Stanley and M A Akbarsha ldquoGiant spermatogonial cellsgenerated by vincristine and their usesrdquoCurrent Science vol 63no 3 pp 144ndash147 1992

[213] C Kuppusamy K Murugan N Arul and P Yasodha ldquoLarvici-dal and insect growth regulator effect of 120572-amyrin acetate fromCatharanthus roseus Linn against the malaria vector Anophelesstephensi Liston (Diptera Culicidae)rdquo Entomological Researchvol 39 no 1 pp 78ndash83 2009

[214] K M Remia and S Logaswamy ldquoLarvicidal efficacy of leafextract of two botanicals against the mosquito vector Aedesaegypti (Diptera Culicidae)rdquo Indian Journal of Natural Productsand Resources vol 1 no 2 pp 208ndash212 2010

[215] M A Akbarsha A Stanley and H I Averal ldquoEffect of vin-cristine on Leydig cell and accessory reproductive organsrdquoCurrent Science vol 68 no 10 pp 1053ndash1057 1995

[216] A Stanley H A Averal and M A Akbarsha ldquoReproductivetoxicity of vincristine inmale ratsrdquo Indian Journal of Experimen-tal Biology vol 31 no 4 pp 380ndash382 1993

[217] A Kurian and A SankarMedicinal Plants Horticulture ScienceSeriesmdash2 New India Publishing Agency 2007

[218] B S Nayak and LM Pinto Pereira ldquoCatharanthus roseus flowerextract has wound-healing activity in Sprague Dawley ratsrdquoBMC Complementary and Alternative Medicine vol 6 article41 2006

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Volume 2014

Zoology


Molecular Biology International

GenomicsInternational Journal of


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Hindawi Publishing Corporationhttpwwwhindawicom

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Stem CellsInternational



Enzyme Research



Microbiology


a result of breeding experiments As previously publishedreviews onMPmostly concentrate on the pharmaceutical andchemical compounds of the herb lack of information aboutthe other features of the species is extremely tangibleThe aimof this review is to provide insights into agrotechnologicalbiological ecological and medicinal aspects (particularlyanticancer compounds) ofMP aswell as updated informationon the new cultivars that have been introduced to thehorticultural industry

2 Botany

21 Taxonomic Classification Inconsistency of nomenclaturein the literature is due to changes made in plant taxonomicclassification with continuous research [8] In the appellationof Catharanthus roseus (L) G Don Catharanthus meansclean or pure flower in Greek roseus signifies being rose-colored in Latin L is the standard abbreviation for Linnaeuswho first published the plantrsquos description and G Don refersto George Don who named the flower as such in 1837 [6]

Catharanthus roseus known as the Madagascar periwin-kle (MP) was formerly classified as the species Vinca roseaL (1759) (basionym or original name) Pervinca rosea (L)Moench (1794) Lochnera rosea (L) Rchb ex Endl (1838) andAmmocallis rosea (L) Small (1903) which are homotypic syn-onyms [9] Vinca guilelmi-waldemarii Klotzsch is recognizedas a heterotypic synonym [10]

Below describes the classification of the Catharanthusroseus species

Domain Eukarya eukaryotesKingdom Plantae plantsSubkingdom Tracheobionta vascular plantsSuperdivision Spermatophyta seed plantsDivision Magnoliophyta flowering plantsClass Magnoliopsida dicotyledonsSubclass AsteridaeSuperorder GentiananaeOrder GentianalesFamily Apocynaceae dogbaneSubfamily RauvolfioideaeTribe VinceaeGenus Catharanthus G DonSpecific epithet roseus (Linnaeus) G DonBotanical name Catharanthus roseus (Linnaeus) GDon (1837) Madagascar periwinkle [8 11ndash13]

Vernacular names of the herb in various cultures andlanguages have been listed in Table 1

22 Morphological Characteristics MP is a perennial orannual evergreen semishrub or herbaceous plant that growsup to one meter in height and secretes milky latex The rootsextend to 70 cm in depth The leaves of the plant are elliptical

Table 1 Vernacular names ofMadagascar periwinkle (Catharanthusroseus) in different languageslowast

Language Common name

Bengali NayantaraChinese Chang Chun HuaDutch Roze maagdenpalm

EnglishBright-eyes Cape periwinkle graveyard plantMadagascar periwinkle old-maidold-maid-flower rose periwinkle rosy periwinkle

Ethiopia PhloxCreole Bigalo

French Pervenche de Madagascar rose amere sorcererrsquosviolet

German ZimmerimmergrunCreole Kaka pouleHindi Sadabahar Baramassi Ainskati UshamanjairiIndonesian Tapak dara kembang sari cinaKonkani SadapushpaMalayalam Nithyakalyani Savakkottappacha UshamalariMalay Kemunting cinaMarathi Sada-phul (Sadaphuli)Myanmarese Thin-Baw-MA-HnyoPersian Gul-e-farang

PortugueseBoa-noite Boa-tarde Lavadeira Pervinca-rosaVinca-de-gatoVinca-de-madagascar Vina-rosea

Punjabi RattanjotSanskrit NityakalyaniKrio NgyangeAfrikaans Kanniedood

Spanish Chatas Chula Pervinca de Madagascar Vincapervinca Hierba doncella

Swedish RosenskonaTamil Sudukattu mallikaiTelugu BillagannerulowastReferences [9 17]

to oblong in shape 25ndash9 cm long 1ndash35 cm broad glossygreen above and pale green below with a pale midrib andopposite in orientation Petioles are green or red and 1ndash18 cmlong The inflorescence is racemose Flowers are pentamer-ous actinomorphic and colored pink rose-purple bluesalmon scarlet or white with purple red pink pale yellowor white ldquoeyerdquo in the center and a mauve throat (Figures1(a)ndash1(c)) The corolla tube is cylindrical 2-3 cm long withfive petal-like lobes Stamens are inserted 04ndash06 cm belowthe corolla mouth consisting of very short white coloredfilaments and filiform subsessile anthers Pistils range from17 to 26mm in length made up of two narrow long carpelsconsisting of a glabrous stigma style ovary and 2-seriate


(a)

(b)

(c)

(d) (e) (f)







4 Genetics





5 Agrotechnology




2O5) and K (K







variationReferences















































Cooler



Heat Wave




Mediterranean



Pacifica










Vitesse






7 Phytochemistry





8 Phytobioactivity



(a) (b)













[179 180]




[213 214]
























10 Conclusion




References














































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


(a)

(b)

(c)

(d) (e) (f)







4 Genetics





5 Agrotechnology




2O5) and K (K







variationReferences















































Cooler



Heat Wave




Mediterranean



Pacifica










Vitesse






7 Phytochemistry





8 Phytobioactivity



(a) (b)













[179 180]




[213 214]
























10 Conclusion




References














































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology






4 Genetics





5 Agrotechnology




2O5) and K (K







variationReferences















































Cooler



Heat Wave




Mediterranean



Pacifica










Vitesse






7 Phytochemistry





8 Phytobioactivity



(a) (b)













[179 180]




[213 214]
























10 Conclusion




References














































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology





variationReferences















































Cooler



Heat Wave




Mediterranean



Pacifica










Vitesse






7 Phytochemistry





8 Phytobioactivity



(a) (b)













[179 180]




[213 214]
























10 Conclusion




References














































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology





























Cooler



Heat Wave




Mediterranean



Pacifica










Vitesse






7 Phytochemistry





8 Phytobioactivity



(a) (b)













[179 180]




[213 214]
























10 Conclusion




References














































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology





7 Phytochemistry





8 Phytobioactivity



(a) (b)













[179 180]




[213 214]
























10 Conclusion




References














































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


(a) (b)













[179 180]




[213 214]
























10 Conclusion




References














































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology







[179 180]




[213 214]
























10 Conclusion




References














































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology



















10 Conclusion




References














































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology









































































































































































































119887-

































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

























Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

review article ornamental exterior versus therapeutic

Documents