Antiparasitic activity in Asteraceae with special attention to ethnobotanical use by the tribes of

25 Pages·2017·0.81 MB·English

Parasite25,10(2018)
©S.K.Pandaand W.Luyten,published byEDP Sciences, 2018
https://doi.org/10.1051/parasite/2018008
Availableonline at:
www.parasite-journal.org
REVIEW ARTICLE
Antiparasitic activity in Asteraceae with special attention to
ethnobotanical use by the tribes of Odisha, India
Sujogya Kumar Panda1,2,* and Walter Luyten2
1 Department of Zoology, North Orissa University, Baripada-757003, India
2 Department of Biology, KU Leuven, 3000 Leuven, Belgium
Received6November2017,Accepted3February2018,Publishedonline12March2018
Abstract--ThepurposeofthisreviewistosurveytheantiparasiticplantsoftheAsteraceaefamilyandtheir
applicability in the treatment of parasites. This review is divided into three major parts: (a) literature on
traditional uses of Asteraceae plants for the treatment of parasites; (b) description of the major classes of
chemicalcompoundsfromAsteraceaeandtheirantiparasiticeffects;and(c)antiparasiticactivitywithspecial
referencetoflavonoidsandterpenoids.ThisreviewprovidesdetailedinformationonthereportedAsteraceae
plantextractsfoundthroughouttheworldandonisolatedsecondarymetabolitesthatcaninhibitprotozoan
parasites such as Plasmodium, Trypanosoma, Leishmania, and intestinal worms. Additionally, special
attentionisgiventotheAsteraceaeplantsofOdisha,usedbythetribesoftheareaasantiparasitics.These
plantsarecomparedtothesameplantsusedtraditionallyinotherregions.Finally,weprovideinformationon
whichplantsidentifiedinOdisha,Indiaandrelatedcompoundsshowpromiseforthedevelopmentofnewdrugs
againstparasiticdiseases.Formostoftheplantsdiscussedinthisreview,theactivecompoundsstillneedtobe
isolatedandtestedfurther.
Keywords:Asteraceae,Plasmodium,Trypanosoma,Leishmania,Odisha(India),antiparasiticdrugs
Résumé -- Activité antiparasitaire chez les Asteraceae avec une attention particulière pour
l’utilisation ethnobotanique par les tribus d’Odisha en Inde. Le but de cette revue est d’étudier les
plantesantiparasitairesdelafamilledesAsteraceaeetleurapplicabilitédansletraitementdesparasites.Cette
revueestdiviséeentroispartiesprincipales:(a)littératuresurlesutilisationstraditionnellesdesAsteraceae
pourletraitementdesparasites;(b)descriptiondesprincipalesclassesdecomposéschimiquesdesAsteraceaeet
leurs effets antiparasitaires; (c) activité antiparasitaire avec référence spéciale aux flavonoïdes et aux
terpénoïdes.Cetterevuefournitdesinformationsdétailléessurlesextraitsd’Asteraceaerapportésàtraversle
monde et sur des métabolites secondaires isolés qui peuvent inhiber les parasites protozoaires, tels que
Plasmodium, Trypanosoma, Leishmania et les vers intestinaux. En outre, une attention particulière est
accordéeauxAsteraceaed’Odisha(Inde),utiliséesparlestribuslocalescommeantiparasitaires.Cesplantes
sontcomparéesauxmêmesespècesutiliséestraditionnellementdansd’autresrégions.Enfin,nousfournissons
des informations sur les plantes identifiées à Odisha et les composés qui seraient prometteurs en tant que
médicamentscandidatscontrelesmaladiesparasitaires.Pourlaplupartdesplantesdiscutéesdanscetterevue,
lescomposésactifsdoiventencoreêtreisolésettestésplusavant.
Introduction (cid:1) Antiparasitic research people worldwide and are associated with significant
morbidity and large economic impacts [88]. The lack of
Parasitediseasesareamajorsourceofdiseaseinboth proper vaccines and the emergence of drug resistance
humans and animals and result in significant economic make the search for new drugs for treatment and
losses.Protozoanparasitesthreatenthelivesofbillionsof prophylaxis more urgent, including from alternative
sourceslikeplants.In2005,Pinketal.publishedareview
*Correspondingauthor:[email protected]; emphasizing that new antiparasitic drugs are urgently
[email protected] needed to treat and control diseases such as malaria,
ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense(http://creativecommons.org/licenses/by/4.0),
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
2 S.K. Panda and W. Luyten: Parasite 2018, 25, 10
leishmaniasis, sleeping sickness and filariasis [124]. 24,000–30,000species [30]. The family has 12subfamilies
The discovery of quinine from Cinchona succirubra and 43tribes, and is distributed worldwide [16], but is
(Rubiaceae) and its subsequent development as an most abundant in the temperate and warm-temperate
antimalarial drug represent a milestone in the history of regions. Most of the species are herbs and shrubs, while
antiparasiticdrugsfromnature.The2015NobelPrizein trees are fewer in number. Asteraceae have been
PhysiologyorMedicinewasawardedforthediscoveryof commonlyusedinthetreatmentofvariousdiseasessince
artemisinin and avermectin, which fundamentally ancienttimes,asattestedbyclassicalliterature.Forthis
changed the treatment of parasitic diseases around the review, we collected literature from scientific journals,
globe. Both compounds are natural products, once again books, theses and reports via a library and electronic
showingthatnaturecanbeapowerfulsourceofmedicines. search(usingdatabasesviz.PubMed,GoogleScholarand
Abreakthroughforthedevelopmentofantimalarialdrugs Scopus). Several researchers have systematically investi-
was the identification of the sesquiterpene artemisinin gated Asteraceae for theirtherapeuticutility. More than
from Artemisia annua (Asteraceae), which can even kill 7000compounds have already been isolated, and 5000
multidrug-resistant strains of Plasmodium falciparum havebeenidentifiedfromthisfamily,oftenassociatedwith
[3,62]. Several semisynthetic derivatives of artemisinin some bioactivity [3]. Members of the Asteraceae are
(e.g., the water-soluble artesunate) have been developed claimed to have various properties: antipyretic, anti-
and areusedinclinicalpractice today[62]. inflammatory, detoxifying, antibacterial, wound-healing,
There are three major protozoan parasitic infections, antihemorrhagic, antalgic (also for headaches), anti-
caused by Plasmodium, Leishmania and Trypanosoma spasmodic, and anti-tussive, and have been considered
species. Plasmodium is the most significant of the beneficial for flatulence, dyspepsia, dysentery, lumbago,
protozoanparasitesthatinfecthumans.Foundintropical leucorrhoea, hemorrhoids, hypotension, and most impor-
and sub-tropical regions of the world, malaria parasites tantly, some are hepatoprotective, antitumor and anti-
threaten the lives of 3.3billion people and cause 0.6– parasitic [68]. The majority of studies on Asteraceae
1.1milliondeathsannually[70].SixspeciesofPlasmodium throughout the world have focused on chemical analysis
areresponsibleforcausingmalariainhumans[144],with (nearly 7000compounds already isolated). There are
PlasmodiumfalciparumandPlasmodiumvivaxbeingthe many papers onin vitro studies, especially on antimicro-
mostcommon and majorcauses.Leishmaniasis iscaused bial, antioxidant and anticarcinogenic properties, using
by Leishmania sp., generating 1–1.5million new cases selectedcellsandcrudeextractsorpurifiedcompounds.In
annually[104].Thediseaseisendemicin98countriesand the few published reviews on pure compounds, the
isoneoftheneglectedtropicaldiseaseswherethemajority structure-activity relations were studied as well as their
oftheaffectedindividualsarerural,underprivileged,and mechanism of action. Despite the discovery of a large
economically disadvantaged. African sleeping sickness number of compounds in Asteraceae around the world,
(trypanosomiasis),iscausedbytwoparasiticprotozoans: and the reported antiparasitic properties of members of
Trypanosoma brucei gambiense (West Africa) and the Asteraceae family, not many bioactivity studies on
Trypanosoma brucei rhodesiense (East Africa) [15]. Asteraceaespecieshaveyetbeencarriedout.InIndia,the
African trypanosomiasis threatens the lives of approxi- family is representedby900speciesfrom167genera.
mately60millionpeopleinsub-SaharanAfricaandisfatal Due to their bioactive properties, plants from the
if untreated [70]. Another species of Trypanosoma (T. Asteraceae family are commonly used in the traditional
cruzi) is responsible for Chagas disease (American treatment of various diseases (Table 1). For instance,
trypanosomiasis), and threatens the lives of millions Ageratum conyzoides has been commonly used in India
primarilyinMexico,LatinAmericaandtheUnitedStates. including in the state of Odisha, where the plant is
The World Health Organization estimates that 8– traditionallyusedfordiarrhoea,dysentery,intestinalcolic
10million people are infected annually. There is also no [118] and malaria. This plant is well-known for the
vaccine for Chagas disease and no clinical trials of new presenceofphytochemicalssuchasalkaloids, coumarins,
drugs are under way; current treatment depends on only flavonoids, benzofurans, sterols and terpenoids, with the
two chemotherapeutics(cid:1)benznidazoleand nifurtimox. following identified compounds: friedelin, various sterols
(including b-sitosterol and stigmasterol), various flavo-
noids, caryophyllene, coumarin, quercetin, as well as
Medicinal uses of Asteraceae with special
fumaricandcaffeicacid[51].Bidenspilosaisalsofoundin
reference to the tribes of Odisha (Orissa), Odisha, and is moreover widely used as folk medicine by
India indigenous tribes of the Amazon in the treatment of
malaria [13]. About 201compounds comprising 70ali-
ThefamilyAsteraceae(Compositae)isalsoknownas phatics, 60flavonoids, 25terpenoids, 19phenylpropa-
the daisy family, sunflower family or thistle family. noids, 13aromatics, 8porphyrins, and 6 other
Asteraceaeisderivedfromtheterm“aster”meaning“star” compounds, have been identified from this plant, as
inLatin,andreferstothecharacteristicinflorescencewith compiled previously [67]. However, the relation between
flower heads composed of florets (small flowers), and Bidenspilosa phytochemicalsandvariousbioactivitiesis
surroundedbybracts[12].ThefamilyAsteraceaeisoneof not yet fully established, and should become a future
the largest families comprising 1600–1700genera and researchfocus[7].Blumealaceraisusedforthetreatment
S.K. Panda and W. Luyten: Parasite 2018, 25, 10 3
Table1. TraditionalusesofplantsoftheAsteraceaefamily
Plant1 TraditionalusesbythetribesofOdisha Other partsofIndia/world
Ageratum conyzoides(L.) L. Herbinfusionisgivenforgastrointestinal Asworm medicinein Cameroon[157].
ailmentssuchas diarrhoea,dysenteryand
intestinalcolicwithflatulence[117,120].Cold
decoctionsfrom theaerial partsareusedtocure
malarialfever(unpublished observations).
Bidenspilosa L. Freshjuicefromtheaerial partsisused for Juiceformtherootand whole plantisused
intestinalworminfections, abdominalpainand forthetreatmentof malaria(Africa,China)
stomachache(unpublished observations). [142,157]. Wholeplantisused bytheBukusu
communityofKenyafortick preventionand
controlonlivestock [159].
Blumea lacera (Burm.f.)DC. Thetribesusefreshleafjuiceofthisplantfor Leafjuiceisused tokillwormsinchildren
thetreatment ofallkinds offever,including bythetribesofMadhyaPradesh, India[136].
malaria(unpublished observations).
CalendulaofficinalisL. Colddecoction ofleafisusedforamoebic and Flowersareused forthetreatmentof
bloodydysentery(unpublished observations). intestinalwormsandamoebal infectionsin
petsandpigsinBritishColumbia,Canada[64].
CaesuliaaxillarisRoxb. Wholeplantextractisgiventocure malaria Thewhole plantiscrushed andjuiceis
[113]. extracted,whichisgivenorally threetimesa
day, alongwithcurdtocure amoebic
dysenterybythetribesofMadhyaPradesh,
India[155].
Centipeda minima(L.) Rootdecoction isusedforthetreatment ofall InChina, decoctionfromwhole plant isused
A.Braun& Asch. kinds offever[112]. Leafdecoctioniscommonly formalariatreatment. Theseed ordried
used forhookwormand roundworm aerialpartsareused asa vermifugeand
(unpublishedobservations). amoebicide(http://uses.plantnet-project.org/
en/Centipeda_minima_(PROSEA).
Eclipta alba(L.)Hassk. Treatmentofmalaria[112]. Leafdecoctionisused bytheRakhaintribal
healersofChittagongDivision,Bangladesh
forthetreatmentof malaria[46].
Eclipta prostrata(L.)L. isa Treatmentofmalaria:decoction ofdriedleaf Infusionor juiceoftheplant mixedwith
synonymofEclipta alba(L.) withtealeaftinctureisadministeredorally honeyisgivenforthetreatment ofmalaria
Hassk. twicea dayforfivedays[118]. bythetribalcommunities ofPakistan[86].
Elephantopus scaberL. Treatmentofmalaria:pastepreparedfromfresh Decoctionfrom aerialpartsisused totreat
rootistakenorallyonceadayforthreedays[118]. malariabythetribesofMadagascar[86].
Juiceofleafisusedinthetreatmentofmalaria[53].
Sphaeranthus indicusL. Helminths:whole plantpaste witha pinchof Rootand seedpowder isgivenorally tokill
saltistakenas ananthelmintic [107]. intestinalwormsinchildren[39]. Whole
plantpaste withapinch ofcommonsaltis
takenasan anthelmintic[61].
TageteserectaL. Colddecoctions ofleafandflowerareused for Plantsused bynativeAmazoniangroups
allkinds ofworm infectionsanddysentery fromthe NanayRiver(Peru)forthe
(unpublishedobservations). treatment ofmalaria[61].
Tridax procumbens(L.)L. Decoctionpreparedfrom leaves ofTridax Usedforthetreatment ofmalariabythe
procumbensand Andrographispaniculata tribesofGhana[59], andKwalecommunity
(Burm.f.)Nees isused forthetreatment of oftheKenyan Coast[90].
malariafever (unpublishedobservations).
4 S.K. Panda and W. Luyten: Parasite 2018, 25, 10
Table 1. (continued).
Plant1 TraditionalusesbythetribesofOdisha Other partsofIndia/world
Vernoniaanthelmintica (L.) Fruitpowder isused inmalariafever,and for Theseedsareused asan anthelmintic
Willd.This name isa stomachacheduring amoebic dysentery[81]. againstparasiticworm (includingtapeworm)
synonymofBaccharoides Seedsareusedas ananthelmintic,especially in infestations[4].
anthelmintica (L.)Moench. children(2-5g withwateron anempty stomach
andCentratherum twicea dayforthreedays) [111,112].
anthelminticum(L.)Kuntze
VernoniaalbicansDC. Filariasis:powderedplant(10-20g)isadvisedto –
This nameisa synonymof beconsumedwith125mLmilk(mixedwith
Cyanthilliumalbicans(DC.) 5-7cardamomfruitsand10gsugarcandy)once
H.Rob. dailyinthemorning,onanemptystomach,for
aboutthreemonths[37].Water-extractofthe
wholeplantisusedinthetreatmentofmalaria[53].
Vernoniacinerea (L.)Less. Treatmentofmalaria;root pasteismixedwith Leafandbark areused bythetribesof
This nameisa synonymof honeyandadministeredorally twice adayfor EquatorialGuinea asfebrifugeandvermifuge
Cyanthilliumcinereum(L.) threedays[118]. Theplantisalsoused for [2],while thetribesofTanzania useitforthe
H.Rob. elephantiasis[120]. treatment ofmalaria[84].
Xanthium strumariumL. CoastaltribesofOdisha usecrushedfresh fruit TribesofBannudistrict,Pakistan,useitfor
forthetreatmentoffilariasis(unpublished thetreatment ofchronicmalaria[154].
observations).
1AlltaxonomicnameswereverifiedintheGlobalCompositeChecklistdatabase(http://compositae.landcareresearch.co.nz/Default.aspx)
of all kinds of fever, including malaria, and contains topin, isodeoxyelephantopin, scabertopin, and isoscaber-
phytocompounds such as fenchone, coniferyl alcohol topin, and lipids like ethyl hexadecanoate, ethyl-9,
derivatives, campesterol, flavonoids, lupeol, hentriacon- 12-octadecadienoate, ethyl-(Z)-9-octadecenoate, ethyl
tane, hentriacontane, a-amyrin, b-sitosterol and triter- octadecanoate,lupeolandstigmasterol[19].Wholeplant
penes [7,80,105]. Calendula officinalis has found many pasteofSphaeranthusindicuswithapinchofsaltistaken
medicinal applications and contains various terpenoids as an anthelmintic by the tribes of Odisha [111]. The
(sitosterols,stigmasterols,erythrodiol,brein,ursadioland phytochemicalstudiesofthisplantsuggestthepresenceof
its derivatives; several triterpene glycosides like calen- eudesmanolides,sesquiterpenoids,sesquiterpenelactones,
dulaglycosideA;glucosidesofoleanolicacid,etc.),various sesquiterpene acids, flavone glycosides, flavonoid
flavonoids (quercetin, isoquercetin, isorhamnetin-3-O- C-glycosides, isoflavone glycosides, sterols, sterol glyco-
b-D-glycoside,narcissin,calendoflaside,calendoflavoside, sides,alkaloids,peptidealkaloids,aminoacidsandsugars
calendoflavobioside, rutin, quercetin-3-O-glucoside and [125]. The essential oil from this plant has been well
quercetin-3-O-rutinoside), coumarins, saponins and qui- studied with the documented presence of bioactive
nones[87]. compounds like sphaeranthine, sphaeranthol, spharerne,
WholeplantextractsofCaesuliaaxillarisarefrequently methyl chavicol, ocimene, geraniol, and methoxy frulla-
used by the coastal tribes of Odisha to cure malaria nolides [71]. Tagetes erecta is an ornamental plant of
[107,113],butnoscientificstudieshaveyetbeenpublished Odishaandisoftenusedbythetribesforthetreatmentof
on this plant. Centipeda minima is widely distributed in various conditions such as anaemia, irregular menstrua-
Odisha, and is frequently used by the local tribes for the tion, abdominal pain, colic, cough and dysentery. Like
treatmentofparasites[112],butnocompoundsresponsi- Sphaeranthusindicus,thisplantisalsowellknownforits
bleforitsantiparasiticactivitieshaveyetbeenidentified. phytoconstituents such as b-sitosterol, b-daucosterol, 7-
Ecliptaprostrata(synonymE.alba)isfrequentlyusedby hydroxy sitosterol, lupeol, erythrodiol, erythrodiol-3-
thetribesforthetreatmentofmalaria[113,130].Theplant palmitate, quercetagetin, quercetagetin-7-methyl ether,
is well studied for its phytochemistry, with documented quercetagetin-7-O-glucoside, gallic acid, syringic acid,
presence of compounds such as eclipline, b-amyrin, quercetin,ocimeneandtagetone[135].Tridaxprocumbens
luteolin-7-O-glucoside,apigenin,cinnaroside,stigmasterol, has been extensively used in Ayurvedic medicine and is
wedelolactone, columbin, triterpene glycosides and well-studied for its phytochemistry, with the presence of
triterpenicacid[47].LikeEcliptaprostrata,Elephantopus compounds like 8,30-dihydroxy-3,7,40-trimethoxy-6-O-
scaber is also frequently used by the tribes for the b-D glucopyranoside flavonol, apigenin-7-O-b-D-gluco-
treatmentofmalaria[118].Thisplantisalsowellstudied side,pentadecane, b-sitosterol,stigmasterol,b-daucesos-
for its phytochemistry with documented presence of terol and bis-(2-ethylhexyl)-phthalate [131]. Several
sesquiterpenelactones such as elescaberin, deoxyelephan- speciesofVernoniahavebeenusedindifferenttraditional
S.K. Panda and W. Luyten: Parasite 2018, 25, 10 5
medicines all over the world. The tribes of Odisha most brevilinAfromCentipedaminimaanddehydrozaluzanin
frequently use different species of Vernonia: V. anthel- CfromMunnoziamaroniiwerediscoveredandreportedas
mintica, V. albicans and V. cinerea. Seeds of Vernonia antiparasitic. Similarly, sesquiterpene lactones from
anthelmintica are used as an anthelmintic, especially in Neuroleaenalobataarewellestablishedforthetreatment
children: 2-5g with water on an empty stomach twice a of Plasmodium infections [28]. In this plant, structure-
day for three days [111,112]. Fruit powder is used in activity relationship analysis revealed that germanocre-
malaria fever, and stomach ache during amoebic dysen- nolidesesquiterpenes,likeneuroleninA(EC =0.92mM)
50
tery [81]. Powdered Vernonia albicans plant (10-20g) is and B (EC =0.62mM), were more potent than furano-
50
advisedtobeconsumedwith125mLmilk(mixedwith5- heliangolides like lobatin A and B (EC =15.62mM and
50
7cardamom fruits and 10g sugar candy) once in the 16.51mM), respectively, against Leishmania promasti-
morning,onanemptystomachforaboutthreemonthsfor gotes and Trypanosoma epimastigotes [28]. Based on
thetreatmentoffilariasis[37].Theaqueousextractofthe ethnozoologicalstudies(wildchimpanzeeswereobserved
whole plant is also used in the treatment of malaria [53]. to chew young stems of Vernonia amygdalina), anti-
Root paste of Vernonia cinerea mixed with honey is plasmodial sesquiterpenes vernodalin and vernolide,
administeredorallytwiceadayforthreedaysformalaria hydroxyverniladinhavebeenisolated[60].Oketch-Rabah
[108].Reportsarealsoavailableontheuseofthisplantfor et al. [101] observed that macrocyclic germancrane
the treatment of elephantiasis [108]. Toyang and Ver- dilactone 16,17-dihydrobrachycalyxolide from Vernonia
poorte [152] published a review article on this genus brachycalyx has both antileishmanial and antiplasmodial
Vernonia(109species)concerningitsethnopharmacology activity.
and phytochemistry. Xanthium strumarium is a weed, PhenolsarewidelydistributedinAsteraceae,andsome
widely distributed in Odisha, and commonly used as a have the ability to inhibit parasites. Gallic acid and its
medicinalplant.Mostofitspharmacologicaleffectscanbe derivativesinhibittheproliferationofTrypanosomacruzi
explained by constituents like sesquiterpene lactones, trypomastigotes in vitro [58]. Higher activities were
glycosides, phenols, as well as polysterols present in all observed for the gallic acid esters ethyl-gallate and n-
plant parts. The bioactive compounds reported for this propyl-gallate,whichhadEC valuesof2.28and1.47mg/
50
plantsarexanthinin,xanthumin,xanthatin(deacetylxan- mL, respectively, possibly due to increased lipophilicity.
thinin), a toxic principle, namely a sulphated glycoside: Oketch-Rabah et al. [101] reported the antiprotozoal
́
xanthostrumarin, atractyloside, carboxyatractyloside, activityfromVernoniabrachycalyx(2-epicycloisobrachy-
phytosterols, xanthanol, isoxanthanol, xanthinosin, coumarinone epoxide and its stereoisomer). Both stereo-
4-oxo-bedfordia acid, hydroquinone, xanthanolides, caf- isomers show similar in vitro activities against
feoylquinic acids, a- and g-tocopherol, thiazinedione and chloroquine-sensitive (CQ-S) and chloroquine-resistant
deacetyl xanthumin, b-sitosterol, g-sitosterol, b-D-gluco- (CQ-R) strains for Plasmodium falciparum, as well as
side of b-sitosterol; isohexacosane, chlorobutanol, stearyl Leishmania major promastigotes, with EC values of
50
alcohol,stromasterolandoleicacid[52]. 0.11mg/mLand0.15mg/mLforPlasmodiumfalciparum,
and 37.1mg/mL and 39.2mg/mL for Leishmania major,
respectively. Like phenols, flavonoids are extensively
Miscellaneous antiparasitic properties of present in Asteraceae plants. Elford et al. [21] demon-
Asteraceae and their phytochemistry strated that methoxylated flavonones artemetin and
casticin act synergistically with artemisinin in vitro
Overthepastdecades,alotofresearchonantiparasitic against Plasmodium falciparum. Later, exiguaflavanone
drugsofplantoriginhasyieldedundisputablemetabolites A and B, isolated from Artemisia indica (Asteraceae),
of interest. Many plant-derived secondary metabolites of wereshowntoexhibitinvitroactivityagainstPlasmodium
Asteraceaehaveexhibitedtarget-specificactivityagainst falciparum.
Plasmodium, Leishmania and Trypanosoma parasites Theflavonoidscanbeclassifiedintoseveralsubtypes:
(Table 2). Plants from the Asteraceae family are widely flavone (1), flavonol (2), flavanone (3), dihydroflavonol
usedasmedicinesduetothepresenceofabroadrangeof (4), flavan-3-ol (5), flavan-3,4-diol (6), chalcone (a
bioactivemetabolitessuchasalkaloids(pyrrolizidineand structure with one opened ring), aurone, and anthocya-
pyridine), flavonoids, phenolic acids, coumarins, terpe- nidine(withapositivechargeonoxygenO-1).Exceptfor
noids (monoterpenes, sesquiterpenes, diterpenes, and thesebasicstructures,flavonoidsalsoexistinbiflavonoid
triterpenes),quinolineandditerpenoidtypes,triterpenoid and glycosidic form in the Asteraceae family. Perez-
sesquiterpene lactones,pyrethrins, and saponins.Several Victoriaetal.[122]suggestedthatflavonoidscouldaffect
sesquiterpenes have been reported as antiprotozoal since transport mechanisms in Leishmania. The C-terminal
the discovery of artemisinin. The sesquiterpene lactone nucleotide-bindingdomainofaP-glycoprotein-liketrans-
parthenin is effective against Plasmodium falciparum in porter,encodedbytheltrmdr1geneinLeishmaniatropica
vitro,withanEC valueof1.29mg/mL[123].Partheninis andinvolvedinparasitemultidrugresistance(MDR),was
50
capable of blocking parasite-specific targets responsible overexpressed in Escherichia coli as a hexahistidine-
forglutathinonylspermidineandtrypanothionesynthesis tagged protein and purified. The Leishmania tropica
from cysteine and glutathione precursors in both Leish- recombinantdomainefficientlybounddifferentclassesof
maniaandTrypanosoma[32].Thesesquiterpenelactones flavonoids with the following relative affinity: flavone>-
6 S.K. Panda and W. Luyten: Parasite 2018, 25, 10
Table2. TherapeuticusesofimportantplantsoftheAsteraceaefamilyreportedasanantiparasitic
Plant1 Plant part Pharmacological Preparation Organism tested Context Reference
used ofuse
Acanthospermum Wholeplant Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
hispidumDC. Leishmania braziliensis
Aerialpart Antitrypanosomal Dichloromethane/ Trypanosoma brucei In vitro [10]
Methanol/ Aqueous brucei
Achyroclineflaccida Wholeplant Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
(Weinm.)DC.
Ageratina Leaf Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
pentlandiana(DC.) Leishmania braziliensis In vitro [69]
R.M. King&H. Rob.
Ageratum Wholeplant Antiparasitic Organic (hexane, Trypanosoma brucei In vitro [98]
conyzoides (L.)L. ethyl acetate, Trypanosoma brucei
chloroform, rhodesiense
methanol)and Trypanosoma cruzi
aqueous extracts Leishmania donovani
Plasmodiumfalciparum
Wholeplant Chagasdisease Aqueousand Trypanosoma cruzi In vitro [149]
ethanolic
Wholeplant Antileishmanial Aqueousand Leishmaniaamazonensis In vitro [149]
ethanolic
Leaf Antiparasitic Aqueousand Heligmosomoides bakeri In vitro [157]
ethanolextract
Leaf Antiparasitic Ethanol extract Rhipicephalusmicroplus In vitro [115]
Artemisiaabsinthium Flower Antiparasitic Di-ethyl ether Toxocara cati In vivo [163]
L. essential oil Trypanosoma cruzi In vitro [74]
Trichomonas vaginalis
Trypanosoma cruzi In vitro [5]
Leishmania infantum
Leaf Schistosomicidal Dichloromethane Schistosoma mansoni In vitro [20]
Artemisiaabyssinica Aerialpart Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [94]
Sch.Bip. exA.Rich. Methanol brucei
Dichloromethane Trypanosoma In vivo [25]
congolense
Aerialpart Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [94]
Methanol brucei
Artemisiaafra Jacq. Leaf Antitrypanosomal Dichloromethane Trypanosoma brucei In vitro [82]
exWilld. rhodesiense /
Trypanosoma cruzi.
Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [94]
methanol brucei
Antimalarial Acetone Plasmodiumfalciparum In vitro [85]
NF54
ArtemisiaannuaL. Aerialpart Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [94]
Methanol brucei
Artemisia – Antileishmanial Aqueous Leishmania tropica In vitro [43]
herba-alba Asso
Baccharissalicifolia Leaf Antileishmanial Ethyl acetate Leishmania braziliensis In vitro [27]
(Ruiz& Pav.)Pers. extract
BaccharisuncinellaDC. Leaf Antileishmanial Ursolic acid Leishmania infantum In vivo [49]
S.K. Panda and W. Luyten: Parasite 2018, 25, 10 7
Table 2. (continued).
Plant1 Plant part Pharmacological Preparation Organism tested Context Reference
used ofuse
Bidenspilosa L. Leaf Antimalarial Organic extracts Plasmodiumfalciparum In vitro [13]
and fractions
Antimalarial Organic extracts Plasmodiumfalciparum In vitro [102]
Antimalarial Organic extracts Plasmodiumfalciparum In vitro [151]
Antimalarial Organic extracts Plasmodiumfalciparum, invitro & [63]
Plasmodiumberghei invivo
NK-65 (mice)
Anthelmintic Ethanol extract Haemonchus contortus In vitro [36]
Antileishmanial Crude extracts Leishmaniaamazonensis In vitro [35,49,151]
Blumea lacera Leaf Anthelmintic Alcoholic and Ascarislumbricoides In vitro [119]
(Burm.f.)DC. aqueous extracts Pheretima posthuma
Calendula Flower Antileishmanial Methanol (80%) Leishmania major In vitro [95]
officinalisL.
Antiparasitic Oleanolic acid Heligmosomoides invitro & [145]
and itsglycosides polygyrus invivo
(mice)
Centipeda Wholeplant Antiparasitic Crude extracts Giardia intestinalis In vitro [164]
minima (L.) and fractions
A.Braun& Asch. Entamoeba histolytica
Plasmodiumfalciparum
Chersodoma Leaf Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
jodopappa Cabrera Leishmania braziliensis
Stem Antileishmanial Ethanol extract Leishmania donovani In vitro [27]
Cichorium intybusL. Leaf Anthelmintic Methanol:water Ascarissuum In vitro [160]
Oesophagostomum
dentatum
Cnicothamnus Leaf Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
lorentziiGriseb. Leishmania donovani
Stem Antileishmanial Ethanol extract Leishmania braziliensis In vitro [27]
Conyza albidaWilld. Wholeplant Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [82]
exSpreng. methanol rhodesiense,
Trypanosoma cruzi
Conyza podocephala Wholeplant Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [82]
DC. methanol rhodesiense,
Trypanosoma cruzi
Conyza scabridaDC. Leaf Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [82]
methanol rhodesiense,
Trypanosoma cruzi
Echinaceapurpurea Wholepart Antileishmanial Ethanol extract Leishmania sp. In vitro [114]
(L.)Moench
Eclipta alba(L.) Leaf Antimalarial Crude extract Plasmodiumberghei In vivo [6]
Hassk.
Antileishmanial Crude extract Leishmania donovani In vitro [138]
Eclipta prostrata Leaf Anthelmintic Ethanol and Pheretima posthuma In vitro [11]
(L.)L. activity aqueous extracts
8 S.K. Panda and W. Luyten: Parasite 2018, 25, 10
Table 2. (continued).
Plant1 Plant part Pharmacological Preparation Organism tested Context Reference
used ofuse
Leaf Anthelmintic Organic extracts Pheretima posthuma In vitro [50]
activity
Leaf Antileishmanial Saponin, Leishmania major, In vitro [56]
dasyscyphin C
Leishmania aethiopica,
Leishmania tropica
Wholeplant Anthelmintic Organic and Haemonchus contortus In vitro [139]
activity water extracts
Elephantopus Leaf Antitrypanosomal Organic extracts Trypanosoma brucei In vitro [165]
scaberL. and sesquiterpene rhodesiense
lactone
Helichrysum Wholeplant Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [82]
nudifolium(L.) Less. methanol rhodesiense,
Trypanosoma cruzi
Inulamontana L. Aerialpart Antileishmanial Methanol Leishmania infantum In vitro [73]
Jasoniaglutinosa(L.) Aerialpart Antileishmanial Acetone Leishmania donovani In vitro [156]
DC.
Kleinia odora Wholeplant Antiparasitic Ursane, Trypanosoma brucei In vitro [89]
(Forssk.)DC. triterpenes Trypanosoma cruzi
oflupane Leishmania infantum
Plasmodiumfalciparum
Munnozia fournetii Leaf Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
H.Rob.(unresolved
name)
Leishmania donovani
Stem Antileishmanial Ethanol extract Leishmania braziliensis In vitro [27]
Neurolaena lobate(L.) Leaf Antileishmanial Ethanol extract Leishmania mexicana In vitro [9]
R.Br.exCass.
Leishmania braziliensis
Oedera genistifolia Wholeplant Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [82]
(L.)Anderb. & K. methanol rhodesiense,
Bremer Trypanosoma cruzi
Ophryosporus Wholeplant Antileishmanial Ethanol extract Leishmania In vitro [27]
piquerioides(DC.) amazonensis
Benth. exBaker Leishmania braziliensis
PentziaglobosaLess. Root Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [82]
methanol rhodesiense
/Trypanosoma cruzi
Perezia multiflora Leaf Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
(Humb.& Bonpl.) Leishmania braziliensis
Less.
Leishmania donovani
Pterocaulon Wholeplant Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
alopecuroideumChodat Leishmania braziliensis
(unresolvedname)
Leishmania donovani
S.K. Panda and W. Luyten: Parasite 2018, 25, 10 9
Table 2. (continued).
Plant1 Plant part Pharmacological Preparation Organism tested Context Reference
used ofuse
Senecioclivicolus Leaf Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
Wedd. Leishmania donovani
Stem Antileishmanial Ethanol extract Leishmania braziliensis In vitro [27]
Solaneciomannii Leaf Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [94]
(Hook.F)C.Jeffrey methanol brucei
Sphaeranthus Wholeplant Anthelmintic Ethanolic and Pheretima posthuma, In vitro [134]
indicusL. aqueous extracts Ascaridia galli
Leaf Macrofilaricidal Methanolic Setaria digitata In vitro [96]
activity
Steviayaconensis Wholeplant Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
Hieron. Leishmania braziliensis
Leishmania donovani
TageteserectaL. Root Antimalarial Organic and Plasmodiumfalciparum In vitro [41]
aqueous extracts
Flower Anthelmintic Organic extracts Pheretima posthuma In vitro [106]
Tithoniadiversifolia Leaf Antitrypanosomal Dichloromethane: Trypanosoma brucei In vivo [103]
(Hemsl.)A.Gray methanol brucei
Tridaxprocumbens Wholeplant Antileishmanial Organicextracts Leishmania mexicana In vitro [75]
(L.)L. property and(3S)-16,17
didehydrofalcarinol
Methanolextract Leishmania mexicana In vivo [33]
andincombination
withAlliumsativum
Oxylipin, (3S)-16,17- Leishmania mexicana In vitro [75]
didehydrofalcarinol
Vernonia Wholeplant Anthelmintic Aqueousand Haemonchus contortus invitro & [45]
anthelmintica (L.) methanolic extracts invivo
Willd.
Seed Anthelmintic Ethanolic extract Haemonchus contortus In vitro [44]
Seed Anthelmintic – Haemonchus contortus In vivo [93]
(buffaloes)
Vernoniaauriculifera Root Antitrypanosomal Dichloromethane Trypanosoma brucei In vitro [29]
Hiern rhodesiense
Vernoniahirsute Wholeplant Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [82]
(DC.)Sch. Bip.ex methanol rhodesiense,
Walp. Trypanosoma cruzi
Vernoniamespilifolia Leaf Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [82]
Less. methanol rhodesiense,
Trypanosoma cruzi
Vernonianatalensis Wholeplant Antitrypanosomal Dichloromethane: Trypanosoma brucei In vitro [82]
Oliv. &Hiern methanol rhodesiense,
Trypanosoma cruzi
Vernoniaoligocephala Leaf Antitrypanosomal Dichloromethane Trypanosoma brucei In vitro [82]
Katt rhodesiense,
Trypanosoma cruzi
10 S.K. Panda and W. Luyten: Parasite 2018, 25, 10
Table 2. (continued).
Plant1 Plant part Pharmacological Preparation Organism tested Context Reference
used ofuse
Vernoniasquamulose Stem Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
Hook. &Arn. Leishmania braziliensis
Leishmania donovani
Wernerianubigena Leaf Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
Kunth Leishmania donovani
Stem Antileishmanial Ethanol extract Leishmania braziliensis In vitro [27]
Xanthium catharticum Leaf Antileishmanial Ethanol extract Leishmaniaamazonensis In vitro [27]
Kunth Leishmania donovani
Stem Antileishmanial Ethanol extract Leishmania braziliensis In vitro [27]
Xanthium strumarium Leaf Antitrypanosomal 50% ethanolic Trypanosoma evansi In vitro [147]
L. extract andin
vivo
Fruit Antimalarial Methanol: water Plasmodiumfalciparum In vitro [153]
extract strainFCR-3
1AlltaxonomicnameswereverifiedintheGlobalCompositeChecklistdatabase(http://compositae.landcareresearch.co.nz/Default.aspx)
flavanone>isoflavone>glucorhamnosyl-flavone. The af- Leishmania tropica (Table 3). A sesquiterpene lactone
finity was dependent on the presence of hydroxyl groups (deoxyelephantopin) was isolated by Zahari et al. [165]
at positions C-5 and C-3, and was further increased by a from E. scaber and proved active against Trypanosoma
hydrophobic1,1-dimethylallylsubstituentatpositionC-8. brucei rhodesience. Similarly, T. procumbens showed
Brandio et al. [13] first reported the antimalarial significant antileishmanial activity against promastigotes
activityofcrudeextractsandtheirfractionsfromdifferent ofLeishmaniamexicana.Theactiveprinciplewasfoundto
speciesofBidens,andprovidedevidencethatthisisdueto beanoxylipin,namely(3S)-16,17-didehydrofalcarinol[76].
the presence of polyacetylene and flavonoids. Later,
Kumari et al. [63] and Tobinaga et al. [151] isolated the
polyacetylene compound (R)-1,2-dihydroxytrideca- Antiparasitic activity of flavonoids and
3,5,7,9,11-pentaynefromleafextractsofB.pilosa,which terpenoids documented in Asteraceae
showed promising antimalarial activity against Plasmo-
diumfalciparum(Table3).Moreover,thiscompoundwas Flavonoids are the class of compound of highest
testedinaninvivomodel(miceinfectedwithPlasmodium occurrence, wide structural diversity, and chemical
berghei NK-65 strain), and results showed that the stability. They have been isolated on a large scale from
compound can decrease the average parasitaemia in red Asteraceaespeciesandcanbeusedastaxonomicmarkers
blood cells,but furtherstudies addressing itsmechanism at lower hierarchical levels [75]. Flavones and flavonols
arerequired.ThegenusCalendulaisverywellstudiedfor are common throughout the Asteraceae, i.e., glycosides
its phytochemistry, with triterpene alcohols, triterpene of apigenin, luteolin, kaempferol, quercetin, flavanone
saponins, flavonoids, carotenoids and polysaccharides as derivatives, ((cid:1))-epicatechin and ((cid:1))-epigallocatechin
themajorclassesofphytoconstituents.Szakieetal.[145] (Figure 1). Although there are fewer reports on anti-
isolated several oleanolic acid glycoside derivatives and giardial activity in Asteraceae, these compounds from
tested them against Heligmosomoides polygyrus; the other families are well-studied against G. lamblia. From
wormicidal activity of the oleanolic acid glycosides was theaerialpartsofHelianthemumglomeratum(Cistaceae),
superior to that of the aglycone, and the level of activity kaempferol, quercetin, ((cid:1))-epicatechin and ((cid:1))-epigallo-
wasdependentonthenatureofthesugarside-chainatthe catechin have shown antigiardial activity against
C-3position.Thefirstsugarmoleculeoftheglucuronides, G. lamblia (in vitro), with IC values of 26.47, 8.73,
50
i.e., the glucuronic acid attached to the aglycone, 1.64and8.06mg/mL,respectively[17].Structure-activity
appeared to be vital for the antiparasitic properties of correlation implies that the 2,3-double bond and 4-keto
thesecompounds[145].E.prostratawasstudiedbyseveral groupofflavonesmightnotberequiredforantiprotozoal
scientists for its antiparasitic properties such as antima- activity since both ((cid:1))-epicatechin and ((cid:1))-epigalloca-
larial [6], antileishmanial [56,138], and anthelmintic techinlackthesestructuralunits,yetmaintainbiological
activities[11,50]. Khannaetal. [56]isolated dasyscyphin activity(Figure1).Also,unlikeflavones,thebenzenediol
Cfromtheleavesandproveditsantileishmanialactivities moietyof((cid:1))-epicatechinand((cid:1))epigallocatechinisnot
against Leishmania major, Leishmania aethiopica and coplanar with the heterocyclic part because C-2 of their